1218 Unit 10 Pharmacology of the Endocrine System
that predisposes the patient to hypoxemia. It is contrain- Because repaglinide is rapidly absorbed, it should be
dicated for 2 days prior to, and 2 days after, receiving IV taken shortly before each meal. It is effective in lowering post-
radiographic contrast. Metformin is used with caution in prandial glucose levels and in reducing A1C levels but has
patients with anemia, diarrhea, vomiting, dehydration, little effect on fasting glucose levels. It undergoes almost no
fever, gastroparesis, or GI obstruction; in older adults; and renal excretion, and so it can be used in patients with CKD.
in those with hyperthyroidism, pituitary insufficiency, or
trauma; or during pregnancy and lactation. Safety in chil- Mechanism of Action: Repaglinide lowers glucose
dren under age 10 has not been established. levels by stimulating insulin release from pancreatic beta
cells. Patients must have some ability to secrete insulin for
Drug Interactions: Alcohol increases the risk for lactic the drug to be effective.
acidosis and should be avoided. Captopril, furosemide, and
nifedipine may increase the risk for hypoglycemia. Use with Pharmacokinetics:
IV radiographic contrast may cause lactic acidosis and
CKD. The following drugs may decrease renal excretion Route(s) PO
of metformin: amiloride, cimetidine, digoxin, dofetilide, Absorption Rapidly absorbed following PO
midodrine, morphine, procainamide, quinidine, ranitidine, administration
triamterene, trimethoprim, and vancomycin. Acarbose may Distribution 98% protein bound
decrease blood levels of metformin. Use with other antidia- Primary metabolism Hepatic (CYP3A4)
betic drugs potentiates hypoglycemic effects. Herbal/Food: Primary excretion 90% in feces
Metformin decreases the absorption of vitamin B12 and folic Onset of action 15–30 min; peak: 1 h
acid. Garlic and ginseng may increase hypoglycemic effects. Duration of action 4h
Pregnancy: Category B. Adverse Effects: Repaglinide is generally well toler-
ated; the most common adverse effect is hypoglycemia.
Treatment of Overdose: For overdose or develop- Other adverse effects include nausea, vomiting, diarrhea,
ment of lactic acidosis, hemodialysis can be used to correct and dyspepsia. Headache, paresthesias, upper respiratory
the acidosis and remove excess metformin. infections, sinusitis, rhinitis, or bronchitis may also occur.
Nursing Responsibilities: Key nursing implications Contraindications/Precautions: Repaglinide is
for patients receiving metformin are included in the Nurs- contraindicated in people with type 1 diabetes or DKA.
ing Practice Application for Patients Receiving Pharmaco- It should be used with caution in patients with hepatic
therapy for Type 2 Diabetes. impairment, during pregnancy or lactation, in older adults,
or in those with systemic infection, surgery, or trauma. Its
Drugs Similar to Metformin safety in children has not been established.
(Glucophage, Glumetza, Others)
Drug Interactions: Drugs that induce hepatic CYP3A4
Metformin is the only biguanide available. enzyme such as barbiturates, carbamazepine, rifampin, and
pioglitazone may increase repaglinide metabolism and cause
Meglitinides hyperglycemia. Drugs that inhibit CYP3A4 such as erythro-
mycin, ketoconazole, and miconazole inhibit repaglinide
The meglitinides act by stimulating the release of insulin metabolism and may potentiate hypoglycemia. Gemfibro-
from pancreatic islet cells in a manner similar to that of the zil may increase risk for hypoglycemia. Use with isophane
sulfonylureas. Both drugs in this class have short dura- insulin may cause myocardial ischemia. Herbal/Food: The
tions of action of 2 to 4 hours. Their efficacy is equal to that concurrent intake of grapefruit juice inhibits metabolism and
of the sulfonylureas, and they are well tolerated. Hypogly- may result in increased repaglinide levels and hypoglyce-
cemia is the most common adverse effect. mia. Garlic and ginseng may increase hypoglycemic effects.
PROTOTYPE DRUG Repaglinide (Prandin) Pregnancy: Category C.
Classification Therapeutic: Antidiabetic drug Treatment of Overdose: During overdose, provide
Pharmacologic: Meglitinide symptomatic therapy and a concentrated source of glucose
for hypoglycemia, preferably by the IV route.
Therapeutic Effects and Uses: Approved in 1997,
repaglinide is used to lower blood glucose levels in Nursing Responsibilities: Key nursing implications
patients with type 2 diabetes as an adjunct to diet and for patients receiving repaglinide are included in the Nurs-
exercise. It may be used alone or in combination with met- ing Practice Application for Patients Receiving Pharmaco-
formin or a thiazolidinedione. therapy for Type 2 Diabetes.
