118 Unit 2 Pharmacology and the Nurse–Patient Relationship
calculated quickly. However, the serum concentrations of weight gain could be caused by edema resulting from poor
many drugs are not proportional to body weight, and body kidney excretion, or weight loss might be due to excessive
weight does not take into consideration pharmacokinetic diuresis. Signs of ototoxicity may go unnoticed for a long
variables such as changes in metabolism and elimination time unless someone checks that the child no longer
rates, as discussed in Section 9.2. responds to verbal commands. It may be necessary to con-
sult a psychologist to identify signs of suicidal ideation
The body surface area (BSA) method uses an estimate from antidepressant use in adolescents.
of the child’s BSA. This method is believed to be the most
valid basis for dosage, because it is related to certain physi- Most types of adverse effects that occur in children age 1
ologic functions that account for the pharmacokinetic dif- or older are the same as those in adults. Like adults, the
ferences in pediatric patients. The BSA method better majority of adverse effects are dose related; thus the nurse
estimates blood volume, metabolism, and the effects of must pay close attention to the proper dose and frequency
drugs. Measurements of the fluid volume compartment of drug administration. Knowing specific drugs and their
and the serum concentrations of drugs also correlate well adverse effects in the adult population will help the nurse
with the BSA. Several different formulas have been used to quickly identify signs and symptoms in pediatric patients.
calculate BSA, and each gives slightly different results. For example, antibiotics such as amoxicillin frequently
There is a lack of consensus as to which calculation method result in diarrhea in both adults and children. Antianxiety
gives the most accurate results. drugs, antidepressants, and antipsychotic drugs that cause
CNS depression will likely cause drowsiness in both adults
Calculators are readily available online to calculate and children.
BSA. The child’s height (in centimeters) and weight (in
kilograms) is entered and the body mass is calculated in A few types of adverse effects are specific to children
square meters. The BSA can then be used to calculate a cor- due to their immature or developing organs and tissues.
rect dose (Medscape, n.d.). For example, tetracycline must be avoided in the neonate
because of the potential for permanent staining of the teeth.
CONNECTIONS: Patient Safety Sulfonamides can cause jaundice in neonates, and aspirin
is contraindicated in children with fever due to the poten-
A Tenfold Error tial for Reye’s syndrome. Glucocorticoids can inhibit
growth. Table 9.3 illustrates a list of commonly used drugs
The nurse is caring for a 6-year-old boy newly diagnosed with and their adverse effects on the pediatric patient.
seizures, tonic-clonic type. In reviewing the written orders, val-
proic acid (Depakene) 150 mg/kg/day is ordered. The phar- CONNECTION Checkpoint 9.3
macist calls the unit to verify the order and the nurse contacts
the prescriber. The order is corrected to 15 mg/kg/day. What The nurse gives a preschooler a sedative but, rather than sleep, the
could be done to prevent this error from recurring? child becomes excited and experiences insomnia. From what you
learned in Chapter 5, this reaction is most likely classified as what
Answers to Patient Safety questions are available on the faculty type of effect? Answers to Connection Checkpoint questions are avail-
resources site. Please consult with your instructor. able on the faculty resources site. Please consult with your instructor.
Adverse Drug Reactions in Like adults, children may also experience drug interac-
Children and Promoting tions. Drugs that are most likely to contribute to drug
Adherence interactions in pediatric patients are those with high
potency, narrow therapeutic index, and extensive protein
9.6 Pediatric patients are more susceptible than binding, and those that affect vital organ functions or
adults to adverse drug effects. hepatic metabolism.
Because of their smaller size and immature or developing Often parents’ first response to their child’s illness is
organ systems, pediatric patients are more susceptible to to provide home remedies. OTC and herbal treatments are
adverse effects. The nurse may find it challenging to iden- extremely common in some households, and research
tify adverse effects because infants and young children suggests that they are on the rise among a large segment
often do not have the maturity or verbal skills to accurately of the population. The nurse must become aware of com-
describe their feelings following the medication adminis- monly used OTC and herbal remedies in order to advise
tration. Identifying pediatric adverse effects will depend the families about the pros and cons. Parents must under-
on the skill and ability of the nurse to assess subtle changes stand that OTC and herbal therapies may have adverse
in patient response. For example, a child on diuretics effects of their own and may interact with prescription
should have strict intake and output measurements to help medications. Herbal remedies commonly used in homes
determine if the drug is working properly. Excessive include St. John’s wort, echinacea, ginseng, licorice, and
sassafras.
Chapter 9 Pharmacotherapy of the Pediatric Patient 119
Table 9.3 Selected Pediatric Drugs for Which Specific Indications and Dosage Guidelines Exist
Drug Dosage/Route (Maximum Dose Where Indicated) Adverse Effects
acetaminophen (Tylenol) PO: 10–15 mg/kg q4–6h for children under age 12, not
to exceed 2.6 g/day Methemoglobinemia, hepatotoxicity
acyclovir (Zovirax) PO: 200 mg 5 times daily for genital herpes
Diarrhea, nausea
amoxicillin (Amoxil, Trimox) or amoxicillin/ PO: 20–40 mg/kg/day Renal failure, seizures
clavulanate (Augmentin)
amphetamine and dextroamphetamine PO: 2.5–5 mg once or twice daily (regular release) or Diarrhea
(Adderall) 10 mg once daily (extended release) Anaphylaxis
ampicillin (Principen) PO: 50–100 mg/kg/day
Insomnia, anorexia, headache
atomoxetine (Strattera) PO: 40–80 mg once daily Tachycardia, psychotic episodes, abuse potential
azithromycin (Zithromax) PO: 5–10 mg/kg/day Diarrhea
Anaphylaxis
budesonide (Rhinocort) Intranasal: 2 sprays in each nostril bid for allergies
Dry mouth, anorexia, insomnia, headache
ceftriaxone (Rocephin) IV/IM: 50–100 mg/kg/day Depression, suicidal ideation
cephalexin (Keflex) PO: 25–50 mg/kg/day q6h Diarrhea
Hepatotoxicity
clarithromycin (Biaxin) PO: 15 mg/kg/day
Headache, fatigue
diphenoxylate and atropine (Lomotil) PO: 1/2–1 tsp, up to 4 doses/day Paresthesia
erythromycin (EryC, Erythrocin) PO: 30–50 mg/kg/day Diarrhea
Colitis
ferrous sulfate (Feosol, Fergon, others) PO: 0.5–1 mg/kg/day maintenance
Diarrhea
fluconazole (Diflucan) PO: 6 mg/kg/day first dose, then 3 mg/kg/day Anaphylaxis, angioedema
fluticasone (Flonase) Intranasal: 1 spray in each nostril once a day; may Vomiting, diarrhea
increase to 2 sprays daily Colitis
gentamicin (Garamycin) IV/IM: 6–7.5 mg/kg/day (2–2.5 mg/kg administered q8h)
Dizziness, sedation
ibuprofen (Advil, Motrin) PO: 5–10 mg/kg/dose given q6–8h Paralytic ileus
imipramine (Tofranil) PO: 25–50 mg/day for nocturnal enuresis Nausea, vomiting
Hepatotoxicity
methylphenidate (Ritalin) PO: 5–10 mg/day (dose not to exceed 60 mg/day,
depending on trade name) Nausea, black stools
minocycline (Minocin) PO: 4 mg/kg/day bid Shock
oxcarbazepine (Trileptal) PO: 8–10 mg/kg/day not to exceed 600 mg/day
Headache, nausea
penicillin G PO: 25–50 mg/kg/day q3–4h Hepatotoxicity
trimethoprim-sulfamethoxazole (Bactrim, PO: 8 mg/kg/day trimethoprim–40 mg/kg/day Nasal dryness
Septra) sulfamethoxazole q12h Epistaxis
valproic acid (Depakene, Depakote) PO: 10–15 mg/kg/day initially (dose not to exceed
60 mg/kg/day) Pain at injection site
Neurotoxicity, nephrotoxicity
Nausea, heartburn
GI bleeding
Urinary retention
Angioedema
Nervousness, insomnia
Palpitations
Dizziness, nausea
Fatigue
Somnolence
Diarrhea
Anaphylaxis
Nausea, rash, anemia
Exfoliative dermatitis
Drowsiness, nausea
Bone marrow suppression
Note: Italics indicate common adverse effects. Underline indicates serious adverse effects.
A drug will fail to achieve optimal therapeutic out- pediatric nurse. The nurse must assess the patient and fam-
comes if it is not taken properly. Adherence, also called ily to determine factors that could affect the family’s ability
compliance, is taking the drug according to the instructions to assist the child with the medication regimen and develop
on the label or as provided by the prescriber. Maximizing strategies that will enhance medication adherence. The
adherence to the medication regimen is a major goal of the more complex, expensive, and inconvenient the medication
120 Unit 2 Pharmacology and the Nurse–Patient Relationship
regimen, the less likely the child and family will adhere. family should be asked directly whether or not they have
Children are most likely to adhere to their medication regi- doubts about their ability to adhere to the regimen. If there is
men if the following conditions exist: doubt, the nurse should explore the areas of concerns with
the family and start by teaching the importance of the drug,
• High expectations of successful outcomes of the route of administration, expected outcomes, and possible
therapy adverse effects. In long-term drug therapy, the nurse may
have to arrange for follow-up appointments to assess drug
• Supportive family members who are able to commu- responses or to administer the oral drug(s) to the child and
nicate with the prescriber observe the drug being swallowed. This technique is known
as directly observed therapy (DOT). In extreme cases when
• Positive interactions with the nurse and caregivers the child does not appear to be responding appropriately to
• Minimal adverse effects from the medications the prescribed regimen, periodic measurement of plasma
• Simple, short-term, inexpensive regimen with mini- drug levels can help determine the amount of drug ingested
and whether it has been taken as prescribed.
mum disruption to daily routine.
The nurse works with the child and family to enhance
adherence by applying direct measures. The patient and
Understanding Chapter 9
Key Concepts Summary 9.4 The nurse is a key member of the healthcare team in
ensuring medication safety in pediatric patients.
9.1 Legislation has attempted to improve the testing and
labeling of pediatric drugs. 9.5 The nurse must be accurate when calculating drug
dosages of pediatric patients.
9.2 Pharmacokinetic responses in children differ from
those in adults. 9.6 Pediatric patients are more susceptible than adults
to adverse drug effects.
9.3 The role of the nurse in administering medications
changes with each developmental age group.
CASE STUDY: Making the Patient Connection
Remember 7-month-old “Liam,” performed: serum electrolytes, complete blood count, blood
the patient introduced at the urea nitrogen, creatinine, urinalysis, and stool for culture
beginning of the chapter? Now and sensitivity. Electrolytes were as follows: sodium,
read the remainder of the case 136 mEq/L; potassium, 4.2 mEq/L; chloride, 114 mEq/L;
study. Based on the information bicarbonate, 9 mEq/L.
presented within this chapter,
respond to the critical thinking questions that follow. An IV line was inserted immediately and a solution of
D5W in 1/3 NSS was started to infuse at 30 mL/h. Liam
Ms. Nguyen reports that Liam has not been eating well for was placed on NPO.
the past 48 hours. Last night he vomited 3 times after drink-
ing sips of water and also had several very loose, green Critical Thinking Questions
foul-smelling bowel movements. He voided only once in
the past 12 hours. For the past 5 days Liam has been taking 1. What primary factors are contributing to Liam’s risk
amoxicillin for an ear infection. Liam lies still on the exami- for deficient fluid balance?
nation table but responds to his mother’s commands. The
nurse prepares Liam for examination. 2. What are some physical signs to assess when evaluat-
ing dehydration in this infant?
Liam’s preliminary diagnosis is gastroenteritis with
mild dehydration. His vital signs are as follows: tempera- 3. What would best explain the cause for diarrhea in this
ture, 39.1°C (102.4°F); heart rate, 160 beats/min; respiration, patient?
38 breaths/min; blood pressure, 100/57 mmHg; and weight,
8.6 kg (19 lb). His skin is dry and warm to touch, and there 4. What are some key points to focus on when monitor-
is slight tenting. The following laboratory studies were ing the infant’s IV fluid intake?
Answers to Critical Thinking Questions are available on the
faculty resources site. Please consult with your instructor.
Chapter 9 Pharmacotherapy of the Pediatric Patient 121
Additional Case Study 1. What nursing actions would take priority?
Sinead, a 3-year-old girl, arrives at the ED in status asthmati- 2. What nursing assessment should the nurse carry out
cus. Her mother informs you that she was diagnosed with immediately?
asthma 9 months ago and since then has been back to the ED
for treatment twice. Two hours prior to admission, Sinead 3. What immediate outcomes could be expected
started coughing and wheezing and then an hour ago started from treatment?
having difficulty breathing. Her mother attempted to relieve
the symptoms by giving steam and fluids but the condition Answers to Additional Case Study questions are available on the
only worsened. Sinead has audible expiratory wheeze, nasal faculty resources site. Please consult with your instructor.
flaring, and inter- and substernal retractions.
Chapter Review 3. “IM injections are encouraged due to their
predictable absorption rate.”
1. The nurse is preparing to administer medication to
the pediatric patient. Which factor(s) is/are true 4. “Strong muscle contractions result in delayed
regarding the pharmacokinetics in the pediatric absorption of IM medication.”
population? (Select all that apply.)
4. It is time to give a 3-year-old oral medication. Which
1. Slower gastric motility in young children will keep comment by the nurse is most therapeutic?
the drug in the stomach longer.
1. “This is the medicine that makes you better.”
2. Before 6 months of age, there is greater plasma 2. “If you don’t take your medicine you can’t
protein binding of drugs, and drug distribution
will be lower in this age group. go home.”
3. “Would you like to take your medicine with water
3. Before age 5, the liver may not metabolize drugs as
readily as an adult’s liver and doses must be or juice?”
adjusted accordingly. 4. “See how easily your roommate has taken
4. Drug excretion by the kidneys will not equal an his medicine?”
adult’s until the child is at least 2 years of age.
5. Drugs that are most likely to create drug interactions
5. Drugs with CNS effects have little to no effect in in pediatric patients are those with:
infants and very young children.
1. Low potency.
2. A mother calls the urgent care center and frantically 2. Wide therapeutic index.
tells the nurse that her toddler drank a bottle of 3. Extensive protein binding.
cleaning fluid. Which of the following is the priority 4. Effects on the skin.
instruction the nurse should give the parent?
6. The healthcare provider knows that the pediatric
1. Contact the poison control center. patient and parents will most likely adhere to the
medication regimen if the:
2. Watch the child closely and call back if there are
signs of respiratory distress. 1. Regimen is simple and inexpensive.
2. Medications are costly but well known.
3. Take the child immediately to the emergency 3. Medications are prescribed for a long period.
department. 4. Medications are taken at different times each day.
4. Give the child syrup of ipecac. See Answers to Chapter Review in Appendix A.
3. The experienced pediatric nurse is teaching a new
nursing student about injections in the pediatric
population. Which statement by the student would
indicate that teaching was effective?
1. “Intramuscular (IM) injections in infants are
absorbed slowly.”
2. “Children experience rapid absorption
of IM medications.”
122 Unit 2 Pharmacology and the Nurse–Patient Relationship
References Off-label prescribing in pediatric outpatients. Pediatrics,
135(1), 49–58. doi:10.1542/peds.2014-0764
American Academy of Pediatrics. (2007). AAP Targeted News Service. (2015, March 31). Pediatric drug
Publications Reaffirmed, January 2007. Policy poisoning on the rise.
statement: Prevention of medication errors in the U.S. Government Accountability Office. (2003). Pediatric
pediatric inpatient setting. Pediatrics, 119(5), 1031. research equity act of 2003. Washington, DC: Author.
doi:10.1542/peds.2007-0471 U.S. Government Accountability Office. (2007). Pediatric
drug research: Studies conducted under best pharmaceuticals
Field, M. J., & Boat, T. F. (2012). Policy framework for for children act. Retrieved from http://www.gao.gov/
BPCA and PREA. In Safe and effective medicines for new.items/d07557.pdf
children: Pediatric studies conducted under the best Wharton, G., Murphy, M., Avant, D., Goldsmith, J., Chai,
pharmaceuticals for children act and the pediatric research G., Rodriguez, W., & Eisenstein, E. (2014). Impact of
equity act (pp. 63–88). Washington, DC: National pediatric exclusivity on drug labeling and
Academies Press. demonstrations of efficacy. Pediatrics, 134(2), e512–518.
doi:10.1542/peds.2013-2987
Medscape. (n.d.). Body surface area based dosing. Retrieved Ziesenitz, V. C., van den Anker, J. N., & Amirshahi, M.
from http://reference.medscape.com/calculator/ (2016). Availability of pediatric formulations for the 100
bsa-dosing most prescribed drugs in pediatric ambulatory care—
2002 vs. 2010. Archives of Disease in Childhood, 101(1),
National Center for Health Statistics. (2014). Health, United e1–e1. doi:10.1136/archdischild-2015-310148.12
States, 2013: With special section on prescription drugs.
Retrieved from http://www.cdc.gov/nchs/data/hus/
hus13.pdf
Palmaro, A., Bissuel, R., Renaud, N., Durrieu, G.,
Escourrou, B., Oustric, S., … Lapeyre-Mestre, M. (2015).
Selected Bibliography De Bie, S., Ferrajolo, C., Straus, S., Verhamme, K.,
Bonhoeffer, J., Wong, I., & Sturkenboom, M. (2015).
Allegaert, K., Velde, M., & Anker, J. (2014). Neonatal Pediatric drug safety surveillance in FDA-AERS: A
clinical pharmacology. Pediatric Anesthesia, 24, 30–38. description of adverse events from GRiP project. PLoS
doi:10.1111/pan.12176 ONE, 10(6), e0130399. doi:10.1371/journal.
pone.0130399
American Association of Family Physicians. (2015). Clinical
practice guideline: Otitis media with effusion. Retrieved Frattarelli, D., Galinkin, J., Green, T., Johnson, T., Neville,
from http://www.aafp.org/patient-care/clinical- K., Paul, I., & Van Den Anker, J. (2014). Off-label use of
recommendations/all/otitis-media-effusion.html drugs in children. Pediatrics, 133(3), 563–567.
doi:10.1542/peds.2013-4060
Chonmaitree, T., Trujillo, R., Jennings, K., Alvarez-
Fernandez, P., Patel, J., Loeffelholz, M., . . . McCormick, Kliegman, R. M., Stanton, B., St. Geme, J., Schor, N., &
D. (2016). Acute otitis media and other complications of Behrman, R. E. (Eds.). (2016). Nelson textbook of pediatrics
viral respiratory infection. Pediatrics, 137(4). (19th ed.). Philadelphia, PA: W. B. Saunders.
doi:10.1542/peds.2015-3555
Rinke, M. L., Bundy, D. G., Velasquez, C. A., Rao, S.,
Committee on Drugs. (2015). Metric units and the Zerhouni, Y., Lobner, K., . . . Miller, M. R. (2014).
preferred dosing of orally administered liquid Interventions to reduce pediatric medication errors: A
medications. Pediatrics, 135(4), 784–787. doi:10.1542/ systematic review. Pediatrics, 136(3), 583. doi:10.1542/
peds.2015-0072 peds.2015-1344
Coppini, R., Simons, S., Mugelli, A., & Allegaert, K. (2016).
Clinical research in neonates and infants: Challenges
and perspectives. Pharmacological Research, 108, 80–87.
doi:10.1016/j.phrs.2016.04.025
Mary Smith, 80 years old, is being
transported via ambulance to the
emergency department. She looks
pale and thin with sunken eyes
and chapped, dry lips. “I’m so
relieved my neighbor came by
to check on me. I have not been
able to get out of bed for 2 days.”
Patient “Mary Smith”
Chapter 10
Pharmacotherapy of the
Geriatric Patient
Chapter Outline Learning Outcomes
cc Polypharmacy After reading this chapter, the student should be able to:
cc Physiologic Changes Related to Aging
cc Pharmacokinetic and Pharmacodynamic Changes 1. Describe factors that lead to polypharmacy in
older adults.
in Older Adults
cc Adherence and Drug Misuse Among Older Adults 2. Identify age-related physiologic changes in the
cc Adverse Drug Reactions in Older Adults older adult.
3. Explain how age-related physiologic changes alter
pharmacokinetics and pharmacodynamics and affect
drug response in older adults.
4. Explain strategies that the nurse may implement to
improve adherence with drug therapy in geriatric
patients.
5. Explain why older adults are more likely to
experience adverse drug reactions and interactions.
6. Identify specific drugs that are particularly
hazardous for use in older patients.
7. Differentiate medication responses that result from
age-related alterations in specific body systems from
those that occur in younger individuals.
8. Develop nursing interventions that maximize
pharmacotherapeutic outcomes in older adults.
9. Generate key points for family and patient
education regarding drug pharmacotherapy for
older adults.
123
124 Unit 2 Pharmacology and the Nurse–Patient Relationship
Key Terms polypharmacy, 124 potentially inappropriate
medications (PIMs), 128
Beers criteria, 128
drug misuse, 127
There is no universally accepted age that is considered comorbidities that occur in a significant number of older
old. The older adult, or an elderly individual, is typically adults are heart disease with arthritis, hypertension with
defined as someone over age 65. Of this age group, those diabetes, and depression with nearly any other chronic
older than 84 years are the fastest growing segment of the disorder.
population. The average age of the population has
increased significantly during the past few decades Comorbidities often result in the need for multiple
because of improved access to healthcare, people choos- drugs, a condition termed polypharmacy. Although not
ing healthier lifestyles, and more effective treatment of unique to older patients, polypharmacy is prevalent in
chronic diseases. With the increase in lifespan, however, this age group because of these comorbidities. The higher
has come an increased reliance on medications to main- the number of drugs taken by a patient, the greater the
tain health. This chapter focuses on aspects of pharmacol- possibility of experiencing adverse effects and drug inter-
ogy unique to geriatric patients and provides steps that actions. As presented in Chapter 5, drugs that may be safe
the nurse can take to provide safe, effective pharmaco- when used as monotherapy can have additive adverse
therapy for this population. effects when combined with other drugs. For example,
taking multiple drugs that cause central nervous system
PharmFACT (CNS) depression can lead to excessive sedation, thus
increasing the risk for injuries due to falls. Taking two or
Between 2012 and 2050, the United States will experience more drugs that cause renal or liver impairment can result
considerable growth in its older population. By the year in additive organ damage in older adults who may already
2050, the population ages 65 and over is projected to be have some degree of function loss due to normal aging
83.7 million, which is almost double its estimated processes.
population of 43.1 million in 2012. The baby boomers are
largely responsible for this increase as they began turning Polypharmacy may also occur when the patient takes
65 in 2011 (Ortman, Velkoff, & Hogan, 2014). over-the-counter (OTC) drugs, herbal products, and dietary
supplements in conjunction with prescribed medications.
