418 Unit 4 Pharmacology of the Central Nervous System
CONNECTIONS: NURSING PRACTICE APPLICATION (continued)
Implementation
Interventions and (Rationales) Patient-Centered Care
Ensuring therapeutic effects: • Teach the patient that pain relief, rather than merely control, is the goal
• Continue assessments as above for therapeutic effects. Give the drug of therapy.
before the start of acute pain when possible. (Consistent use of a pain • Encourage the patient to take the drug before a headache becomes
rating scale by all providers will help quantify the level of pain relief and severe, and to take it consistently as ordered.
leads to better pain control. Encourage the patient to start medication
before the headache becomes severe for better control. Pain relief • Explain the rationale behind the pain rating scale (i.e., it allows
begins within several minutes after administration.) consistency among all providers).
• Encourage the patient to use additional, nonmedicinal pain relief
techniques (e.g., quiet, darkened, cool room).
Minimizing adverse effects: • Instruct the patient to immediately report any chest pain or tightness,
• Monitor blood pressure and pulse periodically, especially in patients or throat pain that is severe or continues following drug dosage.
at risk for undiagnosed cardiovascular disease. Cardiovascular
status should be monitored frequently following the first dose
given. (Triptans and ergot alkaloids cause vasoconstriction.
Lifespan: Postmenopausal women, men over age 40, smokers,
and people with other known coronary artery disease risk factors
may be at greatest risk. Older adults may have undetected
cardiovascular disease, placing them at greater risk for adverse
effects.)
• Observe for changes in severity, character, or duration of headache. • Instruct the patient to immediately report changes in character or
(Sudden severe headaches of “thunderclap” quality can signal duration of headache or if accompanied by additional symptoms such
subarachnoid hemorrhage. Headaches that differ in quality and are as fever, rash, or stiff neck.
accompanied by such signs as fever, rash, or stiff neck may herald
meningitis.)
• Continue to monitor neurologic status periodically. (Dizziness or • Instruct the patient to immediately report increasing dizziness,
lightheadedness may be related to headache, an adverse drug effect, lightheadedness, or blurred vision.
or may signal cerebral ischemia.)
• Monitor dietary intake of foods that contain tyramine, caffeine, alcohol, • Encourage the patient to keep a food diary and correlate symptoms
or other food triggers. (Some foods or beverages may trigger an acute with specific foods or beverages. Teach the patient to avoid or limit
migraine. Correlating symptoms with food or beverages assists in foods containing tyramine, such as pickled foods, beer, wine, and
avoiding the cause of the headache.) aged cheeses, which are often known triggers for migraines.
• Encourage the patient to discuss other methods of migraine • Instruct the patient to discuss treatment options for long-term migraine
control if ergot alkaloids are required for more than short-term relief with the healthcare provider.
use. (Ergot alkaloids cause significant vasoconstriction and cause
dependence. Other, safer drugs may be needed for long-term
relief of migraines.)
• Lifespan: Women who are planning a pregnancy, pregnant, or • Teach women of childbearing age to discuss the use of antimigraine
breastfeeding, should discuss the use of drug therapy and alternative drugs before planning a pregnancy and to discontinue use if pregnant
treatment before using antimigraine drugs. (Triptans are known to or breastfeeding unless directed otherwise by the provider.
cause birth defects in animals. Ergotamine and other ergot alkaloids
are category X drugs.)
Patient understanding of drug therapy: • The patient, family, or caregiver should be able to state the reason for
• Use opportunities during administration of medications and during the drug, appropriate dose and scheduling, what adverse effects to
observe for, and when to report them.
assessments to discuss the rationale for drug therapy, desired
therapeutic outcomes, commonly observed adverse effects,
parameters for when to call the healthcare provider, and any necessary
monitoring or precautions. (Using time during nursing care helps to
optimize and reinforce key teaching areas.)
Patient self-administration of drug therapy: • Teach the patient:
• When administering the medication, instruct the patient, family, or • Take the medication at the first symptoms of a migraine if possible,
before the pain becomes severe.
caregiver in the proper self-administration of drug (e.g., take the drug • Use the drug exactly as prescribed; overuse can lead to rebound
as prescribed when needed). (Utilizing time during nurse administration headaches.
of these drugs helps to reinforce teaching.) • Proper administration of subcutaneous medication and have the
patient or caregiver return demonstrate the technique. (Pain or
redness at the injection site is common but usually disappears
within an hour after the dose is taken.)
• Appropriate intranasal dose is one spray into one nostril unless
otherwise ordered by the healthcare provider.
Chapter 25 Pharmacotherapy of Severe Pain and Migraines 419
Understanding Chapter 25
Key Concepts Summary 25.8 Mixed agonist and antagonist opioids exhibit
moderate analgesia with less risk of dependence
25.1 The primary goal of pain management is to than morphine.
reduce pain to a level that allows the patient to
continue normal daily activities. 25.9 Nonsteroidal anti-inflammatory drugs are the
preferred medications for mild to moderate pain.
25.2 Proper assessment and classification of pain
guides its treatment. 25.10 A few miscellaneous analgesics reduce pain by
acting on the central nervous system.
25.3 Healthcare providers and patients sometimes
hold myths about pain that impede optimal pain 25.11 Adjuvant analgesics have primary indications
management. other than pain control but can enhance analgesia.
25.4 Pain transmission processes allow multiple targets 25.12 The primary indication for an opioid antagonist is
for pharmacologic intervention. opioid-induced respiratory depression.
25.5 Both pharmacologic and nonpharmacologic 25.13 Migraines are a severe type of headache related to
therapies are used in pain management. specific triggers.
25.6 Opioid analgesics exert their effects by interacting 25.14 Analgesics and triptans are the primary classes of
with specific receptors in the central nervous drugs used to abort acute migraine pain.
system.
25.15 Drugs from many different classes are used for
25.7 Opioids are the preferred drugs for moderate to migraine prophylaxis.
severe pain that cannot be controlled with other
classes of analgesics.
CASE STUDY: Making the Patient Connection
Remember the patient “cold electricity” down both legs, with the left greater than
“Larry Smith” at the the right, which increases with standing and walking, as
beginning of the chapter? well as numbness of the middle toes on his left foot. He has
Now read the remainder been using mixed opioid and nonopioid analgesics for the
of the case study. Based past 8 years and previously had used SSRI antidepressants
on the information pre- as adjuvant for his pain. His current healthcare provider
sented within this chapter, weaned him off Vicodin ES about a year ago. He now takes
respond to the critical thinking questions that follow. methadone 20 mg twice a day. When the pain is not relieved,
he uses Norco for breakthrough pain. His use of Norco is
Larry Smith was being seen for an outpatient presurgery 1 to 2 doses per day. Constipation is an ongoing problem,
workup the evening before scheduled urologic surgery. requiring stool softeners and occasional laxatives.
The nurse conducts a thorough history and examination
related to his back pain and current pain management. His Critical Thinking Questions
anticipated hospital stay is 2 days postsurgery.
1. How should Larry’s postoperative pain be managed?
Larry Smith is a 68-year-old man. Vital signs are blood Is there a referral the nurse can make to facilitate effec-
pressure, 108/64 mmHg; pulse, 88 beats/min; respirations, tive pain management?
16 breaths/min. He has a well-healed midline scar on his
back from lumbar vertebrae surgery, with a shorter scar 2. How could the nurse best communicate Larry’s needs
over his right iliac crest. He moves a bit slowly with some to the postoperative nursing staff?
limited lumbar range of motion. He also uses a cane for
ambulating any distance. He describes his pain as a con- 3. What should be included in the care plan for postop-
stant dull ache in the lower back that increases with pro- erative management of analgesic adverse effects?
longed standing or walking. Larry also reports a feeling of
Answers to Critical Thinking Questions are available on the
faculty resources site. Please consult with your instructor.
420 Unit 4 Pharmacology of the Central Nervous System
Additional Case Study Outline a nursing approach to pain management for
the first 24 hours.
Rita Manson presents to the emergency department with
vomiting, severe abdominal and back pain, and jaundice. 3. What adverse effects would the nurse expect?
Her jaundice is recent but the pain and vomiting have contin-
ued for a couple of months. Her diagnostic workup reveals 4. As part of the patient’s pain management, dexametha-
advanced pancreatic cancer with metastasis to the spine. sone (Decadron) 5 mg IV is prescribed every 6 hours
for 2 days. Explain the use of corticosteroids in pain
1. What is the preferred drug for Rita’s pain manage- management.
ment? Which route of administration would be
expected initially? Answers to Additional Case Study questions are available on the
faculty resources site. Please consult with your instructor.
2. Her prescribed pain medication is morphine sulfate
2 to 10 mg IV every 2 hours as needed for pain.
Chapter Review 4. A patient with diabetes reports increasing pain and
numbness in his legs. “It feels like pins and needles all
1. The nurse is monitoring the patient for adverse effects the time, especially at night.” Which drug would the
associated with morphine. Which adverse effects nurse expect to be prescribed for this patient?
would be expected? (Select all that apply.)
1. Ibuprofen (Motrin)
1. Respiratory depression 2. Gabapentin (Neurontin)
2. Hypertension 3. Naloxone (Narcan, Evzio)
3. Urinary retention 4. Methadone
4. Constipation
5. Nausea 5. The emergency department nurse is caring for a
patient with a migraine. Which drug would the nurse
2. Several days postoperative bowel surgery, the patient anticipate administering to abort the patient’s
is eating soft food, ambulating regularly, and using migraine?
hydrocodone (Vicodin) for pain. What should the
nursing care plan include? 1. Morphine
2. Dihydroergotamine (Migranal)
1. Monitoring vital signs for respiratory depression 3. Propranolol (Inderal)
2. Inserting a urinary catheter for urinary retention 4. Ibuprofen (Motrin)
3. Weaning pain medication to prevent addiction
4. Increasing dietary fiber and fluids and 6. The nurse is caring for several patients who are
receiving opioids for pain relief. Which patient is at
administering a stool softener if needed the highest risk of developing hypotension, respira-
tory depression, and mental confusion?
3. A patient who has migraines self-administered sumat-
riptan (Imitrex) for the first time yesterday. Today, the 1. A 23-year-old woman, postoperative ruptured
patient informs the nurse that after taking the medica- appendix
tion, the patient began to experience chest pain. The
patient further states that the drug was effective in 2. A 16-year-old adolescent, post–motorcycle injury
relieving the headache. The nurse should: with lacerations
1. Encourage the patient to continue using the drug 3. A 54-year-old woman, post–myocardial infarction
because it was effective. 4. An 86-year-old man, postoperative femur fracture
2. Advise the patient to tell the healthcare provider See Answers to Chapter Review in Appendix A.
about the chest pain at the next visit.
3. Instruct the patient to contact the healthcare
provider to report the chest pain today and to not
use the sumatriptan until the healthcare provider
has been consulted.
4. Encourage the patient to lie down in a quiet room
and use cold packs during the next migraine.
Chapter 25 Pharmacotherapy of Severe Pain and Migraines 421
References www.jointcommission.org/assets/1/18/SEA_49_
opioids_8_2_12_final.pdf
Chawla, J. (2016). Migraine headache. Retrieved from Voepel-Lewis, T., Zanotti, J., Danmeyer, J. A., & Merkel, S.
http://emedicine.medscape.com/article/1142556- (2010). Reliability and validity of face, legs, activity, cry,
overview consolability behavioral tool in assessing acute pain in
critically ill patients. American Journal of Critical Care, 19,
Mayo Clinic. (n.d.). Migraine. Retrieved from http:// 55–62. doi:10.4037/ajcc2010624
www.mayoclinic.org/diseases-conditions/migraine- Wong, M., Mabuyi, A., & Gonzalez, B. (2013). First national
headache/basics/alternative-medicine/CON-20026358 survey of patient-controlled analgesia practices.
Retrieved from http://www.premiersafetyinstitute.
National Institute of Neurological Disorders and Stroke. org/wp-content/uploads/PPAHS-national-survey-
(2014). Low back pain fact sheet. Retrieved from http:// patient-controlled-analgesia.pdf
www.ninds.nih.gov/disorders/backpain/detail_
backpain.htm
The Joint Commission. (2012). Sentinel event alert issue 49:
Safe use of opioids in hospitals. Retrieved from https://
Selected Bibliography migraine pharmacotherapies. Headache: The Journal of
Head and Face Pain, 55, 3–20. doi:10.1111/head.12499
Chang, K. L., Fillingim, R., Hurley, R. W., & Schmidt, S. McNicol, E. D., Ferguson, M. C., & Hudcova, J. (2015).
(2015). Chronic pain management: Patient controlled opioid analgesia versus non-patient
Nonpharmacological therapies for chronic pain. FP controlled opioid analgesia for postoperative pain
Essentials, 432, 21–26. (Review). Cochrane Database of Systematic Reviews, 6, Art.
No. CD003348. doi:10.1002/14651858.CD003348.pub3
Dart, R. C., Surratt, H. L., Cicero, T. J., Parrino, M. W., Palmer, P. P., Royal, M. A., & Miller, R. D. (2014). Novel
Severtson, S. G., Bucher-Bartelson, B., & Green, J. L. delivery systems for postoperative analgesia. Best
(2015). Trends in opioid analgesic abuse and mortality Practice & Research Clinical Anaesthesiology, 28, 81–90.
in the United States. New England Journal of Medicine, doi:org/10.1016/j.bpa.2013.12.001
372, 241–248. doi:10.1056/NEJMsa1406143 Peck, K. R., Smitherman, T. A., & Baskin, S. M. (2015).
Traditional and alternative treatments for depression:
Drew, D., Gordon, D., Renner, L., Morgan, B., Swensen, Implications for migraine management. Headache: The
H., & Manworren, R. (2014). The use of “as-needed” Journal of Head and Face Pain, 55, 351–355. doi:10.1111/
range orders for opioid analgesics in the management head.12521
of pain. Pain Management Nursing, 15(2), 551–554. Rizzoli, P. (2014). Preventive pharmacotherapy in
doi:10.1016/j.pmn.2014.03.001 migraine. Headache: The Journal of Head and Face Pain, 54,
364–369. doi:10.1111/head.12273
Finnerup, N. B., Attal, N., Haroutounian, S., McNicol, E., Schug, S. A., & Goddard, C. (2014). Recent advances in the
Baron, R., Dworkin, R. H., . . . Wallace, M. (2015). pharmacological management of acute and chronic
Pharmacotherapy for neuropathic pain in adults: A pain. Annals of Palliative Medicine, 3, 263–275.
systematic review and meta-analysis. The Lancet doi:10.3978/j.issn.2224-5820.2014.10.02
Neurology, 14, 162–173. doi:10.1016/
S1474-4422(14)70251-0
Marmura, M. J., Silberstein, S. D., & Schwedt, T. J. (2015).
The acute treatment of migraine in adults: The
American Headache Society evidence assessment of
“I have never had surgery
before. I’m so scared of being
put to sleep.”
Patient “Elena Moore”
Chapter 26
Anesthetics and
Anesthesia Adjuncts
Chapter Outline Learning Outcomes
cc Types of Anesthesia After reading this chapter, the student should be able to:
cc Principles of General Anesthesia
cc Intravenous Anesthetics 1. Compare and contrast the four basic types of
anesthesia.
Opioid Anesthetics
PROTOTYPE Fentanyl (Sublimaze), p. 425 2. Explain the five general purposes of balanced
Benzodiazepine Anesthetics anesthesia.
PROTOTYPE Midazolam (Versed), p. 427
Miscellaneous Intravenous Anesthetics 3. Compare and contrast the four stages of general
PROTOTYPE Propofol (Diprivan), p. 428 anesthesia.
cc Inhalation Anesthetics
PROTOTYPE Nitrous Oxide, p. 430 4. Identify drug classes used to produce general
PROTOTYPE Isoflurane (Forane), p. 432 anesthesia.
cc Local Anesthetics
Classification of Local Anesthetics 5. Describe the nursing care associated with the
Esters administration of regional and general anesthesia.
PROTOTYPE Procaine (Novocaine), p. 438
Amides 6. Explain the rationale for using adjunct agents during
PROTOTYPE Lidocaine (Anestacon, Xylocaine, general anesthesia.
Zingo, Others), p. 439
cc Adjuncts to Anesthesia 7. For each of the classes shown in the chapter outline,
identify the prototype and representative drugs and
explain the mechanism(s) of drug action, primary
indications, contraindications, significant drug
interactions, pregnancy category, and important
adverse effects.
8. Apply the nursing process to care for patients
receiving local or general anesthesia.
422
Chapter 26 Anesthetics and Anesthesia Adjuncts 423
Key Terms local anesthesia, 423 neurolept analgesia, 424
regional anesthesia, 423
amide, 439 minimum alveolar surgical anesthesia, 424
balanced anesthesia, 423 concentration, 430
dissociative anesthesia, 429
esters, 437 monitored anesthesia
general anesthesia, 423 care (MAC), 423
Throughout history, the application of anesthesia has • Moderate (conscious) sedation. Patients respond to
allowed patients to experience a temporary loss of sensation, verbal or light tactile prompting. Airway, ventilation,
resulting in comfort during surgical intervention. The use of and cardiovascular functions are usually adequate.
opium as an anesthetic was recorded as far back as 4200 BC,
and the ancient Chinese recorded acupuncture as a form of • Deep sedation and analgesia. Patients are aroused by
anesthesia. The modern implementation of anesthesia dates repeated or painful stimulation. Airway and ventila-
back to 1846 when Dr. John C. Warren performed a surgical tion intervention may be required. Cardiovascular
procedure using ether. Modern anesthesia now offers safer functions are usually adequate.
and more effective drugs. This chapter introduces drugs
used for general and local anesthesia along with the adju- Principles of General Anesthesia
vant medications administered during surgical procedures.
26.2 Balanced anesthesia uses multiple drugs to
Types of Anesthesia provide for the safe induction and maintenance
of general anesthesia.
26.1 Anesthesia is used to produce a controlled
loss of sensation during a diagnostic or surgical General anesthesia is accomplished by the administration
procedure. of a variety of drugs. The purposes of general anesthesia
include the following:
Certain medical procedures produce a significant degree
of pain and would not be possible without anesthesia. • Analgesia: blocking the sensation of pain
There are four types of anesthesia. The type of anesthesia • Relaxation: relieving the intense anxiety associated
selected depends on the degree of sedation and analgesia
needed to conduct the procedure. with medical procedures
• Hypnosis: producing unconsciousness to block aware-
General anesthesia is the loss of sensation throughout
the entire body, accompanied by loss of consciousness. Gen- ness of the procedure
eral anesthesia is necessary for major surgical procedures. • Amnesia: blocking memory of the events associated
The application of local anesthesia results in loss of with the procedure
sensation to a limited body region without loss of con- • Loss of reflexes: blocking autonomic and other reflexes
sciousness. It affects only the immediate area that sur-
rounds where the anesthetic is administered. Regional that may be affected by the procedure.
anesthesia is similar, except that it encompasses a larger
body area, such as an entire limb. Local and regional anes- Because no single drug can safely accomplish all five pur-
thesias produce fewer adverse effects than general anesthe- poses, a pharmacologic approach called balanced anes-
sia and are thus the methods of choice where applicable. thesia is used. Balanced anesthesia is the use of a
combination of medications to produce general anesthe-
A fourth type of anesthesia is monitored anesthesia care sia. Drugs administered to achieve balanced anesthesia
(MAC), which uses sedatives, analgesics, and other low-dose include neuromuscular blockers, short-acting benzodiaz-
drugs that allow patients to remain responsive and breathe epines, opioids, and general anesthetics. The purpose of
without assistance during a medical procedure. This type of combining these medications is to provide sedation, rapid
anesthesia is used during diagnostic procedures and minor induction of unconsciousness, muscle relaxation, and
surgeries to supplement local and regional anesthesias. Sub- analgesia. The use of multiple drugs reduces the need for
types of MAC are based on the degree of sedation produced: large amounts of inhaled anesthetics, which increases
patient safety.
• Minimal sedation (anxiolysis). Patients respond to
verbal commands. Airway, ventilation, and cardiovas- Balanced anesthesia involves the administration of
cular functions are normal. intravenous (IV) medications prior to the general anes-
thetic. The IV medications produce muscle relaxation,
diminish pain, and promote sleep. After the patient loses
consciousness, inhaled general anesthetics are
424 Unit 4 Pharmacology of the Central Nervous System
Table 26.1 Stages of General Anesthesia the inhaled anesthetic to be reduced. The lower dosage of
inhaled anesthetic produces a better surgical outcome
Stage Characteristics and lowers the risk of serious adverse effects from the
anesthesia. The combined use of IV and inhaled anesthe-
1 Analgesia: The patient loses general sensation but may remain sia also allows for a greater degree of analgesia and
awake. This stage progresses until the patient loses muscle relaxation than when inhalation anesthetics are
consciousness. used alone.
2 Excitement and hyperactivity: The patient may become Fewer than a dozen drugs are used as IV anesthetics.
delirious and attempt to resist treatment. The heart rate and Some of these drugs also have nonanesthetic indications.
respiratory rate may become irregular. The patient’s blood Drugs from the following classes are used for IV
pressure may increase. The administration of IV agents may anesthesia:
calm the patient.
• Opioids
3 Surgical anesthesia: The patient’s skeletal muscles become • Benzodiazepines
relaxed and delirium stabilizes. The cardiopulmonary effects • Miscellaneous agents.
stabilize. The patient becomes still with diminished eye
movements. The surgical procedure is begun. The patient PharmFACT
remains in stage 3 until the procedure ends.
Certified registered nurse anesthetists administer about
4 Paralysis of the medulla: If breathing and cardiac function 43 million anesthetics each year. Nurse anesthetists are the
cease, death could result. This stage of general anesthesia is primary providers of anesthesia care for U.S. armed forces
avoided. (American Association of Nurse Anesthetists, 2016).
administered to maintain the anesthetized state. For short 26.4 Opioids are used as intravenous anesthetics
procedures, lower amounts of anesthesia are administered, to provide analgesia and to accomplish
or parenteral agents alone may be sufficient. neurolept anesthesia.
General anesthesia is a progressive process that occurs As presented in Chapter 25, the opioids, or narcotic anal-
in distinct phases, which are described in Table 26.1. The gesics, are the most effective drugs available for pain relief,
most effective medications can quickly induce all four including perioperative pain management. To produce
stages, whereas others are able to induce only stage 1. deep anesthesia, however, opioids must be combined with
Major surgical procedures require the patient to be main- other anesthetics. Combinations allow lower doses to be
tained in stage 3, which is referred to as surgical anesthesia. used and provide the necessary analgesia for painful
The patient should progress from stage 2 to stage 3 rapidly procedures.
because stage 2 produces excitement, hyperactivity, and a
feeling of panic. During stage 2 the patient is monitored Alfentanil (Alfenta), fentanyl (Sublimaze), remifent-
closely for heart rate irregularities and increases in blood anil (Ultiva), and sufentanil (Sufenta) are opioids used as
pressure. During recovery from general anesthesia, IV anesthetics. These medications are opioid receptor ago-
the patient moves in reverse order back up through the nists that provide a rapid onset of action with a short dura-
four stages. tion of 10 to 30 minutes. Their primary disadvantage is
respiratory depression. Muscle rigidity may occur, which
PharmFACT can further impair ventilation. A complete discussion of the
mechanisms, actions, and adverse effects of the opioids is
About 60% of women giving birth in hospitals receive included in Chapter 25. A prototype feature for morphine
regional anesthesia. Regional anesthesia includes epidural can be found in that chapter. Doses for the opioid anesthet-
analgesia, spinal analgesia, or a combination of the two ics are listed in Table 26.2.
(Satpathy, 2015).
The combination of droperidol and fentanyl produces
Intravenous Anesthetics a type of anesthesia called neurolept analgesia. Neurolept
analgesia produces feelings of indifference to the patient’s
26.3 Intravenous anesthetics include opioids, surroundings. The patient appears to be asleep but does
benzodiazepines, and several miscellaneous not lose consciousness. Fentanyl is a potent opioid agonist
agents. with pharmacologic action that is similar to that of mor-
phine. Droperidol is an antipsychotic drug related to halo-
IV anesthetics are important components of balanced peridol. It has the ability to reduce the nausea and vomiting
anesthesia. After a single IV bolus, these drugs enter the adverse effects of opioids and produces sedation by reduc-
brain, allowing the patient to quickly progress through ing anxiety and motor activity.
stages 1 and 2. They are occasionally used alone for minor
diagnostic and surgical interventions. Concurrent admin-
istration of IV and inhaled anesthetics allows the dose of
Chapter 26 Anesthetics and Anesthesia Adjuncts 425
Table 26.2 Intravenous Anesthetics
Drug Route and Adult Dose Adverse Effects
Opioids (Maximum Dose Where Indicated)
alfentanil (Alfenta) Skeletal muscle rigidity, nausea, vomiting, postoperative
IV: 8–20 mcg/kg for surgery lasting longer than 30 min drowsiness, shivering, HTN, bradycardia, prolonged QT
fentanyl (Sublimaze) Maintenance anesthesia: 3–5 mcg/kg in incremental interval, constipation
remifentanil (Ultiva) doses Apnea, respiratory depression, laryngospasm,
sufentanil (Sufenta) Continuous infusion: 0.5–1 mcg/kg/min bronchospasm, circulatory depression, cardiac arrest,
Total dose: 8–40 mcg/kg respiratory depression, respiratory arrest, anaphylactoid
Benzodiazepines IM/IV: 2–100 mcg/kg with dosage individualized to reaction
diazepam (Valium) patient and indication
midazolam (Versed) IV: 0.5 mcg/kg/min or 1 mcg/kg IV bolus Drowsiness, hypotension, tachycardia, retrograde amnesia
IV: 1–8 mcg/kg; may give additional doses of 10–50 Cardiovascular collapse, respiratory arrest, laryngospasm
Miscellaneous IV Anesthetics mcg if needed
etomidate (Amidate) Primary anesthetic: 1–30 mcg/kg IV administered with Pain on injection, transient skeletal muscle movements
100% oxygen Changes in ventilation (hyper or hypo) and blood pressure
(hyper or hypo)
IV: 5–10 mg, repeat every 10–15 min as needed Respiratory depression, laryngospasm, apnea, nausea,
IV (premedication): 0.15–0.25 mg/kg over 20–30 sec vomiting
IV (unpremedicated patients): 0.3–0.35 mg/kg over HTN, tachycardia, vivid dreams, hallucinations, delirium
20–30 sec Postoperative psychomotor impairment, retrograde amnesia,
hypothermia, sloughing with extravasation, skeletal muscle
IV: 0.2–0.6 mg/kg over a period of 30–60 sec for hyperactivity
induction Circulatory depression, respiratory depression, respiratory
arrest, apnea, anaphylaxis
ketamine (Ketalar) IV: 1–4 mg/kg Pain at injection site, skeletal muscle movements
methohexital (Brevital) IM: 6.5–13 mg/kg Dysrhythmias, hypotension
IV: For induction: 1–1.5 mg/kg at a rate of 1 mL every
5 sec
propofol (Diprivan) IV: 2–2.5 mg/kg every 10 sec until induction onset
Note: Italics indicate common adverse effects. Underline indicates serious adverse effects.