Chapter 66 Pharmacotherapy of Diabetes Mellitus 1219
Drugs Similar to Repaglinide (Prandin) Adverse Effects: Rosiglitazone is generally well toler-
ated. The most prominent adverse effect is edema, including
The only other meglitinide is nateglinide. macular edema. Anemia, headache, back pain, fatigue, diar-
rhea, upper respiratory infection, or sinusitis may occur. The
Nateglinide (Starlix): Approved in 2000, nateglinide has drug can also raise serum lipid levels, including HDL choles-
actions and uses similar to those of repaglinide. It is used terol, triglycerides, and LDL cholesterol. It is recommended
alone or in combination with metformin for managing glu- that baseline liver function tests be obtained prior to initiating
cose levels in patients with type 2 diabetes who have not treatment, and then assessed every 3 to 6 months. Patients
achieved glycemic control through diet and exercise. It is not should be informed of the signs of liver damage (nausea,
effective for type 1 diabetes. Like repaglinide, it is given 5 to fatigue, dark urine, jaundice) as well as the signs of heart fail-
20 minutes before meals. An important difference between ure (dyspnea, weight gain, edema, fatigue) while taking rosi-
these drugs is that nateglinide is primarily excreted by the kid- glitazone. Research has also raised the concern of increased
neys, so it should be used with caution in patients with CKD. fracture risk among women taking drugs in this class. Black
Like repaglinide, nateglinide is well tolerated and hypoglyce- Box Warning: Drugs in this class can cause or worsen heart
mia is usually mild. The drug is pregnancy category C. failure due to increased fluid retention. In addition, rosigli-
tazone may increase the risk of myocardial infarction (MI).
Thiazolidinediones
Contraindications/Precautions: Rosiglitazone is con-
The thiazolidinediones (TZDs), or glitazones, reduce traindicated in people with severe heart failure, liver disease,
blood glucose by decreasing insulin resistance and inhib- or elevated liver enzymes and during pregnancy or lactation.
iting hepatic gluconeogenesis. Optimal lowering of Its safety in children has not been established. Rosiglitazone
blood glucose may require 3 to 4 months of therapy. The is contraindicated in patients with type 1 diabetes or DKA.
most common adverse effects are fluid retention, head-
ache, and weight gain. Hypoglycemia does not occur Drug Interactions: Inducers of hepatic CYP2C8 such
with drugs in this class. Because of their tendency to pro- as rifampin may decrease the effects of rosiglitazone. Inhib-
mote fluid retention, thiazolidinediones are contraindi- itors of CYP2C8 such as azole antifungals, fluvoxamine,
cated in patients with serious heart failure or pulmonary gemfibrozil, and trimethoprim may elevate rosiglitazone
edema. plasma levels and increase the risk for adverse reactions.
Concurrent use of rosiglitazone with insulin can increase
PROTOTYPE DRUG Rosiglitazone (Avandia) edema and the risk for heart failure and myocardial isch-
emia. Other antidiabetic drugs, angiotensin II receptor
Classification Therapeutic: Antidiabetic drug antagonists, and gemfibrozil can increase the hypogly-
Pharmacologic: Thiazolidinedione cemic effects. Use of rosiglitazone with nitrates is not rec-
ommended due to the potential for myocardial ischemia.
Therapeutic Effects and Uses: Approved in 1999, Thiazide diuretics, phenothiazines, and atypical antipsy-
rosiglitazone is used to lower blood glucose levels in chotic drugs can decrease the hypoglycemic effects of rosi-
patients with type 2 diabetes as an adjunct to diet and glitazone by increasing blood glucose levels. Herbal/Food:
exercise. It can be used as monotherapy or in combination Garlic and ginseng can increase the risk for hypoglycemia if
with metformin, a sulfonylurea, or insulin. It is effective in used with rosiglitazone. Cocoa and rosemary may decrease
lowering fasting glucose and A1C levels. Optimal thera- the therapeutic effect and have a hyperglycemic effect.
peutic effects take several weeks to occur.
Pregnancy: Category C.
Mechanism of Action: Rosiglitazone lowers blood
glucose levels by increasing cellular sensitivity to insu- Treatment of Overdose: Standard treatment for
lin, thereby reducing insulin resistance. In addition, it hypoglycemia is initiated during overdose, along with
decreases gluconeogenesis by the liver. symptomatic treatment of edema or fluid overload.
Pharmacokinetics: Nursing Responsibilities: Key nursing implications
for patients receiving rosiglitazone are included in the
Route(s) PO Nursing Practice Application for Patients Receiving Phar-
macotherapy for Type 2 Diabetes.