Polypharmacy For example, older adults frequently seek OTC medica-
tions to treat constipation and minor aches and pains.
10.1 Older adults take more medications than Many also take vitamins, alternative therapies, and dietary
any other segment of the population. supplements. Most patients are unaware that these agents
can interact with prescription medications.
The pharmacotherapy of older adults is more challenging
than that of their middle-age or younger counterparts. To Patients who visit multiple healthcare providers and
deliver safe and effective treatment for patients in this use different pharmacies may experience polypharmacy
age group, the nurse must consider many age-related because each provider or pharmacist may not be aware of
variables that affect pharmacotherapy. In addition, older all the drugs ordered by other prescribers. Nurses should
adults generally experience more chronic conditions than urge patients to report all prescription and OTC products
their younger counterparts. Most of these conditions at each office visit and teach them to use one pharmacy for
require drug therapy to treat and prevent complications. their prescription needs.
Finally, many older adults self-medicate for minor condi-
tions that do not require prescription drug therapy. In addition to polypharmacy, many other factors can
alter a geriatric patient’s response to medication. These
Longevity inevitably leads to increased illnesses, include physiologic changes associated with aging, changes
which, in turn, results in the use of increased numbers of in pharmacokinetics and pharmacodynamics, and patient
medications. Comorbidity, the presence of several chronic adherence with the therapeutic regimen.
medical disorders concurrently, is common among older
adults. By about age 65, half the older population has two CONNECTION Checkpoint 10.1
or more chronic disorders, the most prevalent being a
combination of hypertension and arthritis. Other From what you learned in Chapter 5, state the differences between
additive, synergistic, and antagonistic effects. Answers to Connec-
tion Checkpoint questions are available on the faculty resources site.
Please consult with your instructor.
Physiologic Changes Related Chapter 10 Pharmacotherapy of the Geriatric Patient 125
to Aging
Cardiovascular system changes in the older adult are
10.2 Anatomic and physiologic changes related to changes in cardiac muscle and increased periph-
associated with aging may alter the patient’s eral resistance (hypertension). These physiologic changes
response to medications. lead to decreased contractile force, which diminishes cardiac
output and slows the circulation of nutrients and drugs.
With advancing age, certain anatomic and physiologic
changes occur. These predictable changes should be con- In the nervous system, conduction velocity slows and
sidered a normal part of the aging process, rather than as sensory functions such as vision, hearing, and smell begin to
diseases or pathologic conditions. Awareness of the phys- diminish. Brain mass begins to decline, resulting in a pro-
iologic changes that occur during the lifespan is critically gressive loss of cognitive ability. Additionally, as an adult
important in properly assessing and caring for the older ages the efficiency of the blood–brain barrier declines, allow-
adult (Figure 10.1). Failure to recognize these changes ing more substances to enter the CNS and affect the brain.
may lead to less than optimal therapeutic outcomes and
may endanger patient safety. Older adults undergo a progressive decline in renal
function as a result of decreased renal blood flow, decreased
Giving an “average dose” of a drug to an older adult glomerular filtration rate, and decreased numbers of neph-
may produce a very different response compared to the rons. The kidneys begin to lose their ability to effectively
same dose given to a younger patient, even if the two excrete creatinine and other wastes from the body. The body
patients weigh the same. The pharmacologic action of the retains drugs and other substances for longer periods.
drug in older adults may be enhanced or diminished. The
adverse effects may be more severe or entirely different Normal, age-related physiologic changes in organ sys-
from those observed in younger patients. The older tems can greatly affect responses to medications. Selected
patient may experience more drug interactions. What fac- changes, and their effects on drug response, are shown in
tors are responsible for this wide variation in drug Table 10.1.
response in the geriatric population?
Pharmacokinetic and
In general, physiologic processes slow down with Pharmacodynamic Changes
advancing age. For example, the rate of absorption of in Older Adults
nutrients from the gastrointestinal (GI) system tends to
slow due to the decrease in GI motility and reduced GI 10.3 Normal aging processes can alter
blood flow. Metabolism also diminishes due to decreased pharmacokinetic and pharmacodynamic
liver size and reduced blood flow to this organ. Addition- responses to drugs.
ally, as an individual ages the production of serum albu-
min by the liver declines. The older adult has a decreased To produce therapeutic effects, most drugs must reach
volume of total body water, leading to higher concentra- their target cells in sufficient quantities. To a large extent,
tions of substances in the serum. this depends on what the body does to the medications
after they are administered, a process known as pharmaco-
Figure 10.1 Pharmacology of the older adult can be challenging kinetics. Drug response is also dependent on pharmacody-
due to physiologic changes that occur with aging. namic factors: the mechanisms by which drugs change the
body. The normal physiologic changes of aging affect
Courtesy of Barabasa/Shutterstock. pharmacokinetics and pharmacodynamics. Knowing
about these changes when administering medications to
the older adult helps the nurse to understand the unique
actions of drugs in these patients and to predict and pre-
vent adverse effects.
Absorption: Overall, absorption of nutrients and drugs
tends to slow with aging. Fortunately, although the rate
slows, absorption is usually complete because most drugs
are absorbed by passive diffusion.
Because of the increased gastric pH in older adults,
oral tablets and capsules that require high levels of acid for
absorption may dissolve more slowly and take longer to
reach their target tissues. Furthermore, decreased blood
flow to and from the GI tract in the older adult delays the
absorption and subsequent distribution of medications.
126 Unit 2 Pharmacology and the Nurse–Patient Relationship
Table 10.1 Physiologic Factors Affecting Medication Responses in Older Adults
Body System Changes in Physiologic Factors Effect on Medication Response
Cardiovascular system • Decreased force of contraction and stroke volume • Reduced cardiac output and slowed distribution
Central nervous system • Decreased oxygen uptake by tissues • Decreased metabolism
Endocrine system • Decreased serum albumin and serum-binding capacity • Changed drug distribution, producing unpredictable and
Gastrointestinal system
• Decreased brain size, number of neurons, and peripheral toxic levels of highly protein-bound drugs such as
Musculoskeletal system nerve function phenytoin
Respiratory system • Decreased drug distribution
Urinary system • Declining efficiency of blood–brain barrier
• Increased penetration of drug in the brain
• Alterations in carbohydrate metabolism • Reduced insulin secretion and increased insulin
• Decreased growth hormone production and altered
resistance, manifesting as type 2 diabetes mellitus
corticosteroid activity, leading to increased body fat, • Increased absorption of fat-soluble drugs
decreased muscle, and decreased bone mass
• Slowed rate of absorption
• Decreased GI motility • Increased potential for adverse effects
• Decreased emptying of gastric contents
• Reduced gastric acid production • Slowed metabolism
• Increased gastric pH • Prolonged drug half-life, increasing the potential for
• Decreased blood flow to the GI tract
• Decreased thirst perception, leading to risk for dehydration, adverse effects
• Extended and increased effect of fat-soluble drugs such
electrolyte imbalance, and poor nutritional intake
as diazepam
• Decreased liver size • Decreased chest and lung expansion and response to
• Decreased blood flow to the liver
• Decreased ability of the liver to metabolize drugs hypoxia, resulting in altered rate of absorption and
excretion of some respiratory drugs
• Decreased lean muscle mass and increased and • Higher concentrations of water-soluble drugs
redistributed body fat • Reduced rate of excretion and decreased drug clearance
• Decreased muscle strength and endurance • Decreased drug excretion
• Decreased total fluid volume
• Decreased renal blood flow, glomerular filtration, and tubular
secretory function
• Decreased creatinine clearance
Slowed motility allows drugs to remain longer in the GI fewer binding sites for certain drugs, and higher concentra-
tract, increasing the length of time for absorption and rais- tions of free drugs, which may lead to toxicity. In older
ing the risk for adverse effects such as nausea and vomit- adults taking highly protein-bound drugs such as phenyt-
ing. Physiologic changes that lead to alterations in the rate oin (Dilantin) and warfarin (Coumadin), the nurse must
and quantity of drug absorption are listed in Table 10.1. carefully assess for signs of toxicity, even when the patient
is receiving therapeutic doses.
Distribution: As the body ages, the proportion of body
fat increases, which can cause lipid-soluble drugs such as Higher levels of drugs are able to enter the brain in
diazepam (Valium) to be stored in the body for extended older adults due to the inefficient blood–brain barrier.
periods. This may lead to lower plasma levels and Patients taking drugs such as benzodiazepines, antipsy-
increased drug concentrations in the tissues. The longer a chotic drugs, antiepileptic drugs, or tranquilizers that affect
drug remains in the tissues, the more significant the the CNS must be assessed for signs of adverse effects that
response to the drug will be and the greater the potential often manifest as reduced cognitive function, drowsiness,
for adverse effects. confusion, and even hallucinations and psychoses.
As the body ages, there may be a reduction in total Metabolism: Although most tissues metabolize drugs
body water resulting in water-soluble drugs such as genta- to some extent, the liver is by far the most important organ
micin (Garamycin) and hydrochlorothiazide (Microzide) performing this function. Age-related changes in the liver
having less body fluid for dilution. Therefore, water-soluble include reduced hepatic function, decreased liver mass,
drugs have higher serum concentrations and may produce diminished blood flow, and alteration in the activity of
more intense actions. To prevent toxicity, the peak and some hepatic enzymes.
trough levels of drugs with a low safety index such as
gentam icin are checked periodically, and drug dosages are Age-related changes in liver function are often unpre-
adjusted accordingly. dictable, causing the level of some metabolic enzymes to be
reduced, whereas others remain unchanged. In general,
Because of declining liver function, plasma protein lev- blood flow to the liver decreases and metabolic activity of
els are reduced in the older adult. This decrease results in the CYP450 enzymes is diminished. Reduced metabolism
Chapter 10 Pharmacotherapy of the Geriatric Patient 127
means that drugs will have extended durations of action. Adherence and Drug Misuse
Drugs with a long half-life such as gentamicin, digoxin Among Older Adults
(Lanoxin), and acetaminophen (Tylenol) remain longer in
the body with the potential for accumulation in tissues. 10.4 Adherence with the therapeutic regimen is
Such drugs should be prescribed with longer intervals a major challenge for many older adults.
between doses or in reduced dosages, and the patient
should be monitored closely. Drug adherence or compliance is the willingness and abil-
ity to take medications as instructed on the label or by the
CONNECTIONS: Lifespan healthcare provider. Healthcare providers often assume
Considerations that patients leaving the clinic or hospital will be adherent
by filling their prescriptions and taking their medicines as
Drug Monitoring in the Older Adult directed. It may be surprising to learn that over a third of
patients report they are often nonadherent with drug ther-
To avoid toxicity, a number of drug dosage changes should be apy. Reasons for nonadherence are many and varied and
made for the older adult: include the following: medication not with me when dose
was due, ran out of medication, uncomfortable side effects,
• The older adult should be started on the smallest effective and symptoms resolved (Pasina et al., 2014).
dose of medication and then be titrated upward.
Although nonadherence is not unique to older adults,
• Observe the older patient for signs of drug accumulation this population is especially vulnerable. Older adult patients
about 3 to 5 days after new drug initiation. Consider any are more likely to have visual impairment, functional disabili-
change in physical or emotional behavior as possible drug ties, and cognitive dysfunction that may be sources of medica-
intoxication. tion errors and nonadherence. Functional hearing loss can
prevent older adults from understanding the verbal instruc-
• Monitor hydration and nutritional status, especially among tions given by the healthcare provider. The large number of
older patients, because dehydration and low protein in the drugs taken by some older adults makes for a complicated
diet are primary causes of drug toxicity in this age group. dosing schedule that can be confusing for patients of any age.
Excretion: The kidneys are the primary site for excretion Successful management of medical problems depends on
of most drugs. Renal function declines with aging, result- a patient’s adherence with the regimen. One of the main
ing in a slower clearance of drugs from the body. The half- responsibilities of the nurse is to assess barriers to medication
life of drugs is increased and the dosages or frequency of adherence in the older adult. Studies suggest that nonadher-
administration should be decreased to avoid toxicity due ence is affected by three factors: the individual patient, the
to drug accumulation. Patients who are taking drugs that healthcare provider, and the patient’s social support network.
are excreted primarily by the kidneys should receive peri-
odic serum creatinine tests to assess renal function. Dos- Adherence at the patient level requires the patient’s
ages of drugs must be carefully adjusted in patients with comprehension and commitment to the treatment. The
impaired renal function. Unlike hepatic function, which is patient must be able to afford the medication, believe in its
often unpredictable in older adults, diminished renal func- efficacy, appropriately self-administer, and adjust to life-
tion is mostly consistent from patient to patient. style changes that may be required. The healthcare pro-
vider must be able to effectively instruct the patient
Pharmacodynamic changes: Pharmacodynamic regarding a medication’s efficacy, prescribe cost-effective
changes are usually associated with drug receptors. Evi- medication, decrease the complexity of the regimen, and
dence suggests that older adults have decreased numbers provide manageable and understandable instructions.
of receptors and, possibly, changes in receptor sensitivity. Nurses play a key role in assessing the patient’s under-
In assessing the older adult, the nurse will find a decreased standing of the medications that have been ordered and for
response to beta-adrenergic agonists and antagonists and, assessing patient concerns with cost or effects.
at the same time, an increased response to anticholinergics,
CNS depressants, and drugs such as warfarin. There is The nurse should provide the older adult’s spouse or
limited information on how pharmacodynamic alterations caregiver with adequate information regarding the patient’s
actually occur in older adults. medication regimen, expected lifestyle changes, and the
need for emotional support and monitoring. Table 10.2 lists
CONNECTION Checkpoint 10.2 reasons that patients give for nonadherence and provides
suggestions for the nurse to promote adherence.
From what you learned in Chapter 3, what are CYP450 enzymes?
State the differences between a substrate and an inducer of CYP450 Drug misuse is a specific form of nonadherence that is
enzymes. Answers to Connection Checkpoint questions are available common among older adults. Misuse includes overuse,
on the faculty resources site. Please consult with your instructor. underuse, or, in some cases, erratic use. This misuse may be
unintentional or deliberate. Self-adjusting the medication
128 Unit 2 Pharmacology and the Nurse–Patient Relationship
Table 10.2 Promoting Adherence in the Older Adult Patient (see Chapter 5). Although older adults have many factors
that predispose them to an increased risk of adverse effects,
Reasons for • Unpleasant adverse effects the number of drugs prescribed is probably the most impor-
nonadherence • Forgetfulness tant. The risk of an adverse effect greatly increases with the
• Cognitive or physical impairment number of drugs taken. A survey in the United States of
• Poor or misunderstood instructions 2206 adults ages 62 through 85 years showed that at least
• Complicated regimens one prescription medication was used by 87% of the older
• Inability or refusal to purchase the medication adults, five or more prescription medications were used by
• Health beliefs about medications 36%, and 38% used OTC medications (Qato, Wilder,
Schumm, Gillet, & Alexander, 2016).
Ways the nurse can • Assist the older adult in comprehending and
promote adherence committing to the drug treatment regimen. To minimize adverse effects, prescribers should order
drugs only when they are needed and for the shortest
• Communicate the instructions in such a length of time necessary to produce a therapeutic effect.
manner that the older patient fully understands Medications and doses should be reviewed on a regular
the purpose of the treatment. basis to ensure that the intervention is still necessary.
• Provide the older patient with social support Age-related physiologic changes in renal and hepatic
services to obtain the medications. function are often responsible for placing older patients at
greater risk for adverse effects. As the ability of the kidney
• Work with a pharmacist to ensure that the to excrete drugs diminishes, serum drug levels may rise to
medication is dispensed in containers that are cause toxicity. Loss of the ability of the liver to metabolize
easily opened and in formulations that are drugs can also raise serum drug levels and cause adverse
easily taken. effects. The nurse must be vigilant in assessing laboratory
results of renal and hepatic function in older adult patients.
• Make sure all drugs are clearly labeled with Doses of most drugs must be adjusted with renal or hepatic
instructions. impairment to prevent adverse effects.
• Simplify the regimen to reduce the number of As an individual ages it often becomes difficult for the
drugs and doses per day. nurse to differentiate between behaviors that may be a nat-
ural part of aging and symptoms caused by adverse effects.
• Suggest that the older patient use a daily or For example, a frail older adult who walks with an ataxic
weekly pill counter. gait might be wrongly suspected of having an adverse
effect from benzodiazepines or phenytoin, although the
• Provide the patient with a check-off calendar to condition might be caused by normal aging. Older adults
document each time a medication is taken. are more likely to experience CNS drug adverse effects
such as dizziness and drowsiness, which are also symp-
• Engage family members or friends in toms that are often associated with normal aging processes.
supporting the older patient in efforts to Medications should be considered as an underlying cause
comply. of the following symptoms in older patients:
• Encourage the older patient to report signs of • Sudden change in mental status
adverse effects. • Rapid weight loss
• Dehydration
• Schedule periodic tests to determine plasma • Restlessness
drug levels. • Falls
• Anorexia
• Place follow-up calls to high-risk patients. • Urinary retention or fluid retention
• Change in bowel habits
dose is a common practice: Patients change their dose level • Major change in functional status of any organ
depending on how they feel. Some believe that taking extra
doses will speed their recovery. Uninsured or underinsured system.
patients who cannot afford their medications may try to
make the medications last longer by splitting doses. Patients Combining a thorough literature review with expert
rarely report such practices to their healthcare provider. consensus, healthcare providers have compiled a list of
Drug misuse may have serious consequences: Many older drugs of special concern for older adults. These are some-
adult visits to emergency departments are drug related, with times referred to as potentially inappropriate medications
nonadherence accounting for a substantial percentage. (PIMs). Known as the Beers criteria or Beers list, healthcare
providers should avoid prescribing PIMs to older adults
CONNECTION Checkpoint 10.3
From what you learned in Chapter 2, describe some of the ben-
efits to older adults created by the Medicare Prescription Drug, Im-
provement, and Modernization Act of 2003. Answers to Connection
Checkpoint questions are available on the faculty resources site. Please
consult with your instructor.
Adverse Drug Reactions
in Older Adults
10.5 Older adults are at high risk for experiencing
adverse drug reactions and interactions.
An adverse drug effect is an undesirable and potentially
harmful action caused by the administration of medications
Chapter 10 Pharmacotherapy of the Geriatric Patient 129
Table 10.3 Selected High-Risk Drugs for Older Adults
Drug Adverse Response
antihistamines (e.g., chlorpheniramine, diphenhydramine, hydroxyzine, promethazine) Sedation, confusion, anticholinergic effects
antipsychotic drugs (e.g., chlorpromazine, clozapine, risperidone) Increased mortality (in patients with dementia-related psychosis)
benzodiazepines (e.g., alprazolam, lorazepam, oxazepam) Confusion, depression, anticholinergic effects
digoxin (Lanoxin) Reduced renal clearance (in patients with preexisting chronic
kidney disease)
GI drugs (e.g., ranitidine, cimetidine) Liver dysfunction, blood dyscrasias (ranitidine)
Confusion, depression (cimetidine)
muscle relaxants (e.g., carisoprodol, cyclobenzaprine, oxybutynin) Sedation, weakness, anticholinergic effects
nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g., aspirin, ibuprofen, naproxen) Photosensitivity, nephrotoxicity, fluid retention
opioid analgesics (e.g., meperidine, morphine, oxycodone) Sedation, confusion
phenytoin (Dilantin) Confusion, ataxia, slurred speech, diplopia
skeletal muscle relaxants (e.g., carisoprodol, methocarbamol, cyclobenzaprine) Sedation, confusion
tricyclic antidepressants (e.g., amitriptyline, doxepin, imipramine) Hallucinations, confusion, anticholinergic effects
because they have been found to produce a high incidence patients, providers, and health systems on how to use, and
of adverse effects in this population. In 2015, the American not use, the 2015 AGS Beers criteria. Table 10.3 provides a
Geriatrics Society (AGS) updated the Beers criteria using a select list of PIMs that should be avoided in older adults
comprehensive, systematic review and grading of the evi- along with their specific adverse effects of concern.
dence on adverse drug-related problems in older adults.
The update includes lists of select drugs that should be A drug interaction occurs when a medication interacts
avoided or dose adjusted based on the individual’s renal with another substance and the drug’s actions are affected.
function and drug–drug interactions. In the past, there was The other substance causing the drug interaction may be
controversy around how to translate the criteria into prac- another drug, a dietary supplement, an herbal product, or
tice and, because of this, a supplemental companion piece a food (see Chapter 5). The large number of prescription
to the updated criteria was developed to give guidance to drugs and OTC products taken by older adults predisposes
this population to a high risk for drug interactions.