PROTOTYPE DRUG Fentanyl (Sublimaze) intranasal spray (Lazanda), and transdermal patches
(Duragesic). All of these nonanesthetic formulations of
Classification Therapeutic: Analgesic, anesthetic fentanyl are prescribed for the management of break-
Pharmacologic: Opioid agonist through pain in patients who are already receiving and
who are tolerant to around-the-clock opioid therapy for
Therapeutic Effects and Uses: Fentanyl is an opi- their chronic, persistent pain. Opioids such as fentanyl
oid analgesic that is administered IV for short-duration will result in tolerance if taken in high drug dosages over
analgesia as part of premedication, balanced anesthesia, an extended time. Doses need to be adjusted periodically
induction and maintenance of anesthesia, and for post- for adequate pain management. Physical and psychologic
operative pain. When given IV, it has an immediate onset dependence may occur with continued use. Abrupt dis-
of action, and its analgesic effects last about 60 minutes. continuation of the drug may cause intense withdrawal
As an anesthetic it may be administered with oxygen in symptoms (see Chapter 27). Fentanyl is a Schedule II con-
high-risk patients, such as those undergoing open heart trolled substance. When taken illegally, fentanyl gives the
surgery or certain complicated neurologic or orthopedic same effects as heroin.
procedures.
Mechanism of Action: Fentanyl is an opioid agonist
Since its approval in 1968 as an IV anesthetic, fentanyl at the mu and kappa receptors. The mechanism of action is
has been introduced in multiple formulations, including the same as that of morphine and other opioids. Fentanyl
oral (PO) tablets (Fentora), buccal film (Onsolis), sublin- has a more rapid onset of action than morphine.
gual tablets (Abstral), transmucosal lozenges (Actiq),
426 Unit 4 Pharmacology of the Central Nervous System
Pharmacokinetics: interact with other drugs that induce or inhibit this enzyme.
Cardiovascular depression may occur if nitrous oxide is
Route(s) IV, intramuscular (IM), used with high doses of fentanyl. Herbal/Food: St. John’s
wort may intensify or prolong the effects of fentanyl anesthe-
transdermal, transmucosal, sia and may induce the metabolism of fentanyl via CYP3A4.
Use of valerian or kava may cause additive CNS depression.
epidural
Pregnancy: Categories B (parenteral) and C (transder-
Absorption Rapid mal and transmucosal forms).
Distribution Crosses the placenta; secreted in Treatment of Overdose: In the event of an over-
dose, the patient is supported with mechanical ventila-
breast milk; 80% bound to protein tion until the drug is metabolized and the effects diminish.
The patient may be administered a narcotic antagonist
Primary metabolism Hepatic (CYP3A4) such as naloxone (Narcan) to reverse serious respiratory
depression.
Primary excretion Renal
Nursing Responsibilities: Key nursing implications
Onset of action IV: immediate; IM: 7–15 min; for patients receiving fentanyl are included in the Nursing
Practice Application for Patients Receiving General Anes-
transdermal: 24–72 h peak; thesia in this chapter and in the Nursing Practice Appli-
cation for Patients Receiving Pharmacotherapy for Pain in
transmucosal: 20–30 min peak; Chapter 25.
epidural: 10–15 min Drugs Similar to Fentanyl (Sublimaze)
Duration of action IV: 0.5–1 h; IM: 1–2 h; transdermal: Additional opioid IV general anesthetics include alfent-
anil, remifentanil, and sufentanil.
17-h half-life; transmucosal:
Alfentanil (Alfenta): Approved in 1996, alfentanil is an
unknown; epidural: 2–3 h opiate agonist that has a more rapid onset and a shorter
duration of action than fentanyl. It is administered IV to
Adverse Effects: The most common adverse effects of provide analgesia as a component of balanced anesthesia.
fentanyl include respiratory depression, apnea, skeletal Uses include assisting in intubation, promoting the induc-
muscle rigidity, and bradycardia. The peak respiratory de- tion of anesthesia, and as an infusion for the maintenance of
pression occurs 5 to 15 minutes after an IV dose. The respira- anesthesia. A labeled indication is for the management of
tory depression, however, will continue postoperatively and severe postoperative pain when given by the epidural route.
outlast the analgesic effects of the drug. Nausea, vomiting, The most common adverse effects are respiratory depres-
and constipation are common adverse effects produced by sion, nausea, vomiting, and muscle rigidity. Respiratory
most opioids. Fentanyl may cause syncope and severe bra- depression may be delayed; thus the patient should be mon-
dycardia and hypotension. Transdermal patches can cause itored for some time after surgery. Alfentanil must be used
localized pain, irritation, ulceration, and bleeding. Black with caution with other CNS depressants. Other actions and
Box Warning: Fentanyl carries several black box warnings. adverse effects are the same as those for fentanyl.
This drug has significant abuse potential and should not be
prescribed to patients with a high risk for misuse, abuse, Remifentanil (Ultiva): Approved in 1996, remifentanil
or diversion. The drug carries a high risk for death due to is an IV opioid that is similar to fentanyl. It is rapidly
overdose or respiratory depression. Concurrent use with metabolized, which allows for a shorter duration of
CYP3A4 inhibitors will increase fentanyl plasma concentra- respiratory depression than fentanyl. Recovery from
tions and the risk of serious adverse effects. Concurrent use anesthesia occurs 5 to 10 minutes after discontinuation
with other central nervous system (CNS) depressants such of the drug. This agent is administered during the induc-
as benzodiazepines or alcohol may result in profound seda- tion and maintenance of general anesthesia to provide
tion, respiratory depression, coma, and death. analgesia during the postoperative period. Although it
does not produce deep anesthesia, remifentanil may be
Contraindications/Precautions: Patients with re- used alone or in combination with midazolam in moni-
spiratory impairment should be administered fentanyl tored anesthesia care. Hypotension is greater with remi-
with caution due to the respiratory depression caused by fentanil than with fentanyl. Respiratory depression,
the drug. Patients with hepatic or chronic kidney disease pruritus, sweating, nausea, and vomiting are other
should receive lower doses. The drug may worsen bra-
dydysrhythmia. Patients with head trauma should not
receive fentanyl because intracranial pressure (ICP) may
increase. Fentanyl is secreted in breast milk and can cause
sedation and respiratory depression in the neonate; thus it
should not be administered during lactation.
Drug Interactions: Extreme caution should be used
when administering fentanyl with alcohol or other CNS de-
pressants due to additive sedation and respiratory depres-
sion. Fentanyl is metabolized by CYP450 enzymes (CYP3A4)
in the liver and intestinal mucosa and has the potential to
Chapter 26 Anesthetics and Anesthesia Adjuncts 427
adverse effects. Other actions and adverse effects are the induction and maintenance of general anesthesia, and se-
same as those for fentanyl. dation prior to short diagnostic procedures such as an en-
doscopy. Off-label uses include status epilepticus that is
Sufentanil (Sufenta): Approved in 1984, sufentanil is an refractory to other drugs and for sedation of mechanically
IV opioid used as a component of balanced anesthesia or ventilated patients. Midazolam syrup is indicated for use in
as a primary anesthetic agent. As a primary anesthetic the children to produce sedation, anxiolysis, and amnesia prior
patient should be administered 100% oxygen. During IV to minor medical procedures or induction of anesthesia.
use, the onset of action is immediate and recovery time is
comparable to that of fentanyl. It is sometimes adminis- Induction of anesthesia occurs in 1 to 2 minutes follow-
tered with bupivacaine as an epidural anesthesia adjunct ing an IV bolus of midazolam. If the patient has received an
during labor and delivery. During epidural use, the onset opioid premedication, induction is even more rapid. Awak-
of action is about 10 minutes and recovery time is 1.7 hours. ening and complete recovery of memory occurs in about
Sufentanil is 5 to 10 times more potent than fentanyl. The 2 hours but may extend to 6 hours in older adults or those
most common adverse effects are respiratory depression with heart failure or hepatic impairment.
and muscle rigidity, and the drug must be used with cau-
tion with other CNS depressants. Midazolam is a Schedule IV controlled substance. It has
abuse potential similar to that of other benzodiazepines.
CONNECTION Checkpoint 26.1
Mechanism of Action: Midazolam acts at the limbic,
In pain management, opioids are often available in fixed-dose com- thalamic, and hypothalamic regions of the brain to pro-
binations with nonopioids. From what you learned in Chapter 25, duce CNS depression and skeletal muscle relaxation. This
what is the rationale for using a nonopioid analgesic with an opioid? is the same mechanism of action as other benzodiazepines.
What specific nonopioid analgesic is most frequently found in these
combination drugs? Answers to Connection Checkpoint questions are Pharmacokinetics:
available on the faculty resources site. Please consult with your instructor.
Route(s) IV, IM, PO
26.5 Benzodiazepines are used in anesthesia to
produce relaxation, sedation, and amnesia. Absorption Rapid absorption
The primary indication for benzodiazepines is to treat Distribution Widely distributed; crosses the
symptoms of anxiety (see Chapter 18). For anesthesia, drugs
in this class are used at high doses to cause sedation and blood–brain barrier and the
induce unconsciousness. Benzodiazepines are a component
of balanced anesthesia, most often administered in combi- placenta; secreted in breast milk;
nation with inhalation anesthetics to allow the patient to
feel less anxiety and experience amnesia. They may be 97% protein bound
administered PO as a premedication to relax the patient
prior to minor medical procedures. The most commonly uti- Primary metabolism Hepatic
lized benzodiazepine for surgical procedures is midazolam
(Versed). Diazepam (Valium) and lorazepam have a slower Primary excretion Renal
onset and longer duration than midazolam and are occa-
sionally used as anesthesia adjuncts. A detailed discussion Onset of action IV: 1.5 min; IM: 5–15 min;
of benzodiazepines is found in Chapter 22, along with a
prototype feature for diazepam. Doses for the two benzodi- PO: 10–30 min
azepines used as IV anesthetics are listed in Table 26.2.
Duration of action IV/IM/PO: 2–6 h
PROTOTYPE DRUG Midazolam (Versed)
Adverse Effects: Respiratory depression and apnea
Classification Therapeutic: IV anesthetic are potentially serious adverse events. CNS adverse effects
Pharmacologic: Benzodiazepine, include drowsiness, fatigue, ataxia, slurred speech, and
tremor. Potentially serious cardiovascular effects include
gamma aminobutyric acid (GABA) hypotension, tachycardia, and cardiovascular collapse. La-
receptor agonist ryngospasm is the most severe pulmonary complication
noted with the administration of midazolam. Paradoxi-
Therapeutic Effects and Uses: Approved in 1985, cal reactions such as hyperactivity or aggressive behavior
midazolam is administered to reduce the anxiety and stress have been reported in pediatric patients and in those with
associated with surgery. It is approved by the U.S. Food and preexisting psychiatric disorders. Black Box Warning:
Drug Administration (FDA) for the induction of amnesia, Respiratory depression and arrest have occurred with
midazolam use. Respiratory status must be continuously
monitored and resuscitative equipment must be readily
available. When used concurrently with benzodiazepines
or opioids, the dosage and duration of midazolam anes-
thesia should be limited to the minimum required.
Contraindications/Precautions: Patients who have
acute, closed-angle glaucoma should not be administered
midazolam because the drug may increase intraocular
pressure. Patients experiencing acute alcohol intoxication,
428 Unit 4 Pharmacology of the Central Nervous System
shock, coma, or depressed vital signs should not be ad- 26.6 Propofol and ketamine are widely
ministered benzodiazepines because the drug may worsen used intravenous drugs for inducing and
these conditions. maintaining anesthesia.
Drug Interactions: The administration of benzodiaze- Several miscellaneous drugs are used as parenteral anes-
pines with any medication that depresses the CNS, includ- thetics. Propofol (Diprivan) and ketamine (Ketalar) are
ing alcohol, increases the patient’s risk for sedation. Use two of the widely used IV anesthetics. The two drugs are
of benzodiazepines and phenytoin (Dilantin) will result not related chemically, but both have short durations and
in an increased serum phenytoin level and additive CNS can induce anesthesia rapidly. Etomidate (Amidate) and
depression. Midazolam is metabolized by hepatic CYP3A4 methohexital (Brevital) are much less frequently used in
enzyme, and inhibitors or inducers of this enzyme may balanced anesthesia. Doses for these drugs are listed in
interact with midazolam. Herbal/Food: Increased seda- Table 26.2.
tion may occur if benzodiazepines are administered with
kava or valerian. Grapefruit juice may increase the serum PROTOTYPE DRUG Propofol (Diprivan)
concentration of midazolam. Melatonin should be avoided
because it may increase sedation. Classification Therapeutic: IV anesthetic, sedative–
hypnotic drug
Pregnancy: Category D.
Pharmacologic: N-methyl-D-aspartate
Treatment of Overdose: Overdose with midazolam (NMDA) receptor agonist
causes sedation, confusion, diminished reflexes, and coma.
General supportive measures should be taken, and the pa- Therapeutic Effects and Uses: Approved in 1989,
tient may be treated with flumazenil (Romazicon), which propofol has become the most widely used IV anesthetic
is a specific benzodiazepine antagonist. Flumazenil acts due to its effectiveness and relative safety profile. It is in-
within minutes but may induce seizures with rapid reversal. dicated for the induction and maintenance of general an-
esthesia. In the intensive care unit (ICU), the drug may be
Nursing Responsibilities: Key nursing implications administered to intubated, mechanically ventilated adult
for patients receiving midazolam are included in the Nurs- patients to provide continuous sedation and control of
ing Practice Application for Patients Receiving General stress responses. It has an almost immediate onset of ac-
Anesthesiain this chapter and in the Nursing Practice Ap- tion and is used effectively for conscious sedation. Emer-
plication for Patients Receiving Pharmacotherapy for Anx- gence from anesthesia is rapid, and few adverse effects
iety or Sleep Disorders in Chapter 18. occur during recovery. Unlike other anesthetics that cause
nausea and vomiting, propofol has an antiemetic effect
Drugs Similar to Midazolam (Versed) that can prevent nausea and vomiting in patients receiving
chemotherapy. Off-label uses include refractory migraines,
The only other benzodiazepine administered to produce refractory status epilepticus, and the treatment of agitation
anesthesia is diazepam. associated with alcohol withdrawal.
Diazepam (Valium): Diazepam has been widely prescribed Mechanism of Action: The exact mechanism by
for anxiety and as an adjunct in seizure management. In the which propofol produces anesthesia is not clear. It is be-
surgical suite diazepam is used as a premedication (by the lieved to act by activating GABA receptors, which causes a
IM route) for relief of anxiety associated with the surgical general inhibition of CNS activity.
procedure. It is used by the IV route prior to cardioversion
for the relief of anxiety and tension and to produce amnesia. Pharmacokinetics:
When administered parenterally, it has an onset of action of
1 to 5 minutes and produces short-acting effects. Diazepam Route(s) IV
decreases the patient’s anxiety and relaxes the skeletal mus-
cles. Diazepam impairs the patient’s ability to remember the Absorption Rapid
perioperative events. A prototype feature for diazepam may
be found in Chapter 22. Distribution Widely distributed to body
CONNECTION Checkpoint 26.2 tissues; highly protein bound
Benzodiazepines are sometimes used for seizure control. From what Primary metabolism Hepatic
you learned in Chapter 22, what are the indications for lorazepam
and diazepam in treating seizures? Answers to Connection Check- Primary excretion Renal
point questions are available on the faculty resources site. Please consult
with your instructor. Onset of action Immediate
Duration of action IV: 10–15 min
Adverse Effects: Injection-site pain, apnea, respiratory
depression, and hypotension are common adverse effects.
Propofol has been associated with a collection of meta-
bolic abnormalities and organ system failures, referred to
Chapter 26 Anesthetics and Anesthesia Adjuncts 429
as propofol infusion syndrome (PRIS). The syndrome is has a very rapid onset of action and hypotension is uncom-
characterized by severe metabolic acidosis, hyperkalemia, mon. It provides only 5 to 10 minutes of anesthesia. A
lipemia, rhabdomyolysis, hepatomegaly, and cardiac and major adverse effect is that it suppresses corticosteroid
kidney failure. PRIS is usually associated with prolonged, synthesis and can cause dangerous adrenal insufficiency if
high-dose infusions of the drug. Deaths have resulted from used for long periods. Concurrent use of opioids or benzo-
this syndrome. diazepines can worsen this suppression. This drug is preg-
nancy category C.
Contraindications/Precautions: Propofol is contra-
indicated in patients who have a known hypersensitivity Ketamine (Ketalar): Approved in 1970, ketamine is an
reaction to the medication or its emulsion, which contains IV anesthetic that was initially used in veterinary medi-
soybean and egg products. The emulsion supports rapid cine. It is a rapid-acting drug that produces a trance-like
microorganism growth; unused portions must be dis- feeling of being separated from the environment called
carded. Obstetric patients and those with increased ICP dissociative anesthesia. When used alone, ketamine is
should not be administered propofol. The drug should indicated during surgeries and brief diagnostic proce-
be used with caution in patients with cardiac or respira- dures that do not require skeletal muscle relaxation. It is
tory impairment. It is not recommended for induction of also used prior to the administration of other general
anesthesia in children younger than 3 years. Although anesthetic agents. Ketamine is used with pediatric
not a controlled substance, incidences of propofol abuse patients due to its rapid induction of general anesthesia
have occurred, including the high-profile case of Michael and the fact that it lasts up to 25 minutes. Ketamine has
Jackson, a famous musician, who used this medication strong analgesic actions and immediately increases blood
(among others) to induce sleep. pressure and skeletal muscle tone. The patient’s eyes may
be open during the surgical procedure.
Drug Interactions: The dose of propofol should be
reduced in patients receiving preanesthetic medications Ketamine is a common drug of abuse that is known by
such as opioids or benzodiazepines. Use with other CNS the names jet, super acid, Special K, green K, and cat Valium.
depressants can cause additive CNS and respiratory de- It is a club drug that is similar to phencyclidine (PCP),
pression. Herbal/Food: Unknown. which is popular among teens and young adults. It is easily
added to drinks or administered through injection to cause
Pregnancy: Category B. temporary amnesia and is sometimes referred to as a date-
rape drug (see Chapter 27). Potentially serious cardiovascu-
Treatment of Overdose: Overdose will produce car- lar adverse effects of ketamine include hypertension (HTN)
diac and respiratory depression. The treatment includes and tachycardia. Respiratory depression occurs with the
mechanical ventilation of the patient, increasing the flow administration of IV ketamine. The most serious neurologic
rate of IV fluids, and administering vasopressor agents as adverse effect is emergence phenomena in adult patients,
needed to maintain blood pressure. which can occur for 24 hours postoperatively. Emergence
phenomena include delirium, hallucinations, confusion,
Nursing Responsibilities: Key nursing implications excitement, and irrational behavior. Ketamine is a Schedule
for patients receiving propofol are included in the Nurs- III drug and is pregnancy category C.
ing Practice Application for Patients Receiving General
Anesthesia. Methohexital (Brevital): Approved in 2001, methohexital
is a barbiturate general anesthetic agent that can be used to
Drugs Similar to Propofol induce general anesthesia or administered as a continuous
IV infusion. It is also approved to supplement anesthesia
Other miscellaneous IV anesthetics include etomidate, produced by low-potency drugs such as nitrous oxide.
ketamine, and methohexital. Thiopental sodium (Pento- Like other IV anesthetics, it has a rapid onset, a short dura-
thal) was the gold standard for IV anesthetics for over 70 tion of action, and a relatively fast recovery period. IM and
years. The sole U.S. manufacturer of this drug decided to rectal forms are available for use in children. Severe
discontinue the drug in the United States in 2010, likely adverse reactions include respiratory depression, laryngo-
because of the greater effectiveness, and relative safety of spasm, and hypotension. Adverse CNS effects may persist
propofol. for 24 hours and include confusion, delirium, somnolence,
anxiety, and seizures. Other adverse events include shiver-
Etomidate (Amidate): Approved in 2007, etomidate is a ing, nausea, vomiting, and anaphylaxis. Methohexital is a
hypnotic drug indicated for the IV induction of general Schedule IV controlled substance. Details on the mecha-
anesthesia for short medical–surgical procedures such as nisms of action of barbiturates and their applications as
cardioversion, endotracheal intubation, or reduction of sedatives may be found in Chapter 18. This drug is preg-
dislocations. It is also approved to supplement anesthesia nancy category B.
produced by low-potency drugs such as nitrous oxide. It
430 Unit 4 Pharmacology of the Central Nervous System
Inhalation Anesthetics CONNECTIONS: Using Research
in Practice
26.7 Inhalation anesthetics used to produce
loss of consciousness are classified as gases or Malignant Hyperthermia
volatile liquids. and Anesthetic Agents
Following the administration of IV agents, inhalation anes- Malignant hyperthermia is a rare and potentially fatal condition
thetics are given to rapidly produce unconsciousness and that occurs when a susceptible individual receives certain trig-
total analgesia. Inhalation anesthetics are supplied as gases gering medications (e.g., succinylcholine) during anesthesia. A
or volatile liquids. These drugs produce their effects on the genetic predisposition to malignant hyperthermia has been
CNS by inhibiting the flow of sodium into neurons, which discovered, and recent research suggests a potential link
delays the nerve impulses and dramatically reduces the between a previous diagnosis of statin-associated myopathy
activity of the neurons. Although the mechanism of action from the cholesterol drug group and the risk of malignant
is incompletely understood, inhibitory GABA receptors in hyperthermia (Hedenmalm, Granberg, & Dahl, 2015). Patients
the brain become active and are thought to be responsible with other preexisting musculoskeletal conditions, especially
for the anesthetic action. This action is similar to that of the those that are genetically linked, may be at greater risk, even if
antiepileptic medications described in Chapter 22. Other the true incidence of malignant hyperthermia occurring in
CNS neurotransmitters likely contribute to the sedative these populations is unknown. It has also been noted that the
effects of the inhalation anesthetics. onset of malignant hyperthermia is different for different anes-
thetic agents. Patients given the anesthetic halothane had ear-
The first general anesthetic was the gas diethyl ether, lier onset of malignant hyperthermia than those given other
which was discovered in the 1840s. Although popular for anesthetics when succinylcholine was used concurrently
over 100 years, gaseous anesthetics were explosive and (Visolu, Young, Wieland, & Brandom, 2014). It is also known
presented a danger to the surgical team members, who that not all cases of malignant hyperthermia occur immedi-
were exposed to fumes from the drugs. Furthermore, the ately, but instead occur over a longer period of time with insid-
gases produced a very high incidence of nausea and vomit- ious onset of hypermetabolic symptoms such as hypercapnia,
ing following the procedure. The only gaseous anesthetic elevated temperature, and evidence of rhabdomyolysis
in use today is nitrous oxide. (Heytens, Forget, Scholtès, & Veyckemans, 2015).
The potency of inhalation anesthetics is described by The nurse plays a key role in assessing a patient for pos-
the minimum alveolar concentration: the concentration of sible malignant hyperthermia risk during the preoperative
drug vapor in the alveoli that prevents a motor response in period. Existing myopathies, unusual heat-associated illnesses
50% of patients when exposed to a painful stimulus. A low in a child or adult, or previous history of statin-associated
value of minimum alveolar concentration indicates that a myopathy should be noted and the anesthesiologist or anes-
very small amount of anesthetic is needed to immobilize thetist alerted. A personal or immediate-family history of prob-
the patient. Inhalation anesthetics have low minimum lems with previous anesthetic use should also be noted.
alveolar concentrations and are thus very potent. The Symptoms of malignant hyperthermia often begin with unex-
exception is nitrous oxide, which is a low-potency anes- plained tachycardia. Jaw muscle spasms and rigidity may
thetic with a high minimum alveolar concentration value. occur, followed by a dramatic increase in body temperature,
The minimum alveolar concentration changes with the age rhabdomyolysis indicated by dark brown-colored urine, dys-
of the patient. It is lowest in newborns, peaks in infants, rhythmias, and potential death. Any patient experiencing mild
and gradually declines with age. spasms in the jaw muscles must be observed more closely for
development of malignant hyperthermia for at least 10 hours
Inhalation anesthetics are rapidly absorbed from the postprocedure. Patients with darkened urine or with severe
alveoli into the general circulation. The anesthesiologist jaw rigidity should be hospitalized overnight postoperatively to
controls the length and depth of anesthesia by delivering observe for the development of malignant hyperthermia.
the exact concentration of drug needed to maintain a desir-
able degree of immobility. These drugs are very lipid solu- PROTOTYPE DRUG Nitrous Oxide
ble and quickly cross the blood–brain barrier to produce
sedating effects. Metabolism of inhalation anesthetics is Classification Therapeutic: Gaseous general anesthetic
minimal, and elimination of the drug is mostly by exhala- Pharmacologic: GABA-receptor agonist,
tion. Modern anesthetics are designed to have a fast recov-
ery time so that the patient regains consciousness soon opioid agonist
after the infusion is stopped. Because anesthetics are lipid
soluble, they are stored in fat and slowly released, which Therapeutic Effects and Uses: Nitrous oxide is an
explains why patients with obesity may take longer to odorless, nonirritating, inorganic gas used for a large num-
recover from anesthesia. ber of medical and surgical procedures. When administered
Chapter 26 Anesthetics and Anesthesia Adjuncts 431
alone it is one of the least potent anesthetics and is unable When administered in higher doses, patients exhibit some
to induce deep anesthesia at therapeutic doses. Because of adverse effects of stage 2 anesthesia such as anxiety, ex-
its low potency, the use of nitrous oxide is either limited to citement, and combativeness. Lowering the inhaled dose
minor surgical procedures or combined with the IV anes- quickly reverses these adverse effects. Because nitrous ox-
thetic agents for more complex procedures. The majority of ide is exhaled, the patient may temporarily have some dif-
patients requiring sedation for dental, diagnostic, and sur- ficulty breathing at the end of the procedure.
gical procedures are administered nitrous oxide.