Absorption Rapidly absorbed
Drugs Similar to Rosiglitazone (Avandia)
Distribution Greater than 99% protein bound
The only other drug in this class is pioglitazone.
Primary metabolism Hepatic (CYP2C8)
Pioglitazone (Actos): Approved in 1999, pioglitazone has
Primary excretion Primarily renal, with actions and uses similar to those of rosiglitazone. It is rapidly
approximately 25% in feces
Onset of action Within 1 h; peak: 1 h
Duration of action 12–24 h
1220 Unit 10 Pharmacology of the Endocrine System
absorbed following PO administration, with peak effects Primary excretion Primarily in feces, 30% in urine
occurring within 7 days of beginning therapy. Pioglitazone Onset of action Peak: 1 h
can decrease serum levels of oral contraceptives and can Duration of action 2–4 h
cause nonovulating premenopausal women to resume ovula-
tion; therefore, a reliable form of contraception is recom- Adverse Effects: The most common adverse effects
mended. Excessive alcohol consumption may affect glycemic of acarbose are diarrhea, flatulence, abdominal disten-
control. Hepatic function should be assessed for a baseline tion, borborygmi, anemia (iron deficiency), urticaria, and
and periodically thereafter as with rosiglitazone. Pioglitazone erythema. The GI-related effects may diminish as therapy
has been associated with an increased risk for bladder, pros- progresses; however, they will worsen if the patient does
tate, and pancreatic cancer. The drug carries the same black not adhere to the prescribed diabetic diet. Hypoglycemia
box warnings regarding heart failure and myocardial isch- may occur if acarbose is combined with other hypogly-
emia as rosiglitazone. The drug is pregnancy category C. cemic drugs. If hypoglycemia does develop, it must be
treated with glucose and not sucrose (table sugar), because
Alpha-Glucosidase Inhibitors the drug inhibits the absorption of sucrose. Acarbose may
cause elevation of liver enzymes (plasma transaminases),
The alpha-glucosidase inhibitors act by blocking enzymes in although liver damage has not been reported, but levels
the small intestine responsible for breaking down complex return to normal following drug withdrawal.
carbohydrates into monosaccharides. Because carbohydrates
must be in the monosaccharide form to be absorbed, diges- Contraindications/Precautions: Acarbose is con-
tion of glucose is delayed. These drugs have minimal traindicated in patients with inflammatory bowel disease,
adverse effects, with the most common being GI related, bowel obstruction, or colon ulcers and in those predis-
such as abdominal cramping, diarrhea, and flatulence. posed to bowel obstructions. It is used with caution in
Although alpha-glucosidase inhibitors do not produce hypo- patients with GI distress or liver disorders and during
glycemia when used alone, hypoglycemia may occur when pregnancy or lactation. Safety in children has not been
these drugs are combined with insulin or a sulfonylurea. established.
PROTOTYPE DRUG Acarbose (Precose) Drug Interactions: Use with sulfonylureas may
increase the risk for hypoglycemia. Drugs that cause
Classification Therapeutic: Antidiabetic drug hyperglycemia such as thiazide diuretics, corticosteroids,
Pharmacologic: Alpha-glucosidase phenothiazines, estrogens, phenytoin, or isoniazid may
decrease the effectiveness of acarbose. Herbal/Food: Gin-
inhibitor seng, garlic, black cohosh, juniper berries, aloe, or dande-
lion root can cause hypoglycemia. Cocoa and rosemary
Therapeutic Effects and Uses: Approved in 1995, have a hyperglycemic effect and may decrease the thera-
acarbose lowers blood glucose levels in individuals with peutic effect of acarbose.
type 2 diabetes who cannot adequately manage glucose
levels by diet and exercise alone. It may be used alone or in Pregnancy: Category B.
combination with a sulfonylurea, metformin, or insulin. By
slowing the breakdown and absorption of carbohydrates, Treatment of Overdose: Unlike the sulfonylureas,
the rise in postprandial glucose level is reduced. A1C level overdose with acarbose will not cause hypoglycemia.
is lowered as well. Abdominal pain, flatulence, and diarrhea are treated
symptomatically.
Mechanism of Action: Acarbose lowers glucose lev-
els by interfering with carbohydrate absorption from the Nursing Responsibilities: Key nursing implications
GI tract. It acts locally in the GI tract to inhibit the enzyme for patients receiving acarbose are included in the Nursing
responsible for carbohydrate breakdown. Practice Application for Patients Receiving Pharmacother-
apy for Type 2 Diabetes.