CONNECTIONS: Preparing for Advanced Practice
Complicated Medication Routines and Older Adults
Case asked. Medication adherence should be one of the routine
health history questions for older patients. Medication reconcili-
Mr. Barkins is an 88-year-old who is a frequent patient in our ation is the first step in assisting older adults to manage their
community geriatric clinic. He has lived alone since his wife died medications. A “medication check-in” should be conducted
and visits the clinic often because he is lonely and looking for annually or more often to review all the patient’s medications
conversation and company. He is a favorite patient to most of and to determine which medications and dosage adjustments
the staff. In addition to the social isolation, he has medical issues are needed.
including diabetes mellitus type 2, hypertension, chronic kidney
disease, peptic ulcer disease, and anemia. In fact, while doing Older patients are more likely to adhere to a prescribed
his medication reconciliation you realize he is on 18 different medication that has a simpler dosing schedule, such as once
medications! He tells you that he is having difficulty managing daily, compared to another medication that has a more complex
“all these pills” at home and is not taking all his prescribed medi- dosing schedule, such as twice daily.
cations. You inquire further and find out he is missing doses
because it is “too hard to take all of them,” and that by skipping Many pharmaceutical companies offer medication assis-
some of the medications every day, he keeps the costs down. tance programs to low-income older patients. These programs
What are some of the things you can do to optimize adherence? typically require a provider form and proof of financial status
What community resources are available for Mr. Barkins? from the patient.
Discussion BenefitsCheckUp is a free service of the National Council
on Aging (n.d.), a nonprofit service and advocacy organization in
Oftentimes, older patients may decide to skip doses or stop tak- Washington, D.C. The online service asks a series of questions
ing their medication without telling their provider, until they are and then identifies programs that could help patients pay for
prescriptions, healthcare, food, and other expenses.
130 Unit 2 Pharmacology and the Nurse–Patient Relationship
Table 10.4 Nursing Responsibilities Related to Adverse Drug Reactions and Drug Interactions in Older Adults
Nursing Responsibilities Rationales
• Review the patient’s medications to determine the potential for • Adverse effects are common in older patients because of physiologic changes
adverse effects and drug interactions. Consider cultural and dietary in body composition, multiple illnesses, polypharmacy, and nonadherence.
issues.
• Some dietary practices may lead to adverse effects and interactions (e.g.,
• Instruct the patient about potential adverse effects. low-salt intake may lead to lithium toxicity).
• Assess the patient’s fluid volume. • A well-informed patient is better able to notify the healthcare provider as early
as possible to minimize adverse effects.
• Instruct the patient about the proper time to administer medications.
• Alteration in fluid volume could lead to increased sensitivity to alpha
• Ensure that the fewest number and lowest doses of medications with antagonists and other drugs with effects on blood pressure.
the simplest regimens have been prescribed for the patient.
• Taking medications at the proper time will ensure optimal effectiveness and
• Monitor the patient for expected responses and any changes from lower the chance for adverse effects.
normal.
• Polypharmacy may lead to drug toxicity.
• Discard all unused and expired medications, and instruct the patient
to do the same. • Adverse effects may not always be predictable because they may arise from
sudden changes in the patient’s condition.
• Assess and monitor the patient’s mental status for any alterations that
may be caused by adverse effects. • Drug effects diminish after the expiration date and some drugs can become
toxic over time.
• Periodically review the patient’s OTC medications, nutritional
supplements, and prescribed medications. • Delirium or confusion may be caused by adverse effects of psychoactive
drugs.
• Review of all drugs and alternative therapies can reduce the chances of
adverse effects.
Another factor contributing to the increased risk physiologic conditions of the patient and family. Advanced
for drug interactions is the presence of comorbidities (see age does not negate the patient’s right to know the names of
Section 10.2). For example, the patient with both arthritis and the prescribed medications, the reasons they are being pre-
heart disease may be using nonsteroidal anti-inflammatory scribed, and the potential adverse effects. Table 10.4 high-
drugs (NSAIDs) for pain and warfarin (Coumadin) to lights nursing responsibilities and rationales regarding
prevent blood clots. The NSAID may increase the effect of the adverse effects and drug–drug interactions in older patients.
warfarin, thus raising the potential for bleeding. The patient
with both diabetes and hypertension may be taking thiazides PharmFACT
and insulin. The thiazides reduce the effectiveness of insulin,
thus affecting glycemic control. Routine vaccinations are just as important for the older adult
as for younger patients—maybe even more so as immunity
The nurse plays a key role in optimizing pharmaco- wanes. McIntyre, Zecevic, and Diachun (2014) explored
therapy outcomes in older adult patients, including factors that influenced older adults to either avoid or obtain
addressing adverse effects, drug interactions, and issues of the influenza vaccine. Trust in the healthcare provider’s
polypharmacy. One of the primary nursing responsibilities recommendation was the main reason participants in the
is to make a connection between the patient and family and study received the vaccine, followed by knowing others who
the medication regimens. This entails assessing the level of had received it.
comprehension, cultural beliefs, dietary practices, and
Understanding Chapter 10
Key Concepts Summary 10.3 Normal aging processes can alter pharmacokinetic
and pharmacodynamic responses to drugs.
10.1 Older adults take more medications than any other
segment of the population. 10.4 Adherence with the therapeutic regimen is a major
challenge for many older adults.
10.2 Anatomic and physiologic changes associated
with aging may alter the patient’s response to 10.5 Older adults are at high risk for experiencing
medications. adverse drug reactions and interactions.
Chapter 10 Pharmacotherapy of the Geriatric Patient 131
CASE STUDY: Making the Patient Connection
Remember the patient “Mary anything during the past 24 hours and has only taken sips
Smith” at the beginning of the of water during the past 12 hours. She has voided once in
chapter? Now read the remainder 12 hours.
of the case study. Based on the
information presented within this The following laboratory tests are completed: urinalysis,
chapter, respond to the critical blood urea nitrogen (BUN) and creatinine, complete blood
thinking questions that follow. count (CBC), and basal metabolic panel (BMP). Mary is pre-
scribed IV rehydration fluid and is stabilized in the emer-
Mary has an IV solution of normal saline infusing in her gency department before being admitted to the hospital unit.
left arm and oxygen by mask at 2 L/min. Last week she
heard that her older cousin had passed away, and since Critical Thinking Questions
then she has become extremely depressed. She refuses to
eat or drink but continues to take her medications on a reg- 1. What are some potential predisposing factors that
ular basis. This 80-year-old woman is dehydrated and could lead to this patient’s condition? (The student
somewhat confused. Her neighbor provides the history. may need to consult later chapters or a drug reference
The nurse finds that Mary has been taking a diuretic book for the drugs included.)
(hydrochlorothiazide), an antihypertensive (atenolol), and
multivitamins daily. 2. What are the most immediate patient care priorities for
the nurse to address at this time?
Vital signs are as follows: temperature, 38.6°C (101.4°F);
apical pulse, 100 beats/min; respiratory rate, 32 breaths/ 3. What priority areas will the nurse assess?
min; and blood pressure, 92/62 mmHg. Her skin is dry and
warm to the touch, and her lips are pale, dry, and chapped. 4. What are some of the expected patient outcomes,
She weighs 51.3 kg (113 lb) and her height is 1.7 m (5′7″). including changes in vital signs, following manage-
Her speech is quiet and slurred. Mary has not eaten ment of dehydration?
Answers to Critical Thinking Questions are available on the
faculty resources site. Please consult with your instructor.
Additional Case Study 1. What should the nurse do to assess whether
Ms. Haynes is taking her medications regularly?
Ms. Haynes, 88 years of age, is fiercely independent and What laboratory test will help determine diabetic
lives in an assisted living facility in her own apartment control over a period of time?
with meals taken in a group dining room, which she clearly
enjoys. She has a history of diabetes controlled with an oral 2. If Ms. Haynes is not taking her medications, what
antidiabetic drug, hypertension controlled with an antihy- would the nurse’s next action be?
pertensive drug and a mild diuretic, and occasional stom-
ach upset for which she takes antacids. Her daughter 3. What recommendation should be given to
suspects that her mother has not been taking any of her Ms. Haynes’s daughter?
medications regularly because her blood sugar and blood
pressure have been extremely variable lately and she asks Answers to Additional Case Study questions are available on the
the nurse for assistance. faculty resources site. Please consult with your instructor.
Chapter Review 2. The nurse completes an initial home assessment of an
independent 82-year-old woman recently diagnosed
1. In general, drug absorption in the older adult is some- with type 2 diabetes mellitus managed with insulin
what slowed. What physiologic changes may account injections. What is the most appropriate nursing
for this? (Select all that apply.) action for insulin administration for this patient?
1. Increased gastric pH 1. Teach the daughter how to administer the insulin
2. Decreased rate of blood flow to the GI tract to her mother.
3. Increased gastrointestinal motility
4. Increased body surface area 2. Instruct the patient how to administer the insulin.
5. Decreased cardiac output
132 Unit 2 Pharmacology and the Nurse–Patient Relationship 5. One third of older adult patients report that they are
often nonadherent with drug therapy. Which response
3. Recommend daily visits by a home health aide to is given most frequently for nonadherence?
give the insulin.
1. “The drugs prevented me from doing other things
4. Ask the healthcare provider to change the order to I wanted to do.”
an oral antidiabetic medication.
2. “I didn’t have my medicine with me.”
3. Which age-related change in the older patient makes 3. “I wanted to save money.”
it necessary to reduce drug dosages? 4. “I didn’t believe the drugs were effective.”
1. Decrease in total body fat 6. Which statement by the patient would inform the
2. Decrease in renal blood flow nurse that more teaching is necessary prior to
3. Increase in plasma protein levels discharge?
4. Increase in total body water
1. “It doesn’t matter if the medication works as long
4. Older adults experience adverse effects more as the doctor prescribed it.”
frequently than young adults due to which of the
following? (Select all that apply.) 2. “This medication is fully covered by my health
insurance.”
1. Excessive prescribing
2. Multiple-drug therapy 3. “I have been taking my medications by myself all
3. Increased drug sensitivity my life.”
4. Increased body mass
5. Lack of consistent exercise 4. “I don’t mind making changes to my lifestyle while
I am on this drug.”
See Answers to Chapter Review in Appendix A.
References from https://www.census.gov/prod/2014pubs/
p25-1140.pdf
American Geriatrics Society. (2015). American Geriatrics Pasina, L., Brucato, A., Falcone, C., Cucchi, E., Bresciani,
Society 2015 updated Beers criteria for potentially A., Sottocorno, M., … Nobili, A. (2014). Medication
inappropriate medication use in older adults. Journal of non-adherence among elderly patients newly
the American Geriatrics Society, 63, 2227–2246. discharged and receiving polypharmacy. Drugs &
doi:10.1111/jgs.13702 Aging, 31, 283–289. doi:10.1007/s40266-014-0163-7
Qato, D. M., Wilder, J., Schumm, P., Gillet, V., & Alexander,
McIntyre, A., Zecevic, A., & Diachun, L. (2014). Influenza G. C. (2016). Changes in prescription and over-the-
vaccination: Older adults’ decision-making process. counter medication and dietary supplement use among
Canadian Journal on Aging, 33, 92–98. doi:10.1017/ older adults in the United States, 2005 vs 2011. JAMA
S0714980813000640 Internal Medicine, 176, 473–482. doi:10.1001/
jamainternmed.2015.8581
National Council on Aging. (n.d.). Find my benefits.
Retrieved from https://www.benefitscheckup.org
Ortman, J. M., Velkoff, V. A., & Hogan, H. (2014). An aging
nation: The older population in the United States. Retrieved
Selected Bibliography Opinion on Drug Safety, 13, 57–65. doi:10.1517/14740338
.2013.827660
Maher, R. L., Hanlon, J., & Hajjar, E. R. (2014). Clinical
consequences of polypharmacy in elderly. Expert
“It was so humiliating. When I was
in the hospital, no one ever called
me by name. I overheard someone
refer to me as the Indian woman
in room 425. No one really tried
to communicate with me.”
Patient “Aponi Nampeyo”
Chapter 11
Individual Variations
in Drug Responses
Chapter Outline Learning Outcomes
cc Psychosocial Influences After reading this chapter, the student should be able to:
cc Cultural and Ethnic Variables
cc Genetic Influences 1. Describe the fundamental concepts underlying a
cc Gender Influences holistic approach to patient care and their
importance to pharmacotherapy.
2. Identify psychosocial and spiritual factors that can
affect pharmacotherapeutics.
3. Explain how ethnicity can affect
pharmacotherapeutic outcomes.
4. Identify examples of how cultural values and beliefs
can influence pharmacotherapeutic outcomes.
5. Convey how genetic polymorphisms can influence
pharmacotherapy.
6. Explain how pharmacogenomics may lead to
customized drug therapy.
7. Explain how gender can influence the actions of
certain drugs.
133
134 Unit 2 Pharmacology and the Nurse–Patient Relationship
Key Terms genetic polymorphism, 136 psychosocial, 134
pharmacogenetics, 137
culture, 134
ethnicity, 134
Pharmacotherapy would indeed be simplified if the “aver- financial resources, emotional condition, physical condi-
age” dose given in a drug guide produced the same response tion, and cognitive functioning. For example, does the
in every patient. However, as presented in C hapter 4, patient have a trusting and empathetic relationship with
patients can respond very differently to drug administra- his or her family? Would the family be able and willing to
tion. For example, the same dose of an antihypertensive help the patient through some difficult challenges with
drug can result in a desired therapeutic effect in one patient adverse effects or long-term therapy? Is the patient emo-
and produce no effect or profound hypotension in other tionally stable enough to receive prescription drugs that
patients. The purpose of this chapter is to examine some of have a possible suicidal risk? All of this information is
the factors that may cause this variability, including psycho- important to developing effective health goals and phar-
social influences, culture and ethnicity, genetics, and gen- macotherapeutic outcomes.
der. Knowledge of these factors can contribute to safer and
more effective pharmacotherapy. In some cases the patient assessment may indicate a
need to address psychosocial interventions before pharma-
Psychosocial Influences cotherapy is begun. Behavioral or cognitive therapies may
be employed to reduce negative thoughts and behaviors
11.1 Many psychosocial influences impact that could impact therapy. In children or adolescents,
pharmacotherapy. attempts at psychosocial therapies may be a prerequisite to
initiating pharmacotherapy for conditions such as atten-
The term psychosocial is used in healthcare to describe the tion-deficit/hyperactivity disorder, major depressive dis-
interaction between one’s psychologic development and order, or bipolar disorder. The integrated use of
one’s social environment. Psychosocial nursing is part of a pharmacologic and psychosocial therapies is believed to
holistic model that includes the examination of patients’ increase therapeutic success in addiction treatment.
social roles, environmental stressors, culture, values, and
family, all of which contribute to health and wellness. CONNECTION Checkpoint 11.1
Psychosocial also includes the spiritual nature of an The frequency dose–response curve can be used to depict interpa-
individual. Psycho-social-spiritual is a term that appears in tient variability to drug response. From what you learned in Chapter 4,
the healthcare literature. Studies have established that these draw a typical frequency dose–response curve, labeling the axes and
factors have a tremendous impact on health and well-being. the median effective dose (ED50). Answers to Connection Check-
Healthcare providers recognize that the close relationship point questions are available on the faculty resources site. Please
among the psychologic, social, and spiritual nature of indi- consult with your instructor.
viduals strongly influences their illness and wellness.
Cultural and Ethnic Variables
The psychosocial history of the patient, which is often
collected during the initial assessment, can influence the 11.2 Cultural and ethnic variables can
success of pharmacotherapy. Important assessment data influence pharmacotherapy.
include developmental needs, environmental stressors,
and life transitions that could require major adaptations by Although they are sometimes used interchangeably, culture
the patient. The nurse also considers the patient’s level of and ethnicity differ in their exact definitions. An ethnic
motivation to correct the health issue, because nonadher- group is a community of people who share a common
ence to medication regimens and recommended lifestyle ancestry and similar genetic heritage. Ethnicity implies
adjustments could impede the success of pharmacother- that people have biological and genetic similarities. C ulture
apy. For example, a highly stressed, middle-aged patient is a set of beliefs, values, and norms that provide meaning
who is struggling with a new business might find it diffi- for an individual or group. People within a culture have
cult to focus on wellness goals associated with maintaining common rituals, religious beliefs, language, and certain
normal blood pressure and cholesterol levels. expectations of behavior. Cultural and ethnic variables are
important aspects of patient care that directly relate to
A thorough psychosocial assessment should provide pharmacotherapy. Both can influence the occurrence of spe-
the healthcare provider with a clear picture of the patient’s cific drug effects and patient treatment outcomes.
living arrangements, family involvement and interaction,
Chapter 11 Individual Variations in Drug Responses 135
CONNECTIONS: Treating the Diverse Patient
Medication Refusal for Religious, Moral, or Dietary Reasons
One of the “rights” of medication administration is refusal. Patients Patel (2014) found that for the top 100 drugs most commonly
have the right to refuse their medications due to religious or other prescribed, 74% contained at least one animal-based prod-
reasons. Perhaps most familiar is the refusal to accept blood or uct. Depending on the religious tradition, beef, pork, chicken,
blood products by a Jehovah’s Witness member because of reli- fish, shellfish, or all meat may be refused on religious or moral
gious beliefs. Less familiar is refusal due to the fact that the medi- grounds or for dietary reasons. When a substitution can be
cation or treatment contains animal-derived products. For made, the alternate product should be used. Sensitivity to a
example, acceptance or refusal of porcine (pork) and bovine (beef) patient’s religious beliefs, traditions, moral reasoning, or
drugs or surgical products by members of the Jewish, Muslim, dietary needs should be maintained. When a patient ques-
and Hindu faiths is common; however, this may vary among indi- tions whether or not to use an essential drug or treatment and
vidual members of the faith. People who follow vegetarian or an alternate is not available, encourage the patient to discuss
vegan diets may also shun the use of animal-based products. the information with healthcare providers and informed reli-
gious leaders before making the decision to refuse the
Many medications contain animal-based products, includ- treatment.
ing inactive ingredients such as gelatin or lactose. Tatham and
For most of the history of pharmacology, the impact of • Dietary considerations. Cultures vary in their dietary
cultural and ethnic variables was unknown or regarded as preferences and practices, with diets that include some
unimportant. This was primarily caused by a lack of diver- foods and exclude others. Patients need to understand
sity in the conduct of clinical trials and follow-up reporting. that foods can increase or decrease the effectiveness of
For example, older clinical trials enrolled mostly White certain medications. Spices and herbs can be impor-
males. Little attention was focused on identifying differences tant to a patient’s culture but may affect pharmaco-
in pharmacologic effects in diverse ethnic or cultural groups. logic therapies. For example, some cultures include a
diet high in foods such as cheese, pickled fish, or wine
The protocol for clinical trials now includes participants that can interact with medications to cause adverse
of different ages, genders, and ethnic groups whenever pos- events. Certain herbs can affect anticoagulants, beta
sible. Indeed, much research specifically examines differ- blockers, and antidepressants. Assessing the primary
ences among these populations, and findings are included in foods of a patient’s culture is an important component
drug labels. Research has confirmed that there is a biological of the patient’s psychosocial history.
basis for variations or differences in metabolic response to
drugs among various ethnic groups (see Section 11.3). • Complementary and alternative medicine (CAM).
Various cultural groups use CAM therapies, such as
Certainly there are many more cultures and subcul- vitamins, herbs, or acupuncture, either along with or
tures than ethnic groups. To have complete knowledge in place of modern medicines. Some folk remedies and
about the many variations in culture among a population traditional treatments have existed for thousands of
of patients is impossible. However, nurses can strive to years and helped form the foundation for modern
understand the significance of the cultural traditions and medical practice. For example, ethnic Chinese patients
their potential impact on patients’ pharmacologic regi- may consult with herbalists to treat diseases, whereas
mens. Patients bring cultural (religious or ideological) some Native Americans may collect, store, and use
beliefs that may challenge or conflict with what the health- herbs to treat and prevent disease. Certain Hispanic
care provider believes to be in their best interests. How ill- cultures use spices and herbs to maintain a balance of
ness is defined is sometimes based on the cultural beliefs of hot and cold to promote wellness. The nurse can
an individual. One example that illustrates this point is the assess the treatments used and interpret the effect of
difference in belief systems between age groups—each these CAM therapies on the prescribed medications to
with its own unique culture. maximize positive outcomes. The nurse can explain
that certain herbs or supplements may cause potential
PharmFACT health risks when combined with prescribed drugs.
The infant death rate of Native Americans and Alaska • Beliefs about health and disease. Cultures view health
Natives is 60% higher than that of Caucasians. They are and illness in different ways. Individuals may seek
twice as likely to have diabetes (U.S. Department of Health assistance from people in their own community whom
and Human Services, 2016). they believe have healing powers. Consultation with
traditional healers, prayer or laying-on-of-hands, or
The nurse must keep in mind the following variables other culturally based strategies may be utilized as a
when treating patients from different cultural and ethnic primary source or as a supplement to more traditional
groups.
136 Unit 2 Pharmacology and the Nurse–Patient Relationship 2CVKGPV # JCU PQTOCN 2CVKGPV $ JCU IGPGVKE
IGPG GPEQFKPI HQT FTWI RQN[OQTRJKUO HQT FTWI
Western-based medicine practices such as drug ther- OGVCDQNK\KPI GP\[OG OGVCDQNK\KPI GP\[OG
apy. The nurse’s understanding of the patient’s trust in
alternative healers is important. The more nurses know #)6 % 6 # )) % 6
about the various cultural beliefs, the better support 6%#)# 6 %% )#
and guidance they can provide to patients.
0QTOCN #DPQTOCN
PharmFACT GP\[OG GP\[OG
Although access to healthcare has improved for all
Americans since 2013, large differences among ethnic groups
still persist. About 9% of Whites have no health insurance
coverage; this number is 27% for Hispanic and Latino
populations (National Center for Health Statistics, 2016).
Genetic Influences #FOKPKUVGT
FTWI
11.3 Genetic polymorphisms can affect
drug action. &TWI KPCEVKXCVGF D[ &TWI PQV OGVCDQNK\GF CPF
OGVCDQNKUO TGOCKPU HTGG KP VJG RNCUOC
Scientists have identified specific regions on various chro- VQ RTQFWEG GPJCPEGF GHHGEV
mosomes that influence hepatic metabolism. For example, QT VQZKEKV[
certain drugs, such as antidysrhythmics, antidepressants,
and opioids, are metabolized differently in individuals of Figure 11.1 Consequences of genetic polymorphisms.