Rapid diffusion of the gas from the bloodstream back
One major advantage of nitrous oxide is that it has into the lungs causes alveolar hypoxia, with symptoms that
strong analgesic properties. At a concentration of 20%, include nausea, vomiting, lethargy, and dizziness. Some
nitrous oxide delivers analgesic efficiency equaling that of patients describe these symptoms as equivalent to a “hang-
morphine. This agent has a low potency and does not pro- over” from too much alcohol consumption. Alveolar
duce loss of consciousness or profound skeletal muscle hypoxia can be prevented by breathing 100% oxygen for
relaxation. several minutes following the conclusion of nitrous oxide
therapy.
Nitrous oxide is always combined with oxygen (25–
30%) and is administered in a semiclosed method. The Contraindications/Precautions: When patients
patient may be administered an IV anesthetic to produce must be awake and follow the instructions of the physi-
sedation. When drowsy or asleep, the patient inhales the cian or dentist, nitrous oxide is contraindicated in those
nitrous oxide through a tube or by mask. Nitrous oxide is with an impaired level of consciousness or an inability to
also used for dental procedures in which the mask is placed comply with instructions. Because the diffusion of nitrous
over the nose. Other procedures in which nitrous oxide is oxide may lead to expansion of closed spaces, its use in
administered include those related to obstetrics and sur- patients with conditions such as undiagnosed abdomi-
gery. Nitrous oxide lowers the minimum alveolar concen- nal pain, abdominal distention, bowel obstruction, head
tration of other anesthetics, essentially making them more injury, or pneumothorax is contraindicated. Patients who
potent. This permits a decrease in the dosages required for have hypotension, shock, chronic obstructive pulmonary
IV and inhalation anesthetics. disease, cyanosis, or chest pain should not be adminis-
tered nitrous oxide.
Nitrous oxide has been used illegally to produce relax-
ation, euphoria, and hallucinations. Abusers may steal the Drug Interaction: The administration of adrenergic
nitrous oxide tanks from medical facilities. The gas has also agonists (such as epinephrine) or caffeine with nitrous
been used as a propellant in whipped cream canisters and oxide may exacerbate dysrhythmias. Use with CNS de-
cooking sprays, and abusers can obtain small amounts from pressants may cause additive sedation and respiratory
those sources. Long-term abuse can lead to anemia, deple- depression. Excessive hypotension may result if amioda-
tion of vitamin B12, tinnitus, and peripheral neuropathy. rone or antihypertensive drugs are used concurrently with
nitrous oxide. Herbal/Food: Milk thistle taken before and
Mechanism of Action: The mechanism of action of after anesthesia may lower the potential risk of liver dam-
nitrous oxide is not fully known. Its analgesic effects are age. St. John’s wort should be discontinued 2 to 3 weeks
believed to be due to activation of opioid receptors in the prior to administration of general anesthetics due to pos-
midbrain. The relaxation properties of the drug are likely sible hypotension risk.
due to activation of GABA receptors, which inhibits neu-
ronal firing. Pregnancy: Category C.
Pharmacokinetics: Treatment of Overdose: Effects of the drug usually
diminish quickly after the gas is discontinued. Metoclo-
Route(s) Inhalation pramide (Reglan) or another antiemetic agent may be ad-
ministered to reduce the nausea and vomiting associated
Absorption Rapid with nitrous oxide.
Distribution Crosses the blood–brain barrier Nursing Responsibilities: Key nursing implications
to concentrate in the nerve cells for patients receiving nitrous oxide are included in the
Nursing Practice Application for Patients Receiving Gen-
Primary metabolism Not metabolized eral Anesthesia.
Primary excretion 100% through the lungs, Drugs Similar to Nitrous Oxide
unchanged
Nitrous oxide is the sole gaseous general anesthetic.
Onset of action 2–5 min
Duration of action Half-life is variable;
peak effect: less than 10 min
Adverse Effects: When administered in low to mod-
erate doses, nitrous oxide produces few adverse effects.
432 Unit 4 Pharmacology of the Central Nervous System
PharmFACT PROTOTYPE DRUG Isoflurane (Forane)
The recreational use of nitrous oxide is rising, especially at Classification Therapeutic: Inhaled general anesthetic
festivals and clubs. In these circumstances, the drug is Pharmacologic: GABA and glutamate
inhaled from gas-filled balloons and produces hallucinations
and confusion as desired effects (Kaar et al., 2016). receptor agonist
26.8 Volatile liquid general anesthetics are used Therapeutic Effects and Uses: Approved in 1979,
to induce and maintain deep anesthesia. isoflurane has become a preferred inhalation anesthetic
due to its effectiveness and favorable safety profile. Isoflu-
The volatile liquids form a second class of inhalation anes- rane provides smooth and rapid induction of general an-
thetics. The volatile liquid drugs have a low vapor pres- esthesia with a low degree of metabolism by the body. It is
sure that allows them to vaporize (form a gas) at low almost entirely eliminated through respirations. The drug
temperatures and pressures. An anesthesia machine is provides excellent muscle relaxation. It is FDA approved
used to vaporize the liquid, mix the vapors with oxygen for the induction and maintenance of general anesthesia
and air, and deliver them to patients in precisely controlled and may be used off-label as adjuvant therapy in the treat-
amounts. The anesthesia machine also establishes a partial ment of status asthmaticus.
pressure gradient that ensures the anesthetic will continue
to flow from the machine to the alveoli, to the blood, and Isoflurane does not sensitize the myocardium for dys-
eventually to the brain. Like the gases, the volatile liquid rhythmias, and it produces fewer cardiovascular effects
anesthetics are lipid soluble and rapidly cross the blood– than other general anesthetics. Isoflurane does not cause
brain barrier to cause sedation. the hepatotoxicity observed with halothane.
Desflurane (Suprane), isoflurane (Forane), and sevo- Mechanism of Action: The exact mechanism of ac-
flurane (Ultane) are the most widely used of the volatile tion of isoflurane is unknown. It interacts with multiple
liquid anesthetics. All of these drugs have a rapid onset of receptors in the brain, including glutamate and GABA
action. receptors.
The minimum alveolar concentrations of the volatile Pharmacokinetics:
liquid anesthetics are very low, making them very potent.
This factor contributes to the ability of these drugs to rap- Route(s) Inhalation
idly produce unconsciousness at low doses. Although they
have the ability to produce deep anesthesia, they produce Absorption Rapidly absorbed by the lungs
little analgesia and are usually used in combination with
nitrous oxide and opioids as part of balanced anesthesia. Distribution Crosses the blood–brain barrier
Some volatile liquid anesthetics sensitize the heart to to concentrate in neurons;
the action of catecholamines such as epinephrine, norepi-
nephrine, and dopamine and can cause serious dysrhyth- unknown if it is secreted in
mias. These drugs also depress cardiovascular and
pulmonary function, placing the patient at risk for laryngo- breast milk
spasm or respiratory arrest. The gaseous and volatile liquid
anesthetics are listed in Table 26.3. Primary metabolism Minimal metabolism
Primary excretion 95% pulmonary
Onset of action 7–10 min for surgical anesthesia
Duration of action Patient begins to regain
consciousness less than 1 h after
drug is discontinued
Table 26.3 Inhalation Anesthetics
Drug Adult Concentration Adverse Effects
Gas 70% with 30% oxygen
nitrous oxide Anxiety, nausea, vomiting
Hypoxia, hallucinations, disorientation
Volatile Liquids
Nausea, vomiting, shivering
desflurane (Suprane) 7.3% concentration Laryngospasm, hypotension, apnea, increased secretions, vasodilation,
respiratory depression, tachycardia, malignant hyperthermia,
enflurane (Ethrane) 0.5–3% concentration
isoflurane (Forane) 0.1–2% concentration
sevoflurane (Ultane) 0.5–3% concentration
Note: Italics indicate common adverse effects. Underline indicates serious adverse effects.
Chapter 26 Anesthetics and Anesthesia Adjuncts 433
Adverse Effects: Mild nausea, vomiting, and tremor administered to induce and maintain anesthesia in adults.
are common adverse effects. The drug produces a dose-de- When administered to children it is used to maintain anes-
pendent respiratory depression and a reduction in blood thesia. Adverse effects of desflurane are laryngospasm,
pressure. Malignant hyperthermia with elevated temper- apnea, and increased pulmonary secretions. The drug pro-
ature and unstable blood pressure has been reported, al- duces a dose-dependent reduction in blood pressure, and
though the incidence is rare. malignant hyperthermia has been reported. Desflurane
must be used with IV anesthetics because it may cause
Contraindications/Precautions: Patients with a coughing and excitation during induction. It does not sen-
known history or genetic predisposition to malignant hy- sitize the myocardium for dysrhythmias. This is a preg-
perthermia should not use isoflurane. Caution should be nancy category B drug.
used when treating patients with head trauma or brain
neoplasms due to possible increases in ICP. Safety has not Enflurane (Ethrane): Approved in 1972, enflurane is
been established in patients under age 18. Older adult pa- administered for induction and maintenance of general
tients are more susceptible to the cardiovascular effects of anesthesia, usually in conjunction with other agents as a
the drug. Patients with a prolonged QT interval should be component of balanced anesthesia. It is approved for obstet-
administered isoflurane with caution. ric anesthesia. It has strong muscle relaxant properties. It
does not sensitize the myocardium for dysrhythmias, and
Drug Interactions: Coughing, breath holding, or postanesthesia nausea, vomiting, and CNS stimulation are
laryngospasm may occur when used concurrently with uncommon. When administered in high concentrations,
nitrous oxide. Skeletal muscle weakness, respiratory however, it can cause seizures and is thus contraindicated in
depression, or apnea may occur if isoflurane is adminis- patients with a history of seizure disorders. Rare cases of
tered concurrently with systemic polymyxin or amino- malignant hyperthermia have been reported, and enflurane
glycosides. Additive effects can occur if isoflurane is is contraindicated in patients with a history of this disorder.
administered with other skeletal muscle relaxants. Addi- This is a pregnancy category B drug.
tive hypotension may result if used concurrently with
antihypertensive medications such as beta-adrenergic Sevoflurane (Ultane): Approved in 1995, sevoflurane is a
blockers. Epinephrine, norepinephrine, dopamine, and volatile liquid general anesthetic agent that is adminis-
other adrenergic agonists should be administered tered to induce and maintain sedation. It has a faster
with caution because of the possibility of dysrhythmias. uptake, distribution, and elimination than isoflurane. It
Levodopa should be discontinued 6 to 8 hours before iso- also does not cause the cardiovascular reactions commonly
flurane administration. Isoflurane should be administered encountered with some of the other general anesthetics,
with caution with other drugs that prolong the QT inter- and it is safer to use in patients with coronary artery dis-
val, such as amiodarone, ibutilide, droperidol, and phe- ease. Sevoflurane does not cause respiratory irritation and
nothiazines. Herbal/Food: St. John’s wort should be is safe for administration with children. Furthermore, this
discontinued 2 to 3 weeks prior to administration of gen- drug does not cause coughing and excitation during induc-
eral anesthetics due to possible hypotension risk. tion and can thus be used without IV anesthetics. Sevoflu-
rane produces a dose-dependent reduction in blood
Pregnancy: Category C. pressure, and malignant hyperthermia has been reported.
This is a pregnancy category B drug.
Treatment of Overdose: Isoflurane causes profound
respiratory depression. The patient is treated symptomati- Local Anesthetics
cally until the effects of the drug diminish.
26.9 Local anesthetic agents block pain
Nursing Responsibilities: Key nursing implications transmission in peripheral nerves and are
for patients receiving isoflurane are included in the Nurs- grouped in two major classes.
ing Practice Application for Patients Receiving General
Anesthesia. Local anesthesia results in the loss of sensation to a small,
limited area of the body. The primary advantage of local
Drugs Similar to Isoflurane (Forane) anesthesia is that pain relief can be provided without caus-
ing generalized depression of the CNS and respiratory sys-
Volatile liquid anesthetics similar to isoflurane include tems. The nausea, vomiting, tremors, and anxiety
desflurane, enflurane, and sevoflurane. Halothane (Fluo- associated with general anesthetic recovery are avoided.
thane), the historical prototype for this drug class, was vol- The types of adverse events associated with local anesthe-
untarily removed from the market due to a small incidence sia are relatively minor relative to the potential risks of
of fatal hepatitis associated with the drug. general anesthesia.
Desflurane (Suprane): Desflurane, approved in the 1990s,
produces a rapid induction of general anesthesia. It is
434 Unit 4 Pharmacology of the Central Nervous System
CONNECTIONS: NURSING PRACTICE APPLICATION
Patients Receiving General Anesthesia
Assessment
Baseline assessment prior to administration:
• Obtain a complete health history including cardiovascular, respiratory, hepatic, renal, or neurologic disease, pregnancy, or breastfeeding. Obtain a
drug history including allergies, current prescription and OTC drugs, herbal preparations, caffeine, nicotine, and alcohol use. Be alert to possible drug
interactions.
• Assess for previous history of anesthesia and note any significant reactions. Obtain family history of anesthesia problems, particularly related to use of
neuromuscular blockers (e.g., succinylcholine), or any unusual effects related to surgery.
• Obtain baseline vital signs, height, and weight. Note day and hour the patient last ate or drank.
• Evaluate laboratory findings appropriate to the procedure (e.g., complete blood count [CBC], electrolytes, hepatic or renal function studies, MRI or CT
scan results).
• Obtain required preoperative paperwork (e.g., informed consent, completed history and physical examination).
• Administer any preoperative adjunctive drugs (e.g., sedative, analgesic) as ordered.
• Assess the level of anxiety, and any concerns or questions the patient, family, or caregiver may have. Reinforce preoperative teaching, including deep-
breathing exercises. Provide the family or caregiver with information on the anticipated length of the procedure, the waiting room area, and telephone
and cafeteria or food availability.
• Lifespan: For pediatric patients, allow the parents or caregiver to stay with the child as long as agency policy permits to decrease patient anxiety.
Provide a simple explanation of the procedure appropriate for the age of the child.
• Lifespan: When working with older adults, note assistive devices (e.g., glasses, hearing aids) and remove only when necessary. Give to the family or
caregiver or provide for safekeeping. Ensure that devices are available in the postoperative period.
• Initiate IV access site if required for the procedure.
• Assess the patient’s ability to receive and understand instructions. Include family and caregivers as needed.
Assessment throughout administration:
• Assess for desired therapeutic effects (e.g., diminished level of consciousness).
• Assess vital signs, especially blood pressure and pulse, frequently. Report blood pressure less than 90/60 mmHg, pulse above 100 beats/min, or per
the parameters as ordered by the healthcare provider.
• Maintain operative sterility throughout the procedure.
• Assess level of consciousness in the postoperative period. Continue frequent monitoring of vital signs and pulse oximetry.
• Assess for and promptly report adverse effects: bradycardia or tachycardia, hypotension or HTN, dysrhythmias, dyspnea, jaw muscle rigidity, or dark
brown-colored urine.
Implementation
Interventions and (Rationales) Patient-Centered Care
Ensuring therapeutic effects: • Provide a quiet environment postoperatively, and frequently orient the
• Continue assessments as above for therapeutic effects. Provide for patient to the postanesthesia care unit (PACU).
patient safety during preoperative and operative periods, and assess
level of consciousness, vital signs, and return of motor and sensory
sensation postoperatively. (Duration of anesthetic action will depend on
the drugs used and adjunctive or reversal agents used.)
• Assess for shivering in the postoperative period and provide additional • Continue to orient the patient in the postoperative period, and allay
blankets or warmth as needed. (General anesthetics depress the CNS anxiety about shivering.
and some autonomic activity. As autonomic activity returns, shivering is
common. Warm blankets provide comfort during this period.)
Minimizing adverse effects: • Explain all procedures and monitoring to the patient. Continue to
• Continue to monitor vital signs frequently, including temperature. Report reorient the patient to surroundings frequently in the postoperative
period.
blood pressure below 90/60 mmHg or per the parameters as ordered
by the healthcare provider, tachycardia or significant bradycardia,
dysrhythmias, or dyspnea. Report any jaw muscle rigidity or brown-
colored urine and fever immediately. (CNS depression will cause
decreases in all vital signs but significant bradycardia, hypotension,
decreased respiratory rate, or dyspnea should be reported promptly.
Lifespan: The older adult is more sensitive to the effects of anesthesia
and may be more likely to experience adverse effects such as
hypotension and delirium. Malignant hyperthermia associated with
succinylcholine and some anesthetics is a rare but potentially fatal
adverse effect. Early symptoms include unexplained tachycardia, jaw
muscle spasms or rigidity, and brown-colored urine.)
• Provide adequate pain relief in the immediate postoperative period. • Provide the rationale for pain relief preoperatively and encourage the
(General anesthetics do not necessarily provide analgesia, dependent patient to request pain medication as able. Assure the patient, family,
on the agent. Adequate pain relief begins ideally in the preoperative or caregiver that pain needs will be frequently monitored.
period. Assess for nonverbal signs of pain such as restlessness or
grimacing as the patient regains consciousness.)
• Encourage the patient to take deep breaths and move lower • Teach the patient deep-breathing exercises in the preoperative period,
extremities frequently in the postoperative period. (General anesthetics and that early movement of legs will be encouraged in the early
given by inhalation are excreted via the lungs. Deep breathing assists in postoperative period, unless otherwise ordered by the provider.
removing remaining anesthetic. Early range-of-motion exercises may
help prevent venous thrombosis and complications.)
Chapter 26 Anesthetics and Anesthesia Adjuncts 435
CONNECTIONS: NURSING PRACTICE APPLICATION (continued)
Implementation
Interventions and (Rationales) Patient-Centered Care
• Ensure patient safety in the postoperative period. Frequently orient the
patient to surroundings, day, and time and maintain a safe environment.
(During the period of anesthesia, consciousness is lost along with the
ability to orient to day, time, and person. Confusion related to these effects
in the postoperative period is common. Use of safety measures such as
side rails may be necessary until the patient regains consciousness.)
• For patients receiving ketamine and other drugs causing neurolept • Explain the full procedure and required postprocedural care to the
analgesia, provide a quiet, calm environment postprocedure. Avoid patient, family, or caregiver. Alert the family or caregiver that visiting
overstimulating the patient while taking vital signs. Use a soft touch may be restricted during the immediate recovery period in order to
and voice to explain all procedures performed. (During recovery from minimize sensory stimulation.
neurolept analgesia drugs, confusion and misinterpretation of sensory
stimulation may cause extreme anxiety, fear, or paranoia. Keep all
stimuli to a minimum until the patient regains full consciousness.)
• Lifespan and Diverse Patients: Continue to monitor hepatic function. • Lifespan: Monitor hepatic laboratory values pre- and postoperatively
(Lifespan: Normal physiologic changes related to aging may increase and report abnormalities.
the risk of toxicity in the older adult requiring drugs with hepatic
metabolism. Diverse Patients: Because drugs such as fentanyl and • Diverse Patients: Monitor for therapeutic and adverse effects
midazolam are metabolized through the CYP450 system, they may frequently in ethnically diverse patients.
result in less than optimal results based on differences in enzymes.)
Patient understanding of drug therapy: • The patient should be able to state the reason for the drug(s),
• Use opportunities during the preoperative period to discuss the rationale anticipated sensations, and adverse effects to observe for, and when
to report them.
for the drug therapy, desired therapeutic outcomes, commonly observed
adverse effects, and any necessary monitoring or precautions. (Using time
during nursing care helps to optimize and reinforce key teaching areas.)
Patient self-administration of drug therapy: • Teach the patient to:
• When administering fentanyl for analgesia, instruct the patient, family, • Remove old fentanyl patches and dispose of them safely because
they may still contain some medication.
or caregiver in the proper self-administration of the drug. (Utilizing time • Apply the new fentanyl patch to clean, dry skin. Press firmly on the
during nurse administration of these drugs helps to reinforce teaching.) patch for 30 seconds to ensure proper skin contact.
• Not split, chew, or swallow the transmucosal or buccal forms of
fentanyl.
Several techniques are used to deliver local and anesthetic blocks sensation to multiple nerve roots
regional anesthesia. The method employed is dependent supplying limited regions of the chest, pelvis, abdo-
on the location and extent of the desired anesthesia men, or limbs. It is used for urologic and obstetric
(Figure 26.1): procedures.
• Topical (surface) anesthesia. The drug is applied or Although safer than general anesthetics, the healthcare
sprayed directly on the surface of the skin or mucous provider has less control over the onset and duration of
membrane. The anesthesia does not penetrate into drug action with local anesthetics. The onset of local anes-
deeper skin layers. This is used to provide relief for thesia is dependent on the drug’s ability to diffuse from the
minor skin irritations or prior to needlesticks. application site to the surrounding nerves. In general, local
anesthetics are small, lipid-soluble molecules that can
• Nerve block. The drug is injected surrounding a move quickly through tissues and spaces to enter neurons.
peripheral nerve and all regions innervated by the Local anesthetics are nonselective; they will block trans-
nerve lose sensation. This is used for dental proce- mission at all types of sensory nerves. The sense of sharp
dures or for regional anesthesia. pain is usually affected first, followed by other senses such
as warmth, cold, touch, and pressure. Motor fibers are also
• Infiltration anesthesia. The drug is injected into affected by local anesthetics.
deeper skin layers and travels to surrounding regions.
This provides pain relief during minor skin surgeries Termination of local anesthetic action depends on
or dental procedures, or prior to deep needlesticks. blood flow to the region. Local blood vessels carry the drug
away from the application site to the systemic circulation,
• Spinal anesthesia. The drug is injected into the cere- where it is metabolized and excreted. Usually only mini-
brospinal fluid, usually in the lumbar region. This pro- mal systemic effects are observed because absorption into
cedure is used to block sensation to larger areas of the the general circulation is slow and the drug is sufficiently
lower abdomen or pelvis. diluted by the blood.
• Epidural anesthesia. The drug is injected into the
epidural space surrounding the spinal cord. The
436 Unit 4 Pharmacology of the Central Nervous System (d) Spinal
(e) Epidural
(a) Topical
(c) Infiltration
(b) Ne rve block
Pia mater
Arachnoid mater
Dura mater
Figure 26.1 Techniques for applying local anesthesia: (a) topical; (b) nerve block; (c) infiltration; (d) spinal; (e) epidural.
The duration of anesthetic action may be extended by circulation; therefore, adverse effects from the epinephrine
injecting a vasoconstrictor such as epinephrine in combina- are rare.
tion with the local anesthetic. The epinephrine reduces
blood flow to the region and slows absorption of the anes- The two major classes of local anesthetics are named
thetic. This not only extends the duration of anesthesia, it by their chemical structures: esters and the amides. The
also prevents the anesthetic from reaching the circulation two classes differ primarily by their incidence of allergic
too quickly, which could result in systemic toxicity. The reactions, with the amide type having the lower incidence.
amount of epinephrine used in local anesthesia is very Although they vary in time of onset and duration of action,
small and it is released very slowly into the systemic most local anesthetics have equivalent effectiveness. The
local anesthetics are listed in Table 26.4.
CONNECTIONS: Lifespan Considerations
Postoperative Cognitive Dysfunction and Delirium in the Older Adult After Surgery
Postoperative cognitive dysfunction (POCD) has been noted alcohol abuse or with the use of preoperative opioids (Murthy,
after cardiac surgery in the older adult population. Symptoms Hepner, Cooper, Bader, & Neuman, 2015).
include transient confusion and declines in cognitive skills such
as word recall, word learning, and memory. POCD also occurs The American Geriatrics Society and the American College
after other types of surgeries as well. Older adults are also at of Surgeons have published best practice guidelines for manag-
greater risk for delirium, with an estimated 13% to 50% of older ing the perioperative course of older adults (American Geriatrics
adult patients developing delirium postoperatively (Inouye, Society Expert Panel on Perioperative Delirium in Older Adults,
Westendorp, & Saczynski, 2014). Adults with a higher risk 2015; Mohanty et al., 2016). To reduce the risk of postoperative
included those over the age of 70, those with a history of delirium, it is recommended that benzodiazepines, meperidine,
dementia or cognitive dysfunction, and those with a history of and drugs with anticholinergic side effects such as antihista-
mines (H1 blockers) be avoided.