Pharmacokinetics:
Route(s) PO Drugs Similar to Acarbose (Precose)
Absorption Only 2% absorbed (low absorption is The only other drug in this class is miglitol.
desired because the drug acts locally Miglitol (Glyset): Approved in 1996, miglitol is an alpha-
glucosidase inhibitor used as monotherapy or in combina-
in the GI tract); some metabolites are tion with other antidiabetic drugs for the pharmacotherapy
of type 2 diabetes. It acts by delaying the conversion of com-
absorbed plex carbohydrates to monosaccharides (glucose), thereby
lessening the rise in postprandial serum glucose levels. Like
Distribution Acts locally in the digestive tract
Primary metabolism Metabolized in the GI tract by intes-
tinal bacteria and digestive enzymes
Chapter 66 Pharmacotherapy of Diabetes Mellitus 1221
acarbose, the drug must be present in the intestine at the diet and exercise and can be administered as monotherapy
same time the carbohydrates are being digested; thus, the or in combination with other oral antidiabetic drugs.
drug must be taken with a meal. The adverse effects are
similar with the notable exception of not causing increased The actions of sitagliptin are glucose dependent: They
liver enzymes. Acarbose and miglitol both act locally in the occur only in the presence of elevated serum glucose, and
intestine, although miglitol is completely absorbed and has so the risk for hypoglycemia is reduced. Sitagliptin has the
the potential to produce systemic effects. Overdose does not added benefit of increasing satiety, or the feeling of fullness
cause hypoglycemia. The drug is pregnancy category B. following a meal, resulting in a lower calorie intake and
improved weight control. Sitagliptin lowers both fasting
Incretin Therapies and postprandial glucose levels. Janumet is a fixed-dose
combination drug containing sitagliptin and metformin.
66.8 Incretin therapies offer a different
approach to treating type 2 diabetes. Mechanism of Action: Sitagliptin inhibits DPP-4, the
enzyme responsible for breaking down incretins. Inhibi-
Incretins are hormones released by the mucosa of the tion of DPP-4 reduces the destruction of incretins. Levels
small intestine in response to meals. The most important of incretin hormones increase, thus decreasing blood glu-
incretin is glucagon-like peptide (GLP-1), which acts rap- cose levels in patients with type 2 diabetes.
idly to produce the following effects:
Pharmacokinetics:
• Increase in the amount of insulin secreted by the
pancreas Route(s) PO
• Decrease in the amount of glucagon secreted by the Absorption Rapidly absorbed
pancreas
Distribution Approximately 38% protein bound
• Delay in gastric emptying (slow glucose absorption)
• Decrease in food intake by increasing the level of Primary metabolism 20% metabolized in the liver by
satiety. CYP3A4 and CYP2CB
Two groups of drugs have been developed that can Primary excretion Renal
influence incretin release. The first activates the GLP-1 recep-
tor, causing essentially the same glucose-lowering actions as Onset of action 30–60 min; peak: 1–4 h
the natural hormone. Albiglutide (Tanzeum), exenatide
(Byetta), liraglutide (Victoza), and lixisenatide (Adlyxin) are Duration of action Half-life: 12 h
synthetic drugs that mimic the action of incretin, thus they
are called incretin mimetics or GLP-1 receptor agonists. They Adverse Effects: Sitagliptin is well tolerated by most
are all administered by the subcutaneous route, although patients and adverse effects are generally not serious. Pos-
albiglutide offers the advantage of once-weekly dosing. sible adverse effects include headache, diarrhea, naso-
pharyngitis, and upper respiratory infection. Allergic
The second class of drugs that enhance incretin actions skin reactions and anaphylaxis have been reported. As
are the dipeptidyl peptidase 4 (DPP-4) inhibitors. Alogliptin monotherapy, sitagliptin does not cause hypoglycemia;
(Nesina), linagliptin (Tradjenta), saxagliptin (Onglyza), however, when used concurrently with a sulfonylurea or
and sitagliptin (Januvia) prevent the breakdown of incre- insulin, hypoglycemia may occur.
tins, allowing the hormone levels to rise and produce a
greater response. These incretin enhancers are given orally Contraindications/Precautions: Sitagliptin is con-
and are effective at lowering blood glucose with few traindicated in type 1 diabetes and DKA. It is used with
adverse effects. They work well with other antidiabetic caution in patients with CKD, in older adults, or during
drugs and do not cause hypoglycemia. pregnancy and lactation. Safety for children under age 18
has not been established.
PROTOTYPE DRUG Sitagliptin (Januvia)
Drug Interactions: Sitagliptin may increase digoxin
Classification Therapeutic: Antidiabetic drug levels. Herbal/Food: Cocoa and rosemary may decrease
Pharmacologic: DPP-4 inhibitor, incretin the therapeutic effect and have a hyperglycemic effect.
enhancer Pregnancy: Category C.