African, Native American, and Asian descent. As technol-
ogy advances, nurses will likely begin to see variations in diminished clearance by the kidney can cause INH to accu-
the prescribed amounts and forms of medication based on mulate in the blood to toxic levels. These patients, who are
the ethnicity of the patient. usually Caucasians or African Americans, are known as
slow acetylators. In contrast, mutations in many patients of
People of all races and cultures share remarkable Japanese descent result in rapid acetylation. These patients
deoxyribonucleic acid (DNA) similarities: 99.8% of our will inactivate the drug so quickly that it will not produce a
DNA sequences are identical. However, the remaining therapeutic effect. Procainamide, hydralazine, sulfonamide
0.2% may result in significant differences in patients’ ability antibiotics, and dapsone are other medications that are
to handle medications. Some of these differences arise metabolized by acetylation.
when a mutation occurs in the DNA that encodes for a cer-
tain protein. This creates a genetic polymorphism—two or Several other enzyme polymorphisms have importance
more versions of the same protein. In pharmacology, the to pharmacotherapy. Asian Americans and certain other eth-
best characterized genetic polymorphisms have been dis- nic groups are slow metabolizers of codeine and morphine
covered in the hepatic CYP450 enzymes that metabolize due to an inherent absence of the enzyme CY2D6 (debriso-
drugs and in proteins that serve as receptors for drugs. quine hydroxylase). This genetic polymorphism can lead to
higher than normal plasma drug levels and adverse effects.
How can a genetic polymorphism affect drug action? In Some African Americans have decreased effects from beta-
the case of enzymes, the altered “mutated” form of the adrenergic antagonist drugs such as propranolol (Inderal)
enzyme has a changed structure. The structure of an enzyme because of genetically influenced variances in plasma renin
is intimately related to its function; even a single base muta- levels. Another set of oxidation enzyme polymorphisms has
tion in DNA can cause an amino acid change in the enzyme, been found that alters the response to drugs such as warfa-
altering its function. The mutated version of the enzyme rin (Coumadin) and diazepam (Valium).
may increase or decrease the speed of drug metabolism and
excretion, depending on the specific genetic polymorphism. A second type of genetic polymorphism affects recep-
In some cases, the enzyme becomes totally nonfunctional. tors. Receptors are proteins that have a specific structure
This concept is illustrated in Figure 11.1. that accepts the drug (or other endogenous molecule) in a
lock-and-key-type interaction. Small changes in the struc-
As a specific example, genetic polymorphism has been ture of the protein may result in a defective receptor that no
discovered in the enzyme acetyltransferase, which metabo- longer “accepts” the drug. An active area of current
lizes (deactivates) isoniazid (INH), a drug prescribed for research, receptor polymorphisms have been associated
tuberculosis. The altered form of the enzyme performs its
metabolic process, known as acetylation, more slowly
because of the mutation. The reduced acetylation and
Chapter 11 Individual Variations in Drug Responses 137
Table 11.1 Polymorphisms of Importance to Pharmacotherapy
Type Result of Polymorphism Drugs Affected
Enzymes Slow acetylation in African Americans and Caucasians; fast Hydralazine, INH, and procainamide, sulfonamide
Acetyltransferase acetylation in Japanese and Eskimos antibiotics
Poor metabolism in Asians and African Americans
Debrisoquin hydroxylase (CYP2D6) Codeine, haloperidol, metoprolol, morphine,
Poor metabolism in Asians and African Americans perphenazine, propranolol, tricyclic
Mephenytoin hydroxylase (CYP2C19) antidepressants
Receptors or Drug Targets
Angiotensinogen Barbiturates, diazepam, imipramine, warfarin
Beta2-adrenergic receptor
Dopamine receptor Blood pressure reduction Angiotensin-converting enzyme (ACE) inhibitors
Bronchodilation
Dyskinesias Beta2 agonists
Levodopa, antipsychotics
with an increased risk of schizophrenia, prostate cancer, more attention to changes in health patterns and seek
breast cancer, and many other disorders. Relative to drug healthcare earlier than their male counterparts. How-
therapy, a few receptor polymorphisms have been shown ever, many women do not seek medical attention for
to impact drug action, as shown in Table 11.1. potential cardiac problems, because heart disease has
traditionally been considered to be a “man’s disease.”
Genetic polymorphisms often occur in specific ethnic Alzheimer’s disease affects both men and women, but
groups because members have settled in the same geo- studies in various populations have shown that 1.5 to
graphic area and have married mates within the same eth- 3 times as many women have the disease. Alzheimer’s
nic group for hundreds of generations. This practice results disease is now recognized as a primary “woman’s health
in amplified genetic polymorphisms being expressed issue,” along with osteoporosis, breast cancer, and fertil-
within that specific group. ity disorders.
Pharmacogenetics is the study of specific genetic vari- Adherence to the medication regimen of a particular
ations that alter patients’ responses to medications. Phar- drug class may be influenced by gender because the
macogenomics is a related term that is more general in scope, adverse effects affect only one gender. A common example
referring to the network of genes that govern a patient’s is certain antihypertensive drugs that produce male impo-
response to drug therapy. Both pharmacogenetics and tence. Men may experience strokes if they abruptly stop
pharmacogenomics attempt to identify genetic differences taking their medication to avoid impotence. Some drugs
in metabolism or receptor targets that affect individual
drug responses, with the ultimate goal of improving the TODAY All persons
safety and effectiveness of drug therapy through use of get the same
genetically guided treatment. It is expected that these fields
will reveal data that will someday allow drug therapy that treatment
is customized for each individual patient based on his or
her genetic profile, as illustrated in Figure 11.2. FUTURE: Blood
test determines
CONNECTION Checkpoint 11.2 genetic diversity
The best known genetic polymorphisms are those involving hepatic Normal Slow Toxic
CYP450 enzymes. From what you learned in Chapter 3, e xplain the metabolizers metabolizers responders
type of drug–drug interaction that might occur if drug A induced
CYP450 enzymes and drug B was inactivated by the same en-
zymes. Answers to Connection Checkpoint questions are available on
the faculty resources site. Please consult with your instructor.
Gender Influences Give drug A Give less Give alternative
drug A drug
11.4 Men and women may respond differently
to drugs. Figure 11.2 Pharmacogenomics and the future of
pharmacotherapy.
There are well-established differences in the patterns of
disease between men and women. Women tend to pay
138 Unit 2 Pharmacology and the Nurse–Patient Relationship
can cause gynecomastia, an increase in breast size, which Some of the gender differences in drug response may
can be embarrassing for men. Similarly, certain drugs can be explained by differences in body composition, such as
cause masculine adverse effects such as hirsutism (abnor- the fat-to-muscle ratio. Cerebral blood flow variances in
mal increase in hair growth), which can be a cause of non- genders can alter patient response to specific analgesics. An
adherence in women taking these medications. Also in example is the benzodiazepines given for anxiety. Women
women, the estrogen contained in oral contraceptives experience slower elimination rates and this difference
causes an elevated risk of thromboembolic disorders. becomes more significant if a woman is concurrently tak-
ing oral contraceptives.
Research has found many examples of differences in
drug response between men and women. If males and In the past, the majority of drug research studies were
females contain nearly all the same genes, how can these conducted using only male participants. These studies
differences be explained? Although they may have identi- assumed that there were no differences between genders
cal genes, the “expression” of the genes differs greatly. For and conclusions would apply to both women and men.
example, both males and females possess the same genes Current research, however, recognizes that gender differ-
for hepatic metabolic enzymes, but one gender may pro- ences in drug response may exist, and new drug develop-
duce more of a certain enzyme, thus producing a different ment research now includes both males and females, as
degree of drug action. An example of a gender difference in appropriate. Gender consideration is necessary in the anal-
a pharmacologic outcome is aspirin, which is more effec- yses of clinical data and assessment of potential pharmaco-
tive at preventing heart attacks in men than in women. kinetic and pharmacodynamic differences.
Understanding Chapter 11
Key Concepts Summary 11.3 Genetic polymorphisms can affect drug action.
11.1 Many psychosocial influences impact 11.4 Men and women may respond differently
pharmacotherapy. to drugs.
11.2 Cultural and ethnic variables can influence
pharmacotherapy.
CASE STUDY: Making the Patient Connection
Remember the patient Arizona. She is well educated but she is not overly talkative
“Aponi Nampeyo” at and is comfortable with silence.
the beginning of the
chapter? Now read the Aponi willingly accepts Western medical treatments.
remainder of the case However, she also relies on traditional herbs and remedies
study. Based on the from her youth. As the nurse caring for this patient, you are
information presented curious about her culture and health practices. However,
within this chapter, you do not want to appear nosy or intrusive.
respond to the critical
thinking questions that Critical Thinking Questions
follow.
1. Should nurses discuss cultural beliefs with patients?
While traveling out of state with her husband to visit her Explain your answer.
children and grandchildren, Aponi Nampeyo became ill
and was hospitalized. After being examined in the emer- 2. Describe how the nurse could learn about Mrs.
gency department, she was diagnosed with appendicitis N ampeyo’s culture.
and underwent an emergency appendectomy. Aponi is a
native of the United States and has lived most of her life in 3. Are most healthcare workers culturally competent?
Why? Why not?
Answers to Critical Thinking Questions are available on the
faculty resources site. Please consult with your instructor.
Chapter 11 Individual Variations in Drug Responses 139
Additional Case Study 1. Is it likely that Marjorie will be able to adequately care
for her diabetes?
Marjorie, a 30-year-old woman, is a single parent with three
small children. She works as a self-employed housekeeper 2. List the psychosocial factors that will influence this
and earns minimum wage. Her annual income is $25,600, patient’s ability to adhere to the therapy for her
which pays for her family’s housing, groceries, bus transpor- diabetes.
tation, and clothing. Marjorie needs a job that pays benefits
such as medical insurance. However, she fears that she will 3. What can the nurse do to help this patient?
not be able to secure one because she never finished high
school. She is constantly trying to save money. She has just Answers to Additional Case Study questions are available on
been diagnosed with diabetes and requires insulin therapy. the faculty resources site. Please consult with your instructor.
Chapter Review 4. The nurse knows that patients characterized
as slow acetylators:
1. In initiating holistic care with a patient who has chronic
headaches, which action would the nurse take? 1. Are more prone to drug toxicity.
2. Require more time to absorb enteral medications.
1. Tell the patient to take Tylenol as directed 3. Must be given liquid medications only.
on the label. 4. Should be advised to decrease protein intake.
2. Ask the patient what he or she believes may be 5. Which of the following is considered a gender factor
contributing to the problem. that may influence effective pharmacotherapy?
(Select all that apply.)
3. Monitor the patient’s pupil response to light.
4. Refer the patient to an ophthalmologist for 1. Fat-to-muscle ratio
2. Cerebral blood flow
an eye exam. 3. Limited drug research on females
4. Health beliefs
2. Various psychosocial variables may influence 5. Dietary considerations
nonadherence to pharmacotherapy. An example of
this would occur when the patient reports that the 6. Which is the most effective method for a nurse to
prescribed drug: recognize patient-specific genetic influences?
1. Produces an unpleasant aftertaste. 1. Ask the patient if there have been drug-dose–related
2. Is a very large tablet and difficult to swallow. problems in the past.
3. Is too expensive for the patient to afford.
4. Potentially causes hepatotoxicity. 2. Consult reference books and the internet for
information.
3. A patient of Native American descent states, “I will
only take medications that are approved by the 3. Observe the effects with other patients of similar
S haman.” The nurse understands that this statement racial-ethnic background.
reflects the patient’s:
4. Be cautious with all drugs and observe for
1. Ethnicity. individual patient responses.
2. Cultural belief.
3. Genetic polymorphisms. See Answers to Chapter Review in Appendix A.
4. Health-related bias.
References U.S. Department of Health and Human Services, Office of
Minority Health. (2016). Profile: American Indian/Alaska
National Center for Health Statistics. (2016). Health, United Native. Retrieved from http://minorityhealth.hhs.gov/
States, 2015: With special feature on racial and ethnic health omh/browse.aspx?lvl=3&lvlid=62
disparities (p. 30). Retrieved from http://www.cdc.gov/
nchs/data/hus/hus15.pdf
Tatham, K. C., & Patel, K. P. (2014). Suitability of common
drugs for patients who avoid animal products. BMJ,
348, g401. doi:10.1136/bmj.g401
140 Unit 2 Pharmacology and the Nurse–Patient Relationship
Selected Bibliography Johannessen Landmark, C., & Johannessen, S. I. (2016).
Pharmacotherapy in epilepsy—does gender affect
Cheek, D. J., Bashore, L., & Brazeau, D. A. (2015). safety? Expert Opinion on Drug Safety, 15, 1–4. doi:10.151
Pharmacogenomics and implications for nursing 7/14740338.2016.1117606
practice. Journal of Nursing Scholarship, 47, 496–504.
doi:10.1111/jnu.12168 Krau, S. D. (2016). The role of pharmacogenomics: The
same medications do not work the same on everyone.
Collins, S. L., Carr, D. F., & Pirmohamed, M. (2016). Nursing Clinics, 51, ix–x. doi:10.1016/j.cnur.2015.12.002
Advances in the pharmacogenomics of adverse drug
reactions. Drug Safety, 39, 15–27. doi:10.1007/ Munro, C. L. (2015). Individual genetic and genomic
s40264-015-0367-8 variation: A new opportunity for personalized nursing
interventions. Journal of Advanced Nursing, 71, 35–41.
Dolotovskaya, P. V., Rudnichenko, E. Y., Furman, N. V., & doi:10.1111/jan.12552
Reshet’ko, O. V. (2015). Pharmacotherapy and
outcomes of acute ST-elevation myocardial infarction— Pirmohamed, M. (2014). Personalized pharmacogenomics:
gender differences in real clinical practice. Rational Predicting efficacy and adverse drug reactions. Annual
Pharmacotherapy in Cardiology, 9, 650–654. Review of Genomics and Human Genetics, 15, 349–370.
doi:10.20996/1819-6446-2013-9-6-650-654 doi:10.1146/annurev-genom-090413-025419
Ferdinand, K. C., & Puckrein, G. A. (2015). Race/ethnicity Quigley, P. (2015). Mapping the human genome:
in atrial fibrillation stroke: Epidemiology and Implications for practice. Nursing2015, 45(9), 26–34.
pharmacotherapy. Journal of the National Medical doi:10.1097/01.NURSE.0000470413.71567.fd
Association, 107, 59–67. doi:10.1016/S0027-9684(15)30010-9
Shah, R. R., & Shah, D. R. (2012). Personalized medicine: Is
Grabenstein, J. D. (2013). What the world’s religions teach, it a pharmacogenetic mirage? British Journal of Clinical
applied to vaccines and immune globulins. Vaccine, 31, Pharmacology, 74, 698–721.
2011–2023. doi:10.1016/j.vaccine.2013.02.026 doi:10.1111/j.1365-2125.2012.04328.x
Hill, P. (2014). Psychosocial aspects of chronic pain. Journal Vargas, S. M., Cabassa, L. J., Nicasio, A., De La Cruz, A. A.,
of Pain & Palliative Care Pharmacotherapy, 28, 399–401. Jackson, E., Rosario, M., . . . Lewis-Fernández, R. (2015).
doi:10.3109/15360288.2014.972003 Toward a cultural adaptation of pharmacotherapy:
Latino views of depression and antidepressant therapy.
Huey, Jr., S. J., Tilley, J. L., Jones, E. O., & Smith, C. A. Transcultural Psychiatry, 52, 244–273.
(2014). The contribution of cultural competence to doi:10.1177/1363461515574159
evidence-based care for ethnically diverse populations.
Annual Review of Clinical Psychology, 10, 305–338.
doi:10.1146/annurev-clinpsy-032813-153729
Unit 3
Pharmacology of the
Autonomic Nervous System
CHAPTER 12 Review of Neurotransmitters and the Autonomic Nervous System / 142
CHAPTER 13 Cholinergic Agonists / 155
CHAPTER 14 Cholinergic Antagonists / 170
CHAPTER 15 Adrenergic Agonists / 185
CHAPTER 16 Adrenergic Antagonists / 201
141
Chapter 12
Review of Neurotransmitters
and the Autonomic Nervous System
Chapter Outline Learning Outcomes
cc Overview of the Nervous System After reading this chapter, the student should be able to:
cc Structure and Function of the Autonomic
1. Distinguish between the functions of the central and
Nervous System peripheral nervous systems.
cc Synaptic Transmission
cc Cholinergic Transmission 2. Compare and contrast the two divisions of the
peripheral nervous system.
Cholinergic Receptors and Neurotransmitters
Termination of Acetylcholine Action 3. Compare and contrast the actions of the sympathetic
cc Adrenergic Transmission and parasympathetic divisions of the autonomic
Alpha-Adrenergic Receptors nervous system.
Beta-Adrenergic Receptors
Termination of Norepinephrine Action 4. Explain the process of synaptic transmission.
cc Regulation of Autonomic Functions 5. Explain mechanisms by which drugs affect
cc Classifying Autonomic Drugs
synaptic transmission.
6. Describe the actions of acetylcholine at
cholinergic synapses.
7. Describe the actions of norepinephrine at
adrenergic synapses.
8. Compare the actions of the adrenal medulla with
those of other sympathetic effector organs.
9. Explain how higher centers in the brain can
influence autonomic function.
10. Design a method for classifying autonomic drugs
based on which receptors are affected.
142
Chapter 12 Review of Neurotransmitters and the Autonomic Nervous System 143
Key Terms cholinergic, 148 norepinephrine (NE), 146
fight-or-flight response, 144 parasympathetic nervous
acetylcholine (ACh), 146 ganglia, 146
acetylcholinesterase (AChE), 150 monoamine oxidase (MAO), 151 system, 145
adrenergic, 150 muscarinic, 149 rest-and-digest response, 145
autonomic nervous system neuroeffector junction, 146 somatic nervous system, 143
neurotransmitters, 146 sympathetic nervous system, 144
(ANS), 143 nicotinic receptors, 149 synapse, 146
autonomic tone, 145 synaptic cleft, 147
catecholamines, 150
catechol-O-methyltransferase
(COMT), 151
Neuropharmacology represents one of the largest, most com- The nervous system has two major divisions: the cen-
plicated, and least understood branches of pharmacology. tral nervous system (CNS) and the peripheral nervous sys-
Nervous system drugs are used to treat a large and diverse set tem. The CNS is made up of the brain and spinal cord,
of conditions, including pain, anxiety, depression, schizophre- whereas the peripheral division consists of spinal nerves
nia, insomnia, and seizures. Through their action on nerves, that carry messages to and from the CNS. Drugs used to
these medications are used to treat disorders affecting other treat disorders and conditions of the CNS are discussed in
body systems such as abnormalities in heart rate and rhythm, Chapters 17 through 26. The functional divisions of the ner-
hypertension, glaucoma, asthma, and even a runny nose. vous system are illustrated in Figure 12.1.
Traditionally, the study of neuropharmacology begins 12.2 The peripheral nervous system is divided
with the autonomic nervous system. This is because auto- into somatic and autonomic components.
nomic physiology lays the foundation for understanding
nervous, cardiovascular, and respiratory pharmacology. With its immense potential and complexity, the human brain
This chapter serves two purposes. First, it provides a com- requires a continuous flow of information to accomplish its
prehensive review of autonomic nervous system physiol- functions. In addition, the brain would be useless without a
ogy, a subject that is sometimes covered superficially in means to carry out its commands. The peripheral nervous
anatomy and physiology classes. Second, it introduces the system provides the brain the means to communicate with
four fundamental classes of autonomic medications, which and receive sensory messages from the outside world.
are presented in depth in Chapters 13 through 16.
Neurons in the peripheral nervous system recognize
Overview of the Nervous System changes to the environment (sensory division) and respond to
those changes by moving muscles or secreting chemicals
12.1 The two major subdivisions of the nervous (motor division). The sensory division consists of specialized
system are the central nervous system and the nerves that recognize touch, pain, heat, body position, light, or
peripheral nervous system. specific chemicals in body fluids. These sensory neurons send
their messages to the spinal cord. Based on this information, the
The nervous system is the master controller of most activi- brain determines what messages are important, determines
ties occurring within the body. Compared to the other whether an action is needed, and plans an appropriate response.
major regulator, the endocrine system, the nervous system
has the ability to act instantaneously to maintain homeo- The motor division is divided into two components.
stasis. The brain, spinal cord, and peripheral nerves act as The somatic nervous system consists of nerves that provide
a smoothly integrated whole to accomplish minute-to- for the voluntary control of skeletal muscle. The nerves of
minute changes in essential functions such as heart rate, the autonomic nervous system (ANS) provide for the
blood pressure, pupil size, and intestinal movement. The involuntary control of vital functions of the cardiovascular,
fundamental functions of the nervous system are to: digestive, respiratory, and genitourinary systems. The ANS
controls vital life activities without people being aware of its
• Monitor the internal and external environment of the functions. The three main activities of the ANS are:
body and alert the brain of important changes.
• Contraction of smooth muscle of the bronchi, blood
• Process and integrate the environmental changes that vessels, gastrointestinal (GI) tract, eye, and genitouri-
are perceived and determine an appropriate response. nary tract
• Respond to the environmental changes by producing • Contraction of cardiac muscle
an action or a response. • Secretion of salivary, sweat, gastric, and bronchial glands.