Chapter 26 Anesthetics and Anesthesia Adjuncts 437
Table 26.4 Local Anesthetics
Drug Route and Adult Dose Adverse Effects
(Maximum Dose Where Indicated)
Topical applications:
Ester Type Erythema, dermatitis, burning
Anaphylaxis
benzocaine (Americaine, Anbesol, Topical: 5–8% spray, cream, ointment Infiltration, nerve block, epidural applications:
others) 20% spray, ointment, gel, liquid, otic solution Postspinal headache, sedation, paresthesia, blurred
vision, urinary retention
chloroprocaine (Nesacaine) Infiltration and nerve block: 1–2% solution (max: 800 mg Myocardial depression, anaphylactic reactions,
without epinephrine, 1 g with epinephrine) cardiac arrest, respiratory arrest, seizures, fetal
bradycardia
Caudal and epidural block: 2–3% solution (max: 800 mg
without epinephrine, 1 g with epinephrine) Topical applications:
Erythema, dermatitis, burning
procaine (Novocaine) Spinal: 10% solution diluted in normal saline at 1 mL/5 sec Infiltration, nerve block, epidural applications:
subcutaneous Hypersensitivity, dizziness, drowsiness, urinary
retention, fecal incontinence, slowing of labor,
Infiltration or peripheral nerve block: 0.25–0.5% solution numbness of lips or tongue, hypotension, blurred or
subcutaneous double vision
Laryngeal edema, bradycardia, anaphylactoid
tetracaine (Pontocaine) Topical: 1–2 drops of 0.5% solution or 1.25–2.5 cm of reaction, respiratory arrest, seizures, rectal bleeding
ointment or 0.5% solution to the nose or throat (dibucaine)
Spinal: 1% solution diluted with equal volume of 10%
dextrose injected in the subarachnoid space
Amide Type
articaine (Septocaine, Zorcaine) Infiltration: 0.5–2.5 mL (20–100 mg)
Nerve block: 0.5–3.4 mL (20–136 mg)
Oral surgery: 1–5.1 mL (40–204 mg)
bupivacaine (Exparel, Marcaine, Local infiltration, sympathetic block: 0.25% solution
Sensorcaine) Epidural, caudal, or retrobulbar block: 0.25–0.75% solutions
Liposomal (Exparel): 8–20 mL of 1.3% solution
dibucaine (Nupercainal) Topical: Apply to skin 1 ounce q24h
lidocaine (Anestacon, Xylocaine, Infiltration: 0.5–1% solution
Zingo, others) Nerve block or epidural: 1–2% solution
Caudal: 1–1.5% solution
Spinal: 5% solution with dextrose
Saddle block: 1.5% with dextrose
Topical: 2.5–5% jelly, ointment, cream, or solution
mepivacaine (Carbocaine, Isocaine, Subcutaneous: 1–5 cartridges, each containing
Polocaine) approximately 1.8 mL (54 mg) of a 3% solution
prilocaine (Citanest) Infiltration: 1–2 mL (40–80 mg) of a 4% solution for dental use
ropivacaine (Naropin) Surgical anesthesia: Intrathecal administration:
Epidural or nerve block: 5–250 mg (0.5–1% solution)
Labor pain: 20–40 mg (0.2% solution)
Postoperative pain management:
Epidural: 12–20 mg/h (0.2% solution)
Infiltration: 2–200 mg (0.2–0.5% solution)
Note: Italics indicate common adverse effects. Underline indicates serious adverse effects.
26.10 Ester-type local anesthetics have been Esters act by decreasing the amount of sodium that
widely used for topical and spinal anesthesia. enters the neuron, thereby depressing depolarization and
preventing conduction of the pain impulse. Esters may be
Cocaine was the first local anesthetic to be widely used for administered with epinephrine as a vasoconstrictor to limit
medical procedures. Cocaine is a natural ester found in the blood loss at the surgical site and to decrease the amount of
leaves of Erythroxylum coca, a plant native to the Andes anesthetic absorbed systemically. The local anesthetic effect
Mountains in Peru. Cocaine was discovered by a German of an ester is rapid, occurring in 1 to 8 minutes. The dura-
chemist in 1855 and ultimately used in 1884 as a topical tion ranges from 15 to 60 minutes.
eye anesthetic. Although still approved by the FDA as a
local anesthetic, cocaine is a Schedule II controlled sub- Ester-type anesthetics are generally safe when applied
stance and is rarely used because of its high potential for as directed. All can cause serious CNS and cardiac toxic-
abuse. In 1904 a German chemist named Einhorn discov- ity, however, if they reach the blood in high concentra-
ered procaine (Novocaine), which soon came into wide- tions. The first CNS symptoms may be stimulatory:
spread use, especially in dental offices. anxiety, nervousness, dizziness, tremor, or seizures.
438 Unit 4 Pharmacology of the Central Nervous System
Subsequent CNS depression may cause the patient to Spinal anesthesia with procaine can cause headache, pal-
become drowsy, experience respiratory depression, and sies, spinal nerve paralysis, and meningism (nuchal rigid-
enter a coma. High amounts can cause dysrhythmias, QT ity, photophobia, and headache). Cutaneous lesions can
prolongation, hypotension, and cardiac arrest. Care must occur in a delayed time frame. The caudal or epidural ad-
be taken that the drug is administered correctly to prevent ministration of procaine in the obstetric patient can result
serious adverse effects. in urinary incontinence, loss of perineal sensation, slowing
of labor, and increased incidence of forceps delivery.
PROTOTYPE DRUG Procaine (Novocaine)
Contraindications/Precautions: Patients who have
Classification Therapeutic: Local anesthetic experienced hypersensitivity to any ester anesthetic or
Pharmacologic: Ester, sodium channel agent containing para-aminobenzoic acid (PABA) should
not receive procaine. Patients with generalized septice-
blocker mia, inflammation, or sepsis should not be injected with
procaine. It is also contraindicated in patients with heart
Therapeutic Effects and Uses: Procaine is used for block, hypotension, HTN, or altered coagulation. It should
spinal, epidural, and peripheral nerve blocks through in- be used cautiously in older and acutely ill patients. Pa-
jection or infiltration. It produces local anesthesia with loss tients who have increased abdominal pressure should be
of sensation close to the injection or application site. It has administered procaine cautiously.
a short duration of action. An off-label use is for the treat-
ment of severe pain due to cancer, herpes, or burns. Once Drug Interactions: Ester anesthetics such as procaine
used widely in dentistry, it has largely been replaced by may antagonize the antimicrobial effects of sulfonamides.
other local anesthetics. Risk of hypotension increases when administered with an-
tihypertensives. Procaine is incompatible with aminophyl-
Procaine causes vasodilation, which could potentially line, chlorothiazide, magnesium sulfate, phenobarbital,
increase its rate of absorption from tissues and cause sys- phenytoin, secobarbital, and sodium bicarbonate. Herbal/
temic toxicity. Some procaine solutions contain small Food: Unknown.
amounts of epinephrine, which constricts arteries to keep
the procaine localized and prolong the anesthetic effect. Pregnancy: Category C.
The drug is rapidly metabolized to inactive metabolites by
esterase, an enzyme found in the plasma. Once it reaches Treatment of Overdose: The effects of procaine over-
the plasma, the half-life of procaine is only 40 seconds. dosage are treated symptomatically. Rapid systemic ab-
sorption will affect the cardiovascular system and could
Mechanism of Action: Procaine decreases the influx require cardiopulmonary resuscitation.
of sodium into the neuron, which increases the thresh-
old for depolarization and prevents the conduction of the Nursing Responsibilities: Key nursing implica-
nerve impulse. tions for patients receiving procaine are included in the
Nursing Practice Application for Patients Receiving Local
Pharmacokinetics: Anesthesia.
Route(s) Subcutaneous Drugs Similar to Procaine (Novocaine)
Absorption Rapid Other local anesthetic esters include benzocaine, chloro-
procaine, and tetracaine.
Distribution Not distributed; highly bound to
Benzocaine (Americaine, Anbesol, others): Approved in
plasma proteins 1938, benzocaine is an over-the-counter (OTC) local anes-
thetic ester applied topically as a lotion, cream, ointment,
Primary metabolism Metabolized by plasma esterase spray, gel, or otic solution. Chemically it is almost identical
to procaine, but it has a prolonged duration of anesthetic
Primary excretion Renal: 80% as metabolites action. It provides temporary relief of pain and discomfort
due to sunburn, minor wounds, pruritus, serous otitis
Onset of action 2–5 min media, swimmer’s ear, otitis externa, canker sores, sore
throat, hemorrhoids, and anal fissures. It can be applied to
Duration of action 1 h the penis as a male desensitizer to slow the onset of ejacu-
lation. Benzocaine preparations are commonly used as an
Adverse Effects: With therapeutic doses, adverse ef- anesthetic for the passage of catheters and endoscopic
fects are rare. Adverse events may occur, however, if mul- tubes. Onset of anesthetic action occurs in less than a
tiple doses of procaine are administered or if it is injected
intravascularly. The most severe adverse effects include
respiratory arrest and anaphylaxis. A patient who has ex-
perienced an allergic reaction to procaine will likely be al-
lergic to other esters. Myocardial depression may result
in atrioventricular (AV) block dysrhythmias or cardiac
arrest. CNS effects are stimulatory and usually transient;
nervousness, dizziness, confusion, and tremor may occur.
Chapter 26 Anesthetics and Anesthesia Adjuncts 439
minute, and because absorption of benzocaine is minimal, PROTOTYPE DRUG Lidocaine (Anestacon, Xylocaine,
systemic effects are rare. Contact dermatitis can occur and Zingo, Others)
is more common with benzocaine than with some of the
other topical anesthetics. Although rare, benzocaine sprays Classification Therapeutic: Local anesthetic
have been associated with serious methemoglobinemia, a Pharmacologic: Amide, sodium channel
condition in which hemoglobin is unable to bind sufficient
oxygen. This drug is pregnancy category C. blocker
Chloroprocaine (Nesacaine): Approved in 1957, chloro- Therapeutic Effects and Uses: Lidocaine is a lo-
procaine is a short-acting local anesthetic ester that is used cal anesthetic that has a prompt onset of action of 2 to
for infiltration, epidural, and caudal anesthesia. It is not 5 minutes. It has a longer duration of action than procaine,
effective as a topical agent. Anesthesia occurs in 6 to lasting 10 to 90 minutes, depending on its route of adminis-
12 minutes and can last up to 90 minutes if epinephrine is tration. It may be administered as a surface and infiltration
added to the injection. A test dose is given before epidural anesthetic agent to block the nerve. It is also used in cau-
use to assess for intravascular or subarachnoid injection. In dal and spinal block anesthesia to relieve local discomfort
the event of intravascular injection, the patient would of the skin and mucous membranes. Lidocaine patches are
experience an epinephrine response with tachycardia, cir- administered to relieve pain related to post-herpetic neu-
cumoral pallor, palpitations, and nervousness. Signs of ralgia (Lidoderm) or dental procedures (DentiPatch). Par-
subarachnoid injection include motor paralysis and exten- enteral lidocaine is administered to treat life-threatening
sive sensory anesthesia. Like other ester anesthetics, aller- ventricular dysrhythmias (see Chapter 37). Zingo (lidocaine
gic reactions such as rash, pruritus, and anaphylaxis are hydrochloride monohydrate) is a needle-free intradermal
possible. This drug is pregnancy category C. injection system. Zingo is indicated for rapid local anesthe-
sia for procedures such as IV insertions or blood draws.
Tetracaine (Pontocaine): Tetracaine is a local anesthetic
ester that is used in spinal anesthesia and topically. It may Mechanism of Action: Lidocaine blocks the conduc-
be used to anesthetize the conjunctiva during eye surgery tion of action potentials by reducing the sodium perme-
and in the nose and throat to eliminate the laryngeal and ability, thus decreasing the action potential and slowing
esophageal reflexes. It is administered on the skin to nerve conduction.
relieve pruritus, pain, and burning. An OTC preparation
(Viractin) is available for topical treatment of pain associ- Pharmacokinetics:
ated with cold sores and fever blisters. Onset of action is
rapid for topical use (3–10 minutes) but longer following Route(s) Subcutaneous, IM, IV, IV bolus;
spinal administration (15 minutes). Of the topical anesthet-
ics, tetracaine is the most likely to cause skin sensitivity, topical
including rash, erythema, pruritus, burning, and edema.
Systemic absorption can cause significant CNS and cardiac Absorption Topical absorption: 3% through
toxicity. Tetracaine is contraindicated in patients who are
hypersensitive to ester-type anesthetics, sulfites, or PABA. intact skin
This drug is pregnancy category C.
Distribution Crosses the blood–brain barrier
26.11 Local anesthetics from the amide class
have a lower incidence of adverse effects than and the placenta; secreted in
those from the ester class.
breast milk
Amide-type local anesthetics have largely replaced the
administration of drugs from the ester class. The amides Primary metabolism Hepatic via CYP3A4 and 2D6
produce less effect on myocardial contractility, and the
incidence of allergic reactions is lower. Amides and esters Primary excretion Renal
have the same mechanism of action: decreasing the
sodium flux into the neuron, thus inhibiting the initial Onset of action IV: 45–90 sec; IM: 5–15 min;
depolarization and conduction of the nerve impulse.
Whereas the esters are inactivated by the enzyme esterase topical: 2–5 min
in the plasma, the amides are metabolized by hepatic
CYP450 enzymes. Caution should be exercised when Duration of action IV: 10–20 min; IM: 60–90 min;
administering large amounts of amide anesthetics to
patients with hepatic impairment. topical: 30–60 min
Half-life: 1.5–2 h
Adverse Effects: When used topically, adverse re-
actions to lidocaine are uncommon. Mild and transient
reactions at the site of application include erythema, pru-
ritus, dermatitis, and burning. The transoral DentiPatch
may cause alterations in taste, headache, and gingivitis.
Should the drug be unintentionally injected intravascu-
larly, CNS adverse effects will be those of stimulation
(anxiety, tremors, shivering, and seizures) followed by
depression (drowsiness, respiratory depression, and
coma). Cardiovascular effects include hypotension, dys-
rhythmias, cardiovascular collapse, and cardiac arrest.
440 Unit 4 Pharmacology of the Central Nervous System
Black Box Warning: Significant systemic absorption may Bupivacaine (Exparel, Marcaine, Sensorcaine): Approved
occur with topical use. in 1972, bupivacaine is an amide local anesthetic that is
used for infiltration anesthesia, peripheral sympathetic
Contraindications/Precautions: Patients who have nerve block, and epidural block. Bupivacaine in dextrose
experienced a hypersensitivity reaction to amide-type local solution is administered for spinal anesthesia. Its 3- to
anesthetics should not be administered lidocaine. Topical 9-hour duration of action is one of the longest of any
lidocaine should not be applied to skin seriously damaged local anesthetic. A liposomal form (Exparel) provides
by trauma, burns, or eczema. analgesia for up to 72 hours. The anesthetic is injected
into the surgical area for procedures such as bunionec-
Other precautions apply to patients receiving paren- tomy and hemorrhoidectomy. Adverse effects are similar
teral lidocaine, although these also apply to situations in to those of other amide anesthetics. This drug is preg-
which the drug is unintentionally injected intravascularly. nancy category C.
Patients who have been diagnosed with Stokes–Adams
syndrome, untreated sinus bradycardia, or sinoatrial, AV, Dibucaine (Nupercainal): Approved in 1947, dibucaine is
or intraventricular heart block should not be administered administered to relieve pain and itching related to hemor-
lidocaine. The medication should be used cautiously in the rhoids and other anorectal disorders. It is also adminis-
presence of liver or kidney disease, myasthenia gravis, and tered to relieve discomfort from insect bites, sunburn,
hypovolemia as well as in debilitated patients and older minor burns, cuts, and scratches. It is a long-acting amide
patients or when there is a family history of malignant anesthetic that inhibits the initiation and conduction of
hyperthermia. nerve impulses by reducing the permeability of nerve cells
to sodium ions. It is available OTC. This drug is pregnancy
Drug Interactions: Lidocaine patches can cause toxic category C.
effects with tocainide and mexiletine. Barbiturates decrease
lidocaine activity. Increased pharmacologic effects of lido- Mepivacaine (Carbocaine, Isocaine, Polocaine): Approved
caine will be noted if it is administered with cimetidine, in 1960, mepivacaine is an amide anesthetic used for infil-
beta blockers, or quinidine. Herbal/Food: After receiving tration, transtracheal anesthesia, and epidural nerve blocks
transoral lidocaine, patients should not eat or drink until in surgical and dental procedures. Onset of action is very
the effects of the anesthesia have worn off. rapid—less than a minute for the upper and lower jaws.
Epidural onset is 7 to 15 minutes. This drug has an inter-
Pregnancy: Category B. mediate duration of action of 60 to 100 minutes for soft tis-
sue and 115 to 150 minutes for epidural. Mepivacaine is
Treatment of Overdose: Overdose may occur if sometimes combined with levonordefrin, a vasoconstrictor
the drug is injected intravascularly. The patient is treated that prolongs the duration of action of the local anesthetic.
through symptom management. The adverse effects are the same as those of other amide
anesthetics. This drug is pregnancy category C.
Nursing Responsibilities: Key nursing implica-
tions for patients receiving lidocaine are included in the Prilocaine (Citanest): Approved in 1965, prilocaine is
Nursing Practice Application for Patients Receiving Local used for dental anesthesia via infiltration. Onset of action
Anesthesia. is 2 minutes and its duration is 1 to 2 hours. The adverse
effects are the same as those of other amide anesthetics.
Drugs Similar to Lidocaine (Anestacon, This drug is pregnancy category B.
Xylocaine, Zingo, Others)
Ropivacaine (Naropin): Ropivacaine is a newer local
Other local anesthetic amides include articaine, bupiva- anesthetic agent approved in 1996 that is used in epidural
caine, dibucaine, mepivacaine, prilocaine, and ropivacaine. anesthesia and postoperative pain management. It has an
The amides levobupivacaine (Chirocaine) and etidocaine onset of action of 1 to 30 minutes and a duration of anes-
(Duranest) have been removed from the U.S. market. thetic action of 2 to 6 hours. It is important that disinfect-
ing agents with heavy metal content not be used to
Articaine (Septocaine, Zorcaine): Approved in 2000, artic- disinfect the skin prior to the insertion of the epidural
aine is approved for administration by infiltration or by catheter because these have been associated with swelling
nerve block for dental procedures. It is unique because it and edema. Also, the container of ropivacaine should not
has both an amide and an ester group. Anesthesia is rapid, be cleaned with a heavy metal disinfecting agent. Unlike
occurring in 1 to 6 minutes, and lasts up to an hour. Artic- most local anesthetics, the presence of epinephrine does
aine appears to diffuse through soft tissue and bone better not affect the systemic absorption of ropivacaine. Like
than other local anesthetics. It is combined with epineph- other amide anesthetics, high serum concentrations may
rine, which provides vasoconstriction and prolongs the cause serious CNS and cardiac toxicity; care must be taken
duration of action. The adverse effects are the same as
those of other amide anesthetics. This drug is pregnancy
category C.
Chapter 26 Anesthetics and Anesthesia Adjuncts 441
not to inject the drug intravascularly or intrathecally. This Neuromuscular blockers: Skeletal muscle relaxation is
drug is pregnancy category B. an important component of general anesthesia. Insertion
of an endotracheal tube would be difficult and painful
Adjuncts to Anesthesia without muscle relaxation, and contraction or spasticity of
muscles during a surgical procedure could render some
26.12 Adjunctive agents are used during the operations impossible. Complete paralysis of muscle is
perioperative phase to enhance anesthesia necessary for major surgical procedures. Although some of
or to treat the potential adverse effects of the the general anesthetics do have mild to moderate ability to
anesthetics. relax skeletal muscles, most are incapable of causing the
degree of relaxation necessary for surgery.
Surgery is often a stressful and painful procedure for
patients. In addition, anesthetics dampen vital reflexes, It is important to note that neuromuscular blockers do
which can lead to aspiration pneumonia. Diminished auto- not enter the CNS. Although these drugs cause muscle
nomic function can have serious adverse effects on the car- paralysis, they do not induce unconsciousness or provide
diovascular and gastrointestinal (GI) systems. Adjunctive analgesia. The patient is still able to feel pain and is aware
medications are those used to enhance anesthesia or to of his or her surroundings.
make the procedure safer and less unpleasant for patients.
The nondepolarizing neuromuscular blocking agents
Preoperative medications: The most common preoper- such as atracurium (Tracrium) and cisatracurium (Nimbex)
ative symptom is anxiety. Oral benzodiazepines may be have a short duration of action and bind competitively
given for several days prior to a major procedure to lessen with acetylcholine to produce skeletal muscle relaxation.
anxiety. Just prior to surgery, midazolam (Versed) may be The depolarizing neuromuscular blocking agents such as
administered parenterally to sedate the patient and to succinylcholine (Anectine) are ultra-short acting and pos-
cause perioperative amnesia (see Section 26.5). sess a high affinity for the acetylcholine receptor sites.
Aspiration pneumonia is a potentially serious problem The neuromuscular blocking agents are very danger-
during a surgical procedure because the patient may lose ous; the diaphragm and intercostal muscles are paralyzed
protective airway reflexes. Histamine (H2) receptor antago- and breathing requires a mechanical ventilator. Serious car-
nists such as ranitidine (Zantac) or famotidine (Pepcid) can diovascular adverse effects are possible. Details of the
reduce the possibility of aspiration pneumonia by decreas- actions, indications, and adverse effects of the neuromus-
ing gastric fluid volume and reducing acidity. For aspira- cular blockers are included in Chapter 14. A prototype fea-
tion prophylaxis, the H2 receptor antagonist may be given ture for succinylcholine is included in that chapter.
PO the night prior to surgery and by IV infusion an hour
before the procedure. A drug prototype feature for raniti- Postoperative medications: Because many anesthetics
dine is found in Chapter 59. induce severe nausea and vomiting in the postanesthesia
phase, the administration of antiemetic drugs is indicated for
Anticholinergics such as atropine may be administered prophylaxis in high-risk patients or for treatment. Several
prior to surgery to reduce salivary and airway secretions. drugs have been used as antiemetics. Promethazine (Phener-
Atropine also blocks the bradycardia caused by some anes- gan) is an older antiemetic that may be administered pre- or
thetics. The drug is given by the IM route 45 to 60 minutes postoperatively. It has the advantage of also being a sedative;
prior to anesthesia. A prototype feature for atropine is pre- thus it can be used in the induction phase of anesthesia. Also
sented in Chapter 14. an older medication, metoclopramide (Reglan), may be
administered near the end of the surgical procedure for pro-
Pain management: Pain reduction is an important com- phylaxis of postanesthetic nausea and vomiting. A newer and
ponent of preanesthesia and postanesthesia care. Opioids very effective antiemetic is ondansetron (Zofran, Zuplenz), a
are used when the pain is expected to be severe, but these 5-HT3 antagonist. Commonly used to prevent the acute nau-
drugs can cause significant respiratory depression. If the sea and vomiting caused by cancer chemotherapeutic agents,
pain level is moderate or mild, nonsteroidal anti- ondansetron may be injected just prior to chemotherapy or
inflammatory drugs (NSAIDs) are administered because 30 minutes before the end of the surgical procedure.
they cause fewer serious adverse reactions than the opi-
oids. Clonidine (Catapres, Duraclon) is a centrally acting CONNECTION Checkpoint 26.3
alpha2-adrenergic agonist that has been used to reduce
severe pain associated with surgery. When administered Atropine and succinylcholine are both cholinergic blockers but they
epidurally Duraclon allows the dosages of the anesthetic produce very different effects. From what you learned in Chapter 14,
and opioids to be reduced. The primary indication of cloni- explain the mechanisms for the differences in pharmacologic actions.
dine is HTN (Catapres), but it has largely been replaced by (Hint: One drug affects the muscarinic receptor and the other the
safer antihypertensives (see Chapter 34). nicotinic receptor.) Answers to Connection Checkpoint questions are
available on the faculty resources site. Please consult with your instructor.
442 Unit 4 Pharmacology of the Central Nervous System
CONNECTIONS: NURSING PRACTICE APPLICATION
Patients Receiving Local Anesthesia
Assessment
Baseline assessment prior to administration:
• Obtain a complete health history including cardiovascular, hepatic, renal, respiratory, or neurologic disease, pregnancy, or breastfeeding. Obtain a
drug history including allergies, current prescription and OTC drugs, herbal preparations, caffeine, nicotine, and alcohol use. If the patient reports
allergy to “caine” drugs, note the specific drug and reactions the patient experienced. Be alert to possible drug interactions.
• Obtain baseline vital signs and weight.
• Assess for areas of broken skin, abrasions, burns, or other wounds in the area to be treated with a local anesthetic.
• Evaluate laboratory findings appropriate to the procedure (e.g., CBC, electrolytes, hepatic or renal function studies).
• Assess the patient’s ability to receive and understand instructions. Include family and caregivers as needed.
Assessment throughout administration:
• Assess for desired therapeutic effects (e.g., local or regional area numbness).
• Assess vital signs, especially blood pressure and pulse, if regional block is used. Report a blood pressure less than 90/60 mmHg, pulse above
100 beats/min, or per the parameters as ordered by the healthcare provider.
• Assess the local or regional area blocked. Expect blanching in the localized area if the local anesthetic contained epinephrine. If a regional area was
blocked, periodically assess the patient’s ability to move limbs distal to the block.
• Assess level of consciousness if a large regional block was given. Report any increasing drowsiness, dizziness, lightheadedness, confusion, or
agitation immediately.
• Assess for and promptly report adverse effects: bradycardia or tachycardia, hypotension or HTN, or dyspnea.
Implementation
Interventions and (Rationales) Patient-Centered Care
Ensuring therapeutic effects: • Teach the patient that:
• Continue assessments as above for therapeutic effects. Assess the • The area may be numb for several hours after the procedure is
completed.
localized area for numbness and blanching if the local anesthetic • It is normal that a slight pressure sensation may remain during
included epinephrine. Assess the patient’s ability to move limbs distal anesthesia (e.g., sensation of “tugging” during suturing) but that no
to the regional anesthetic. (Duration of anesthetic action will depend pain should be felt. Have the patient alert the healthcare provider if
on the solution used and whether it contains epinephrine. If a large more than slight pressure sensation or any pain is noticed during
regional area is blocked [e.g., epidural], the patient may regain some anesthesia.
motor ability before sensation returns and the return of motor activity • It is normal to regain some ability to move limbs (e.g., after epidural
signals decreasing levels of anesthesia. An ability to perceive anesthetic), and movement may return before the ability to feel the
pressure-type sensations may remain during anesthesia and may be movement.
alarming to the patient. Epinephrine in the anesthetic solution will
constrict localized blood vessels and result in blanching of the area.)