Therapeutic Effects and Uses: Approved in 2006, Treatment of Overdose: Overdose is treated symp-
sitagliptin is an oral incretin enhancer that is used to help tomatically. If used in combination with other glucose-
lower glucose levels in patients with type 2 diabetes who are lowering drugs and hypoglycemia occurs, a concentrated
unable to achieve normal glucose levels with diet and exer- source of glucose should be administered by the IV route.
cise alone. The drug is used as adjunct therapy along with
Nursing Responsibilities: Key nursing implications
for patients receiving sitagliptin are included in the Nurs-
ing Practice Application for Patients Receiving Pharmaco-
therapy for Type 2 Diabetes.
1222 Unit 10 Pharmacology of the Endocrine System
Drugs Similar to Sitagliptin (Januvia) glucose levels and causes a consistent, slow weight loss. A
disadvantage of exenatide is that it must be given twice
Other incretin modulators include the GLP-1 agonists albi- daily by the subcutaneous route, within 60 minutes before
glutide, dulaglutide, exenatide, liraglutide, and lixisena- the morning and evening meals. It is available as a pen
tide, and the DPP-4 inhibitors alogliptin, linagliptin, and injector. Adverse effects include nausea, vomiting, diar-
saxagliptin. rhea, dyspepsia, anorexia, and gastroesophageal reflux. It
can also cause nervousness, dizziness, and diaphoresis.
Albiglutide (Tanzeum): Albiglutide is a GLP-1 receptor Like sitagliptin, it does not cause hypoglycemia. The drug
agonist, approved in 2014 to improve glycemic control in is pregnancy category C.
adults with type 2 diabetes mellitus. It is not used for
patients with type 1 diabetes mellitus or as first-line ther- Linagliptin (Tradjenta): Approved in 2011, linagliptin is a
apy for those unable to control blood glucose through diet DPP-4 inhibitor. The drug is well tolerated and has the
and exercise. Although it must be administered by the sub- same actions and adverse effects as sitagliptin. One poten-
cutaneous route, it has the advantage of once-weekly dos- tial advantage over the other DPP-4 inhibitors is that lina-
ing and may be given without regard to meals or time of gliptin is excreted through the liver rather than the
day. It is packaged as a single-dose pen for ease of admin- kidneys. This allows the drug to be used in patients with
istration. The drug carries a black box warning that it may significant CKD. In 2012 a fixed-dose combination of lina-
increase the risk for thyroid gland tumors. It is contraindi- gliptin with metformin (Jentadueto) was approved. Jenta-
cated in patients with a health or family history of thyroid dueto carries a black box warning that patients may be at
tumors or multiple endocrine neoplasia syndrome type 2. risk for lactic acidosis from accumulation of metformin.
Acute pancreatitis has occurred in some patients taking The drug is pregnancy category B.
this medication. This drug is pregnancy category C.
Liraglutide (Victoza): Approved in 2010 for glycemic con-
Alogliptin (Nesina): One of the newer DPP-4 inhibitors, trol in patients with type 2 diabetes mellitus, liraglutide is
alogliptin was approved in 2013 for patients who are a GLP-1 receptor agonist. Like exenatide, liraglutide is
unable to control their blood glucose through exercise and effective at reducing A1C levels as well as decreasing
diet alone. The drug works by the same mechanism and appetite and producing a desirable weight loss. An advan-
has the same effectiveness and side effects as the other tage over exenatide is that it can be given once daily.
DPP-4 inhibitors. When approving alogliptin, the FDA Because of its positive effects on weight loss, liraglutide
simultaneously approved two fixed-dose combinations of (Saxenda) was subsequently approved for chronic weight
alogliptin with metformin (Kazano) and pioglitazone management. Although Victoza and Saxenda have the
(Oseni). Kazano carries a black box warning due to the same active ingredient, Saxenda is approved only for
possibility of lactic acidosis (from metformin), and Oseni weight management. Liraglutide is well tolerated, with the
due to the possibility of heart failure (from pioglitazone). most common adverse effects being headache, nausea, diar-
Alogliptin is pregnancy category B. rhea, and anti-liraglutide antibody formation. Hypoglyce-
mia is not a problem with monotherapy, but it may occur if
Dulaglutide (Trulicity): One of the newer drugs in this used in combination with other antidiabetic drugs. Pancre-
class, dulaglutide was approved in 2014 as an adjunct to atitis has been reported with other incretin enhancers and
diet and exercise in improving glycemic control in patients may also occur in patients taking liraglutide. Like albiglu-
with type 2 diabetes. Given by the subcutaneous route once tide, the drug carries a black box warning about the possi-
weekly, dulaglutide is a GLP-1 receptor agonist that causes bility of thyroid tumors. Patients with a personal or family
increased insulin release by the pancreas. The drug may be history of thyroid cancer should not take this drug. In
used alone or in combination with metformin. Actions and 2016, the FDA approved Xultophy, a combination contain-
side effects are the same as other GLP-1 agonists such as ing liraglutide and insulin degludec for type 2 diabetes.