144 Unit 3 Pharmacology of the Autonomic Nervous System
The Nervous System
Central Nervous System (CNS) Peripheral Nervous System (PNS)
(receives and processes sensory input; (carries nerve impulses between the
initiates action) CNS and the rest of the body)
Brain Spinal Cord Motor Division Sensory Division
(receives and processes (conducts nerve impulses (carries nerve impulses (carries nerve impulses
sensory information; to and from the brain; from the CNS to to the CNS from
initiates responses; controls reflex activities) muscles and glands) sensory organs)
stores memories;
generates thoughts
and emotions)
Somatic Nervous System Autonomic Nervous System
(controls voluntary (controls involuntary responses
movements of
skeletal muscles) of glands, cardiac muscle,
and smooth muscle)
Sympathetic Division Parasympathetic Division
(prepares body for (dominates during periods of
stressful or energetic “rest and digest”;
activity; “fight or flight”) directs maintenance activities)
Adrenergic Receptors Cholinergic (muscarinic) Receptors
Alpha Beta
Figure 12.1 Functional divisions of the nervous system. action of the cardiac muscle, smooth muscle, or gland
depends on which branch is sending the most signals at
The ANS is particularly important to pharmacology any given time. The major actions of the two divisions are
because a large number of medications affect autonomic shown in Figure 12.2. It is essential for the student to learn
nerves. Some of these drug actions produce desirable, ther- these actions early in the study of pharmacology because
apeutic effects, whereas others produce adverse effects. knowledge of autonomic effects is used to predict the
The remainder of this chapter reviews the structure and actions and adverse effects of many drugs.
function of this complex system.
The sympathetic nervous system is activated under
Structure and Function of the emergency conditions or stress and produces a set of
Autonomic Nervous System actions called the fight-or-flight response. Activation of
this branch prepares the body for heightened activity and
12.3 The autonomic nervous system is divided for an immediate response to a threat. The brain experi-
into two mostly opposing components: the ences an increase in alertness and readiness. Heart rate and
sympathetic and parasympathetic branches. blood pressure increase and blood is shunted to skeletal
muscles, thus preparing the body for sudden, intense phys-
The ANS has two distinct divisions: the sympathetic ner- ical activity. The liver immediately produces more glucose
vous system and the parasympathetic nervous system. Most for energy. The bronchi dilate to allow maximum airflow
organs and glands receive nerves from both branches, and into the lungs, and breathing becomes faster and deeper.
the two divisions have opposing actions. For example, one The pupils dilate to provide better vision for dealing with
branch causes cardiac muscle to contract faster and with the emergency. The body warms and perspiration increases.
greater force; the other causes it to relax. The ultimate
PARASYMPATHETIC Chapter 12 Review of Neurotransmitters and the Autonomic Nervous System 145
DIVISION
SYMPATHETIC
“rest and digest” DIVISION
Constricts
pupil “fight or flight”
Stimulates Dilates pupil
salivation
Slows Cranial Inhibits
heart nerves salivation
Accelerates
Constricts Cervical heart
breathing nerves
Facilitates
breathing
Stimulates Thoracic Inhibits
digestion nerves digestion
Stimulates Lumbar
gallbladder nerves Stimulates
release of
Contracts Sacral glucose
bladder nerves Secretes
Stimulates epinephrine and
sex organs norepinephrine
Relaxes
bladder
Inhibits sex
organs
Figure 12.2 Effects of the sympathetic and parasympathetic nervous systems.
From Biology: A Guide to the Natural World (5th ed., Figure 27.8), by D. Krogh, © 2011. Reprinted and electronically reproduced by permission of
Pearson Education, Inc., Upper Saddle River, New Jersey.
At the same time the body is preparing for the threat, non- achieved by changing one or both branches. For example,
emergency maintenance functions such as peristalsis and heart rate can be increased by either increasing the firing of
urine formation are temporarily reduced. sympathetic nerves or by decreasing the firing of parasym-
pathetic nerves. This allows the body to fine-tune its essen-
The parasympathetic nervous system is activated tial organ systems.
under less stressful conditions and produces a set of actions
known as rest-and-digest responses, which promote relax- Some degree of autonomic activity is always occur-
ation and body maintenance activities. Digestive secretions ring even in the absence of stimuli. This background level
increase, peristalsis propels substances along the alimen- of activity is known as autonomic tone. For example, sym-
tary canal, and defecation is promoted. Heart rate and pathetic nerves are constantly firing, keeping arterioles in
blood pressure decline. Because less air is needed, the bron- a constant state of constriction. This sympathetic tone
chi constrict and respiration slows. The student should allows for faster changes in blood pressure because the
notice that the actions of the parasympathetic division are vessels are in a constant state of readiness. On the other
opposite to those of the sympathetic division. hand, parasympathetic tone on the smooth muscle of the
alimentary and urinary tracts maintains continuous con-
Under most conditions, the two branches of the ANS tractions and keeps intestinal peristalsis and urine flow
cooperate to achieve a balance of readiness and relaxation. steady. With the important exception of the vascular
Because they have opposite effects, homeostasis may be
146 Unit 3 Pharmacology of the Autonomic Nervous System
Autonomic
ganglion
Spinal cord Preganglionic Smooth
neuron muscle
Postganglionic
neuron Glands
Cardiac
muscle
Effector organs
Figure 12.3 Basic structure of an autonomic pathway.
system, the predominant tone of autonomic tissues is from neuron, which is waiting to receive the action potential.
the parasympathetic nervous system. The basic structure of an autonomic pathway is shown in
Figure 12.3.
The sympathetic and parasympathetic divisions do
not always have opposite effects. For example, the con- Before the message can be transferred from one nerve
striction of arterioles is controlled entirely by the sympa- to another, however, it must cross the synapse, a physical
thetic branch. Sympathetic stimulation causes constriction space between the two neurons. The communication of the
of arterioles, whereas lack of stimulation causes vasodila- message from one cell to another, or synaptic transmission,
tion. Only sympathetic nerves control the adrenal utilizes chemical messengers called neurotransmitters. It is
medulla and the sweat glands. The sympathetic division important to study the details of synaptic transmission
is also solely responsible for the release of renin by the because a large number of drugs affect this process. The
kidneys, an action that increases blood pressure. Meta- process of synaptic transmission is illustrated in Pharmaco-
bolic effects such as increases in blood glucose and mobi- therapy Illustrated 12.1.
lization of lipids for energy are uniquely sympathetic
functions. In the male reproductive system, the roles are The second (postganglionic) neuron terminates on
complementary. Erection of the penis is a function of the smooth muscle, cardiac muscle, or a gland at a specialized
parasympathetic division, and the sympathetic branch synapse called the neuroeffector junction. Synaptic transmis-
controls ejaculation. sion across the neuroeffector junction occurs in several steps.
Synaptic Transmission 1. Synthesis of the neurotransmitter. The neurotrans-
mitter is synthesized in the cell body of the neuron or
12.4 Synaptic transmission allows information in the axon terminal where the synapse is located. Over
to be communicated between two nerves or from 50 different neurotransmitters have been identified, the
nerves to muscles or glands. most common of which are shown in Table 12.1. Each
neurotransmitter is associated with a unique set of
For information to be transmitted throughout the ner- functions and responses. The two primary neurotrans-
vous system, neurons must communicate with each other mitters of the ANS are norepinephrine (NE) and
and with muscles and glands. The basic unit of the ANS a cetylcholine (ACh).
is a two-neuron chain. The first neuron, called the pre-
ganglionic neuron, originates in the CNS. The pregangli- 2. Storage of the neurotransmitter. Because nerve
onic neuron connects with the second nerve outside the impulses travel rapidly from neuron to neuron, there
CNS in structures called ganglia. A ganglion (singular of must be an ample and continuous supply of the neu-
ganglia) contains the cell body of the postganglionic rotransmitter. At the terminal ends of each axon lie
millions of granules or vesicles loaded with neurotrans-
mitters, waiting for an action potential to release them.
Chapter 12 Review of Neurotransmitters and the Autonomic Nervous System 147
Pharmacotherapy Illustrated 12.1
Synaptic Transmission
1
An action potential
is initiated.
2 Presynaptic
Action potential neuron
reaches the synapse.
3
Synaptic Neurotransmitter released
vesicle from synaptic vesicles.
Neurotransmitter Synaptic
cleft
Ion
channel 4
5 Neurotransmitter binds
Action potential to receptor and opens
continues. ion channel.
Postsynaptic
neuron
3. Release of the neurotransmitter. When the nerve 4. Binding to the receptor. The neurotransmitter diffuses
impulse reaches the end of the axon, it stimulates some across the synaptic cleft to reach receptors waiting on
of the vesicles to release their stored neurotransmitter the surface of the postsynaptic cell. There is a brief delay
into the synapse. The neurotransmitter enters the syn- in impulse conduction of about 0.2 to 0.5 msec for the
aptic cleft, which must be bridged for the impulse to neurotransmitter to cross the synapse. Once the neu-
reach the postganglionic neuron or organ. rotransmitter binds to its receptor, the message is
Table 12.1 Selected Neurotransmitters and Their Receptors: Effects and Clinical Applications
Neurotransmitter Primary Locations of Receptors Clinical Application (Chapter Number)
Acetylcholine Synapses throughout the CNS; preganglionic neurons ending in the Alzheimer’s disease (21); myasthenia
ganglia in both the sympathetic and parasympathetic nervous gravis (13)
Dopamine systems (nicotinic); postganglionic neurons ending in neuroeffector
Gamma aminobutyric acid (GABA) target tissues in the parasympathetic nervous system (muscarinic) Attention-deficit/hyperactivity disorder (24);
Glutamate Limbic system and hypothalamus; some sympathetic ganglia Parkinson’s disease (21); psychoses (20)
Nitrous oxide Anesthesia (26); anxiety (18); seizures (22)
Norepinephrine Throughout the CNS Seizures (22)
Throughout the CNS Impotence (71)
Serotonin (5-HT) CNS, adrenal gland, and nerves to the penis Attention-deficit/hyperactivity disorder (24);
Substance P Throughout the CNS; most neuroeffector target junctions in the cocaine and amphetamine abuse (27);
sympathetic nervous system depression (19)
Anxiety (18); depression (19); nausea and
Limbic system and hypothalamus; primary neurotransmitter in the vomiting (60); psychoses (20)
extrapyramidal system; GI tract Analgesia (25)
Pain pathways in the spinal cord; brain and sensory neurons
148 Unit 3 Pharmacology of the Autonomic Nervous System
conveyed to the postsynaptic cell. The neurotransmitter • Medications can influence the release of the neurotrans-
induces the target muscle cell, glandular cell, or another mitter from the preganglionic nerve. Promoting neu-
neuron tissue to elicit its characteristic response. Gener- rotransmitter release stimulates autonomic responses,
ally, the more neurotransmitter released into the syn- whereas preventing neurotransmitter release has the
apse, the more intense and longer lasting the response. opposite effect.
5. Termination of neurotransmitter action. Once the
message is transmitted, the neuron and the effector cell • Medications can bind to the neurotransmitter receptors
must quickly return to baseline conditions and ready on the postganglionic cell. Drugs that bind to recep-
themselves for future messages. This is accomplished by tors and stimulate the cell will increase autonomic
removal of the neurotransmitter. The neurotransmitter responses. Those that attach to the postganglionic cell
is either degraded in the synaptic cleft by enzymes, or it and prevent the natural neurotransmitter from reach-
diffuses back into the preganglionic neuron, thus stop- ing its receptors will inhibit autonomic actions.
ping the action of the muscle or gland.
• Medications can prevent the destruction or reuptake of
Conduction of action potentials in the ANS is much the neurotransmitter. These drugs cause the neu-
slower than in the somatic nervous system. Because somatic rotransmitter to remain in the synapse for a longer
nerves are myelinated and have no ganglia, impulses more time and will stimulate autonomic actions.
quickly reach their target tissues. Autonomic messages
must cross the synaptic cleft, and postganglionic nerves are It is important to understand that autonomic drugs are
unmyelinated, which slows the action potential. rarely given to correct physiologic defects in the ANS itself.
Compared to other body systems, the ANS has remarkably
12.5 Autonomic drugs exert their effects by little disease. Rather, medications are used to stimulate or
acting at synapses. inhibit target organs or glands of the ANS, such as the
heart, lungs, or digestive tract. With few exceptions, the
The student may be wondering why it is necessary to disorder lies in the target organ, not the ANS. Thus when
learn ANS anatomy and physiology in such depth. The an autonomic drug is administered, the goal is not to treat
reason is that a large number of drugs act by altering an autonomic disease; it is to correct disorders of target
neurotransmitter activity in the ANS. Some medications organs through its effects on autonomic nerves.
are identical to endogenous neurotransmitters, or have a
very similar chemical structure, and are able to directly Cholinergic Transmission
activate a gland or muscle. Other drugs are used to stim-
ulate or block the actions of natural neurotransmitters. 12.6 Acetylcholine is the neurotransmitter
A firm grasp of autonomic physiology is essential to released at cholinergic receptors, which may be
understanding the actions and adverse effects of hun- nicotinic or muscarinic.
dreds of drugs.
ACh was the first neurotransmitter to be identified. Neu-
The two-neuron chain of the ANS allows multiple rons releasing ACh are called cholinergic nerves. Located
locations at which drugs can act. Some medications affect on postganglionic or neuroeffector cell membranes, cholin-
the outflow of nervous impulses at their source—the CNS. ergic receptors bind ACh and either continue the impulse
A second potential site for drug action is at the ganglia, the (at the ganglia) or cause an autonomic action (at the neu-
synapse where the preganglionic and postganglionic neu- roeffector organ). When reading the following sections, the
rons meet. Yet a third possible site is at the end of the chain, student should refer to the sites of ACh and NE action
at the neuroeffector junction of the target organs. shown in Figure 12.4.
Although complex, actions of drugs affecting this ANS ACh is synthesized in the preganglionic nerve termi-
can be grouped into just a few categories. The five general nal and stored in synaptic vesicles. A preganglionic neuron
mechanisms by which drugs affect synaptic transmission may contain 300,000 vesicles, each housing as many as
in the ANS are as follows: 50,000 ACh molecules. When an action potential reaches
the nerve terminal, a brief burst of ACh is released into the
• Medications may affect the synthesis of the neurotrans- synaptic cleft, where it diffuses across to attach to its recep-
mitter in the preganglionic nerve. Drugs that decrease tors on the postganglionic cell.
neurotransmitter synthesis inhibit autonomic
responses. Those that increase neurotransmitter syn- PharmFACT
thesis have the opposite effect.
Sir Henry Dale identified acetylcholine as a neurotransmitter
• Medications can prevent the storage of the neurotrans- in 1914, and Otto Loewi demonstrated its physiology. The
mitter in vesicles within the preganglionic nerve. Pre- pair was awarded the Nobel Prize in Physiology or Medicine
vention of neurotransmitter storage inhibits autonomic in 1936 for their work (Nobelprize.org, 2016).
actions.
Chapter 12 Review of Neurotransmitters and the Autonomic Nervous System 149
(a) Sympathetic pathway Cholinergic receptors Adrenergic
(nicotinic) receptor
ACh
NE (a or b)
Preganglionic Postganglionic Target
neuron neuron cell
(b) Parasympathetic pathway Ganglia Cholinergic receptors Cholinergic
(nicotinic) receptor
ACh
(muscarinic)
ACh
Preganglionic Postganglionic Target
neuron neuron cell
Ganglia ACh = Acetylcholine
NE = Norepinephrine
Figure 12.4 Receptors in the autonomic nervous system: (a) Sympathetic pathway: ACh is released at the ganglia
(nicotinic receptor) and NE at the effector organ (adrenergic receptor). (b) Parasympathetic pathway: ACh is released
at both the ganglia (nicotinic receptor) and effector organ (cholinergic receptor).
Cholinergic Receptors used for this purpose today due to the discovery of safer
and Neurotransmitters drugs. The primary current therapeutic application of these
drugs is to produce skeletal muscle relaxation (a somatic
Two types of cholinergic receptors bind ACh. These are effect) during surgical procedures. A complete discussion
named after certain chemicals that bind to them: of nicotinic blockers can be found in Chapter 14.
• Nicotinic receptors. Located at preganglionic neurons CONNECTION Checkpoint 12.1
ending in the ganglia in both the sympathetic and
parasympathetic nervous systems Nicotine induces hepatic microsomal (CYP450) enzymes. From what
you learned in Chapter 5, how can this induction affect the actions of
• Muscarinic receptors. Located at postganglionic neu- medications? Answers to Connection Checkpoint questions are avail-
rons ending in neuroeffector target tissues in the para- able on the faculty resources site. Please consult with your instructor.
sympathetic nervous system.
Activation of ACh receptors at postganglionic nerve
Early research on laboratory animals found that the endings in the parasympathetic nervous system results in
actions of ACh at the ganglia resembled those of nicotine, the classic symptoms of parasympathetic stimulation shown
the active chemical in tobacco products. Because of this in Figure 12.2. Early research determined that these actions
similarity, receptors for ACh in the ganglia are called nico- closely resembled those produced after eating the poisonous
tinic receptors. Nicotinic receptors are also found in skele- mushroom Amanita muscaria. The active substance in this
tal muscle, which is controlled by the somatic nervous mushroom is the chemical muscarine; thus, these ACh
system, and in the adrenal medulla. Because nicotinic receptors were named muscarinic receptors. Muscarinic
receptors are present in so many locations, drugs affecting receptors are also found in most sweat glands and in blood
these receptors produce profound effects on both the ANS vessels serving skeletal muscles. The locations of nicotinic
and somatic nervous system. Activation of ACh nicotinic and muscarinic receptors are illustrated in Figure 12.4.
receptors always produces stimulatory actions. Nicotinic
actions include increased sweat production, increased Unlike the actions of ACh at nicotinic receptors, which
release of adrenal medullary hormones, and enhanced are always stimulatory, ACh action at muscarinic receptors
nerve conduction in the ganglia; and tachycardia, hyper- may be stimulatory or inhibitory, depending on the target
tension, and increased tone and motility in the digestive organ. For example, activation of muscarinic receptors in the
tract. Although nicotinic receptor blockers were some of heart will decrease the heart rate, but activation of muscarinic
the first drugs used to treat hypertension, they are rarely receptors in the intestine will increase peristalsis. Drugs that
150 Unit 3 Pharmacology of the Autonomic Nervous System
Table 12.2 Types of Autonomic Receptors
Neurotransmitter Receptor Primary Locations Selected Responses
Acetylcholine Muscarinic Parasympathetic target organs (other than the heart) Stimulation of smooth muscle and exocrine gland secretions
(cholinergic) Heart Decreased heart rate and force of contraction
Nicotinic Stimulation of smooth muscle and gland secretions
Norepinephrine Postganglionic neurons and neuromuscular junctions
(adrenergic) Alpha1 of skeletal muscle Constriction of blood vessels; dilation of pupils
Alpha2 Inhibition of norepinephrine release
Beta1 All sympathetic target organs except the heart Increased heart rate and force of contraction; release of renin
Beta2 Inhibition of smooth muscle contraction
Presynaptic adrenergic nerve terminals
Heart and kidneys
All sympathetic target organs except the heart
affect muscarinic receptors have more pharmacologic appli- Adrenergic Transmission
cations than those affecting nicotinic receptors. Medications
that block muscarinic receptors are used during ophthalmic 12.7 Norepinephrine is the primary
procedures, as preanesthetic drugs, and in the pharmaco- neurotransmitter released at adrenergic
therapy of asthma and bradycardia (see Chapter 16). receptors, which may be alpha or beta.
Although ACh itself can stimulate both muscarinic In the sympathetic nervous system, NE is the neurotrans-
and nicotinic receptors, some drugs are selective to only mitter released at almost all postganglionic nerves. NE
one type. Table 12.2 summarizes the types of responses belongs to a class of hormones called catecholamines, all
produced by activation of the two types of ACh receptors. of which are involved in neurotransmission. Other endog-
enous catecholamines include epinephrine (adrenalin) and
Termination of Acetylcholine Action dopamine. The receptors at the ends of postganglionic
sympathetic neurons are called adrenergic, which is
The goal of nerve transmission is to produce an immedi- derived from the word adrenaline.
ate, though transient, response. To accomplish this, ACh
must be rapidly removed from the synaptic cleft after pro- Presynaptic
ducing its effect. The enzyme that resides in the synaptic neuron
cleft and catalyzes the destruction of ACh is called acetyl-
cholinesterase (AChE), or cholinesterase (Note: The suffix = acetylcholine
-erase can be thought of as “wiping out” the ACh.) AChE is Synaptic
quite efficient at performing its task. It is estimated that vesicles
over half the ACh molecules released from the vesicles are with ACh
destroyed before they have a chance to reach their recep-
tors. Following the breakdown of ACh, choline is re- Acetyl CoA + choline ACh
formed and is taken up by the preganglionic neuron,
where it is used to synthesize more ACh. The lifecycle of 1 4
ACh in the neuron is shown in Figure 12.5. 2
AChE
Medications can interfere with the lifecycle of ACh. 3
Some drugs (and poisons) can prevent the inactivation of
ACh by blocking the acetylcholinesterase enzyme. These ACh Postsynaptic
drugs will cause a prolonged action of ACh at the synapse. receptor neuron
Other medications will prevent ACh from reaching its recep-
tors, thus blocking its actions. Medications that interfere with Figure 12.5 Lifecycle of acetylcholine (ACh): (1) ACh is released
the lifecycle of ACh are presented in Chapters 13 and 14. into the synaptic cleft. (2) ACh binds to receptors on the
postsynaptic membrane. (3) ACh is broken down into acetate and
Pseudocholinesterase, also known as plasma cholines- choline. (4) Choline is returned to the presynaptic neuron and
terase, is another enzyme that destroys ACh. Found pri- recycled to make additional ACh.
marily in the liver, pseudocholinesterase rapidly inactivates
ACh and drugs with a chemical structure similar to ACh as
they circulate in the plasma. Some people are born with a
genetic deficiency of this enzyme and are unable to inacti-
vate succinylcholine, a surgical drug structurally similar to
ACh. These patients are particularly sensitive to the effects
of succinylcholine (see Chapter 26).
Chapter 12 Review of Neurotransmitters and the Autonomic Nervous System 151
NE is synthesized in the nerve terminal and stored in receptors increases the heart rate and strength of contrac-
vesicles until an action potential triggers its release into the tion and dilates the coronary arteries, thus preparing the
synaptic cleft. NE then diffuses across the cleft to bind to its heart for fight or flight. Beta1 receptors in the kidney
receptors on the effector cell. respond by releasing renin, which helps to maintain
(increase) blood pressure.