Minimizing adverse effects: • Instruct the patient to report any increasing nausea, drowsiness,
• Continue to monitor vital signs, especially blood pressure and pulse, for dizziness, lightheadedness, confusion, or anxiety immediately. If
dizziness occurs, the patient should sit or lie down and not attempt to
patients given regional anesthesia. Report blood pressure below 90/60 stand or walk until the sensation passes.
mmHg or per the parameters as ordered by the healthcare provider,
tachycardia, bradycardia, changes in level of consciousness, dyspnea,
or decrease in respiratory rate, immediately. (Adverse effects of local
anesthesia are rare. Regional blocks may cause hypotension with the
possibility of reflex tachycardia. Be particularly cautious with older adults
who are at increased risk for hypotension due to physiologic changes
related to aging or concurrent vasoactive drug use. Bradycardia,
hypotension, decreased level of consciousness, decreased respiratory
rate, and dyspnea may signal that the anesthesia has entered the
systemic circulation and is acting as a general anesthetic.)
• Diverse Patients: Continue to monitor hepatic function and drug • Teach ethnically diverse patients to observe and report effects of local
effects. (Because amide anesthetics such as lidocaine are metabolized anesthetic use to ensure therapeutic results.
through the CYP450 system, they may result in less than optimal
results based on differences in enzymes.)
• Caution the patient not to eat, chew gum, or drink until mouth sensation • Instruct the patient to refrain from eating or drinking for 1 h or more
has returned if local (dental) or oral or throat anesthesia has been used. postanesthesia, or until sensation has completely returned to the oral
If throat anesthesia is used, assess gag reflex before eating. (Local cavity or throat.
anesthetics are effective for up to 3 h or more. Biting injuries to oral
mucous membranes may occur while tissue is numb. Aspiration of food
or liquids is possible until swallowing sensation and gag reflex return.)
• Ensure patient safety; monitor motor coordination and ambulation • Instruct the patient to call for assistance prior to getting out of bed or
post-regional block until certain that motor movement is unaffected. attempting to walk alone post-epidural block, and to avoid driving or
other activities requiring physical coordination (e.g., regional upper limb
Lifespan: Be particularly cautious with older adults who are at increased block) until residual effects of the drug are known.
risk for falls. (Numbness or effects on motor ability post-regional
anesthetic may impair movement and increase the risk of falls or injuries.)
Chapter 26 Anesthetics and Anesthesia Adjuncts 443
CONNECTIONS: NURSING PRACTICE APPLICATION (continued)
Implementation
Interventions and (Rationales) Patient-Centered Care
• Assess areas of abrasion, burns, or open wounds if a local anesthetic • Instruct the patient to report increased redness, swelling, or drainage
is applied to area. (Large open or denuded areas may increase the from open areas under treatment.
amount of drug absorption into the general circulation. Use sterile
technique to apply the drug to open areas.)
• Read all labels carefully before using parenteral solutions. (Solutions • Provide an explanation of desired effects of the local anesthetic and
containing epinephrine must never be used IV or for local anesthesia in the need for postprocedure monitoring.
areas of decreased circulation [e.g., fingertips, toes, earlobes, tip of
nose, penile tissue] due to vasoconstrictive effects.)
• Monitor pain relief in patients post-regional block (e.g., epidural). (Pain • Teach the patient to report any discomfort or pain as anesthesia
sensation will increase as the regional block wears off. Additional pain wears off.
relief may be required.)
Patient understanding of drug therapy: • The patient, family, or caregiver should be able to state the reason for
• Use opportunities during administration of medications and during the drug, anticipated sensations, adverse effects to observe for, and
when to report them.
assessments to discuss the rationale for the drug therapy, desired
therapeutic outcomes, commonly observed adverse effects,
parameters for when to call the healthcare provider, and any necessary
monitoring or precautions. (Using time during nursing care helps to
optimize and reinforce key teaching areas.)
Patient self-administration of drug therapy: • Teach the patient to take oral medication (e.g., lidocaine viscous) by
• When administering the medication, instruct the patient, family, or swishing and spitting if used for oral cavity, or by gargling, and do not
swallow unless directed by the healthcare provider. Apply topical
caregiver in proper self-administration of the drug, e.g., take the drug medication in a thin layer to the skin area as directed.
as prescribed when needed. (Utilizing time during nurse administration
of these drugs helps to reinforce teaching.)
Understanding Chapter 26
Key Concepts Summary 26.7 Inhalation anesthetics used to produce loss
of consciousness are classified as gases or
26.1 Anesthesia is used to produce a controlled loss volatile liquids.
of sensation during a diagnostic or surgical
procedure. 26.8 Volatile liquid general anesthetics are used to
induce and maintain deep anesthesia.
26.2 Balanced anesthesia uses multiple drugs to
provide for the safe induction and maintenance 26.9 Local anesthetic agents block pain transmission in
of general anesthesia. peripheral nerves and are grouped in two major
classes.
26.3 Intravenous anesthetics include opioids,
benzodiazepines, and several miscellaneous 26.10 Ester-type local anesthetics have been widely used
agents. for topical and spinal anesthesia.
26.4 Opioids are used as intravenous anesthetics 26.11 Local anesthetics from the amide class have a
to provide analgesia and to accomplish lower incidence of adverse effects than those
neurolept anesthesia. from the ester class.
26.5 Benzodiazepines are used in anesthesia to 26.12 Adjunctive agents are used during the
produce relaxation, sedation, and amnesia. perioperative phase to enhance anesthesia
or to treat the potential adverse effects of the
26.6 Propofol and ketamine are widely used anesthetics.
intravenous drugs for inducing and maintaining
anesthesia.
444 Unit 4 Pharmacology of the Central Nervous System
CASE STUDY: Making the Patient Connection
Remember the patient “Elena The patient’s vital signs are as follows: blood pressure,
Moore” at the beginning of the 138/88 mmHg; temperature, 36.3°C (97.4°F); pulse,
chapter? Now read the remain- 94 beats/min; and respiration, 20 breaths/min. She denies
der of the case study. Based on pain and states that she is concerned she will wake up dur-
the information presented ing the surgery. She is to receive balanced anesthesia.
within this chapter, respond to
the critical thinking questions that follow. Critical Thinking Questions
Elena is a 37-year-old woman who is scheduled for a vagi- 1. In your own words, how would you describe balanced
nal hysterectomy after a positive Pap smear returned with anesthesia to Elena?
results suggestive of cancer. While in the holding area of
the operating room suite, she states that she is fearful of 2. How does nitrous oxide differ from IV anesthetic
general anesthesia. The preoperative nurse caring for this agents?
patient notices that she is very anxious. Upon further
assessment and conversation, she states that her mother 3. How should the nurse educate a patient regarding the
died of breast cancer when she was young. use of IV propofol?
Answers to Critical Thinking Questions are available on the
faculty resources site. Please consult with your instructor.
Additional Case Study 1. What is the action of lidocaine?
2. Why is lidocaine preferred over procaine?
Anthony Holiday is a 28-year-old steelworker for a heating
and cooling company. While on the job he cut his right Answers to Additional Case Study questions are available on
hand with a piece of steel for an air-conditioning vent. He the faculty resources site. Please consult with your instructor.
is admitted to the emergency department for sutures to the
right middle finger and palm. The laceration will be anes-
thetized with lidocaine prior to suturing.
Chapter Review combativeness. The nurse would anticipate what
change in the patient’s anesthesia is needed?
1. The surgical nurse becomes alerted that the patient
who is receiving general anesthesia has become excit- 1. The nitrous oxide dose will be increased.
able and hyperactive with irregular heart and respira-
tory rates. The nurse knows that the patient has 2. Propofol (Diprivan) will be given along with the
entered which stage of general anesthesia? nitrous oxide.
1. Stage 1 3. Succinylcholine (Anectine) will be given to the
2. Stage 2 patient.
3. Stage 3
4. Stage 4 4. The nitrous oxide dose will be decreased.
2. The nurse should question the administration of pro- 4. The nurse is providing the patient, who will be receiv-
pofol (Diprivan) for which patient? An individual ing ketamine (Ketalar), with preoperative instruc-
with: tions. Which statement, if made by the patient,
indicates that teaching is successful?
1. Allergy to eggs or soy products.
2. Allergy to iodine. 1. “The medication will decrease anxiety during
3. Kidney disease. surgery.”
4. Addison’s disease.
2. “I will experience increased energy due to this drug.”
3. During the administration of nitrous oxide, the
patient develops anxiety, excitement, and 3. “I may experience a feeling of being separated
from the environment.”
4. “The drug will cause me to have dry mouth after
the operation.”
Chapter 26 Anesthetics and Anesthesia Adjuncts 445
5. The patient who is having a scalp laceration sutured 6. Identify the general anesthetic agents that are paren-
will be receiving local anesthesia with lidocaine (Xylo- teral opioid agents. (Select all that apply.)
caine) that contains epinephrine. The nurse knows
that the purpose of this drug combination is to: 1. Nitrous oxide
2. Alfentanil (Alfenta)
1. Increase the duration of the anesthetic action. 3. Sufentanil (Sufenta)
4. Remifentanil (Ultiva)
2. Increase vasodilation at the site of the laceration. 5. Succinylcholine (Anectine)
3. Decrease blood pressure in individuals who are See Answers to Chapter Review in Appendix A.
hypertensive.
4. Ensure that infection at the wound site will not occur.
References Kaar, S. J., Ferris, J., Waldron, J., Devaney, M., Ramsey, J.,
& Winstock, A. R. (2016). Up: The rise of nitrous oxide
American Association of Nurse Anesthetists. (2016). abuse. An international survey of contemporary nitrous
Certified registered nurse anesthetists at a glance. Retrieved oxide use. Journal of Psychopharmacology, 30, 395–401.
from http://www.aana.com/ceandeducation/ doi:10.1177/0269881116632375
becomeacrna/Pages/Nurse-Anesthetists-at-a-Glance.
aspx Mohanty, S., Rosenthal, R. A., Russell, M. M., Neuman,
M. D., Ko, C. Y., & Esnaola, N. A. (2016). Optimal
American Geriatrics Society Expert Panel on Perioperative perioperative management of the geriatric patient: A
Delirium in Older Adults. (2015). Postoperative best practices guideline from the American College of
delirium in older adults: Best practice statement from Surgeons NSQIP and the American Geriatrics Society.
the American Geriatrics Society. Journal of the American Journal of the American College of Surgeons, 222, 930–947.
College of Surgeons, 220, 136–148.e1. doi:10.1016/j. doi:10.1016/j.jamcollsurg.2015.12.026
jamcollsurg.2014.10.019
Murthy, S., Hepner, D. L., Cooper, Z., Bader, A. M., &
Hedenmalm, K., Granberg, A. G., & Dahl, M. L. (2015). Neuman, M. D. (2015). Controversies in anaesthesia for
Statin-induced muscle toxicity and susceptibility to noncardiac surgery in older adults. British Journal of
malignant hyperthermia and other muscle disorders: A Anaesthesia, 115(Suppl. 2), ii15–ii25. doi:10.1093/bja/
population-based case-control study including 1st and aev396
2nd degree relatives. European Journal of Clinical
Pharmacology, 71, 117–124. doi:10.1007/ Satpathy, H. K. (2015). Labor and delivery, analgesia, regional
s00228-014-1776-9 and local. Retrieved from http://emedicine.medscape.
com/article/149337-overview
Heytens, L., Forget, P., Scholtès, J. L., & Veyckemans, F.
(2015). The changing face of malignant hyperthermia: Visolu, M., Young, M. C., Wieland, K., & Brandom, B. W.
Less fulminant, more insidious. Anaesthesia and (2014). Anesthetic drugs and onset of malignant
Intensive Care, 43, 506–511. hyperthermia. Anesthesia & Analgesia, 118, 388–396.
doi:10.1213/ANE.0000000000000062
Inouye, S. K., Westendorp, R. G., & Saczynski, J. S. (2014).
Delirium in elderly people. Lancet, 383, 911–922.
doi:10.1016/S0140-6736(13)60688-1
Selected Bibliography Bozimowski, G., Groh, D. C., Rouen, P., & Dosch, M.
(2014). The prevalence and patterns of substance
Alai, A. N. (2014). Nitrous oxide administration. Retrieved abuse among nurse anesthesia students. AANA Journal,
from http://emedicine.medscape.com/ 82(4), 277.
article/1413427-overview
Gan, T. J., Diemunsch, P., Habib, A. S., Kovac, A., Kranke,
Association of periOperative Registered Nurses. (2015). P., Meyer, T. A., … Tramèr, M. R. (2014). Consensus
Guidelines for perioperative practice. Denver, CO: guidelines for the management of postoperative nausea
AORN Inc. and vomiting. Anesthesia & Analgesia, 118, 85–113.
doi:10.1213/ANE.0000000000000002
Bailard, N. S., Ortiz, J., & Flores, R. A. (2014). Additives to
local anesthetics for peripheral nerve blocks: Evidence,
limitations, and recommendations. American Journal of
Health-System Pharmacy, 71(5). doi:10.2146/ajhp130336
446 Unit 4 Pharmacology of the Central Nervous System Tse, L., Barr, A. M., Scarapicchia, V., & Vila-Rodriguez, F.
(2015). Neuroleptic malignant syndrome: A review
Kapitanyan, R. (2016). Local anesthetic toxicity. Retrieved from a clinically oriented perspective. Current
from http://emedicine.medscape.com/ Neuropharmacology, 13, 395–406. doi:10.2174/15701
article/1844551-overview 59X13999150424113345
Lirk, P., Picardi, S., & Hollmann, M. W. (2014). Local U.S. Drug Enforcement Administration. (2013). Ketamine.
anaesthetics: 10 essentials. European Journal of Retrieved from http://www.deadiversion.usdoj.gov/
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EJA.0000000000000137
Press, C. D. (2015). General anesthesia. Retrieved from
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article/1271543-overview
“I have been getting high
since I was 14 years old.
Do I need to stop just because
I am pregnant?”
Patient “Jamie Wilkins”
Chapter 27
Pharmacology of Substance Abuse
Chapter Outline Learning Outcomes
cc Fundamental Concepts of Substance Abuse After reading this chapter, the student should be able to:
Legislation of Controlled Substances
Addiction and Dependence 1. Describe the types of substances abused by
Tolerance individuals.
cc Central Nervous System Depressants 2. Identify the five drug schedules of controlled
Sedatives and Antianxiety Drugs substances and give examples of drugs in each
Opioids schedule.
PROTOTYPE Buprenorphine with Naloxone
(Suboxone, Zubsolv, Others), p. 454 3. Explain major legislation regulating controlled
Alcohol (Ethanol) substances in the United States.
PROTOTYPE Disulfiram (Antabuse), p. 457
4. Identify factors contributing to addiction.
cc Marijuana and Related Substances
cc Hallucinogens 5. Compare and contrast physical and psychologic
dependence.
LSD and Similar Hallucinogens
Club Drugs and Miscellaneous Hallucinogens 6. Compare and contrast withdrawal syndromes for
cc Central Nervous System Stimulants the different classes of abused substances.
Amphetamines and Methylphenidate
Cocaine 7. Discuss the significance of drug tolerance to
Caffeine pharmacology.
cc Nicotine
PROTOTYPE Varenicline (Chantix), p. 464 8. Explain the major characteristics of abuse,
cc Inhalants dependence, and tolerance resulting from use of the
cc Anabolic Steroids following substances: sedatives, opioids, alcohol,
marijuana, hallucinogens, club drugs, amphetamines,
methylphenidate, cocaine, caffeine, nicotine,
inhalants, and anabolic steroids.
9. Identify the role of the nurse in recognizing,
preventing, and treating substance abuse.
447
448 Unit 4 Pharmacology of the Central Nervous System
Key Terms physical dependence, 450 substance abuse, 448
psychologic dependence, 450 tachyphylaxis, 452
anterograde amnesia, 452 rebound effects, 450 tetrahydrocannabinol (THC), 458
club drug, 460 reticular formation, 461 tolerance, 451
cross-tolerance, 452 sedatives, 452 withdrawal syndrome, 450
delirium tremens, 456
hallucinogens, 459
Throughout history individuals have consumed sub- among proper use, misuse, and substance abuse is often
stances to increase performance, assist with relaxation, not clear.
induce spiritual visions, or simply fit in with their peer
group. S ubstance abuse is the self-administration of a Certain characteristics, however, assist in the proper
drug in a manner that does not conform to the norms diagnosis of substance abuse. Nurses should be aware of
within the individual’s given culture or society. The term these characteristics because they may be the first to recog-
substance abuse is preferred over the term drug abuse, nize the following when obtaining a patient history:
because some of these agents are not considered to be
drugs by the users. The Diagnostic and Statistical Manual of • Craving for a specific substance despite an under-
Mental Disorders, Fifth Edition (DSM-5), no longer uses the standing that the substance is lowering the patient’s
terms substance abuse and substance dependence; rather it quality of life (physical dependence)
refers to substance use disorder (American P sychiatric Asso-
ciation, 2013). It defines substance use as mild, moderate, • Failure to maintain normal work or home relation-
or severe depending on the number of diagnostic criteria ships because a substance is being used repeatedly
met by an individual. According to the DSM-5, a diagnosis
of substance use disorder is based on evidence of impaired • Recognition that, over time, increased amounts of the
control, social impairment, risky use, and pharmacologic substance are needed to produce the desired effect
criteria. However, because most nurses are still familiar (tolerance)
with the term substance abuse, that term will continue to be
used in this chapter. • Repeated, unsuccessful attempts have been made to
discontinue using the substance
This chapter introduces the types of drugs commonly
abused by patients and the pharmacologic management of • Recognition that behavioral changes occur when the
withdrawal syndromes. substance is discontinued, such as agitation, drowsi-
ness, anxiety, or pain (withdrawal syndrome)
Fundamental Concepts
of Substance Abuse • Increased amount of time is devoted to obtaining or
using the substance, which reduces time available for
27.1 A wide variety of substances may be work, home, or leisure activities.
abused by patients.
Abused substances belong to a large number of
Characteristics of substance abuse vary widely from diverse chemical classes. Although they have few struc-
drug to drug and person to person. Diagnosis of this dis- tural similarities, most have in common the ability to
order is often difficult, even for experienced healthcare affect the brain. Some illicit drugs are taken to stimulate
providers. Recognition of abuse is relatively easy for the brain, whereas others are used to sedate the brain or
substances such as heroin, cocaine, or hallucinogens. dull the sensation of pain. Still other substances, such as
However, what about legal substances such as alcohol, lysergic acid diethylamide (LSD), and club drugs, such as
tobacco, or marijuana (in some states)? How many beers ecstasy, are used to provide alternative psychoactive
must one drink or cigarettes must one smoke before it is experiences such as visions or hallucinations. An impor-
labeled as substance abuse? And with legal prescription tant exception is the anabolic steroids, which are used for
drugs, is it considered substance abuse if a patient con- their effects on the muscular system rather than the ner-
tinues to refill prescriptions, such as oxycodone, even vous system.
after symptoms have resolved? It is apparent that, with
the exception of certain illegal substances, the distinction Although the public associates substance abuse with ille-
gal drugs, this is not necessarily the case. Alcohol and nico-
tine are the two most commonly abused substances and both
are legal for adults. In addition, legal prescription drugs,
such as oxycodone (OxyContin), methylphenidate (Adderall),
and alprazolam (Xanax), are frequent drugs of abuse.
Several drugs that were once used therapeutically are
now illegal due to their high potential for abuse. Cocaine
Chapter 27 Pharmacology of Substance Abuse 449
was once used as a local anesthetic, but today all the cocaine placement of drugs in the schedules. For example, gamma
acquired by users is obtained illegally. LSD is now illegal hydroxybutyrate (GHB) is used illegally as a club drug as a
although it was briefly used in psychotherapy in the 1940s stimulant or aphrodisiac and is classified as a Schedule I
and 1950s. Phencyclidine (PCP) was popular back in the drug that has “no therapeutic use.” However, this same
early 1960s as an anesthetic but was withdrawn from the substance is approved to treat narcolepsy as the drug
market due to patients reporting serious adverse effects Xyrem, a Schedule III drug. As another example, marijuana
while recovering from anesthesia. Many amphetamines is a Schedule I agent, yet some states have legalized its use
once used for bronchodilation were discontinued in the for specific medical indications and recreational use.
1980s after psychotic episodes were reported.
CONNECTION Checkpoint 27.1
PharmFACT
Prior to the CSA, other attempts were made to legislate narcotics.
As encouraging trends, the use of heroin, methamphetamine, From what you learned in Chapter 2, name the first major law in the
and cocaine among teens has been steadily declining and United States that was passed in 1914 to control narcotic use and
alcohol use is at historically low levels. However, the daily use explain its major provisions. Answers to Critical Thinking Questions are
of marijuana among 12th graders (6%) now exceeds the daily available on the faculty resources site. Please consult with your instructor.
use of tobacco (National Institute on Drug Abuse, 2016).
Addiction and Dependence
Legislation of Controlled Substances
27.3 Addiction is an overwhelming compulsion
27.2 Drugs with a potential for abuse are to continue repeated drug use.
restricted by the Controlled Substances Act
and are categorized into schedules. Addiction is an overwhelming compulsion that drives some-
one to repeat drug-taking behavior, despite serious health
It is not surprising that drugs and other substances with and social consequences. Why would someone continue to
abuse potential are highly regulated. Many of these sub- abuse drugs even when he or she is aware of its compelling
stances can cause significant harm to the user and those negative consequences? The drug experience is highly per-
surrounding the user when memory or performance sonal for each user, and it is difficult to generalize reasons for
becomes impaired. A significant percentage of motor vehi- continued substance abuse. In summary, the drug experience
cle crashes and other injuries result from substance abuse. brings some degree of pleasure or satisfaction to the user.
The government clearly has a role in protecting the public Whether it be euphoria, sedation, hallucinations, or feelings
from such dangerous drugs. The Controlled Substances of well-being or excitement, the substance abuser finds the
Act (CSA), the primary legislation establishing scheduled drug experience reinforcing and worth repeating.
drugs, was discussed in Chapter 2.
Addiction depends on multiple, complex, and interact-
Diversion from medical use is a source of some of the ing variables. These variables focus on the following
abused drugs. Because of this, legislation has been enacted categories:
to closely track potential drugs of abuse from manufacturer
to consumer. Prescription drugs may be stolen from phar- • Agent or drug factors. Cost, availability, dose, mode
macies, healthcare provider offices, or patients, and sold of administration (e.g., oral [PO], intravenous [IV],
illegally, sometimes at a very high profit. In some cases, inhalation), speed of onset, duration of drug action,
healthcare workers who have the responsibility of dispens- length of drug use
ing or administering the medications conduct the theft.
• User factors. Genetic factors (e.g., metabolic enzymes,
Patients contribute to the diversion by faking or exag- innate tolerance), risk-taking behavior, prior experi-
gerating their symptoms to obtain prescriptions for pain ences with drugs, pathologic state (such as severe
medication or sedatives. Some patients obtain the same pain) that may indicate a drug with abuse potential
prescription from several healthcare providers, commonly
referred to as “doctor shopping,” and sell their pills to sub- • Environmental factors. Social and community norms,
stance abusers. Because of the multitude of ways that legal role models, peer influences, educational opportunities.
drugs can be diverted to abusers, the tracking of drugs
with abuse potential must be closely monitored. In the case of legal prescription drugs, addiction may
begin with a legitimate need for pharmacotherapy. For
In the United States, controlled substances are classi- example, narcotic analgesics may be indicated for pain
fied according to their potential for abuse and toxicity. This relief or sedatives for a sleep disorder. These drugs may
classification uses five schedules, with Schedule I drugs result in a favorable experience, such as pain relief or sleep,
having the highest potential for abuse (see Chapter 2). In and patients will want to repeat these positive experiences.
recent years, a few exceptions have been made to the If pharmacotherapy is not carefully monitored, patients
may take these drugs at high doses for prolonged periods,
thus increasing the risk of addiction.
450 Unit 4 Pharmacology of the Central Nervous System
It is a common misunderstanding, even among some occur in patients who are addicted, it is important to under-
healthcare providers, that the therapeutic use of scheduled stand that the two terms have different meanings.
drugs creates large numbers of addicted patients. In fact,
prescription drugs infrequently cause addiction when used In contrast, psychologic dependence produces no
according to accepted medical protocols. The risk of addic- signs of physical discomfort after the agent is discontinued.
tion for prescription medications is primarily a function of The user, however, has an intense emotional desire to con-
the dose and the length of therapy. Because of this, medica- tinue despite obvious negative economic, physical, or
tions having a potential for abuse are prescribed at the low- social consequences. This intense craving may become
est effective dose and for the shortest time necessary to worse if the patient has an unsupportive home environ-
treat the medical problem. Nurses should administer these ment or social contacts who have substance use disorders.
medications as prescribed for the relief of patient symp- Strong psychologic craving for a substance is responsible
toms without undue fear of producing dependency. for relapses during substance abuse therapy and often
causes a return to drug-seeking behavior. The development
PharmFACT of psychologic dependence usually requires the use of rela-
tively high doses for a prolonged time, such as with mari-
In 2013, almost 25 million Americans age 12 years or older juana and antianxiety drugs. However, psychologic
used illicit drugs in the past month. This estimate represents dependence may also develop quickly, perhaps after only
9.4% of the population age 12 years or older (Substance one use, such as with crack cocaine. Whereas physical
Abuse and Mental Health Services Administration dependence is often overcome within a few days or weeks
[SAMHSA], 2014). after discontinuing the drug, psychologic dependence may
persist for months, years, or even an entire lifetime.
27.4 Physical and psychologic dependence lead
to continued drug-seeking behavior despite 27.5 A withdrawal syndrome is a set of
negative health and social consequences. characteristic symptoms that occurs when an
abused substance is discontinued.