albiglutide. Like albiglutide, dulaglutide carries a black box Liraglutide is pregnancy category C.
warning that it may increase the risk for thyroid gland
tumors and thus is contraindicated in patients with a his- In postmarket reviews following its initial approval,
tory of thyroid tumors or multiple endocrine neoplasia research determined that use of liraglutide reduced the
syndrome type 2. This drug is pregnancy category C. rates of cardiovascular deaths and other adverse cardiovas-
cular events. In 2017, the FDA added a new indication for
Exenatide (Byetta): Exenatide was approved in 2005 for liraglutide: to reduce the risk of major cardiovascular
patients with type 2 diabetes who are unable to achieve events in adult patients with type 2 diabetes mellitus and
adequate glycemic control following metformin or sulfo- high cardiovascular risk.
nylurea monotherapy. A GLP-1 receptor agonist, exenatide
mimics the actions of the incretin hormones normally Lixisenatide (Adlyxin): Approved in 2016, lixisenatide is
secreted by the intestines, which slow the absorption of one of the newest GLP-1 receptor agonists. It is adminis-
glucose. It is effective in lowering fasting and postprandial tered once daily by subcutaneous injection for glycemic
Chapter 66 Pharmacotherapy of Diabetes Mellitus 1223
control in patients with type 2 diabetes. Its actions, effec- agonist but its mechanism for improving glycemic control
tiveness, and safety are similar to other incretin mimetics. is not known. The drug is also approved for acromegaly,
Common side effects include nausea, vomiting, headache, Parkinson’s disease, and hyperprolactinemia. Common
diarrhea, dizziness, and hypoglycemia. In 2016, the FDA adverse effects include nausea, fatigue, dizziness, vomit-
also approved Soliqua, a combination containing ing, and headache.
lixisenatide and insulin glargine for type 2 diabetes.
Lixisenatide does not have a pregnancy category but the In 2013, the FDA approved canagliflozin (Invokana), the
manufacturer recommends that the drug only be given to first in a new class of drugs called the sodium-glucose co-
pregnant patients if the potential benefits outweigh the transporter (SGLT) inhibitors. Inhibiting the SGLT in the kid-
potential risks to the fetus. ney allows more glucose to leave the blood and be excreted
via the urine. This drug has the advantage of promoting
Saxagliptin (Onglyza): Saxagliptin is a DPP-4 inhibitor weight loss; however, it is contraindicated in patients with
approved in 2009 to improve glycemic control in patients chronic kidney disease. The added glucose in the urine
with type 2 diabetes. The drug is well tolerated and has the serves as a substrate for bacterial and fungal growth, thus
same actions and adverse effects as sitagliptin. Kombig- increasing the frequency of mycotic infections of the urinary
lyze XR is a fixed-dose combination of saxagliptin and tract and genitalia. Canagliflozin is pregnancy category C.
metformin. Qtern is a combination of saxagliptin with Two additional drugs in this class, dapagliflozin (Farxiga)
dapagliflozin. Saxagliptin is pregnancy category B. and empagliflozin (Jardiance), were approved in 2014 and
have very similar actions and adverse effects.
Miscellaneous Antidiabetic Drugs
In postmarket reviews following its initial approval,
A few miscellaneous drugs play minor roles in treating research determined that use of empagliflozin rapidly
type 2 diabetes. Bromocriptine (Cycloset) is an older drug reduced the rates of cardiovascular deaths and hospitaliza-
that was approved for a new indication, treating type 2 tions due to heart failure. In 2016, the FDA added a new
diabetes, in 2009. Bromocriptine is a dopamine receptor indication for empagliflozin: to reduce the risk of cardio-
vascular death in adult patients with type 2 diabetes mel-
litus and cardiovascular disease.
CONNECTIONS: NURSING PRACTICE APPLICATION
Patients Receiving Pharmacotherapy for Type 2 Diabetes
Assessment
Baseline assessment prior to administration:
• Obtain a complete health history including endocrine, cardiovascular, hepatic, or kidney disease; pregnancy; or breastfeeding. Obtain a drug history
including allergies, current prescription and OTC drugs, herbal preparations, caffeine, nicotine, and alcohol use. Be alert to possible drug interactions.
• Obtain a history of current symptoms, duration and severity, and other related signs or symptoms (e.g., paresthesias of hands or feet). Assess feet
and lower extremities for possible ulcerations.