Adrenergic receptors are of two basic types: alpha (α)
and beta (β). These receptors are further divided into the Beta2 receptors are more widely distributed than beta1
subtypes beta1, beta2, alpha1, and alpha2. Activation of each receptors, with locations in the smooth muscle in arterioles,
type of subreceptor results in a characteristic set of physi- the GI tract, and the lungs. Activation of these receptors
ologic responses, which are summarized in Table 12.2. will dilate arteries to skeletal muscles, dilate bronchioles,
slow peristalsis, and decrease urine production.
PharmFACT
The significance of adrenergic receptor subtypes to
According to Aronson (2000), adrenaline was isolated and pharmacology cannot be overstated. Some drugs are selec-
identified by John Jacob Abel in 1897, who founded the very tive and activate only one type of adrenergic receptor,
first Department of Pharmacology at the University of whereas others affect all of them. Furthermore, a drug may
Michigan. The name was changed to“epinephrine”in the activate one type of receptor at low doses and begin to affect
United States because Parke, Davis, and Co. owned the other receptor subtypes as the dose is increased. Commit-
trademark rights to the word adrenalin (without a final“e”). ting the receptor types and their responses to memory is an
It is still known as adrenaline in the rest of the world. essential step in learning autonomic pharmacology.
Alpha-Adrenergic Receptors Other types of adrenergic receptors exist. Although the
functional role of dopamine was once thought to be only a
When alpha receptors are stimulated, enzymes on the chemical precursor to NE, research has determined that this
inside of the plasma membrane are activated and a cas- agent serves a larger role as a neurotransmitter. Five dopa-
cade of changes occurs within the cell. These changes minergic receptors (D1 through D5) have been discovered in
occur due to the production of a second messenger, the the CNS. Dopaminergic receptors are important to the action
G-protein, which initiates the cascade. In alpha1 receptors of certain antipsychotic medicines (see Chapter 20) and in
intracellular calcium stores are released, causing excitatory the treatment of Parkinson’s disease (see Chapter 21). Dopa-
effects such as smooth muscle contraction or sphincter clo- mine receptors in the peripheral nervous system are located
sure. Drugs affecting alpha1 receptors are primarily used in the arterioles of the kidney and other viscera. Although
for their effects on vascular smooth muscle in the treat- these receptors likely have a role in autonomic function,
ment of hypertension (see Chapters 16 and 34). Drugs that their therapeutic importance has yet to be discovered.
block the alpha1 receptor are used to treat benign prostatic
hyperplasia (see Chapters 14 and 71). Termination of Norepinephrine
Action
Stimulation of alpha2 receptors causes different effects
due to the activation of a separate cascade of events in the The termination of NE action occurs through mechanisms
target cells. By increasing cyclic adenosine monophosphate different from those of ACh. The majority of the NE (50%
(cAMP) within the cell, activation of alpha2 receptors inhib- to 80%) is taken back into the nerve terminal, a process
its NE release from sympathetic nerve endings, causing known as reuptake. Following its reuptake, NE is repack-
mostly inhibitory actions. In addition, activation of alpha2 aged in vesicles for future use or destroyed enzymatically
receptors in the CNS can suppress the outflow of sympa- by monoamine oxidase (MAO). NE entering the circula-
thetic activity from the brain. Indeed, as will be discussed tion, such as that secreted by the adrenal glands or given
in Chapter 15, drugs that affect alpha2 receptors are usually as medication, is destroyed by the enzyme catechol-O-
used for their ability to decrease blood pressure due to their methyltransferase (COMT) in kidney and liver cells.
effects on the CNS, not the ANS. Many drugs affect autonomic function by influencing the
synthesis, storage, release, reuptake, or destruction of NE.
Beta-Adrenergic Receptors The lifecycle of NE is shown in Figure 12.6.
Three subtypes of beta-adrenergic receptors have been iden- Activation of the sympathetic division produces lon-
tified, although only beta1 and beta2 have pharmacologic ger lasting effects than those of parasympathetic activation.
importance. Beta receptors act by increasing the second mes- This is because NE acts indirectly through a second messen-
senger cAMP in target cells. The specific response caused by ger mechanism. Its effects are produced more slowly than
activation of the beta receptor depends on its location. ACh, which acts directly at cholinergic sites. Furthermore,
the primary means of inactivation of NE is through reup-
The primary tissues served by beta1 receptors are the take, which is a slower process than the direct enzymatic
heart, coronary vessels, and kidneys. Activation of these destruction of ACh.
152 Unit 3 Pharmacology of the Autonomic Nervous System
6[TQUKPG 2TGU[PCRVKE lasting effects than those produced by activation of sympa-
&QRC PGWTQP thetic neurons in the ANS. In addition, the bloodstream dis-
tributes these agents to all body cells, not just those innervated
&QRCOKPG by the ANS. Significant concentrations of epinephrine and NE
may persist for as long as 30 seconds, and their effects on tis-
+PCEVKXG sues may continue for several minutes until the liver eventu-
RTQFWEVU ally deactivates the hormones. It is estimated that 25% to 50%
of all sympathetic nervous system responses at any given time
/#1 are due to circulating hormones from the adrenal medulla.
Regulation of Autonomic Functions
0' TGWRVCMG
VTCPURQTVGT 12.9 The autonomic nervous system is
influenced by higher levels of control in the
+PCEVKXG cerebral cortex and hypothalamus.
RTQFWEVU
%1/6 Although it is often stated that control of the ANS is invol-
untary, this is an oversimplification. For example, strong
emotions such as rage are seated in the brain, but they trig-
ger the heart to race, the blood pressure to rise, and the res-
piration rate to increase. Mental depression can have the
opposite effects. The smell of steak or chicken cooking on
0' 2QUVU[PCRVKE the grill can increase peristalsis, resulting in “grumbling” of
TGEGRVQT PGWTQP the stomach and increased salivation. Clearly, autonomic
actions can be modified by higher brain centers.
Figure 12.6 Lifecycle of norepinephrine (NE): (1) NE is synthesized
from the amino acid tyrosine. (2) NE is released into the synaptic The roles of higher centers in regulating the ANS are
cleft. (3) NE binds to receptors on the postsynaptic membrane. shown in Figure 12.7. The hypothalamus is thought to be
(4) NE is taken back into the presynaptic neuron. (5) NE is degraded the main integration center of the ANS. This tissue receives
by MAO. (6) Small amounts of NE are degraded by COMT. signals from the cerebrum and sensory input, such as emo-
tions, from the limbic system of the brain. The hypothala-
CONNECTION Checkpoint 12.2 mus interprets the information and responds by sending
messages to the various portions of the ANS, such as
The herb St. John’s wort is believed to inhibit the reuptake of sero- increasing peristalsis and salivation when the sights,
tonin into presynaptic nerve terminals in the CNS. From what you sounds, and smells of the grilled steak are experienced.
learned in Chapter 7, what is the most common indication for using this Messages from the hypothalamus travel along the medulla
herb? Answers to Connection Checkpoint questions are available on the oblongata, the brainstem, and the spinal cord.
faculty resources site. Please consult with your instructor.
Drugs can affect the ANS by influencing these higher
12.8 The adrenal medulla is a specialized centers. For example, drugs that decrease anxiety or dimin-
type of sympathetic nervous system tissue that ish the incidence of panic attacks can slow the heart rate
secretes epinephrine and norepinephrine. and lower blood pressure through their ability to affect
conscious thought. It is important to understand that these
Lying in the inner portion of each adrenal gland, the adrenal drugs do not necessarily act on autonomic receptors, nor
medulla is closely associated with the sympathetic nervous do patients consciously lower their blood pressure or heart
system but has a different anatomic and physiologic arrange- rate. The autonomic effect is indirect, caused by a reduction
ment than the rest of the sympathetic branch. Early in of stress, and it is at a subconscious level. Controlling auto-
embryonic life, the adrenal medulla is part of the neural tis- nomic activity through conscious thought is the principle
sue that is destined to become the sympathetic nervous sys- underlying biofeedback therapy.
tem. This primitive tissue splits, however, and the adrenal
medulla becomes its own functional division. Preganglionic Classifying Autonomic Drugs
neurons from the spinal cord terminate in the adrenal
medulla and release the neurotransmitters epinephrine and 12.10 Autonomic drugs are classified by which
NE directly into the blood. Approximately 80% of the secre- receptors they stimulate or block.
tion is epinephrine, with the other 20% being NE. Once
released, these agents are widely distributed to target organs, At this point of the chapter, it is normal for students to feel
where they elicit the classic fight-or-flight symptoms. overwhelmed by the complexity of the various autonomic
receptors and their actions. It is the existence of these
Once released into the systemic circulation by the adrenal
gland, epinephrine and NE produce more diffuse and longer
Cerebral Cortex Chapter 12 Review of Neurotransmitters and the Autonomic Nervous System 153
Thoughts
Limbic System
Emotions
Hypothalamus
ANS integration
Pons and Medulla
Cardiac, respiratory,
blood pressure, swallowing
centers
Spinal Cord
Reflexes for defecation,
urination, erection, and
ejaculation
Figure 12.7 Higher centers influencing autonomic function.
different receptors, however, that allows drugs to cause Table 12.3 Indications for Autonomic Drugs
very specific therapeutic actions. For example, it is desir-
able to have drugs that affect blood pressure without Indication Autonomic Class Chapter
increasing heart rate, or drugs that dilate bronchi without 45
causing hypertension. At this stage in the study of phar- Allergic rhinitis and the Alpha1-adrenergic agonists
macology, the student can just memorize the receptor common cold 21
types and actions, because applications in the coming Alzheimer’s disease Cholinergic agonists 35
chapters will provide clarity to this subject. Angina pectoris Beta-adrenergic blockers 44
Asthma and COPD Beta-adrenergic agonists
Given the opposite actions of the sympathetic and Anticholinergics 71
parasympathetic nervous systems, autonomic drugs are Benign prostatic hyperplasia Alpha1-adrenergic blockers 37
classified based on one of four possible actions: Dysrhythmias Beta-adrenergic blockers 74
Eye examinations Anticholinergics 74
1. Stimulation of the sympathetic nervous system. Glaucoma Alpha-adrenergic blockers
These drugs are called sympathomimetics or adrener- Beta-adrenergic blockers 36
gic agonists and they produce the classic symptoms of Heart failure Cholinergic agonists
the fight-or-flight response. Beta-adrenergic blockers 34
Hypertension Beta-adrenergic agonists
2. Stimulation of the parasympathetic nervous system. Alpha1-adrenergic blockers 15
These drugs are called parasympathomimetics or mus- Hypotension and shock Alpha2-adrenergic agonists 13
carinic agonists and they produce the characteristic Myasthenia gravis Beta-adrenergic blockers 35
symptoms of the rest-and-digest response. Myocardial infarction Beta-adrenergic agonists 21
Parkinson’s disease Cholinergic agonists 59
3. Inhibition of the sympathetic nervous system. These Peptic ulcer disease Beta-adrenergic blockers 67
drugs are called adrenergic antagonists or adrenergic Thyroid crisis (storm) Anticholinergics
blockers and they produce actions opposite to those of Anticholinergics
the sympathomimetics. Beta-adrenergic blockers
4. Inhibition of the parasympathetic nervous system.
These drugs are called anticholinergics, parasympatho-
lytics, or muscarinic blockers and they produce actions
opposite to those of the parasympathomimetics.
154 Unit 3 Pharmacology of the Autonomic Nervous System
There is a method for simplifying the learning of auto- effects of slowing heart rate and constricting the pupils.
nomic pharmacology. On examining the preceding four Although this is an oversimplification and exceptions exist,
drug classes, it is evident that only one group need be it is a time-saving means of learning the basic actions and
learned because the others are logical extensions of the adverse effects of dozens of drugs affecting the ANS. It
first. If the fight-or-flight symptoms of the sympathomi- should be emphasized again that mastering the actions and
metics are learned, the other three groups are either the terminology of autonomic drugs early in the study of phar-
same or opposite. For example, both the sympathomimet- macology will reap rewards later in the course when these
ics and the anticholinergics increase heart rate and dilate drugs are applied to various systems. Table 12.3 shows the
the pupils. The other two groups, the parasympathomi- many applications of autonomic drugs in medicine and the
metics and the adrenergic antagonists, have the opposite chapter in this text in which each is covered.
Understanding Chapter 12
Key Concepts Summary 12.6 Acetylcholine is the neurotransmitter released at
cholinergic receptors, which may be nicotinic or
12.1 The two major subdivisions of the nervous system muscarinic.
are the central nervous system and the peripheral
nervous system. 12.7 Norepinephrine is the primary neurotransmitter
released at adrenergic receptors, which may be
12.2 The peripheral nervous system is divided into alpha or beta.
somatic and autonomic components.
12.8 The adrenal medulla is a specialized type of
12.3 The autonomic nervous system is divided sympathetic nervous system tissue that secretes
into two mostly opposing components: the epinephrine and norepinephrine.
sympathetic and parasympathetic branches.
12.9 The autonomic nervous system is influenced by
12.4 Synaptic transmission allows information to higher levels of control in the cerebral cortex and
be communicated between two nerves or from hypothalamus.
nerves to muscles or glands.
12.10 Autonomic drugs are classified by which
12.5 Autonomic drugs exert their effects by acting at receptors they stimulate or block.
synapses.
References Nobelprize.org. (2016). The Nobel Prize in Physiology or
Medicine 1936. Retrieved from http://www.nobelprize.
Aronson, J. K. (2000). Where name and image meet—the org/nobel_prizes/medicine/laureates/1936/index.html
argument for “adrenaline.” BMJ, 320, 506–509.
doi:10.1136/bmj.320.7233.506
Krogh, D. (2011). Biology: A guide to the natural world
(5th ed.). Upper Saddle River, NJ: Pearson.
Selected Bibliography Silverthorn, D. U. (2016). Human physiology: An integrated
approach (7th ed.). Hoboken, NJ: Pearson.
Bear, M. F., Connors, B. W., & Paradiso, M. A. (2016).
Neuroscience: Exploring the brain (4th ed.). Philadelphia, Squire, L. R., Berg, D., Bloom, F. E., Du Lac, S., Ghosh, A.,
PA: Wolters Kluwer. & Spitzer, N. C. (Eds.). (2013). Fundamental neuroscience
(4th ed.). Waltham, MA: Academic Press.
Hall, J. E. (2015). Guyton & Hall textbook of medical
physiology (13th ed.). Philadelphia, PA: Elsevier. Thorp, A. A., & Schlaich, M. P. (2015). Relevance of
sympathetic nervous system activation in obesity and
Martini, F. H., Nath, J. L., & Bartholomew, E. F. (2014). metabolic syndrome. Journal of Diabetes Research 2015,
Fundamentals of human anatomy and physiology (10th ed.). Article ID 341583. doi:10.1155/2015/341583
Hoboken, NJ: Pearson.
“It’s rather embarrassing that I’ve had
some ‘accidents’ these past 2 days since
my surgery. They say I’m not passing my
urine as I should. I just received this new
prescription. What do I need to know about
this bladder medicine I’m supposed to take?”
Patient “Patricia Sparks”
Chapter 13
Cholinergic Agonists
Chapter Outline Learning Outcomes
cc Cholinergic Receptors After reading this chapter, the student should be able to:
cc Muscarinic Agonists
1. Compare and contrast the mechanisms of action for
Direct-Acting Muscarinic Agonists direct- and indirect-acting cholinergic agonists.
PROTOTYPE Bethanechol (Urecholine), p. 159
Indirect-Acting Muscarinic Agonists 2. Identify the actions of muscarinic agonists and their
(acetylcholinesterase inhibitors) pharmacologic uses.
cc Cholinergic Crisis
cc Pharmacotherapy of Myasthenia Gravis 3. Describe the pharmacotherapy of myasthenia gravis.
PROTOTYPE Pyridostigmine
(Mestinon, Regonol), p. 163 4. Differentiate between the treatment of cholinergic
cc Nicotinic Agonists crisis and myasthenic crisis.
5. Explain the actions and pharmacologic applications
of nicotine.
6. 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.
7. Apply the nursing process to care for patients
receiving pharmacotherapy with cholinergic
agonists.
155
156 Unit 3 Pharmacology of the Autonomic Nervous System
Key Terms muscarinic agonist, 156 reflex tachycardia, 159
myasthenia gravis (MG), 161 Sjögren’s syndrome, 159
acetylcholinesterase (AChE) myasthenic crisis, 163 xerostomia, 159
inhibitors, 160 nicotinic agonist, 156
cholinergic agonists, 156
cholinergic crisis, 161
Of the four classes of autonomic drugs, the cholinergic ago- In the somatic nervous system:
nists comprise the smallest and least prescribed group.
Because cholinergic synapses are so widely dispersed • At the neuromuscular junctions, which result in skele-
throughout the central and peripheral nervous systems, tal muscle contraction.
drugs affecting these receptors will have diverse effects. A
few have applications in the treatment of glaucoma, myas- In addition, cholinergic synapses are present throughout
thenia gravis, and early Alzheimer’s disease. the central nervous system (CNS). These locations are sum-
marized in Figure 13.1.
Cholinergic Receptors
The degree of activation at a cholinergic synapse is
13.1 Drugs can activate cholinergic receptors dependent on the amount of neurotransmitter, acetylcholine
either directly or indirectly. (ACh), interacting with its receptors. Drugs and other chem-
icals that increase the action of ACh at cholinergic receptors
Recall from Chapter 12 that cholinergic receptors are will promote rest-and-digest responses. These substances
located throughout the peripheral nervous system. To are called cholinergic agonists, or parasympathomimetics.
understand the effects of cholinergic drugs, it is important
to review these locations. In the autonomic nervous Also recall from Chapter 12 that there are two primary
system: types of cholinergic receptors: muscarinic and nicotinic.
Although ACh itself stimulates both types of receptors,
• At the neuroeffector junctions in the parasympathetic drugs may be selective for only one type. For example,
division bethanechol is selective for muscarinic receptors and thus
it is called a muscarinic agonist. On the other hand, nico-
• At the ganglia in both the parasympathetic and sym- tine is selective for nicotinic receptors and therefore is clas-
pathetic divisions. sified as a nicotinic agonist. Note that both bethanechol
and nicotine are considered cholinergic agonists: The terms
2CTCU[O #%J #%J
RCVJGVKE
&KXKUKQP )CPINKC 0'
#%J 6CTIGV
#WVQPQOKE 1TICPU
0GTXQWU )CPINKC
5[UVGO #%J
5[ORCVJGVKE
&KXKUKQP
5QOCVKE 0GTXQWU
5[UVGO
Figure 13.1 Locations of cholinergic synapses. Acetylcholine is released at the ganglia in both the parasympathetic and sympathetic
divisions, at the neuroeffector junctions in the parasympathetic division, and in the somatic nervous system at neuromuscular synapses.
Chapter 13 Cholinergic Agonists 157
Table 13.1 Types of Cholinergic Receptors and Their Actions
Muscarinic Nicotinic
Receptor location Glands, smooth muscle, cardiac muscle Skeletal muscle, autonomic ganglia, brain, adrenal gland
General actions
Pupil constriction Skeletal muscle contraction
Decreased accommodation of the eye Initial stimulation of glandular secretion, followed by
Increased GI motility inhibition
Decreased heart rate Increased heart rate
Decreased blood pressure Increased blood pressure
Increased glandular secretions (salivary, lacrimal, and sweat)
Constriction of bronchial smooth muscle
muscarinic and nicotinic are used to specify which choliner- enter the synaptic cleft and bind to ACh receptors to produce
gic synapses are activated. If the student has not yet learned typical rest-and-digest responses. Some of these direct-acting
the differences between muscarinic and nicotinic receptors, drugs cause the release of additional ACh into the synaptic
then Section 12.6 should be reviewed before continuing. A cleft, thus enhancing the normal physiologic responses
summary of the differences is provided in Table 13.1. caused by ACh. The direct-acting cholinergic agonists essen-
tially act by the same mechanism as ACh itself. The direct
Cholinergic agonists can activate cholinergic receptors mechanism of cholinergic activation is shown in Figure 13.2a.
directly or indirectly. Direct-acting drugs, such as bethanechol,
2TGU[PCRVKE PGWTQP 2TGU[PCRVKE PGWTQP
# #EGV[NEJQNKPG #
%J &TWI %J
# # # #
%J %J %J %J
# #
%J %J
# #
%J %J
#
# # # %J #
%J %J %J %J
# # # #
%J # %J %J %J
%J
5[PCRVKE #
ENGHV # # ## 5[PCRVKE # %J
%J %J %J %J %J
#
%J # # ENGHV
# %J %J
%J # #
%J # %J
# #%J'
# # %J %J #
%J %J %J #
%J
#%J'
# #
%J %J
#%J #%J
TGEGRVQT TGEGRVQT
2QUVU[PCRVKE PGWTQP 2QUVU[PCRVKE PGWTQP
C &KTGEV %JQNKPGTIKE #IQPKUV
D +PFKTGEV %JQNKPGTIKE #IQPKUV
Figure 13.2 (a) Mechanisms of action for direct cholinergic agonists. Direct cholinergic agonists can activate the
cholinergic receptor by two mechanisms: (1) The drug can cause more acetylcholine (ACh) to be released into the
synaptic cleft, resulting in additional ACh occupying ACh receptors. (2) The drug can bind to ACh receptors, enhancing
the action potential on the postsynaptic neuron. (3) Inactivation of drug action is achieved by acetylcholinesterase
(AChE). (b) Mechanism of action for indirect cholinergic agonists: (1) The drug binds the enzyme (AChE), which
prevents the ACh from being destroyed. This increases the amount of ACh remaining in the synaptic cleft, (2) thus
enhancing the action potential on the postsynaptic neuron.