Whether or not a drug is addictive is related to how easily
someone can stop taking the substance on a repetitive basis. Once a patient becomes physically dependent and the sub-
Substance dependence occurs when an individual has an stance is abruptly discontinued, a withdrawal syndrome
overwhelming craving to take a drug and cannot stop. Sub- will occur. Some substances exhibit severe and prolonged
stance dependence is classified by two distinct categories: withdrawal symptoms, whereas others produce barely
physical dependence and psychologic dependence. noticeable symptoms. Because the withdrawal syndrome
may be particularly acute for patients dependent on alco-
Physical dependence occurs when the body adapts to hol and sedatives, the process of withdrawal from these
repeated use of the substance by altering normal physiol- agents is best accomplished in a substance abuse treatment
ogy. Essentially, the cells adapt and view the medication- facility. Examples of the types of withdrawal syndromes
altered environment as normal. These changes in physiology experienced with the different abused substances are
are reversible and when the agent is discontinued, uncom- shown in Table 27.1. In a medical setting a withdrawal
fortable symptoms known as withdrawal result (see syndrome may be induced by a rapid dosage reduction or
Section 27.5). Opioids, such as morphine and heroin, may by the administration of an antagonist drug in patients
produce physical dependence relatively quickly with who are physically dependent.
repeated doses, particularly when taken IV. Alcohol, central
nervous system (CNS) depressants, some stimulants, and In general, symptoms of withdrawal are opposite to
nicotine are other examples of substances that may produce those of the drug’s effects. For example, an individual may
physical dependence relatively easily with extended use. use alprazolam to reduce anxiety, but withdrawal may cause
intense anxiety symptoms. People may abuse metham-
It is important to understand that physical dependence phetamine as a stimulant to stay awake, but during with-
is not the same as addiction. Physical dependence may drawal they will experience lethargy and fatigue. Once
occur during the normal course of therapy, such as in these rebound effects become intense, people are driven to
patients receiving high doses of narcotic analgesics during take additional doses of the abused substance because that
cancer treatment. A patient with cancer may be physically will cause the withdrawal symptoms to disappear. For
dependent, that is, withdrawal symptoms may occur on some patients, avoidance of withdrawal symptoms is the
discontinuing the drug. However, withdrawal from a med- major motivator for continuing drug use. Thus, the cycle of
ication taken under medical supervision such as analge- continued substance abuse is perpetuated.
sics, antidepressants, or antianxiety drugs should not be
considered as evidence that the patient has a substance use Prescription drugs may be used to reduce the severity
disorder. Addiction implies destructive, compulsive sub- of withdrawal symptoms. For example, alcohol withdrawal
stance use. Although physical dependence does indeed can be treated with a short-acting benzodiazepine such as
oxazepam (Serax), and opioid withdrawal can be treated
Chapter 27 Pharmacology of Substance Abuse 451
Table 27.1 Withdrawal Symptoms and Treatment for Selected Drugs of Abuse
Drug Class Symptoms Treatment
Alcohol Tremors, fatigue, anxiety, abdominal cramping, Benzodiazepines, antiseizure drugs; disulfiram and naltrexone
hallucinations, confusion, seizures, delirium after withdrawal is over
Anabolic steroids
Mood swings, fatigue, restlessness, anorexia, insomnia, Behavioral therapy, symptomatic treatment such as
Barbiturates and other reduced sex drive, depression, psychologic craving for steroids antidepressants
sedative–hypnotics
Benzodiazepines Insomnia, anxiety, weakness, abdominal cramps, tremor, Similar to alcohol
anorexia, seizures, hallucinations, delirium
Cocaine and Gradual tapering of dosage over several weeks or months; for
amphetamines Insomnia, irritability, abdominal pain, nausea, sensitivity acute benzodiazepine intoxication, flumazenil (Romazicon) is
Hallucinogens to light and sound, headache, fatigue, tremors administered by rapid IV infusion (15–20 sec)
Marijuana Mental depression, anxiety, agitation, irritability, extreme Behavioral therapy; no specific pharmacologic treatment available
Nicotine fatigue, hunger, disturbed sleep, psychologic craving
Treatment usually is not necessary; symptoms resolve in about
Opioids Dependent on the specific drug; may include anxiety, 12 h; PCP excretion is pH dependent and acidification of the urine
mental depression, insomnia, paranoid delusions, panic increases the clearance rate of PCP by about 100-fold
attacks, lethargy
No treatment
Irritability, restlessness, insomnia, tremor, chills, weight loss
Nicotine replacement therapy, varenicline (Chantix) or bupropion
Irritability, anxiety, restlessness, headaches, increased (Zyban)
appetite, insomnia, inability to concentrate, decrease in
heart rate and blood pressure Methadone maintenance; buprenorphine therapy; clonidine
reduces anxiety, agitation, cramping, and sweating; oxazepam
Excessive sweating, restlessness, dilated pupils, agitation, reduces muscle spasms and insomnia; antiemetics such as
goose bumps, tremor, violent yawning, increased heart ondansetron for nausea and vomiting; detoxification can be
rate and blood pressure, nausea, vomiting, abdominal completed in 2–3 days; withdrawal may be done more rapidly
cramps and pain, muscle spasms with kicking movements, using naltrexone in combination with propofol anesthetic, the
weight loss antidiarrheal octreotide, and clonidine and benzodiazepines for
other symptoms
with methadone. Symptoms of nicotine withdrawal may asleep. Development of drug tolerance is common for drugs
be relieved by nicotine replacement therapy in the form of that affect the nervous system. Tolerance should be consid-
patches or chewing gum. No specific pharmacologic inter- ered a natural consequence of continued drug use: Develop-
vention is indicated for withdrawal from CNS stimulants, ment of tolerance is not evidence of addiction or drug abuse.
hallucinogens, marijuana, or inhalants. Indeed, tolerance is an expression of natural homeostasis—
the body’s attempt to return systems to normal.
With chronic substance abuse, patients will often associ-
ate the drug use with their surroundings, including social Tolerance does not develop at the same rate for all
contacts with other users. Users tend to revert back to drug- actions of a drug. For example, patients usually develop
seeking behavior when they return to the company of other tolerance to the nausea and vomiting produced by narcotic
substance abusers. Counselors often encourage users to analgesics after only a few doses. Tolerance to the mood-
refrain from associating with past social contacts or relation- altering effects of these drugs and to their ability to reduce
ships with other substance abusers to lessen the possibility pain develops more slowly but eventually may be com-
for relapse. The formation of new social contacts, including plete. Tolerance to the drug’s ability to constrict the pupils
association with self-help groups such as Alcoholics Anony- never develops. Patients will often endure annoying side
mous, helps some patients transition to a drug-free lifestyle. effects of drugs, such as the sedation caused by antihista-
mines, if they know that tolerance to these effects will
Tolerance develop quickly. Thus knowing details regarding the
development of tolerance helps the nurse to deliver essen-
27.6 Tolerance occurs when the body adapts to tial patient information that may enhance adherence.
a drug and larger doses are needed to produce a
therapeutic effect. Tolerance may lead to serious consequences for those
patients abusing hazardous substances. As a patient self-
Tolerance is a biological condition that occurs when the administers higher and higher doses to obtain a desired effect
body adapts to a substance after repeated administration. such as euphoria or sedation, the risk of overdose escalates.
Over time, larger doses of the drug are required to produce In some cases, the drug abuser may reach a daily dose that
the same initial effect. For example, at the start of pharmaco- would be lethal for a nonaddicted individual. Tolerance fades
therapy, a patient may find that 2 mg of a sedative is effective after the patient discontinues the abused drug, often after
at inducing sleep. After taking the medication for several 10 to 14 days. If the patient should return to drug-taking
months, the patient may require 4 or perhaps 6 mg to fall behavior with the same high dose, the results may be fatal.
452 Unit 4 Pharmacology of the Central Nervous System
The rapid development of tolerance after only a couple Doses may be 3 or more times above normal due to the
of doses, called tachyphylaxis, occurs with drugs such as development of tolerance. Abusers often combine seda-
cocaine, LSD, and amphetamines but is not unique to abused tives with other substances, such as stimulants or alcohol.
substances. For example, patients with coronary artery dis- Addicts often alternate between amphetamines (uppers),
ease will exhibit acute tachyphylaxis to the therapeutic effects which keep them awake for several days, and sedatives
of nitroglycerin. Tachyphylaxis can occur to virtually any (downers), which are needed to relax and fall asleep.
action of a drug, adverse effects as well as therapeutic effects.
Tachyphylaxis is beneficial when it occurs to an adverse Sedative users appear dull or apathetic and exhibit
effect of a drug, such as nausea, vomiting, or dizziness. signs similar to alcohol intoxication such as slurred speech
and motor incoordination. The medical use of barbiturates
Cross-tolerance occurs between closely related drugs. and nonbarbiturate sedative–hypnotics has declined mark-
The more two drugs are similar chemically, the greater the edly over the past two decades because safer alternatives
possibility of cross-tolerance between them. This occurs such as the benzodiazepines are available. With the decline
frequently between drugs in the same class, such as among in therapeutic use, fewer cases of illicit barbiturate use have
different barbiturates or among various opioids. It some- been reported. The use of the barbiturates in treating sleep
times occurs between dissimilar drugs that have the same disorders was discussed in Chapter 18, and their use in epi-
pharmacologic action. For example, patients who are phys- lepsy was presented in Chapter 22.
ically dependent on ethanol exhibit cross-tolerance to other
CNS depressant drugs such as benzodiazepines and barbi- Overdoses of sedatives are extremely dangerous
turates. Ethanol-dependent patients will require higher because the drugs suppress the respiratory centers in the
doses of these drugs to produce a therapeutic effect. E thanol brain—very high doses are often fatal. In the 1960s to 1970s,
does not exhibit cross-tolerance to drugs in very different barbiturates were the drugs most commonly used to com-
pharmacologic classes, such as amphetamines or LSD. mit suicide. The withdrawal syndrome from these drugs
resembles that of alcohol and may be life threatening.
The term resistance is often confused with tolerance.
Resistance, however, refers to microorganisms and infec- Starting in the 1970s, the benzodiazepine class of CNS
tions and should not be used interchangeably with toler- depressants began to replace barbiturates because they
ance. For example, microorganisms may become resistant exhibited an improved safety profile. Benzodiazepines are
to the effects of an antibiotic; they do not become tolerant. more accurately called antianxiety drugs instead of seda-
Patients may become tolerant to the effects of pain reliev- tives. They are one of the most widely prescribed classes of
ers; they do not become resistant. drugs, and a drug class commonly abused among teens
and college students. Although their primary indication is
Central Nervous System anxiety, they may be used to treat seizures, sleep disorders,
Depressants and muscle spasms. Benzodiazepines include alprazolam
(Xanax), clonazepam (Klonopin), diazepam (Valium),
27.7 Central nervous system depressants, which temazepam (Restoril), triazolam (Halcion), and midazolam
include sedatives, opioids, and alcohol, decrease (Versed).
the activity of the central nervous system.
Flunitrazepam (Rohypnol) is an infamous benzodiaze-
CNS depressants form a diverse group of drugs that cause pine of abuse because it causes anterograde amnesia, a type
patients to feel sedated or relaxed (see Chapters 18 and 25). of short-term memory loss in which the user cannot remem-
Drugs in this group include sedatives, antianxiety drugs, ber events that occur while under the influence of the drug.
opioids, and alcohol. Although the majority are legal sub- Effects begin 30 minutes after PO administration and last
stances, these classes of drugs are strictly controlled due to for 8 hours or longer. The abuser is conscious during this
their abuse potential. time but is unable to transfer thoughts from short-term to
long-term memory. Flunitrazepam is called a “date-rape”
Sedatives and Antianxiety Drugs drug because sexual predators can expose an unknowing
individual to the drug and perform a physical assault with
Sedatives, also known as sedative–hypnotics and tranquil- the likelihood that the victim will not remember the event.
izers, are primarily prescribed for sleep disorders and cer- Flunitrazepam is not approved by the U.S. Food and Drug
tain forms of epilepsy. The two general classes of sedatives Administration (FDA) for any medical condition.
are the barbiturates and the nonbarbiturate sedative–
hypnotics. The safety profiles and addictive potential of Patients on high doses of antianxiety drugs appear
the two classes are roughly equivalent. detached, sleepy, or disoriented. Often, patients will appear
carefree and without worry. Despite their enormous popu-
Physical and psychologic dependence develop when larity, however, benzodiazepines are not frequently abused
high doses of barbiturates are taken for extended periods. in high doses. Users sometimes combine these drugs with
alcohol, cocaine, or heroin to augment their drug experience.
In terms of acute toxicity, benzodiazepines are safer than
Chapter 27 Pharmacology of Substance Abuse 453
barbiturates and other sedatives. Serious respiratory depres- activities and profound sedation. Other symptoms include
sion is rare and death due to overdose usually only occurs slurred speech, constricted pupils (miosis), an increase in
with extremely high doses. However, if combined with alco- the pain threshold, and respiratory depression. Tolerance
hol, cocaine, or heroin, overdose may be lethal. Withdrawal develops rapidly to most effects of opioids, and a patient
symptoms are less severe than with barbiturates. who is addicted may eventually require 10 times the initial
dose to achieve the desired effects.
Another popular abused CNS depressant is a substance
that occurs naturally in the body called gamma-hydroxybu- Opioid dependence can occur rapidly and withdrawal
tyric acid (GHB). The drug is approved by the FDA as produces very intense and unpleasant symptoms that start
sodium oxybate (Xyrem) to treat patients with narcolepsy within a few hours after discontinuation of parenteral
who experience excessive daytime sleepiness or cataplexy agents and within 3 to 5 days for those dependent on oral
(weak or paralyzed muscles). Although Xyrem is regulated opiates. Withdrawal symptoms include dysphoria, diapho-
as a Schedule III drug, its active ingredient, GHB, is classi- resis, violent yawning, lacrimation, rhinorrhea, pupil dila-
fied as Schedule I. It is very unusual for the FDA to classify tion (mydriasis), fever, diarrhea, goose bumps, and muscle
a drug in two schedules. Xyrem is distributed to prescribers cramping and tremor. Although extremely unpleasant,
and patients only through a single centralized pharmacy. withdrawal from opioids is not life threatening, compared
to barbiturate or alcohol withdrawal, and the patient is not
Once sold in health food stores as a dietary supple- delirious. The withdrawal syndrome is self-limiting, peak-
ment to enhance athletic performance, GHB is now abused ing within 36 to 72 hours after discontinuation of parenteral
by recreational users for its ability to produce euphoria at opioids, and individual symptoms are treated as necessary.
low doses. Like flunitrazepam, GHB is called a date-rape For patients dependent on low to moderate doses, with-
drug because it induces retrograde amnesia in the user and drawal symptoms are relatively mild and resemble a case of
has been used in sexual assaults. Most illegal GHB is the flu. Babies born to pregnant opioid users will experience
obtained through home laboratories in the United States, withdrawal symptoms following birth.
with batches varying widely in purity and potency. The
drug is usually dissolved in liquid and doses are difficult to Abuse-deterrent opioids: In the 1990s, pharmaceutical
estimate. The same enzyme that metabolizes ethanol also companies developed extended release (ER) opioids that
metabolizes GHB; concurrent use, which is common, leads offered around-the-clock pain control. Abusers soon dis-
to prolonged effects of GHB and an increased risk of over- covered, however, that ER opioids such as oxycodone
dose. Overdose causes severe respiratory depression, sei- (OxyContin) could be crushed and snorted or dissolved
zures, and coma. Death from GHB overdose is sometimes and injected for an intense high. Oxycodone soon became
caused by the aspiration of vomitus, because the patient the world’s most commonly abused prescription drug,
may experience coma, vomiting, and seizures simultane- which signaled the start of a serious opioid epidemic.
ously. There is no antidote for overdose with GHB.
The FDA (2017) responded to this public health crisis
Opioids by encouraging pharmaceutical companies to reformulate
ER opioids to make them less susceptible to abuse. The
Opioids, also known as opiates or narcotic analgesics, are result has been approval of a number of opioids with abuse-
morphine-like substances prescribed for severe pain, anes- deterrent (AD) properties. The properties are not intended
thesia, persistent cough, and life-threatening diarrhea. The to render the drug abuse-proof, but they make it more diffi-
opioid class includes morphine, codeine, meperidine cult to mishandle the drug by crushing, snorting, or dissolv-
(Demerol), oxycodone (OxyContin), fentanyl (Duragesic, ing it for injection. The following are examples of approved
Sublimaze), methadone, and heroin. The therapeutic opioids with AD properties listed on the medication labels:
effects of the opioids are discussed in detail in Chapter 25.
• Opioids combined with an antagonist: When mis-
PharmFACT handled, the euphoric effects of the opioid are blocked
by an antagonist. These include oxycodone with nal-
Among adolescents ages 12 to 17, the rates for nonmedical trexone (Troxyca ER, Targiniq), oxycodone with nalox-
use of prescription drugs have been declining. For prescription one (Oxycodone ER), and morphine with naltrexone
pain relievers, the rates in this population declined from 3.2% (Embeda).
in 2003 to 1.7% in 2013 (SAMHSA, 2014).
• Resistant tablets: These use special polymers that
The effects of oral opioids begin within 30 minutes and make the tablets difficult to crush, break, melt, or dis-
may last over a day. Injecting or smoking opium produces solve using conventional tools and methods. These
immediate effects, including the brief, intense rush of medications form a viscous gel if the tablet is broken,
euphoria sought by heroin addicts. Individuals experience which is difficult to inject. Medications include hydro-
a range of emotions, from extreme pleasure to slowed body codone (Hysingla ER) and morphine (Arymo ER,
MorphaBond).
454 Unit 4 Pharmacology of the Central Nervous System
• Resistant beads: Oxycodone (Xtampza ER) capsules can with naloxone offers certain advantages. It is unlikely that
be opened, which is important to patients with difficulty the combination drug will be abused because the presence of
swallowing. However, the medication is coated with naloxone would cause unpleasant effects identical to with-
fatty acid and waxes that resist dissolving or melting. drawal symptoms. Detoxification can be more rapid and the
maintenance can be conducted through office environments,
Treatment of opioid addiction: Methadone has been rather than a daily visit to a methadone clinic.
the conventional treatment of choice for opioid addiction.
Although methadone has addictive properties of its own, it Mechanism of Action: Buprenorphine produces its
does not produce the same degree of euphoria as other opi- analgesic effects by occupying mu receptors in the brain
oids; it may be taken PO and its effects last 24 hours. Her- and dorsal horn of the spinal cord in a manner similar
oin addicts are switched to methadone during the to that of other opioid agonists. Because buprenorphine
detoxification phase of treatment to prevent unpleasant exhibits some opioid antagonist activity at the kappa re-
withdrawal symptoms. If the patient decides to take heroin ceptor, it is considered a mixed opioid agonist-antagonist.
during methadone therapy, most of the euphoric rush will Naloxone competes with opioid agonists for the mu and
be blocked because most of the opiate receptors are already kappa receptors, thus antagonizing the effects of morphine
occupied by methadone. During maintenance therapy, and other opioids.
patients must report to the methadone clinic daily for their
dose and to receive counseling. In some cases, patients who Pharmacokinetics:
have remained heroin-free may be trusted with several
doses for home administration. Patients sometimes remain Route(s) Sublingual tablets or film; buccal
on methadone maintenance the remainder of their lives,
although most patients eventually choose to detoxify and film
discontinue methadone use altogether. Gradual dose
reduction occurs over a period of about 6 months. With- Absorption Variable (buprenorphine well
drawal from methadone is more prolonged than with her-
oin or morphine, but the symptoms are less intense. absorbed; naloxone poorly
For many healthcare providers, buprenorphine has absorbed)
become an important alternative to methadone therapy.
Options include buprenorphine (Subutex) as monotherapy Distribution Bound to plasma protein (96%
or buprenorphine combined with naloxone (Suboxone,
Zubsolv). These are Schedule III drugs intended for the buprenorphine, 45% naloxone);
office management of opioid dependence. Naloxone is also
used alone for the emergency treatment of severe opioid- crosses the placenta; secreted in
induced respiratory depression (see Chapter 25).
breast milk
PROTOTYPE DRUG Buprenorphine with Naloxone
(Suboxone, Zubsolv, Others) Primary metabolism Hepatic
Classification Therapeutic: Drug for treating opioid Primary excretion Renal (30%) and feces (69%)
addiction, narcotic analgesic
Onset of action Approximately 45 min
Pharmacologic: Opioid
agonist-antagonist Duration of action 8–12 h (may be as long as 72 h at
Therapeutic Effects and Uses: Approved in 2002, high doses)
buprenorphine is a Schedule III narcotic analgesic that pro-
duces analgesia when given by the IM/IV (Buprenex) or Adverse Effects: Buprenorphine with naloxone is
transdermal (Butrans) routes for moderate to severe pain. a relatively safe drug that produces mild and transient
The combination of buprenorphine with naloxone, a narcotic side effects. The most frequently reported adverse events
antagonist, is given by the sublingual (Suboxone, Zubsolv) include headache, nausea, vomiting, hyperhidrosis, con-
or buccal (Bunavail) routes for the maintenance treatment of stipation, insomnia, pain, and peripheral edema. Abrupt
opioid dependence. When taken as directed, the combina- discontinuation of the drug will precipitate immediate
tion drug reduces craving in opioid-dependent patients and opioid withdrawal symptoms. Respiratory depression and
prevents the unpleasant symptoms of withdrawal. death have occurred with high doses, although these have
been with the IV route.
Although methadone maintenance has been the tradi-
tional preferred treatment for opioid addicts, buprenorphine Buprenorphine is an opioid and thus can produce
dependence when taken on a chronic basis. Although Sub-
oxone and Zubsolv are both sublingual forms of the drug,
they are not dose equivalent and care must be taken when
switching between products.
Contraindications/Precautions: Buprenorphine
with naloxone is contraindicated in patients with hyper-
sensitivity to either drug. This combination may induce
withdrawal in patients who have chronic physical depen-
dence on opioids. Naloxone should be used with caution
in patients with cardiovascular disease. It may precipitate
seizures in patients with seizure disorders.
Chapter 27 Pharmacology of Substance Abuse 455
Drug Interactions: Caution should be used when tak- consuming alcohol. Patients who are alcohol dependent and
ing buprenorphine with other narcotic analgesics and CNS those who drink alcoholic beverages regularly have higher
depressants because additive sedation will occur. Deaths amounts of these enzymes and thus are able to drink greater
have occurred when taking very high doses of buprenor- quantities of alcohol without becoming intoxicated.
phine concomitantly with benzodiazepines. The use of bu-
prenorphine is contraindicated with alvimopan (Entereg). The elimination of alcohol from tissues occurs at a con-
stant rate, which is independent of the concentration of
Pregnancy: Category C. alcohol in the blood. The blood alcohol level declines at
about 15 mg/h; no food or drug can speed up the rate of
Treatment of Overdose: Buprenorphine overdose alcohol excretion once it has reached the blood. Eating
can cause coma, hypotension, and life-threatening respira- pizza or drinking strong coffee following an alcohol binge
tory depression, and requires immediate treatment. Addi- does nothing to speed up excretion of the drug. It is a sim-
tional naloxone doses are indicated to reverse the opioid ple fact that if an individual drinks alcohol at a faster rate
intoxication. than it can be metabolized, intoxication will occur and will
continue until the body eventually metabolizes the alcohol
Nursing Responsibilities: Key nursing implications that has accumulated in the blood. The average rate of
for patients receiving buprenorphine are included in the metabolism is one alcoholic drink per hour. Because alco-
Nursing Practice Application for Patients Receiving Phar- hol is vaporized and excreted by the lungs, breath testing
macotherapy for Substance Abuse Disorders. can be used to estimate the amount of alcohol in the blood,
a common practice in law enforcement.
Drugs Similar to Buprenorphine with
Naloxone (Suboxone, Zubsolv, Others) Alcohol is classified as a CNS depressant because it has
the ability to slow the region of the brain controlling alert-
Naltrexone is an opioid antagonist that exhibits actions ness and wakefulness. Effects of alcohol include sedation,
similar to those of naloxone. It is presented later in this relaxation, loss of motor coordination, reduced judgment,
chapter as a treatment for alcohol dependence. and decreased inhibition. Alcohol intoxication may cause
partial or total amnesia, resulting in an inability to remem-
Alcohol (Ethanol) ber details that occurred during an alcohol binge. Alcohol
also increases blood flow in certain areas of the skin, caus-
One of the most commonly abused drugs is alcohol, the ing a flushed face, pink cheeks, or red nose. Like most
pharmacologically active agent in beer, wine, and liquor. drugs, the effects of alcohol are directly related to the
Although there are many types of alcohol, the only one amount consumed. Acute overdoses of alcohol produce
having widespread medical significance is ethanol or ethyl vomiting, severe hypotension, respiratory failure, and
alcohol. Therefore, in this text, the terms ethanol and alcohol coma. Death due to alcohol poisoning is not uncommon.
are used interchangeably. The economic, social, and health
consequences of alcohol abuse are staggering. Small quan- Chronic alcohol consumption produces both psycho-
tities of alcohol consumed on a daily basis, however, have logic and physiologic dependence and leads directly to a
been found to reduce the risk of stroke and heart attack. large number of adverse health effects. Not surprisingly, the
organ most affected by chronic alcohol abuse is the liver,
Alcohol is readily absorbed across the gastrointestinal which is responsible for metabolizing and detoxifying alco-
(GI) tract, primarily from the small intestine. Food slows hol. Hepatitis occurs in up to 90% of heavy users. Alcohol-
the absorption of alcohol by prolonging gastric emptying ism is a common cause of cirrhosis, a debilitating and often
time and diluting the alcohol, thus delaying its onset of fatal failure of the liver to perform its vital functions. Liver
action. Once it has entered the blood, alcohol is immedi- impairment results in abnormalities in blood clotting and
ately distributed to the tissues. The drug easily crosses the nutritional deficiencies and makes the patient very sensitive
blood–brain barrier so its effects on the brain are observed to the effects of medications. Chronic alcohol use also dam-
quickly, within 5 to 30 minutes after consumption. ages the brain, impairing memory and cognitive function.