• Obtain a dietary history including caloric intake and number of meals and snacks per day. Assess fluid intake and type of fluids consumed.
• Obtain baseline vital signs, height, and weight.
• Evaluate appropriate laboratory findings (e.g., CBC, electrolytes, glucose, A1C level, lipid profile, hepatic and renal function studies).
• Assess the patient’s ability to receive and understand instructions. Include family and caregivers as needed.
Assessment throughout administration:
• Assess for desired therapeutic effects (e.g., glucose levels remain within normal limits, A1C levels demonstrate adequate glucose control).
• Continue periodic monitoring of hepatic function studies.
• Assess for and report promptly any adverse effects appropriate to the type of oral drug: signs of hypoglycemia (e.g., nausea, paleness, sweating,
diaphoresis, tremors, irritability, headache, light-headedness, anxiety, or decreased level of consciousness) most commonly associated with
sulfonylureas and meglitinides, and hyperglycemia (e.g., flushed or dry skin, polyuria, polyphagia, polydipsia, drowsiness, glycosuria, ketonuria, or
acetone breath), gastric upset, diarrhea, infection, edema.
Implementation
Interventions and (Rationales) Patient-Centered Care
Ensuring therapeutic effects: • Teach the patient to report any return of original symptoms.
• Continue assessments as above for therapeutic effects. (Depending on • Teach the patient the symptoms of hyper- and hypoglycemia to
the severity of hyperglycemia, supplemental insulin may be needed for observe for and to check capillary glucose level routinely and if
blood glucose levels to return gradually to normal.) symptoms are present. Promptly report any noticeable symptoms
and concurrent capillary glucose level to the healthcare provider.
(continued )
1224 Unit 10 Pharmacology of the Endocrine System
CONNECTIONS: NURSING PRACTICE APPLICATION (continued)
Implementation
Interventions and (Rationales) Patient-Centered Care
• Ensure that dietary needs are met based on the need to lose, gain, or • Review current diet, lifestyle, and activity level with the patient. Arrange
maintain current weight and glucose levels. Consult with the dietitian as a dietitian consult based on the need to alter diet or food choices.
needed. Limit or eliminate alcohol use. (Adequate caloric protein, Teach the patient to limit or eliminate alcohol use. If alcoholic
carbohydrate, and fat amounts support the oral hypoglycemic regimen beverages are consumed, limit to one per day and consume along
for glucose control. Activity and lifestyle will also be factored into dietary with a complete meal to ensure food intake balances alcohol
management. As alcohol is metabolized, it can raise and then metabolism.
precipitously lower blood glucose, raising the risk of hypoglycemia.
Patients on sulfonylureas should avoid or eliminate alcohol entirely • Instruct patients on sulfonylureas (e.g., glyburide) to avoid or eliminate
because a disulfiram-like reaction with severe nausea, vomiting, and alcohol use.
potential hypotension may result.)
Minimizing adverse effects: • Instruct the patient on appropriate blood glucose monitoring
• Continue to monitor capillary glucose levels. Check with the healthcare techniques to obtain capillary blood glucose levels, followed by return
demonstration, and when to contact the healthcare provider (e.g.,
provider before giving an oral hypoglycemic if blood sugar is less than glucose less than 70 mg/dL). Monitor use and ensure proper
70 mg/dL or per the parameters as ordered by the healthcare provider. functioning of all equipment to be used at home.
(Daily glucose levels, especially before meals, will assist in maintaining
adequate control of blood glucose and aid in assessing the
appropriateness of current drug therapy.)
• Continue to monitor periodic laboratory work: CBC, electrolytes, glucose, • Instruct the patient on the need to return periodically for laboratory
A1C level, lipid profile, hepatic and renal function studies. (Periodic work.
monitoring of laboratory work assists in determining glucose control and
the need for any change in medication and assesses for complications. • Teach patients on sulfonylureas to immediately report any nausea,
A1C levels provide a measure of glucose control over several months’ vomiting, yellowing of the skin or sclera, abdominal pain, light or clay-
time. Sulfonylureas may cause hepatotoxicity. Biguanides may cause colored stools, or darkening of urine to the healthcare provider.
lactic acidosis. Lifespan: Age-related physiologic differences may place
the older adult at greater risk for hepatotoxicity.) • Teach patients on biguanides to immediately report any drowsiness,
malaise, decreased respiratory rate, or general body aches to the
healthcare provider.