158 Unit 3 Pharmacology of the Autonomic Nervous System
Table 13.2 Cholinergic Agonists
Drug Route and Adult Dose (Maximum Dose Where Indicated) Adverse Effects
Direct Acting (Muscarinic Agonists) Increased salivation, abdominal cramping,
sweating, flushing of the skin, miosis, blurred
bethanechol (Urecholine) PO: 10–50 mg tid or qid (max: 200 mg/day) vision, nausea, vomiting
Orthostatic hypotension with possible syncope,
carbachol (Miostat) Intraocular: Instill 0.5 mL into anterior chamber of eye bradycardia, reflex tachycardia, complete heart
block, acute bronchospasm
cevimeline (Evoxac) PO: 30 mg tid (max: 90 mg/day)
Involuntary contraction or twitching of muscles,
pilocarpine Topical: 1–2 drops in affected eye tid or qid for chronic glaucoma nausea, vomiting, miosis, increased salivation
Bradycardia, hypotension, dyspnea, seizures,
(Isopto-Carpine, Salagen) PO: 5–10 mg tid for xerostomia (max: 10 mg/dose, 30 mg/day) bronchospasm, cholinergic crisis, death due to
paralysis of respiratory muscles
Indirect Acting (Acetylcholinesterase Inhibitors)
donepezil (Aricept) PO or orally disintegrating tablet (ODT): 5–10 mg (max: 10 mg/day)
galantamine (Razadyne) PO: 4 mg bid for 4 wk; may increase by 4 mg bid q4wk to target dose of
12 mg bid (max: 24 mg/day)
neostigmine (Bloxiverz) IM/subcutaneous: 0.5–2.5 mg q1–3 h (max: 10 mg/day)
IV: 0.5–2.5 mg (max: 5 mg/day)
physostigmine (Antilirium) IM/IV: 0.5–2 mg (IV not faster than 1 mg/min); repeat as needed
pyridostigmine PO: 60 mg–1.5 g/day; sustained release: 180–540 mg 1–2 times/day at
(Mestinon, Regonol) intervals of at least 6 h
IV: 0.1–0.25 mg/kg
rivastigmine (Exelon) PO: Start with 1.5 mg bid; may increase to target dose of 3–6 mg bid (max:
12 mg/day)
Transdermal: Start with one 4.6-mg patch daily (max: one 9.5-mg patch daily)
Note: Italics indicate common adverse effects. Underline indicates serious adverse effects.
Indirect-acting drugs inhibit acetylcholinesterase because it is rapidly destroyed both in the bloodstream
(AChE) (also called cholinesterase), the enzyme in cholin- and in synapses (by AChE) and produces many adverse
ergic synapses that destroys ACh. By blocking the destruc- effects. Muscarinic agonists used as medications are rela-
tion of ACh, the neurotransmitter accumulates and remains tively resistant to destruction by AChE and exhibit a lon-
in the synaptic cleft for a longer time to produce enhanced ger duration of action than ACh. Muscarinic agonists are
rest-and-digest responses. Some indirect drugs such as poorly absorbed across the gastrointestinal (GI) tract and
neostigmine bind only briefly to AChE and exhibit short generally do not cross the blood–brain barrier. They have
durations of action. These drugs are called reversible acetyl- minimal effects on ACh nicotinic receptors in the ganglia.
cholinesterase inhibitors. Because of the potential for serious adverse effects, few
muscarinic agonists are widely used in pharmacotherapy.
Certain chemicals bind irreversibly to AChE. For exam- Available drugs are listed in Table 13.2.
ple, certain insecticides and nerve gas agents bind to AChE
for prolonged periods and can cause significant mortality if Muscarinic agonists have widespread effects on the
ingested or absorbed. Because of the hazardous nature of body, nearly all of which are due to parasympathetic acti-
these chemicals, irreversible acetylcholinesterase inhibitors vation. All of these drugs can increase the degree of smooth
are not widely used in medicine. muscle tone and contractions of the GI tract. When admin-
istered before meals, stomach emptying is promoted due to
Note that physiologically it does not matter whether increased peristalsis of the alimentary canal. Muscarinic
the cholinergic synapse was activated directly or indirectly: agonists should never be administered to patients with
The parasympathetic responses are the same. There are suspected obstructive disease of the GI tract because the
some important differences, however, as will be discussed increased peristaltic contractions could lead to injury or
in Section 13.3. The indirect mechanism of cholinergic acti- rupture to the mucosa.
vation is shown in Figure 13.2b.
Muscarinic Agonists CONNECTION Checkpoint 13.1
13.2 Muscarinic agonists produce their effects From what you learned in Chapter 12, would you expect the cho-
by directly stimulating cholinergic receptors. linergic agonists to have similar or opposite effects to the following:
adrenergic agonists, adrenergic antagonists, cholinergic antago-
Muscarinic agonists are drugs that activate cholinergic nists? Answers to Connection Checkpoint questions are available on
receptors located at the neuroeffector junctions in the para- the faculty resources site. Please consult with your instructor.
sympathetic nervous system. Although ACh itself is a
muscarinic agonist, it has little therapeutic value as a drug Muscarinic agonists also stimulate the smooth muscle
of the urinary tract, increasing ureteral peristalsis and
Chapter 13 Cholinergic Agonists 159
promoting emptying of the bladder. These are considered amounts of muscarine, the original cholinergic agonist iso-
therapeutic actions in patients with urinary retention. Care lated from the mushroom Amanita muscaria. A. muscaria
must be taken not to administer muscarinic agonists when itself has only small amounts of muscarine, but several
obstructive uropathy is present, however, because the other species of fungi possess significant amounts of this
increased smooth muscle contractions of the ureters and toxin that can cause severe illness if ingested. Symptoms of
bladder could aggravate pain and bleeding. acute poisoning appear 30 to 90 minutes after ingestion
and resemble an overdose of cholinergic agonists: an exag-
Muscarinic agonists stimulate most exocrine glands, gerated parasympathetic response. Symptoms may persist
increasing lacrimal, sweat, digestive, and salivary secre- for 24 hours. Amanita species are sometimes intentionally
tions. This action has been used to advantage in treating ingested to obtain psychotic effects, reportedly to expand
patients with xerostomia (dry mouth) or those with or alter spatiotemporal awareness.
Sjögren’s syndrome, a chronic autoimmune disorder char-
acterized by excessive dryness of mucous membranes, PharmFACT
which is associated with rheumatoid arthritis in meno-
pausal women. In addition to creating discomfort for the Muscarinic receptors are named after muscarine, which is
patient, xerostomia can promote dental caries, periodontal obtained from the mushroom Amanita muscaria. The actual
disease, oral ulcers, and candidiasis. chemical that causes poisoning in patients eating this
mushroom, however, is primarily ibotenic acid, which
In the eye, muscarinic agonists cause the muscles of causes excitement, hallucinations, and confusion. Death
the iris to contract and produce pupillary constriction, or from Amanita mushroom poisoning is rare (Rolston-
miosis. Miosis has no therapeutic application and is con- Cregler, 2015).
sidered an adverse effect of muscarinic agonists. A second
effect on the eye is contraction of the ciliary muscle, which Symptoms of parasympathetic stimulation, whether
causes loss of ability to focus for near vision. Although caused by medications or poisoning, may be reversed by
this action may cause blurred vision, ciliary muscle con- administering an anticholinergic drug. Atropine is consid-
traction has an indirect, beneficial effect: It allows fluid to ered the specific antidote for these conditions. Acute symp-
drain from the anterior chamber of the eye, reducing toms of parasympathetic stimulation will begin to resolve
intraocular pressure. When applied topically to the eye, within minutes after a subcutaneous injection of atropine.
cholinergic agonists, such as pilocarpine, can be of value Atropine is a prototype cholinergic antagonist presented in
in treating glaucoma. Cholinergic agonists are considered Chapter 14.
second-line drugs for glaucoma therapy, however, having
been replaced by safer, more effective alternatives (see PROTOTYPE DRUGS Bethanechol (Urecholine)
Chapter 74).
Classification Therapeutic: Drug to treat urinary
Muscarinic agonists contract bronchial smooth muscle, retention
causing the airways to narrow. In patients with respiratory
disease, bronchoconstriction may trigger episodes of breath- Pharmacologic: Cholinergic agonist,
lessness or an asthma attack. This is why muscarinic ago- muscarinic agonist (direct acting)
nists are contraindicated in patients with a history of asthma.
Therapeutic Effects and Uses: Approved in 1948 by
When activated, muscarinic receptors in the cardio- the U.S. Food and Drug Administration (FDA), bethanechol
vascular system slow the heart rate and lower blood pres- is available in tablet form. Effects of bethanechol are most
sure. Baroreceptors in the carotid arteries and aortic arch, noted in the digestive and urinary tracts, where it stimu-
however, recognize the falling blood pressure and signal lates smooth muscle contraction. In the urinary tract,
the vasomotor center in the medulla to increase the heart bethanechol relaxes the sphincters and causes the detrusor
rate. This phenomenon, known as reflex tachycardia, is muscle of the bladder to contract. These combined actions
not unique to the cholinergic agonists; it can occur with result in voiding; thus it is used to treat nonobstructive uri-
any drug that causes blood pressure to fall. When admin- nary retention in patients with atony of the bladder. Off-
istering cholinergic agonists by the oral (PO) or parenteral label uses include the treatment of adynamic ileus and
routes, the patients’ heart rate must be closely monitored gastric atony.
to avoid bradycardia. Blood pressure must also be moni-
tored to prevent serious hypotension, particularly in those Mechanism of Action: Structurally similar to ACh,
with preexisting cardiovascular disease. Patients with bethanechol interacts directly with muscarinic receptors
hyperthyroidism may experience atrial fibrillation. Seri- to cause body responses typical of parasympathetic stim-
ous heart disease is a contraindication to therapy with cho- ulation. This drug is selective for muscarinic receptors.
linergic agonists. Bethanechol is not destroyed by AChE; therefore, its actions
are more prolonged than those of ACh.
Occasionally, patients experience acute poisoning from
eating certain species of mushrooms containing high
160 Unit 3 Pharmacology of the Autonomic Nervous System
Pharmacokinetics: PO Administration of subcutaneous atropine quickly reverses
Route(s) Poorly absorbed PO most symptoms.
Absorption Widely distributed; does not
Distribution cross the blood–brain barrier Nursing Responsibilities: Key nursing implications
Unknown for patients receiving bethanechol are included in the
Primary metabolism Renal Nursing Practice Application for Patients Receiving Phar-
Primary excretion 30–60 min macotherapy with Cholinergic Agonists.
Onset of action 1–6 h
Duration of action Drugs Similar to Bethanechol (Urecholine)
Adverse Effects: The adverse effects of bethanechol Other direct-acting cholinergic agonists include carbachol,
are predictable knowing its parasympathetic actions. Com- cevimeline, and pilocarpine.
mon adverse effects include increased salivation, abdominal
cramping, sweating, flushing of the skin, miosis, blurred Carbachol (Miostat): Carbachol is a direct-acting choliner-
vision, nausea, and vomiting. Serious effects include ortho- gic agonist. Carbachol intraocular (Miostat) is a solution
static hypotension with possible syncope, bradycardia, reflex for injection into the anterior chamber of the eye to pro-
tachycardia, complete heart block, and acute bronchospasm. mote miosis during surgery. Vision may be clouded due to
pupillary constriction. Should absorption occur, adverse
Contraindications/Precautions: Bethanechol effects would be those of parasympathetic stimulation.
should be used with extreme caution in patients with dis- This drug is pregnancy category C.
orders that could be aggravated by increased contractions
of the GI tract, such as suspected bowel obstruction, re- Cevimeline (Evoxac): Cevimeline is a direct-acting cholin-
cent GI surgery, an active ulcer, or an inflammatory dis- ergic drug whose only indication is the treatment of xero-
ease. Patients with suspected urinary obstruction or those stomia in patients with Sjögren’s syndrome. Given orally,
who have had recent bladder surgery should not receive cevimeline increases saliva flow, relieving dry mouth. The
this drug, because the increased smooth muscle contrac- most common adverse effect is excessive sweating,
tions could worsen these conditions. Patients with cystitis although this occurs less frequently than with pilocarpine.
should not be given bethanechol because contractions of Other signs of parasympathetic stimulation are possible,
the bladder may force urine up the ureters to the kidneys such as diarrhea, runny nose, miosis, and bradycardia.
if the sphincter fails to open. Because of the possibility of This drug is pregnancy category C.
bronchoconstriction, administration of bethanechol to pa-
tients with asthma or chronic obstructive pulmonary dis- Pilocarpine (Isopto-Carpine, Salagen): Pilocarpine is a
ease (COPD) is contraindicated. Muscarinic agonists such direct cholinergic agonist that is administered orally or as
as bethanechol can slow the heart rate; thus they are contra- an ophthalmic solution. Salagen is an oral preparation of
indicated in patients with recent myocardial infarction (MI), pilocarpine given for xerostomia due to its ability to stimu-
severe bradycardia, hypotension, or hypertension. Patients late salivary flow. When given orally, the adverse effects of
with hyperthyroidism can experience dysrhythmias with pilocarpine are those expected of parasympathetic stimu-
bethanechol use. Other contraindications include peritonitis, lation, which include diarrhea, runny nose, miosis, and
epilepsy, and Parkinson’s disease. bradycardia. Excessive sweating occurs in 30% to 60% of
patients taking oral pilocarpine.
Drug Interactions: Concurrent therapy with AChE
inhibitors should be avoided because this class also stimu- Pilocarpine is also approved as eyedrops to treat cer-
lates muscarinic receptors, and excessive parasympathetic tain types of glaucoma and to counteract the effects of
activity will result. Procainamide, quinidine, atropine, and mydriatics and cycloplegics following eye examinations.
epinephrine antagonize the effects of bethanechol. Concur- This drug is pregnancy category C.
rent administration of bethanechol with ganglionic block-
ers may result in a rapid fall in blood pressure. Herbal/ 13.3 Acetylcholinesterase inhibitors are used to
Food: Unknown. treat Alzheimer’s disease and myasthenia gravis.
Pregnancy: Category C. The indirect-acting cholinergic agonists inhibit the enzy-
matic destruction of ACh, allowing the neurotransmitter to
Treatment of Overdose: Overdose will result in se- remain on cholinergic receptors for a longer time. Like the
rious cholinergic symptoms such as nausea, vomiting, ab- direct-acting agonists, these drugs essentially prolong the
dominal cramping, diarrhea, salivation, and hypotension. actions of ACh. Unlike the direct-acting (muscarinic) ago-
nists, however, the acetylcholinesterase (AChE) inhibitors
are nonselective and affect ACh synapses located at the
autonomic ganglia, muscarinic receptors, neuromuscular
junctions, and synapses in the CNS.
Chapter 13 Cholinergic Agonists 161
The muscarinic actions of the AChE inhibitors are twitching and increase muscle strength. It is a specific anti-
identical to those described for the direct-acting drugs. As dote for poisoning by organophosphate insecticides and is
such, these drugs would be expected to increase peristalsis used to control overdoses of the AChE inhibitors used to
in the GI and urinary tracts, and some can decrease intra- treat myasthenia gravis. In acute poisoning, pralidoxime is
ocular pressure. administered by IV infusion over 15 to 30 minutes. To be
most effective, pralidoxime must be given as soon as possi-
The AChE inhibitors have some additional nonauto- ble after the suspected poisoning or overdose. Furthermore,
nomic indications due to their actions in the CNS and on it should always be administered concurrently with atro-
motor nerve endings in skeletal muscle. AChE inhibitors pine (which blocks muscarinic sites). DuoDote is a drug that
used to treat mild to moderate Alzheimer’s disease include contains both pralidoxime and atropine combined in a sin-
galantamine (Razadyne), donepezil (Aricept), and rivastig- gle intramuscular (IM) injection.
mine (Exelon). These drugs increase the amount of ACh in
cholinergic synapses in the brain, which improves memory Pharmacotherapy of
and cognitive function. The AChE inhibitors do not cure or Myasthenia Gravis
slow the progress of Alzheimer’s disease: Improvement is
limited and short lived. Donepezil is presented as a proto- 13.5 Acetylcholinesterase inhibitors are used
type drug for Alzheimer’s disease in Chapter 21. in the pharmacotherapy of myasthenia gravis to
increase the strength of muscular contraction.
Some cholinergic agonists are used in the pharmaco-
therapy of myasthenia gravis. This indication is presented Myasthenia gravis (MG), which literally means “grave
in Section 13.5. muscular weakness,” first appeared in medical reports in
1672 and afflicts about 125 per million people in the United
Cholinergic Crisis States. It is one of the best understood autoimmune dis-
eases of the nervous system. The disease occurs when anti-
13.4 A cholinergic crisis may develop with bodies attack nicotinic synapses on skeletal muscles,
overdoses of AChE inhibitors or with certain resulting in symptoms of extreme fatigue, double vision,
toxins. speech impairment, and difficulty chewing or swallowing.
The most visible symptom is an obvious drooping of the
When cholinergic receptors are overstimulated, a medical eyelids (ptosis) due to muscular weakness. The ocular
emergency known as a cholinergic crisis may result. Over- muscles may become so fatigued that the patient is unable
doses of AChE inhibitor medications, or exposure to toxic to open the eyelids. Muscle fatigue worsens after exercise,
nerve gases (such as Sarin) or organophosphate insecti- or late in the day. MG is considered a progressive disease,
cides (such as Malathion), may cause an acute accumula- although the severity of symptoms fluctuates over time.
tion of ACh at cholinergic synapses. The use of nerve gases
as a bioterrorist threat is discussed in Chapter 75. PharmFACT
A cholinergic crisis is recognized by signs of intense The mean age of onset of MG is 28 years in women and
parasympathetic stimulation such as miosis, nausea, vomit- 42 years in men. Most mortality from the disease occurs
ing, urinary incontinence, increased exocrine secretions, within 3 years following diagnosis. Worsening of the disease
abdominal cramping, and diarrhea. As the crisis progresses, is uncommon after 3 years (Shah, 2016).
signs of sympathetic and nicotinic stimulation appear,
including tachycardia, hyperglycemia, and muscle twitch- MG is diagnosed by the anti–acetylcholine receptor
ing, with progressive muscle weakness and possibly flaccid (AChR) antibody test. An individual without MG should
paralysis. In massive overdoses, mechanical ventilation have virtually no antibodies to the acetylcholine receptor. In a
may be required and paralysis of respiratory muscles may patient with MG, the body forms antibodies to the ACh recep-
cause death. CNS effects are prominent with the organo- tor, and these can be measured in the blood with an accuracy
phosphates and include headache, blurred vision, anxiety, of almost 100%. For confirmation, an electromyelography test
delirium, convulsions, and coma. In general, overdose with may be conducted to test for muscle activity and fatigue.
AChE drugs produces less severe and shorter duration
effects than does poisoning with organophosphates. For patients with suspected MG, it is important to per-
form an accurate baseline physical assessment of neuro-
The treatment of cholinergic crisis includes adminis- muscular and respiratory function. The patient’s
tration of atropine, the specific antidote that reverses mus- swallowing ability should be assessed prior to medication
carinic effects. Subcutaneous atropine can act within administration due to decreased muscle strength caused by
minutes. Because some insecticides have long-lasting the disease process. Subsequent assessments are important
effects, atropine therapy may continue for several weeks. for monitoring the progress of pharmacotherapy.
Pralidoxime (Protopam) is a cholinergic agonist that
has primarily antinicotinic action, which can reverse muscle
162 Unit 3 Pharmacology of the Autonomic Nervous System
Management of MG is divided into symptomatic con- mild symptoms, act rapidly, and produce few serious
trol and immunosuppression as shown in Pharmacother- adverse effects at low to moderate doses. Muscarinic side
apy Illustrated 13.1. In the early stages of the disease, effects such as diarrhea and abdominal cramps are com-
symptoms can be controlled successfully with AChE inhib- mon, and muscle twitching can occur. High doses should
itors, usually pyridostigmine. These drugs are effective for not be used because AChE inhibitors can begin to affect
Pharmacotherapy Illustrated 13.1
Myasthenia Gravis
Neuron Skeletal muscle
Patient with myasthenia gravis
showing muscle fatigue.
ACh receptors covered Weak muscle
by AChR antibodies, contraction
inhibiting neuromuscular
transmission = ACh receptor (AChR)
= AChR antibody
Cholinesterase = ACh
inhibitors
Immunosuppressants
More ACh in Fewer antibodies
synaptic cleft: blocking AChR:
stronger muscle stronger muscle
contraction contraction
Chapter 13 Cholinergic Agonists 163
ACh nicotinic receptors, worsening the degree of muscle routes for the symptomatic treatment of MG. Affecting
weakness. the neuromuscular synapses, pyridostigmine increases the
strength of skeletal muscle contraction and delays fatigue.