Alcohol is metabolized and excreted at a constant rate, Drug doses for patients with alcoholism should be
depending on the activity of two hepatic enzymes, alcohol decreased to avoid toxicity because such patients are more
dehydrogenase and aldehyde dehydrogenase. Metabolism susceptible to adverse drug effects and drug interactions.
is a two-step process, first yielding acetaldehyde and then Combining alcohol with nonsteroidal anti-inflammatory
acetic acid, or acetate, as shown in Pharmacotherapy Illus- drugs (NSAIDs) such as aspirin can promote serious GI
trated 27.1. Wide genetic variability is seen in the amounts bleeding. Combining alcohol with acetaminophen can
and activity of these enzymes. For example, a significant increase the risk of fatal hepatic injury. Alcohol should never
number of Asians have a deficiency of aldehyde dehydroge- be combined with other CNS depressants, because their
nase, resulting in an accumulation of acetaldehyde and effects are cumulative and profound sedation or coma may
severe flushing and other uncomfortable symptoms when result. Combining alcohol with sedatives, benzodiazepines,
456 Unit 4 Pharmacology of the Central Nervous System
Pharmacotherapy Illustrated 27.1
Metabolism of Alcohol
1 2
Alcohol (ethanol) is readily absorbed The enzyme alcohol dehydrogenase
and distributed to most tissues, (AD) rapidly metabolizes alcohol in the
including the brain. liver to acetaldehyde.
3
Acetaldehyde is more toxic than
alcohol and is responsible for ill e ects
such as hangover symptoms.
2
AD 3
1
CH3CH2OH CH3CHO
alcohol acetaldehyde
4
ALDH
5 4
CH3COOH The enzyme aldehyde dehydrogenase
acetic acid (ALDH) slowly converts acetaldehyde to
acetic acid. Disulfiram (Antabuse)
5 blocks this enzyme and causes
Acetic acid (acetate) leaves the liver accumulation of acetaldehyde.
and can be used to generate ATP in the
Kreb’s cycle.
or opioids may be fatal. Selected drug interactions involving is no safe “dose” for alcohol consumption during pregnancy;
alcohol are shown in Table 27.2. thus use of this drug must be strictly avoided. Additional
details on alcohol as a teratogen are presented in Chapter 8.
CONNECTION Checkpoint 27.2
Alcohol withdrawal is severe and may be life threaten-
Alcohol induces CYP3A and increases the formation of a toxic me- ing. About 5% to 10% of withdrawal cases proceed to delir-
tabolite of acetaminophen. From what you learned in Chapter 3, what ium tremens, a syndrome of intense agitation, confusion,
is CYP3A and what is its importance to pharmacotherapy? Answers terrifying hallucinations, uncontrollable tremors, panic
to Critical Thinking Questions are available on the faculty resources site. attacks, and paranoia. Without treatment, 35% of the
Please consult with your instructor. patients with delirium tremens will die. Prevention of sei-
zures and delirium tremens is a top priority and may be
One of the major adverse effects of alcohol consumption accomplished by administering a benzodiazepine such as
occurs not in the patient, but in the fetus of a pregnant alcohol lorazepam (Ativan) or diazepam (Valium). Hallucinations
user. These effects, known as fetal alcohol syndrome, include may require the administration of an antipsychotic drug
birth defects and major health challenges for the child. There such as risperidone (Risperdal).
Chapter 27 Pharmacology of Substance Abuse 457
Table 27.2 Drug–Drug Interactions with Alcohol
Class Example Drug(s) Interaction Consequences
Increased acetaminophen metabolism Severe, possibly fatal liver damage
Acetaminophen — to toxic metabolites
Cross-tolerance Larger anesthetic doses needed
Anesthetics propofol (Diprivan), enflurane (Ethrane) to induce anesthesia
Additive hepatic toxicity Increased risk of liver damage
Antianginal medications nitroglycerin, isosorbide dinitrate (Isordil) Additive effects on blood pressure Hypotension, dizziness, possible fainting
Antibiotics Additive toxicity Nausea, vomiting, headache, possible
furazolidone (Furoxone), griseofulvin, seizures, reduced antibiotic effectiveness
Anticoagulants metronidazole (Flagyl) Acute consumption enhances warfarin Modification of coagulation: bleeding
bioavailability; chronic consumption disorders, hemorrhage
warfarin (Coumadin) reduces its availability
Additive CNS depression or sedation Drowsiness, lethargy
Antidepressants amitriptyline (Elavil), paroxetine (Paxil),
Antihistamines sertraline (Zoloft), fluoxetine (Prozac) Additive CNS depression Drowsiness, lethargy, dizziness
Antipsychotics
diphenhydramine (Benadryl, others), Additive CNS depression Drowsiness, lethargy
loratadine (Claritin), cetirizine (Zyrtec) Additive hepatotoxicity Increased risk of liver damage
Chronic alcohol use may decrease Increased risk of seizures
chlorpromazine (Thorazine) phenytoin bioavailability
Decreased bioavailability Decreased effectiveness in eliminating
Antiseizure medications phenytoin (Dilantin) tuberculosis
Additive effects on blood pressure Hypotension, dizziness, possible fainting
Antituberculars isoniazid, rifampin Additive hepatotoxicity Liver damage
Beta blockers propranolol (Inderal) Additive GI toxicity Increased risk of GI bleeding
atorvastatin (Lipitor), simvastatin (Zocor) Additive CNS depression and sedation Drowsiness, lethargy
HMG-CoA reductase Additive CNS depression and sedation Drowsiness, lethargy
inhibitors (statins) aspirin, ibuprofen, naproxen, others
morphine, codeine, meperidine (Demerol) Disulfiram-like reaction Facial flushing, nausea, vomiting
NSAIDs diazepam (Valium), lorazepam (Ativan),
alprazolam (Xanax), phenobarbital (Luminal)
Opioids sulfonylureas, metronidazole (Flagyl),
isoniazid (INH)
Sedatives and
antianxiety drugs
Miscellaneous
Long-term therapy for alcohol dependence includes protective action of disulfiram may last for 2 weeks after it
behavioral counseling and self-help groups such as Alco- is discontinued. Disulfiram should only be administered to
holics Anonymous. Pharmacologic management of alcohol patients who are fully informed of its effects and who are
dependence includes disulfiram and naltrexone. Disulfi- motivated to maintain sobriety.
ram (Antabuse) is given to discourage relapses.
Mechanism of Action: Disulfiram irreversibly in-
PROTOTYPE DRUG Disulfiram (Antabuse) hibits the enzyme acetaldehyde dehydrogenase, causing
toxic acetaldehyde to build up in the blood. Acetaldehyde
Classification T herapeutic: Drug for treating alcohol is sometimes called the “hangover” chemical because it is
abuse responsible for causing miserable symptoms following a
night of high alcohol consumption.
Pharmacologic: Alcohol antagonist;
acetaldehyde dehydrogenase inhibitor Pharmacokinetics: PO
Route(s) Rapidly absorbed
Therapeutic Effects and Uses: By itself, disulfiram Absorption Crosses the placenta;
produces few effects. If alcohol is consumed while taking Distribution secreted in breast milk
disulfiram, however, the patient becomes violently ill in Hepatic
a syndrome called the disulfiram–alcohol reaction. Ap- Primary metabolism Lung and feces
proved in 1951, the only indication for disulfiram is the Primary excretion 12 h
management of chronic alcohol abuse. The use of disulfi- Onset of action 1–2 weeks
ram does not cure alcohol abuse; it only prevents impul- Duration of action
sive drinking as long as the patient chooses to take it. The
458 Unit 4 Pharmacology of the Central Nervous System
Adverse Effects: At therapeutic doses, disulfiram pro- naltrexone, the CNS effects of alcohol or opioids will
duces few adverse effects, unless ingested with alcohol. At return. Severe opioid withdrawal may occur if the drug is
extreme doses, the drug itself can cause neurologic toxicity, administered to a patient who has received opioids within
psychosis, hepatotoxicity, and blood dyscrasias. 5 to 7 days prior to naltrexone dosing; thus the drug is con-
traindicated in these patients.
Because the disulfiram–alcohol reaction can be serious
and even fatal, disulfiram therapy should not be initiated A fixed-dose combination of naltrexone with morphine
in patients at high risk for returning to alcohol abuse. Disul- (Embeda) is approved to treat moderate to severe pain. Mor-
firam is contraindicated in patients who are receiving met- phine is used to provide analgesia, and naltrexone is included
ronidazole because acute psychosis may occur. All products to block some of the side effects of morphine and to prevent
containing alcohol must be strictly avoided, including product misuse. Naltrexone may be used off-label to treat
cough syrups, mouthwashes, or liquid vitamins. Even topi- nicotine withdrawal. Naltrexone has been awarded orphan
cal products containing alcohol should be avoided because drug status by the FDA to treat symptoms of childhood
the alcohol may be absorbed across the skin. Disulfiram is autism. Patients with serious hepatic impairment should not
also contraindicated in patients with severe heart disease receive naltrexone. This drug is pregnancy category C.
and psychoses. Black Box Warning: Disulfiram should
never be administered to a patient in a state of alcohol Marijuana and Related Substances
intoxication or without the patient’s full knowledge.
27.8 Marijuana is the most frequently abused
Drug Interactions: Ingestion of even small amounts of illicit substance.
alcohol will immediately result in headache, palpitations,
chest pain, dyspnea, nausea, violent vomiting, and, some- Cannabinoids are natural products obtained from the
times, bizarre behaviors. Severe respiratory depression hemp plant Cannabis sativa, which thrives in tropical cli-
may occur. Symptoms begin within 5 to 10 minutes after mates. Cannabinoids include marijuana, hashish, and hash
alcohol consumption and may continue for several hours. oil. Hashish is a solid, dried resin of the plant that is
extremely potent. Hash oil is made by dissolving hashish
Pregnancy: Category C. or marijuana in a solvent such as alcohol, then allowing
the liquid to evaporate to form a thick, oily concentrated
Treatment of Overdose: No specific treatment for form of cannabis.
disulfiram overdose is available.
Although more than 70 natural cannabinoid sub-
Nursing Responsibilities: Key nursing implications stances have been identified, the ingredient responsible for
for patients receiving disulfiram are included in the Nurs- most of the psychoactive properties is tetrahydrocannabi-
ing Practice Application for Patients Receiving Pharmaco- nol (THC). Selective breeding and cultivation of Cannabis
therapy for Substance Abuse Disorders. has produced varieties of the plant that produce much
higher concentrations of THC than in previous decades.
Drugs Similar to Disulfiram (Antabuse) The THC content of marijuana varies from 5% to 25%;
hashish from 20% to 60%; and hash oil from 30% to 80%.
Naltrexone is one of the few drugs other than disulfiram
for treating alcohol dependence. Humans, as well as many other mammals, fish, and
birds, produce small amounts of endogenous cannabi-
Naltrexone (ReVia, Vivitrol, others): Approved in 1984, noids. These substances, known as endocannabinoids, are
naltrexone is an opioid antagonist that reduces the psycho- types of internal messengers that allow for intercellular
logic craving for alcohol. Why does a drug that blocks opi- communication. The exact purpose of the endocannabi-
ate receptors have an effect on alcohol dependence? noids has yet to be discovered, although they have some of
Although the mechanism is unclear, endogenous opioids the same characteristics as neurotransmitters and can mod-
appear to be involved in “reward pathways” for alcohol. ulate neuronal function. The endocannabinoids have some
Blocking the reward pathways with naltrexone affects the structural similarities to THC and bind to the same recep-
psychologic experience or craving characteristic of alcohol tors, known as CB1 and CB2 receptors. Agonists and antag-
dependence. Naltrexone does not produce a “hangover” onists to CB1 and CB2 have been discovered, with the hope
reaction when an individual consumes alcohol, as does that the research may lead to new pharmacologic agents.
disulfiram. Oral naltrexone may be given once daily for
several months up to a year. An intramuscular (IM) sus- Marijuana, also known as grass, pot, weed, reefer, or
pension of naltrexone (Vivitrol) offers the convenience of dope, is the most commonly used illicit drug in the United
once-a-month injections. Naltrexone is also approved to States. Marijuana is usually smoked as cigarettes (joints),
treat opiate dependence. Successful use of naltrexone in but it may be used in pipes, brewed as teas, or added to
alcohol or opioid rehabilitation programs is entirely food. Oral absorption results in a lower serum blood level
dependent on patient adherence; if the patient stops taking of the drug than does inhalation.
Chapter 27 Pharmacology of Substance Abuse 459
When inhaled, marijuana produces effects that occur Hallucinogens
within minutes and last 1 to 3 hours. Use of marijuana
slows motor activity, decreases coordination, and causes 27.9 Hallucinogens and club drugs cause an
disconnected thoughts and euphoria. The experience is altered state of thought and perception.
nearly always pleasant and involves laughter and an
increase in the subjective perception of sounds, colors, and Hallucinogens are a diverse class of chemicals that have in
thoughts. The subjective experience is dependent on the common the ability to produce an altered, dreamlike state
social surroundings during drug use. Positive, friendly, of consciousness. These drugs sometimes produce a pro-
happy surroundings produce a more favorable drug expe- found emotional experience, allowing the user to feel
rience than taking the drug alone. Time appears to pass enhanced interconnectedness with others and experience a
more slowly. It increases thirst and a craving for food, par- higher, spiritual plane of consciousness. Sometimes called
ticularly chocolate and other sweets. One hallmark symp- psychedelics, the prototype drug for this class is LSD. More
tom of marijuana use is red or bloodshot eyes, caused by recently, some drugs in this class have become closely
dilation of blood vessels. associated with the nightclub scene and are abused by
those seeking a drug-induced experience from the music,
Following feelings of euphoria, the individual may dancing, and social contact; thus the name “club drugs.”
become sleepy or depressed or experience paranoia. Driv-
ing is sometimes impaired, particularly when the drug is For nearly all drugs of abuse, predictable symptoms
combined with alcohol. Because marijuana smoke is occur in every user. Effects from hallucinogens, however, are
inhaled more deeply and held within the lungs for a lon- highly variable and depend on the mood and expectations of
ger period than cigarette smoke, marijuana smoke intro- the user and the surrounding environment in which the sub-
duces 4 times more particulates (tar) into the lungs than stance is used. Two patients taking the same drug will report
does tobacco smoke. Smoking marijuana on a daily basis completely different experiences, and the same patient may
may increase the risk of lung cancer and other respiratory report different symptoms with each use. All hallucinogens
disorders. Chronic use is associated with apathy and a lack are Schedule I drugs: They have no medical use.
of motivation in achieving or pursuing life goals, and very
high doses may cause hallucinations. THC accumulates in LSD and Similar Hallucinogens
reproductive tissues, particularly the gonads, and has
been reported to cause amenorrhea and decreased LSD, also called acid, the beast, blotter acid, and California
spermatogenesis. sunshine, is derived from a fungus that grows on rye and
other grains. LSD is nearly always administered PO and
Marijuana produces less physical dependence or toler- can be manufactured in capsule, tablet, or liquid form. A
ance than many other abused substances. At usual doses, common and inexpensive method for distributing LSD is
withdrawal symptoms are mild, if they are experienced at to place drops of the drug on paper, often containing
all. After chronic abuse of high doses, patients may experi- the images of cartoon characters or graphics related to the
ence irritability, restlessness, and insomnia. Psychologic drug culture, as shown in Figure 27.1. After drying, the
dependence occurs when the drug is taken on a chronic paper is then cut into small squares to be ingested, with
basis. Metabolites of THC remain in the body for months to each square representing a “dose.” The drug is extremely
years, allowing laboratory specialists to easily determine potent, with doses as low as 25 mcg producing an effect.
whether someone has taken marijuana. For 3 to 5 days after
a single use, THC can be detected in the urine. Figure 27.1 Psychoactive substances: (left) Psilocybin is obtained
from a species of mushroom; (right) LSD is often blotted on paper
Medical marijuana is a controversial topic; many before ingesting.
healthcare providers and politicians are reluctant to
endorse a drug that impairs judgment and may harm users. Courtesy of Cbaloga/fotolia (left); Joe Bird/Joe Bird/Alamy Stock Photo (right).
THC appears to reduce the pressure in the eyeball (glau-
coma). Patients receiving antineoplastic drugs have
reported that THC reduces the severe nausea and vomiting
associated with these drugs. The ability of THC to reduce
muscle spasticity may lead to applications for patients with
multiple sclerosis and other spasticity disorders. In most
cases, however, current drugs for these conditions have
been demonstrated to be more effective and safer. Although
the medical value of the drug remains to be proven through
randomized clinical studies, several states allow the medi-
cal and recreational use of marijuana, despite its being a
Schedule I drug.
460 Unit 4 Pharmacology of the Central Nervous System
Immediately after use, LSD is widely distributed H OCH3
throughout the body, including the brain. Effects begin
within an hour and may last from 6 to 12 hours. Although H2N CH2 C OCH3
the exact mechanism of action of the drug is unclear, it
affects the central and autonomic nervous systems, increas- H OCH3
ing blood pressure, elevating body temperature, dilating Mescaline
pupils, causing dry mouth, and increasing the heart rate.
Figure 27.2 The chemical structure of mescaline, derived from the
LSD and other hallucinogens are used for their psy- peyote cactus.
choactive, rather than their physical, effects. LSD users
may experience symptoms such as laughter, visions, reli- Courtesy of R. Konig/Jacana/Science Source.
gious revelations, or deep personal insights. Common
occurrences are hallucinations and after-images being pro- in their spiritual ceremonies to induce visions. The
jected onto people as they move. Users also report extremely drug is usually smoked but may be snuffed (snorted
bright lights and vivid colors. Some users hear voices; oth- through the nostrils), injected, or taken PO.
ers report seeing sounds and hearing colors. Many experi-
ence a profound sense of truth and deep directed thoughts. Club Drugs and Miscellaneous
The user’s sense of time is altered. Hallucinogens
Unpleasant experiences with LSD, known as “bad Club drug refers to substances taken by people at festivals,
trips,” can be terrifying and may include acute anxiety, dance clubs, all-night parties, and raves. It is a vague term
panic attacks, confusion, severe depression, and paranoia. that refers to a diverse group of abused substances that
Repeated use may impair memory and the ability to rea- includes ecstasy, GHB, methamphetamine, Rohypnol, ket-
son. In extreme cases, patients may develop psychoses. amine, and other agents, usually ingested with alcohol.
One common adverse effect is flashbacks, in which the user Not all club drugs are hallucinogens, and some of these are
experiences the effects of the drug again, sometimes weeks, covered in other sections of this chapter. The following are
months, or years after the drug was initially taken. Flash- descriptions of several major club drugs and some miscel-
backs may occur without warning. laneous hallucinogens:
LSD is considered a recreational drug: Users rarely • MDMA (3, 4-methylenedioxymethamphetamine,
become dependent on the drug, and there are no with- XTC, or ecstasy). An amphetamine originally synthe-
drawal symptoms. Continuous users will experience toler- sized for research purposes that has since become popu-
ance very quickly, sometimes after only 2 to 3 days. lar among teens and young adults. Taken PO, its effects
last 3 to 6 hours. The drug is unique because it produces
The following drugs are considered similar to LSD and both stimulant and hallucinogenic effects simultane-
produce equivalent psychoactive effects: ously. MDMA enhances emotions and awareness,
increases social and extroversion behaviors, and allows
• Psilocybin. The primary psychoactive substance in the user to stay awake and physically active for long
over 100 species of psilocybin mushrooms found in periods. Chronic users exhibit behavioral disorders such
Mexico and Central America (see Figure 27.1). Known as depression, anxiety, sleeplessness, and hostility. It has
as “magic mushrooms” or “shrooms,” psilocybin is a a narrow therapeutic index and overdoses may be fatal.
prodrug that is metabolized to its active metabolite
psilocin. Possession of these mushroom species is ille- • MDA (3, 4-methylenedioxyamphetamine). Called the
gal. Psilocybin and psilocin are listed as Schedule I “love drug” due to a belief that it enhances sexual
drugs. The drug is taken by eating fresh psilocybin desires. This drug is sometimes a component of ecstasy.
mushrooms or by ingesting dried extracts.
• DOM (2, 5 dimethoxy-4-methylamphetamine). A rec-
• Mescaline. Found in the peyote cactus and several reational drug popular at rave parties; also called STP,
other cacti species of Mexico and Central America, as
shown in Figure 27.2. The drug is usually taken in cap-
sules consisting of dried cactus. The cactus, which
grows very slowly, has become quite rare due to over-
harvesting. In the United States, peyote use is illegal
for all but members of the Native American Church,
who use the drug in religious ceremonies.
• Dimethyltryptamine (DMT). A natural substance
found in many species of plants in Central and South
America and the Caribbean Islands. Like some of the
other hallucinogens, DMT was used by native cultures
Chapter 27 Pharmacology of Substance Abuse 461
CONNECTIONS: Using Research in Practice
Screening, Brief Intervention, and Referral to Treatment (SBIRT)
Approximately 21.5 million people age 12 or older had a sub- risk of developing these disorders (Center for Behavioral Health
stance use disorder (SUD) in 2014. This included 17 million peo- Statistics and Quality, 2015).
ple with an alcohol use disorder, 7.1 million with an illicit drug
use disorder, and 2.6 million who had both alcohol use and illicit Screening: Assessing a patient for risky sub-
drug use disorders. By 2020, mental and substance use disor-
ders will surpass all physical diseases as major causes of dis- stance use behaviors by using stan-
ability (Center for Behavioral Health Statistics and Quality, 2015).
dardized screening tools. Screening
Screening, Brief Intervention, and Referral to Treatment (SBIRT)
is “an evidence-based practice used to identify, reduce, and pre- can occur in any healthcare setting.
vent problematic use, abuse, and dependence on alcohol and illicit
drugs” (SAMHSA-HRSA Center for Integrated Health Solutions, Brief Intervention: Engaging a patient showing risky
n.d.). The SBIRT model was prompted by an Institute of Medicine
recommendation that called for community-based screening for substance use behaviors in a short
health risk behaviors and specifically included substance use.
conversation, providing feedback
SBIRT is an approach to the delivery of early intervention and
treatment to people with substance use disorders and those at and advice.
Referral to Treatment: Providing a referral to brief therapy or
additional treatment to patients who
screen in need of additional services.
For more information, visit the SAMHSA-HRSA Center for Integrated Health
Solutions website.
the drug has effects similar to LSD but with a longer ketamine. Effects include slurred speech, dizziness,
duration. drowsiness, euphoria, and lack of motor coordina-
• Phencyclidine (PCP, crystal, angel dust). Produces a tion. Overdose can cause brain damage, seizures,
trancelike state without loss of consciousness that may stroke, hypothermia, and death. Because cold medi-
last for days. Once available as an anesthetic, the sub- cines often contain multiple drugs, abusers of dextro-
stance was removed from the market in 1965 because methorphan may experience toxicity due to overdoses
patients experienced delirium and panic attacks as of antihistamines, aspirin, or acetaminophen. Pure
they recovered from anesthesia. The powdered drug is dextromethorphan is also available on the black mar-
sometimes sprinkled on marijuana and smoked, or it ket in high-dosage tablet form.
may be snorted or taken as tablets. Typical effects
include slurred speech, detachment from reality, time Central Nervous System Stimulants
distortion, and a sensation of floating in space. It does
not produce the same types of hallucinations seen with 27.10 Stimulants such as amphetamines and
LSD. Phencyclidine is probably the most dangerous of cocaine increase the activity of the central
the hallucinogens because high doses can cause severe nervous system.
and violent panic attacks, seizures, coma, and death.
• Ketamine (K, kitkat, or special K). Closely related to The stimulants include a diverse family of drugs with the
phencyclidine, ketamine has been used historically as ability to excite the CNS. Some are prescription drugs used
an anesthetic but is now rarely used for that purpose. to treat narcolepsy and attention-deficit/hyperactivity dis-
The most common source of the drug is diversion order (ADHD). As drugs of abuse, stimulants are taken to
from veterinary offices. Liquid ketamine may be produce a sense of exhilaration, improve mental and phys-
added to drinks, injected, or evaporated to a solid ical performance, reduce appetite, or prolong wakefulness.
form, which is snorted or taken as pills. Effects are Stimulants include the amphetamines, methylphenidate,
similar to those of phencyclidine, although they only and cocaine. Some CNS stimulants are club drugs. Caf-
last 35 to 40 minutes. Unconsciousness and amnesia feine is also included as a CNS stimulant although it does
may occur at high doses, and psychoses can be not have the same negative health characteristics as the
induced with continued use. other drugs in this group.
• Dextromethorphan (DXM, robo). A substance included
in over-the-counter (OTC) cold remedies for its cough Amphetamines and Methylphenidate
suppressant properties. Of the drugs of abuse, it is the
only substance that can be readily and legally pur- Amphetamines produce their effects by increasing the activ-
chased by teens. Abusers will purchase extra-strength ity of the endogenous neurotransmitters norepinephrine,
remedies and consume large quantities to achieve dis- serotonin (5-HT), and dopamine. Norepinephrine affects
sociative effects similar to those of phencyclidine and awareness and wakefulness by activating neurons in a part
of the brain called the reticular formation. High doses of
462 Unit 4 Pharmacology of the Central Nervous System
amphetamines give the user a feeling of self-confidence, Cat), is made illegally and snorted, taken PO, or injected IV.
elevated mood, euphoria, and empowerment. Fatigue is Methcathinone is a Schedule I agent.
diminished and the individual can perform at a high level
of alertness for an extended time. Appetite is suppressed. Methylphenidate (Ritalin) is a CNS stimulant widely
prescribed for children diagnosed with ADHD because the
By increasing the activity of norepinephrine, many drug exerts a calming effect in children who are inattentive
physiologic actions of amphetamines resemble those of or hyperactive. The drug stimulates the alertness center in
sympathetic nervous system activation (see Chapter 15). the brain and the child is able to focus on complex tasks for
Cardiovascular and respiratory activities are significantly longer periods. The therapeutic applications of methylphe-
affected, resulting in increased heart rate, high blood pres- nidate are discussed in Chapter 24.
sure, and increased breathing rate. Other symptoms
include dilated pupils, sweating, and tremors. Overdoses Methylphenidate is a Schedule II drug that has many
of some stimulants lead to seizures, dysrhythmias, stroke, of the same pharmacologic actions as cocaine and amphet-
and cardiac arrest. amines. It is sometimes abused by adolescents and adults
seeking euphoria, increased alertness, or appetite suppres-
Although short-term use of amphetamines induces sion. Tablets are crushed and snorted or dissolved in liquid
pleasurable feelings, long-term use causes restlessness, and injected IV. Ritalin is sometimes mixed with heroin, a
anxiety, defensiveness, and fits of rage, especially when the combination called a “speedball.” Most Ritalin used ille-
user is coming down from a prolonged drug experience. gally is obtained by diversion from legal prescriptions, by
Chronic use can lead to a psychosis that closely resembles theft, or by patients selling or sharing their drugs.
paranoid schizophrenia, although this condition usually
resolves within several days after discontinuation of the Cocaine
drug. Tolerance to the pleasurable effects of amphetamines
occurs very quickly, especially if the drugs are injected. Cocaine is a natural substance obtained from leaves of the
coca plant, which grows in the Andes Mountains of South
Amphetamines and dextroamphetamines were once America. Natives in this region chew the coca leaves, or
widely prescribed to treat depression, weight loss, drowsi- make teas of the substance. Much of the cocaine entering
ness, and congestion. Because of their ability to enhance the United States comes from Colombia and other South
alertness, pilots, students, and healthcare workers on long American countries. It was once used as an anesthetic for
shifts have historically abused amphetamines. In the 1970s eye, nose, and throat surgery but is no longer used for this
it was recognized that the adverse effects and abuse poten- purpose.
tial of amphetamines outweighed their legitimate medical
uses. Current therapeutic applications of these drugs Cocaine is a Schedule II drug that produces psycho-
are extremely limited. Most substance abusers obtain these active and physiologic actions similar to the amphet-
drugs from illegal laboratories, which can produce some amines, although its effects can be much more rapid and
of the amphetamines using readily available chemicals intense. It is the second most commonly used illicit drug
and make tremendous profits. Physical dependence to in the United States. Routes of administration include
amphetamines is unusual and withdrawal symptoms are snorting, smoking, inhaling vapors, and injecting. Injec-
not life threatening. The only potentially serious symptom tion or inhalation of cocaine produces an instantaneous
of amphetamine withdrawal is depression. euphoria that lasts 10 to 20 seconds. In small doses,
cocaine produces feelings of intense euphoria, a decrease
Dextroamphetamine (Dexedrine) may be used for in hunger and pain, illusions of physical strength, and
short-term weight loss, when all other attempts to reduce increased sensory perception. Larger doses will increase
weight have been exhausted, and to treat narcolepsy, a rare these effects and cause rapid heartbeat, dysrhythmias,
disease in which patients fall asleep unexpectedly. Meth- sweating, dilation of the pupils, and an elevated body
amphetamine, commonly called ice, is often used as a recre- temperature. The half-life of cocaine is short, 60 to
ational drug for users who like the rush of euphoria that it 90 minutes when injected, and tolerance rapidly devel-
gives them. It is usually administered in powder or crystal ops to the pleasurable aspects of the drug. Because of the
form (crystal meth) but it may also be smoked. Metham- short half-life, addicts may take cocaine at intervals of
phetamine is a Schedule II drug marketed under the trade 10 to 45 minutes, sometimes for several consecutive days.
name Desoxyn, although most abusers obtain it from ille- Unfortunately, tolerance develops slowly to the cardio-
gal methamphetamine laboratories. Methamphetamine vascular actions of cocaine. As the abuser escalates the
can be easily synthesized from pseudoephedrine, an OTC doses to produce a desired level of euphoria, cardiovas-
decongestant. This has led to states placing pseudoephed- cular damage may be progressive.
rine behind the pharmacy counter and has motivated phar-
maceutical manufacturers to find a replacement drug for Cocaine readily crosses the placenta to produce
pseudoephedrine in cold and flu remedies. A structural marked effects on the fetus. Because the fetus does not have
analog of methamphetamine, methcathinone (street name the hepatic enzymes necessary to metabolize cocaine, drug
Chapter 27 Pharmacology of Substance Abuse 463
effects are prolonged. Reports of cocaine-related changes consequences place it into a class by itself. Nicotine is
include increased risk of miscarriage, preterm labor, low unique among abused substances in that it is legal, strongly
birth weight, and, possibly, birth defects. Newborns have addictive, and highly carcinogenic. Furthermore, tobacco
increased irritability, feeding difficulties, and are easily use can cause harmful effects to those in the immediate
startled. area due to secondhand smoke. Patients often do not con-
sider tobacco use to be substance abuse. It is the most com-
The adverse effects of cocaine use are essentially the mon form of chemical dependence in the United States.
same as those for amphetamines. Metabolism by the liver Tobacco use among young people has been declining: The
forms an active metabolite that is more toxic than cocaine rate of smoking among youths ages 12 to 17 in 2012 was
itself. After the feelings of euphoria diminish, the cocaine half of the rate reported in 2002.
user may be left with a sense of irritability, exhaustion,
insomnia, depression, and extreme distrust. Some users The most common method by which nicotine enters
report the sensation that insects are crawling under the the body is through the inhalation of cigarette, pipe, or
skin. Users who snort cocaine develop a runny nose, a cigar smoke. Tobacco smoke contains several thousand
crusty redness around the nostrils, and deterioration of chemicals, a significant number of which are carcinogens.
the nasal cartilage. Overdose can result in dysrhythmias, The primary addictive drug present in cigarette smoke is
seizures, stroke, or death due to respiratory arrest. Psy- nicotine, which reaches the brain in only 15 seconds, with
chologic dependence often leads to intense craving for effects that last from 30 minutes to several hours.
the drug. Although nicotine has a half-life of only 2 to 3 hours, it
accumulates in the body and is slowly released from the
Caffeine tissues, giving the patient virtually a 24-hour exposure to
the drug.
Caffeine is a natural substance found in the seeds, leaves,
or fruits of more than 63 plant species throughout the Nicotine affects many body systems, including the
world. Significant amounts of caffeine are consumed in nervous, cardiovascular, and endocrine systems. Nico-
chocolate, coffee, tea, soft drinks, and ice cream. Caffeine is tine promotes the release of epinephrine and has a direct
sometimes added to OTC pain relievers and stimulants stimulatory effect on the reticular activating system of
because it has been shown to increase the effectiveness of the brain, causing symptoms that range from increased
these medications. Caffeine is rapidly distributed to almost alertness and ability to focus to feelings of relaxation or
all parts of the body after ingestion, and several hours are lightheadedness. The psychoactive effects of smoking are
needed to metabolize and eliminate the drug. Caffeine has generally described as pleasurable. The cardiovascular
a pronounced diuretic effect. effects of nicotine include an accelerated heart rate and
increased blood pressure, caused by activation of nico-
Caffeine is considered a CNS stimulant because it pro- tinic receptors located throughout the autonomic ner-
duces increased mental alertness, restlessness, nervous- vous system (see Chapter 12). The cardiovascular effects
ness, irritability, and insomnia. The physical effects of of nicotine are particularly serious in smokers who are
caffeine include dilation of the respiratory passages, taking oral contraceptives—their risk of a fatal heart
increased blood pressure, increased production of stomach attack is 5 times greater than that of nonsmokers. Muscu-
acid, and changes in blood glucose levels. Repeated use of lar tremors may occur with moderate doses of nicotine,
caffeine may result in physical dependence and tolerance. and convulsions result from very high doses. Nicotine
Withdrawal symptoms include severe headaches, fatigue, produces lower body weight by reducing appetite and
depression, and impaired performance of daily activities. increasing body metabolism. Chronic use leads to emphy-
sema, heart disease, and lung cancer. There is clear evi-
PharmFACT dence that tobacco use affects the reproductive system.
Smokers are much more likely to be infertile, and smok-
In 2012, an estimated 66.9 million Americans ages 12 years and ing during pregnancy can cause birth defects and lower
older were current users of a tobacco product. This represents birth weight.
25.5% of the population in that age range (SAMHSA, 2014).
Both psychologic and physical dependence occur rela-
Nicotine tively quickly with nicotine. Patients tend to continue their
drug use for many years, despite overwhelming medical
27.11 Nicotine is a powerful and highly evidence that the quality of their life will be adversely
addictive cardiovascular and central nervous affected and their lifespan shortened. Furthermore, a large
system stimulant. majority of smokers try to quit each year and are unsuc-
cessful and state that they wish they had never started the
Although nicotine is sometimes considered a CNS stimu- habit. Only 25% of those who attempt to stop smoking
lant because it enhances alertness, its actions and long-term remain tobacco-free 1 year later.
464 Unit 4 Pharmacology of the Central Nervous System
Varenicline (Chantix) is approved to manage nicotine
withdrawal in patients seeking smoking cessation. Com-
mon side effects include nausea, vision changes, fainting,
and unusual dreams. Both bupropion and varenicline carry
a warning that advises patients of serious neuropsychiatric
events such as hostility or suicidal thoughts that can occur
during therapy or shortly after discontinuation of the drug.
PROTOTYPE DRUG Varenicline (Chantix)
Figure 27.3 Nicotine replacement therapy: transdermal patch. Classification Therapeutic: Drug for smoking cessation
Pharmacologic: Nicotinic receptor
Courtesy of Ruth Jenkinson/Dorling Kindersley, Ltd.
agonist
Discontinuation of tobacco results in a withdrawal
syndrome that includes agitation, impaired concentration, Therapeutic Effects and Uses: Approved in 2006,
weight gain, anxiety, headache, and an extreme craving for the only indication for varenicline is smoking cessation
the drug. The syndrome peaks at 24 to 48 hours after the treatment. Doses are gradually increased over an 8-day
last dose and may continue over several weeks. Symptoms period and maintained for 12 to 24 weeks to reduce with-
vary in intensity among patients and are not related to dose drawal symptoms and cravings for smoking. It also pre-
or duration of use; those who are light smokers or who vents nicotine from reaching its receptors, thus blocking
have smoked for a shorter length of time do not necessarily some of the pleasurable sensations should the individual
have less intense withdrawal symptoms. Approximately relapse and start smoking again.
90% of individuals who successfully stop smoking do so
without any treatment. Mechanism of Action: Varenicline activates nicotinic
acetylcholine receptors in the brain and blocks nicotine
Nicotine replacement therapy (NRT) is based on the from reaching the brain’s receptors.
assumption that the blood level of nicotine is what drives
people to continue smoking. When blood nicotine levels Pharmacokinetics: PO
fall, the individual begins to experience early symptoms of Route(s) Completely absorbed
withdrawal, which are quickly eliminated by smoking Absorption Bound to plasma protein (20%)
another cigarette. Indeed, blood nicotine levels have clearly Distribution Mostly unmetabolized
been shown to influence smoking behavior. For example, if Primary metabolism Renal
a smoker switches to low-nicotine cigarettes, he or she will Primary excretion 3–4 h
take longer and more frequent puffs. NRT delivery systems Onset of action 24 h
include transdermal patches (Figure 27.3), nasal sprays, Duration of action
and chewing gum that raise serum nicotine levels and help
patients to deal with the unpleasant withdrawal symp- Adverse Effects: Nausea, vomiting, vivid dreams,
toms. Tobacco use, however, has a strong psychologic com- and constipation are the most common side effects. Rare
ponent and simply replacing nicotine with patches or gum adverse events include angioedema, serious skin reac-
is ineffective for a large number of patients. tions, and myocardial infarction. Serious neuropsychiatric
events can occur during therapy or shortly after discon-
Two prescription medications are used to promote tinuation of the drug. Patients experiencing changes in
smoking cessation. Bupropion (Zyban), classified as an behavior such as agitation, hostility, depressed mood, or
antidepressant, reduces cravings for nicotine and has been thoughts of suicide should contact their healthcare pro-
found to double the likelihood of becoming tobacco-free if vider immediately.
it is taken for 3 to 6 months. Therapy generally begins 1 to
2 weeks before smoking cessation to lessen the severity Contraindications/Precautions: The only con-
of withdrawal symptoms. Bupropion is sometimes given traindication is a history of serious skin reactions with
concurrently with NRT. Common side effects include varenicline.
insomnia, agitation, headache, and dry mouth.
Drug Interactions: When used in combination with
NRT, varenicline causes an increased incidence of nausea,
vomiting, headache, dizziness, and fatigue, which may
result in a premature termination of therapy.
Chapter 27 Pharmacology of Substance Abuse 465
Pregnancy: Category C. Inhalants differ greatly in their chemical structures and
include nearly any chemical that can be vaporized. Prod-
Treatment of Overdose: No specific treatment for ucts abused as inhalants include adhesives and glues, aero-
varenicline overdose is available. sols, cleaning agents, solvents, and fuels. These products
are readily available and can be purchased at hardware or
Nursing Responsibilities: Key nursing implications office supply stores. The highest use of inhalants is found
for patients receiving varenicline are included in the Nurs- among teens and preteens, probably because these agents
ing Practice Application for Patients Receiving Pharmaco- can be found in nearly every household (see Table 27.3).
therapy for Substance Abuse Disorders. Legal anesthetics such as nitrous oxide that are sometimes
abused by medical personnel are also classified as inhalant-
Drugs Similar to Varenicline (Chantix) sand are discussed in Chapter 26.
There are no drugs similar to varenicline. The inhalation route affords almost instantaneous
drug action and, because most of the inhalants are lipid
CONNECTIONS: Lifespan soluble, the substances quickly enter the brain. The spe-
Considerations cific psychoactive effects depend on the inhalant used but
generally include lightheadedness, drowsiness, exhilara-
Abuse of Volatile Inhalants by Children tion, and euphoria. Hallucinations are common. Symp-
and Adolescents toms of inhalant abuse often resemble alcohol intoxication.
Because most psychoactive effects of inhalants are tran-
Many parents are concerned that their children will smoke sient and disappear within minutes, the user may repeat
tobacco or marijuana or become addicted to crack or amphet- the drug use multiple times over a period of several hours.
amines. Few parents realize that the most commonly abused Coma and death are possible with repeated exposure or
substances are readily available in their own homes. Inhaling high doses.
volatile chemicals, known as huffing, bagging, or sniffing, is
most prevalent in the 13- to 20-year-old age group. In fact, Because most inhalant abuse is sporadic, physical
inhalants are often one of the first drugs that young adoles- dependence is not observed, and it is unknown whether
cents use, and they are used more by younger adolescents tolerance develops. Some of the inhalants cause hangover-
than older ones (Center for Behavioral Health Statistics and like symptoms after the psychoactive effects wear off.
Quality, 2015). Virtually any organic compound can be huffed, When chronic abuse does occur, it is generally in adult
including nail polish remover, spray paint, household glue, cor- men. Chronic effects can be serious and permanent, with
rection fluid, propane, gasoline, and even whipped cream pro- the most obvious effects on the nervous system. Cognitive
pellants. These agents are available in the home, in stores, impairment, tremors, loss of coordination, hallucinations,
and in the workplace. They are inexpensive, legal, and can be psychosis, and dementia may be observed. Nephrotoxicity
used anytime and anywhere. Children can die after a single is common with certain inhalants. The breathing reflex
exposure or sustain brain damage, which may be manifested may be diminished and patients may suffocate from plac-
as slurred or slow speech, tremor, memory loss, or personality ing a plastic bag over their heads.
changes. Nurses who work with pediatric patients should be
aware of the widespread nature of this type of abuse and Treatment for inhalant abuse is symptomatic. Long-
advise parents to keep a close watch on volatile substances. term behavioral therapy may be needed to reinforce to the
patient that permanent damage will result from chronic,
Inhalants continued abuse.
27.12 Inhalant abuse occurs when patients Table 27.3 Monitoring the Future Study: Trends in
breathe the fumes of vaporized substances.
Prevalence of Inhalants for 8th Graders, 10th Graders, and
Inhalants are a diverse group of substances that have in 12th Graders; 2016 (in percent)*
common the ability to vaporize or form a gas at room tem-
perature. Some are already in gaseous form, whereas oth- Drug Time 8th 10th 12th
ers are liquids that have the property of volatility—rapid Period Graders Graders Graders
evaporation when exposed to air. Sometimes the liquids
are heated to increase the speed or extent of vaporization. Inhalants Lifetime [7.70] 6.60 5.00
Most drugs in this class are placed in a paper or plastic bag Past Year [3.80] 2.40 1.70
or soaked on a cloth and deeply inhaled. Inhaling the
fumes is known as huffing. Past Month 1.80 1.00 0.80
* Data in brackets indicate a statistically significant change from the previous year.
From Inhalants: How Many Teens Use Inhalants?, National Institute on Drug Abuse for
Teens, 2017. Retrieved from https://teens.drugabuse.gov/drug-facts/inhalants.
466 Unit 4 Pharmacology of the Central Nervous System
CONNECTIONS: NURSING PRACTICE APPLICATION
Patients Receiving Pharmacotherapy for Substance Abuse Disorders
Assessment
Baseline assessment prior to administration:
• Obtain a complete health history including cardiovascular, neurologic, respiratory, or hepatic disease, pregnancy, or breastfeeding. Obtain a drug
history including allergies, substance used in disorder, current prescription and OTC drugs, and herbal preparations. Be alert to possible drug
interactions.
• Obtain a dietary history, especially noting possible vitamin deficiencies.
• Assess for the presence and level of pain.
• Obtain baseline vital signs and weight.
• Evaluate appropriate laboratory findings (e.g., hepatic function studies, complete blood count [CBC]).
• Assess the patient’s commitment to treatment and the ability to receive and understand instructions. Include family and caregivers as needed.
Assessment throughout administration:
• Assess for desired therapeutic effects (e.g., decreased use or abstinence from the substance).
• Continue periodic monitoring of hepatic function studies, CBC.
• Assess vital signs, especially blood pressure and pulse.
• Assess for and report adverse effects: headache, nausea, vomiting, insomnia, constipation, pain, skin rashes, excessive dizziness, drowsiness,
confusion, agitation, thoughts of suicide, seizures.
Implementation
Interventions and (Rationales) Patient-Centered Care
Ensuring therapeutic effects: • Teach the patient that maintaining consistency of treatment to de-
• Continue assessments as above for therapeutic effects. Substance use crease substance use and eventual abstinence is the goal of therapy.
treatment requires commitment and continuing treatment and follow-
up. (Nonpharmacologic measures such as group therapy may assist
the patient in remaining substance-free. Regularly scheduled visits with
the healthcare provider are opportunities to evaluate the success of
treatment and possibility for relapse.)
Minimizing adverse effects: • Teach the patient receiving buprenorphine to maintain the dosage as
• Continue to monitor vital signs, including respiratory rate, pulse, prescribed and to not increase the dose.
and blood pressure as ordered in patients receiving buprenorphine • Teach the patient receiving disulfiram that all forms of alcohol must be
and disulfiram. (Buprenorphine [Suboxone, Zubsolv] is an opioid avoided, including skin preparations and mouth rinses that contain
and may cause opioid-related adverse effects in higher dosages. alcohol. A reaction may occur up to 14 days after the last dose.
Disulfiram [Antabuse] may cause intense reactions when alcohol
is ingested or absorbed through the skin and may cause cardio-
vascular effects such as dysrhythmias, chest pain, and respiratory
depression.)
• Monitor for changes in behavior, including depression, hostility, • Instruct the patient, family, or caregiver to report immediately any
agitation, or thoughts of suicide in patients taking varenicline unusual changes in mood or behavior.
(Chantix). (The drug carries a black box warning for serious
neuropsychiatric events.)
• Monitor for skin rashes and facial or throat edema in patients taking • Instruct the patient, family, or caregiver to report immediately any un-
varenicline. (Serious dermatologic reactions including angioedema usual rashes, changes in skin condition, or swelling of the tongue, face,
have been noted.) or throat.
• Additional NRT should not be used during smoking cessation therapy • Teach the patient that other NRT, including OTC patches and gum,
with varenicline (Chantix). (Additional NRT will increase the incidence of should not be used while taking varenicline.
adverse drug effects and may lead to early cessation of therapy.)
• Provide referrals to supportive therapies as an adjunct to sub- • Provide referral to supportive therapies such as Alcoholics Anonymous
stance use treatment. (Nonpharmacologic measures such as group or Narcotics Anonymous and smoking cessation groups.
therapy may be beneficial during therapy and assist in maintaining a
substance-free state after treatment.)
Patient understanding of drug therapy: • The patient, family, or caregiver should be able to state the reason for
• Use opportunities during administration of medications and during the drug, appropriate dose and scheduling, what adverse effects to
observe for, and when to report them.
assessments to discuss the rationale for drug therapy, desired thera-
peutic outcomes, commonly observed adverse effects, parameters
for when to call the healthcare provider, and any necessary monitoring
or precautions. (Using time during nursing care helps to optimize and
reinforce key teaching areas.)
Patient self-administration of drug therapy: • The patient, family, or caregiver is able to discuss appropriate dosing
• When administering the medication, instruct the patient, family, or and administration needs.
caregiver in the proper self-administration of the drug (e.g., take the • Teach the patient taking buprenorphine (Suboxone, Zubsolv) to take
drug exactly as prescribed). (Utilizing time during nurse administration the medication sublingually by placing the tablet under the tongue and
of these drugs helps to reinforce teaching.) allowing it to dissolve. Do not chew or swallow the tablet. If more than
one tablet is used, place all tablets under the tongue at the same time.
Chapter 27 Pharmacology of Substance Abuse 467
Anabolic Steroids enlargement (gynecomastia). Women taking anabolic ste-
roids will develop masculine characteristics, excessive
27.13 Anabolic steroids are abused for their growth of body hair (hirsutism), shrinking of breast size,
ability to increase muscle strength. menstrual irregularities, and deepening of the voice. The
most serious adverse effects, in both men and women,
All of the drugs presented thus far in this chapter have in include hepatic cysts, elevated cholesterol, myocardial
common the ability to affect the CNS and produce psycho- infarction, and stroke. Personality changes include aggres-
active effects. Many produce euphoria, some induce relax- sion, violent behavior, depression, insomnia, anorexia, and
ation, and yet others enhance alertness. In most cases, the decreased libido.
user views the drug experience as pleasurable and the
drug effects are experienced soon after it is taken, some- Anabolic steroids are classified as Schedule II drugs
times within seconds. Anabolic steroids, however, are not due to their abuse potential. In an attempt to stem the ris-
taken for their CNS actions, and their desirable effects may ing abuse of these drugs, Congress passed the Anabolic
be delayed for weeks or months. Steroid Control Act of 2004 to control 26 different steroid
precursors, such as androstenedione (Andro). Some com-
Anabolic steroids are similar to testosterone, the pri- panies were legally selling these precursors as dietary sup-
mary male sex hormone or androgen. The term anabolic plements, despite the fact that these agents are metabolized
means “growth” or “building up.” Because these substances to steroids in the body and essentially carry the same risks.
can add to skeletal muscle mass and increase strength, they It is interesting to note that one of the most popular supple-
are usually abused in an attempt to enhance athletic perfor- ments, dehydroepiandrosterone (DHEA), was specifically
mance. Do these drugs actually boost performance? The and intentionally omitted from that list and remains legal.
answer is a qualified yes. The most important aspects of DHEA is a natural steroid precursor secreted by the adre-
athletic performance are skill, training, and confidence. If nal gland that is claimed to have antiaging and perfor-
these factors are equal among performers, anabolic steroids mance-enhancing properties.
may indeed provide an extra boost in performance, which is
all important in a competitive sport such as track, downhill 27.14 The nurse has a pivotal role in
skiing, or swimming where a few hundredths of a second recognizing and treating substance abuse.
can mean the difference between first and sixth place. On
the other hand, no amount of steroid is able to overcome The nurse serves a key role in the prevention, diagnosis,
lack of athletic skill or inadequate training. Amateur and and treatment of substance abuse. During assessment,
professional sports organizations have banned the use of nurses may be the first members of the healthcare team to
these drugs and athletes may be eliminated from competi- recognize symptoms and signs of substance abuse. Patients
tion if they test positive for anabolic steroids. Some abusers are often reluctant to report their drug use for fear of
take anabolic steroids to enhance their appearance and self- embarrassment or being arrested. In known IV drug users,
confidence, rather than for athletic competition. the nurse must consider the possibility of HIV infection,
hepatitis, tuberculosis, and associated diagnoses. The
Anabolic steroids have legitimate medical uses as nurse must be knowledgeable about the signs and symp-
replacement therapy for men who secrete deficient quanti- toms of substance abuse and develop a keen sense of per-
ties of testosterone and they are occasionally used to treat ception during the assessment process. In their role as
certain cancers. Doses used by abusers, however, are 10 to educators, nurses distribute important information on
100 times higher than those required for therapeutic use. substance abuse prevention and the proper use of pre-
scription drugs. A trusting nurse–patient relationship is
Anabolic steroids may be taken as tablets, as IM injec- essential to helping patients deal with their dependence.
tions, or applied as ointments or as a transdermal patch.
Abusers may take two or more different types of steroids It is often difficult for a practitioner not to condemn or
concurrently, sometimes by different routes, a practice stigmatize a patient for his or her substance abuse. Nurses,
called “stacking.” The drugs may be taken in a cyclic pat- especially those in large cities, are all too familiar with the
tern called “pyramiding” in which the dose is progres- devastating medical, economic, and social consequences of
sively increased over 6 to 12 weeks, then slowly decreased drug abuse. The nurse must be firm in disapproving sub-
to zero. Abusers believe that this is a safer and more effec- stance abuse, yet compassionate in trying to help the
tive way to obtain benefits from the drugs. patient receive treatment. A list of social agencies dealing
with dependency should be readily available to provide to
One of the ironies of steroid abuse is that the very drug patients. Whenever possible, the nurse should attempt to
that is being taken to enhance appearance and performance involve family members and other close contacts in the
eventually produces serious consequences that have the treatment regimen.
opposite effect. Men may believe that anabolic steroids
make them appear more masculine, but the drugs can
cause infertility, impotence, testicular atrophy, and breast
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