As MG progresses, immunosuppressant drugs such as An average dose is ten 60-mg tablets per day, spaced apart
corticosteroids are added to the regimen. Corticosteroids to provide for maximum muscle strength. The sustained
such as prednisone reduce AChE receptor antibody levels release form (Mestinon Timespan) consists of 180-mg tab-
and result in symptomatic improvement. Care must be taken lets that are taken once or twice daily.
when initiating corticosteroid therapy because patient symp-
toms may dramatically worsen during the first few days of Pyridostigmine is also approved for military personnel
therapy. Doses of prednisone are gradually increased until with potential exposure to certain nerve gases. Pyridostig-
the desired therapeutic effect is obtained. Unfortunately, mine is only effective if administered several hours prior to
improvement may take weeks or even months, and cortico- nerve gas exposure. If exposure occurs, pyridostigmine is
steroids can exhibit considerable toxicity when given on a discontinued and the antidotes (atropine and pralidoxime)
long-term basis (see Chapter 68). Therapy with corticoste- are administered.
roids is limited to the shortest time necessary, although some
patients may require these drugs for the rest of their life. The intravenous (IV) form of pyridostigmine (Regonol)
is administered to reverse the neuromuscular blocking
Other immunosuppressants such as azathioprine action of nondepolarizing muscle relaxants. When given
(Imuran), cyclosporine (Sandimmune), or mycophenolate by the IV route, extreme caution should be used to avoid
mofetil (CellCept) may be administered as alternatives to overdosage, which can worsen neuromuscular blockade.
corticosteroids. Occasionally, these alternatives are admin-
istered concurrently with prednisone to allow for lower Mechanism of Action: Pyridostigmine reversibly in-
doses of the corticosteroid. Immunosuppressants are dis- hibits the action of AChE at cholinergic synapses, which
cussed in Chapter 42. allows ACh to accumulate and cause a greater effect. Its
use in treating MG is due to its effects on nicotinic ACh
A myasthenic crisis may occur if a patient with MG receptors in skeletal muscle.
abruptly discontinues the medication. This leads to extreme
muscular weakness and symptoms similar to those of a Pharmacokinetics: PO and IV
cholinergic crisis. Rapid, correct diagnosis is essential, Route(s)
however, because antidotes for the myasthenic crisis and Absorption PO: only 1–2% is absorbed; the
the cholinergic crisis are very different. Weakness that oral dose is much higher than
appears approximately 1 hour after drug administration Distribution the parenteral dose
that is accompanied by signs of muscarinic overstimula-
tion suggests cholinergic crisis (overdose) and is treated by Primary metabolism Distributed to most tissues;
prompt withdrawal of neostigmine and immediate admin- crosses the placenta; does not
istration of atropine. Weakness that occurs 3 hours or more Primary excretion cross the blood–brain barrier
after drug administration without muscarinic overstimula- Onset of action
tion is more likely due to myasthenic crisis (underdose, Duration of action Hepatic and plasma, by
abrupt discontinuation, or drug resistance) and is treated cholinesterases
by more intensive AChE therapy.
Kidneys
It should be clearly understood that MG is a disease
affecting skeletal muscle; it is not a disorder of the autonomic PO: 15–30 min; IV: 2–5 min
nervous system. It is presented in this chapter dealing with
the autonomic nervous system because the primary phar- 3–6 h (regular), 6–12 h
macotherapy for the disease is AChE inhibitors. Although (e xtended release)
these drugs provide symptomatic relief, they do not cure or
slow the progression of MG. With treatment, however, Adverse Effects: In addition to its effects on nicotinic
patients may experience a near-normal life expectancy. receptors, pyridostigmine also affects muscarinic recep-
tors. At muscarinic synapses, pyridostigmine will enhance
PROTOTYPE DRUGS P yridostigmine (Mestinon, the parasympathetic response, resulting in increased
Regonol) peristalsis, bronchoconstriction, bradycardia, and hypo-
tension. Common adverse effects include involuntary con-
Classification Therapeutic: Drug for myasthenia gravis traction or twitching of muscles, nausea, vomiting, miosis,
Pharmacologic: Indirect-acting and increased salivation. Potentially serious adverse ef-
fects include those of cholinergic crisis.
cholinergic agonist, AChE inhibitor
Contraindications/Precautions: Pyridostigmine
Therapeutic Effects and Uses: Approved in 1955, should be used with caution in patients with disorders
pyridostigmine is available by both oral and parenteral that could be aggravated by increased contractions of the
GI tract, such as suspected bowel obstruction or active ul-
cers. Patients with suspected urinary obstruction should
164 Unit 3 Pharmacology of the Autonomic Nervous System
not receive this drug because the increased smooth muscle Pregnancy: Category C.
contractions could worsen this condition. Because of the
potential for bronchoconstriction, patients with asthma Treatment of Overdose: Overdose with pyridostig-
or COPD should be treated cautiously with cholinergic mine may be life threatening because the drug can
agonists. Cholinergic agonists such as pyridostigmine cause a cholinergic crisis leading to respiratory failure.
can cause bradycardia; thus they are used cautiously in The administration of atropine reverses most overdose
patients with recent MI or heart failure. symptoms.
Drug Interactions: Because of the potential for Nursing Responsibilities: Key nursing implications
additive effects, other cholinergic agonists should not be for patients receiving pyridostigmine are included in the
administered concurrently with pyridostigmine. Drugs Nursing Practice Application for Patients Receiving Phar-
that interfere with neuromuscular transmission such as macotherapy with Cholinergic Agonists.
local anesthetics, some general anesthetics, and antidys-
rhythmic drugs should be used cautiously in patients Drugs Similar to Pyridostigmine
with MG because severe muscular weakness may re- (Mestinon, Regonol)
sult. If administered to patients with MG, the dose of
pyridostigmine should be increased. Cholinergic drugs The other AChE inhibitor for MG is neostigmine.
increase gastric acid secretion and should be used with
caution with other ulcer-promoting drugs such as cor- Neostigmine (Bloxiverz): Neostigmine has a shorter dura-
ticosteroids or nonsteroidal anti-inflammatory drugs tion of action than pyridostigmine and causes a higher fre-
(NSAIDs). Herbal/Food: Unknown. quency of adverse effects. The adverse effects result from
its ability to stimulate the parasympathetic nervous system.
CONNECTIONS: NURSING PRACTICE APPLICATION
Patients Receiving Pharmacotherapy with Cholinergic Agonists
Assessment
Baseline assessment prior to administration:
• Obtain a complete health history including cardiovascular, cerebrovascular, respiratory, musculoskeletal, or thyroid diseases, GI or genitourinary
obstruction, or diabetes. Obtain a drug history including allergies, current prescription and OTC drugs, and herbal preparations. Be alert to possible drug
interactions.
• Evaluate appropriate laboratory findings such as hepatic or renal function studies.
• Obtain baseline vital signs, bowel sounds, urinary output, muscle strength, and mental status as appropriate. Assess the patient’s ability to swallow.
• Assess the patient’s ability to receive and understand instructions. Include family and caregiver as needed.
Assessment throughout administration:
• Assess for desired therapeutic effects (e.g., increased ease of urination, improved muscle strength and coordination, lessened ptosis, and improved
swallowing).
• Continue frequent and careful monitoring of vital signs, mental status, bowel sounds, urinary output, and musculoskeletal function, including swallowing
ability as appropriate.
• Assess for and promptly report adverse effects: bradycardia, hypotension, dysrhythmias, tremors, dizziness, headache, dyspnea, decreased urinary
output, abdominal pain, or changes in mental status.
Implementation
Interventions and (Rationales) Patient-Centered Care
Ensuring therapeutic effects: • Encourage the patient, family, or caregiver to practice supportive
• Continue frequent assessments as above for therapeutic effects. (Ability to measures along with drug therapy to maximize therapeutic effects
(e.g., adequate rest periods in MG).
carry out activities of daily living [ADLs] has improved; urinary elimination
and output are improved; musculoskeletal weakness, ptosis, diplopia, • Have the patient, family, or caregiver maintain a diary of variations
chewing, and swallowing are improved. A larger percentage of the dose in muscle strength, particularly periods of weakness, to assist the
may be needed at times of greater fatigue such as late afternoon and at provider in choosing an appropriate dosage.
mealtimes or during periods of increased stress. A decrease in dosage
during remission may be needed.) Lifespan: Assess for subtle changes in • Instruct the patient not to self-regulate the dosage to avoid over- or
muscle strength or voice quality or slurred speech in the older adult. (Subtle underdosage. If periods of weakness occur, the provider will adjust the
changes that occur during the day, especially if timed around drug peaks or dosage after determining the cause (e.g., under- vs. overdosage).
troughs, may indicate underdosage rather than age-related changes.)
• Lifespan: Teach the patient, family, or caregiver the importance of
noting even subtle changes in the diary and the timing of doses taken.
• Continue frequent monitoring of bowel sounds and urine output if drugs • Instruct the patient to have bathroom facilities nearby after taking the
are given postoperatively or postpartum. (Assessments will detect early drug. The patient may need assistance to the toilet or commode if
signs of adverse effects as well as monitoring for therapeutic action. Drug dizziness occurs.
onset is in approximately 60 min with increased urination and peristalsis
following. Drugs are not given if a mechanical obstruction is known or
suspected. Lifespan: Be aware that the male older adult is at higher risk
for mechanical obstruction due to an enlarged prostate.)
Chapter 13 Cholinergic Agonists 165
CONNECTIONS: NURSING PRACTICE APPLICATION (continued)
Implementation
Interventions and (Rationales) Patient-Centered Care
• Provide supportive nursing measures; e.g., regular toileting schedule • Assess ability of the patient, family, or caregiver to perform ADLs
and safety measures. (Nursing measures such as assisting the patient at home, and explore the need for additional healthcare referrals.
to normal voiding position will supplement therapeutic drug effects and Evaluate home safety needs.
optimize outcome. Lifespan: A home assessment is especially important
for the older adult. The presence of throw rugs and other hazards that
obstruct mobility increases the risk for falls.)
• Schedule activities and allow for adequate periods of rest to avoid fatigue. • Instruct the patient to plan activities according to muscle strength and
(Excess fatigue can lead to either a cholinergic or a myasthenic crisis in fatigue and to allow for frequent and adequate rest periods.
patients with MG.)
• Instruct the patient to report extreme fatigue immediately.
• Follow appropriate administration techniques for ophthalmic doses. • Instruct the patient in proper administration techniques, followed by a
Sustained release tablets should not be crushed or chewed. Administer teach-back.
the drug with food, milk, or small snack. (Administering with food helps to
minimize adverse effects. Sustained release tablets must be swallowed • Have the patient report any difficulty in swallowing if sustained release
whole and a change of dosage form may be needed if dysphagia is present.) tablets are used.
Minimizing adverse effects: • Instruct the patient to promptly report tremors, palpitations, changes
• Monitor for signs of excessive ANS stimulation and notify the healthcare in blood pressure, dizziness, urinary retention, abdominal pain, or
changes in behavior (e.g., confusion, depression, or drowsiness).
provider if pulse is less than 60 beats/min or blood pressure is below Instruct the patient to report dyspnea, salivation, sweating, or extreme
established parameters. (Cholinergic agonists decrease heart rate and fatigue immediately, because these are signs of a potential overdose.
blood pressure. Atropine may be ordered to counteract drug effects.)
• Help the patient to rise from lying or sitting to standing until drug effects • Instruct the patient to rise from lying or sitting to standing slowly and to
are assessed. (Direct-acting cholinergic agonists may cause significant avoid prolonged standing in one place to avoid dizziness or falls.
orthostatic hypotension. Lifespan: Be aware that dizziness may increase
the risk of falls in the older adult.)
• Report periods of muscle weakness and association to dosage time to • Instruct the patient to report any severe muscle weakness that occurs
the provider promptly. (Muscle weakness occurring within 1 h of dose may 1 h after taking the drug or if it occurs 3 or more hours after taking the
indicate overdosage or cholinergic crisis. Weakness occurring 3 h or longer medication.
after dose may indicate underdosage, drug resistance, or myasthenic crisis.)
• Assist the patient, family, or caregiver to record variations of muscle
strength, particularly periods of weakness, and associated dose times
to assist the provider in appropriate dosage.
• Continue to monitor hepatic function laboratory values. (Cholinergic • Teach the patient, family, or caregiver about the importance of
agonists may cause liver toxicity, and liver enzymes may be monitored returning for follow-up laboratory studies.
weekly for up to 6 weeks.)
• Provide for eye comfort such as an adequately lighted room and • Caution the patient about driving in low-light conditions, at night, or if
appropriate safety measures. (Cholinergic agonists cause miosis with vision is blurred. Night-light use at home and safety measures may be
difficulty seeing in low-light levels and blurred vision.) needed to prevent falls.
• Carefully calculate and monitor doses. (Careful calculation will avoid • Ensure that the patient, family, or caregiver is administering the correct
overdosage.) dose by observing teach-back.
Patient understanding of drug therapy: • The patient, family, or caregiver should be able to state the reason
• Use opportunities during administration of medications and during for the drug; appropriate dose and scheduling; what adverse effects
to observe for and when to report them; equipment needed as
assessments to discuss the rationale for drug therapy, desired therapeutic appropriate and how to use that equipment; and the required length
outcomes, commonly observed adverse effects, parameters for when to of medication therapy needed with any special instructions regarding
call the healthcare provider, and any necessary monitoring or precautions. renewing or continuing the prescription as appropriate.
(Using time during nursing care helps to optimize and reinforce key
teaching areas.) • Instruct the patient to wear a medic-alert bracelet or other device
describing the disease and the medications used.
Patient self-administration of drug therapy: • Instruct the patient in proper administration techniques, followed by
• When administering the medications, instruct the patient, family, or caregiver teach-back.
in proper self-administration of drugs and ophthalmic drops. (Utilizing time • The patient, family, or caregiver is able to discuss appropriate dosing
during nurse administration of these drugs helps to reinforce teaching.) and administration needs.
Common adverse effects include involuntary contraction Patients with obstructive disorders of the GI or urinary
or twitching of muscles, nausea, vomiting, miosis, and tracts should not receive this drug because the increased
increased salivation. Potentially serious adverse effects smooth muscle contractions could worsen these condi-
include those of cholinergic crisis. If using large doses of tions. This drug should be used with caution in patients
neostigmine to treat MG, atropine (an anticholinergic) is with asthma, bradycardia, recent MI, or heart failure. This
sometimes administered concurrently to reverse the mus- drug is pregnancy category C.
carinic adverse effects of neostigmine.
166 Unit 3 Pharmacology of the Autonomic Nervous System
Nicotinic Agonists decrease due to the baroreceptor reflex. The emetic center in
the CNS is triggered, causing a feeling of nausea. As the level
13.6 Nicotine acts by activating ACh receptors of nicotine in the blood falls, these same organ systems
at the ganglia. become depressed. Nicotine is pregnancy category D.
Very few drugs are used for their effects on ACh nicotinic Nicotine is an extremely dangerous substance. Acute
receptors located in the autonomic ganglia. These ganglia toxicity, which can occur due to the unintentional ingestion
synapse with neurons leading to skeletal muscles (nico- of insecticides containing nicotine, may cause death due to
tinic receptors) as well as those leading to effector organs paralysis of the respiratory muscles. The chronic effects of
(muscarinic receptors). Drugs affecting the ganglia have nicotine in tobacco smokers such as lung cancer and emphy-
the potential to produce widespread, nonselective effects sema are well documented and presented in Chapter 27.
on the autonomic nervous system.
As a drug, nicotine is used as nicotine replacement
The only drug in widespread use that activates gangli- therapy (NRT) in tobacco cessation programs. Delivery
onic receptors is nicotine. The most active component of systems include chewing gum (Nicorette), transdermal
tobacco smoke, nicotine is well absorbed from the GI and patches (Habitrol, NicoDerm), and nasal spray (Nicotrol).
respiratory mucosa as well as from the skin. Because nicotine Use of these products reduces the uncomfortable symp-
acts at the ganglia, both parasympathetic and sympathetic toms of nicotine withdrawal, such as difficulty sleeping,
responses are stimulated. Stimulation of organ activity gen- lack of concentration, depression, headaches, and food
erally occurs with low doses, such as those acquired from cravings. As tobacco use diminishes over an 8- to 12-week
cigarette smoking. Within seconds after smoking, activation period, these products are gradually withdrawn.
of the CNS increases alertness. The heart rate and blood pres-
sure increase, although these parameters may subsequently The goal of NRT is to gradually reduce the patient’s
physical dependence on nicotine. The nurse should
CONNECTIONS: Preparing for Advanced Practice
Myasthenia Gravis: Future Treatments
Case Corticosteroids suppress the immune system and may promote
the formation of new acetylcholine receptors in muscle cell
Jane Richard is an active, busy 26-year-old mother of two membranes. Patients taking corticosteroids such as prednisone
young children, Amy, age 1, and Grant, age 4. One day she for an extended time may be susceptible to bone thinning.
began to have facial weakness and reports that her “lower jaw Taking adequate amounts of calcium and vitamin D is important.
gets tired and begins to twitch” when she chews. She has even Foods to include are milk products, cooked dark green vegeta-
had episodes of choking. She also mentions having double bles, salmon, dried beans, and calcium-fortified juices and cere-
vision when she reads, especially late at night. Of most concern, als. Because corticosteroids can cause fluid retention, salt
however, is that she is experiencing muscle weakness and has a substitutes or spices may be healthy alternatives to table salt.
hard time caring for Amy, her 1-year-old. She is afraid she will Cured or smoked meats, canned vegetables and soups, salty
drop her when she picks her up. snacks, and pickled foods should be avoided.
Her neurologic examination showed ptosis, drooping of Plasmapheresis, or taking the fluid part of the blood
both eyelids. Electromyographic (EMG) testing further revealed (plasma) containing the abnormal antibodies out and replacing it
that she had progressive weakness and decreased contraction with other fluids, can be life changing for MG patients. Because
of the distal arm muscles on repeated mild shocks (5 shocks the effects of plasmapheresis often last only 2 weeks, a series of
per second) of the ulnar and median nerves. Blood testing treatments is usually necessary.
revealed high levels of an anti–acetylcholine receptor antibody in
her plasma, and a diagnosis of myasthenia gravis was made. The current standard of care in MG mainly consists of gener-
alized immunosuppression. However, the future of MG treatment
She began treatment with pyridostigmine, a long-acting will be based on increased understanding of the immune function
acetylcholinesterase inhibitor, and was given a prescription for and use of immunosuppressive drugs. Immunosuppressive drugs
prednisone to suppress the immune system and promote the that were originally developed to prevent immune rejection of
formation of new acetylcholine receptors in muscle cell mem- transplanted organs have been useful in treating MG. Additionally,
branes. She also underwent occasional plasmapheresis when the long-awaited study results from the “Randomized Trial of
her symptoms became especially severe. She was given a pre- Thymectomy in Myasthenia Gravis” compared patients who
scription of atropine as needed to reduce the nausea, abdomi- received a thymectomy plus prednisone to a group that received
nal cramps, diarrhea, and excessive salivation she experienced only prednisone (Wolfe et al., 2016). Those who received surgery
as side effects of the pyridostigmine. plus prednisone had an overall reduction in muscle weakness and
required lower daily doses of prednisone (Kaufman et al., 2016).
Discussion Based on this, treatment of MG with combined surgery and medi-
cation for those who meet surgical criteria, should be considered.
MG is no longer considered a fatal disease, and most patients
lead near normal lives with the help of either drugs or surgery.
Chapter 13 Cholinergic Agonists 167
remember, however, that psychologic dependence also CONNECTION Checkpoint 13.2
occurs with nicotine and that most successful smoking ces-
sation programs include behavioral modification therapy Some cholinergic agonists activate both muscarinic and nicotinic
such as self-help groups. The consistent use of NRT roughly receptors. From what you learned in Chapter 12, give the locations
doubles a patient’s chances of quitting smoking, but a great where each of these receptors may be found. Answers to Connec-
deal of persistence and motivation is required. tion Checkpoint questions are available on the faculty resources site.
Please consult with your instructor.
Understanding Chapter 13
Key Concepts Summary 13.4 A cholinergic crisis may develop with overdoses of
AChE inhibitors or with certain toxins.
13.1 Drugs can activate cholinergic receptors either
directly or indirectly. 13.5 Acetylcholinesterase inhibitors are used in the
pharmacotherapy of myasthenia gravis to increase
13.2 Muscarinic agonists produce their effects by the strength of muscular contraction.
directly stimulating cholinergic receptors.
13.6 Nicotine acts by activating ACh receptors at the
13.3 Acetylcholinesterase inhibitors are used to treat ganglia.
Alzheimer’s disease and myasthenia gravis.
CASE STUDY: Making the Patient Connection
Remember the patient “Patricia amount of urine, estimated at 900 mL on this visit, and a
Sparks” at the beginning of the diagnosis of “overflow incontinence” is made. Her pro-
chapter? Now read the vider gives her a short-term prescription for bethanechol
remainder of the case study. and she is to return to the office in 3 days.
Based on the information
presented within this chapter, Critical Thinking Questions
respond to the critical thinking
questions that follow. 1. As Mrs. Sparks’ nurse, you will be reviewing her
medications before she leaves the office. What pertinent
Patricia Sparks is an 82-year-old patient who lives alone in a information should she receive about bethanechol?
two-story house. She has been in excellent health and has
required no medications other than an occasional aspirin 2. Mrs. Sparks states, “Sometimes, my memory is not so
for osteoarthritis pain. Due to the osteoarthritis, she has had good and I forget to take my medication.” What
a left knee replacement. Patricia bounced back relatively should she do if she forgets a dose? List suggestions
quickly after surgery, but required two straight-catheteriza- that you could provide this patient to help remember
tions due to urinary retention in the postoperative period. her medication times and to ensure safe and effective
administration.
During the past two days, she noticed leakage of urine
and felt as if she was not emptying her bladder. When she 3. What parameters would you use to determine the
returned to her provider on her third postoperative day, effectiveness of this drug therapy?
she reported these symptoms to the nurse. A bladder scan
confirmed that Mrs. Sparks was retaining a significant Answers to Critical Thinking Questions are available on the
faculty resources site. Please consult with your instructor.
Additional Case Study 1. What should the nurse tell this patient about her
continued thoughts and cravings for cigarettes?
The patient has smoked cigarettes for the past 25 years.
She tells the nurse that she has been using nicotine 2. Identify two websites with helpful tips that might aid
replacement therapy (Nicorette) as prescribed, for the this patient with smoking cessation.
past week. However, she continues to think about and
crave cigarettes, especially when she is with a group of Answers to Additional Case Study questions are available on the
her coworkers who smoke. faculty resources site. Please consult with your instructor.
The words you are searching are inside this book. To get more targeted content, please make full-text search by clicking here.
Home
Explore
(GNUR 294) 1 Adams, Michael Patrick_ Urban, Carol Quam - Pharmacology_ connections to nursing practice (2018_2019, Pearson) - libgen.li-1-400
View in Fullscreen
(GNUR 294) 1 Adams, Michael Patrick_ Urban, Carol Quam - Pharmacology_ connections to nursing practice (2018_2019, Pearson) - libgen.li-1-400
Discover the best professional documents and content resources in AnyFlip Document Base.
Search