• Assess for symptoms of hypoglycemia. If symptoms are noted, provide • Teach the patient to always carry a quick-acting carbohydrate source
a quick-acting carbohydrate source (e.g., juice or other simple sugar), in case symptoms of hypoglycemia occur. If unsure whether
and then check capillary glucose level. Report to the healthcare provider symptoms indicate hypo- or hyperglycemia, treat as hypoglycemia
if glucose is less than 70 mg/dL or as ordered. If mealtime is not and then check capillary glucose. If symptoms are not relieved in
immediate, provide a longer acting protein source to ensure that 10–15 min, or if blood sugar is below 70 mg/dL (or the parameters as
hypoglycemia does not recur. (Hypoglycemia is especially likely to occur ordered), immediately notify the healthcare provider.
if the patient is taking sulfonylureas or meglitinides, although it may
occur with other types of oral antidiabetic drugs, especially if food
sources are inadequate. Lifespan: Age-related physiologic differences
may place the older adult at greater risk for hypoglycemia. Providing a
quick-acting carbohydrate source and then checking the capillary
glucose level will ensure glucose does not decrease further while
locating the glucose testing equipment. When in doubt, treating
symptoms for suspected hypoglycemia is safer than allowing further
decreases in glucose and possible loss of consciousness with adverse
effects. Small additional amounts of carbohydrates will not dramatically
increase blood sugar if testing shows a hyperglycemic episode.)
• Monitor blood glucose more frequently during periods of illness or • Instruct the patient to check glucose levels more frequently when ill or
stress. (Blood glucose levels may increase or decrease during periods under stress. Stress may increase blood glucose because the stress
of illness or stress. Frequent monitoring during these times helps to response can cause glycogenolysis. Supplemental insulin may be
prevent hypoglycemia and ensures adequate glucose control.) required if oral antidiabetic drugs do not adequately control the blood
sugar. Illness, especially associated with anorexia, nausea, or
vomiting, may decrease the need for an oral hypoglycemic drug.
Notify the healthcare provider if unable to eat normal meals during
periods of illness or stress for possible change in drug regimen.
• Encourage increased activity and exercise, but monitor blood glucose • Teach the patient the benefits of increased activity and exercise and
before and after exercise and begin any new or increased exercise to begin any new routine or increase in exercise gradually.
routine gradually. Continue to monitor for hypoglycemia for up to 48 h
after exercise. (Exercise assists muscles to use glucose more efficiently • Instruct the patient to check glucose levels more frequently before
and increases insulin receptor sites in the tissues, lowering the blood and after exercise.
sugar and assisting with weight control. Benefits of exercise and
lowered blood sugar may continue for up to 48 h, increasing the risk of
hypoglycemia during this time. Frequent monitoring helps to prevent
hypoglycemia and ensures adequate glucose control.)
• Monitor for hypersensitivity and allergic reactions. Continue to monitor • Teach the patient to immediately report any itching, rashes, swelling,
the patient throughout therapy. (Anaphylactic reactions are possible particularly of the face or tongue, urticaria, flushing, dizziness,
although rare. As sensitivity occurs, reactions may continue to develop.) syncope, wheezing, throat tightness, or difficulty breathing.
• Assess for pregnancy or the possibility of pregnancy. (Some oral antidiabetic • Teach female patients of childbearing age to monitor for pregnancy
drugs are category C and must be stopped during pregnancy. Due to the and alert the healthcare provider if pregnant or if pregnancy is
increasing metabolic needs of pregnancy, supplemental insulin or switching suspected to discuss medication needs.
to insulin coverage may be required for the duration of the pregnancy.)
Chapter 66 Pharmacotherapy of Diabetes Mellitus 1225
CONNECTIONS: NURSING PRACTICE APPLICATION (continued)
Implementation
Interventions and (Rationales) Patient-Centered Care
• Continue to monitor for edema, blood pressure, and lung sounds in • Instruct the patient to immediately report any edema of the hands or
patients taking thiazolidinediones. (Drugs such as rosiglitazone may feet, dyspnea, or excessive fatigue to the healthcare provider.
cause edema and worsening of heart failure.)
• Monitor for hypoglycemia more frequently in patients on concurrent • Teach patients on concurrent beta-blocker therapy to monitor
beta-blocker therapy. (Beta blockers antagonize the action of some oral capillary blood glucose more frequently and to check blood glucose if
antidiabetic drugs and may mask the symptoms of a hypoglycemic minor changes in overall feeling are perceived (e.g., minor agitation or
episode, allowing the blood sugar to drop lower before it is perceived.) anxiety, slight tremors).
Patient understanding of drug therapy: • The patient, family, or caregiver should be able to state the reason for
• Use opportunities during administration of medications and during the drug, appropriate dose and scheduling, what adverse effects to
observe for and when to report them, and any special requirements of
assessments to discuss the rationale for drug therapy, desired medication therapy (e.g., drug needs during exercise or illness).
therapeutic outcomes, commonly observed adverse effects, parameters
for when to call the healthcare provider, and any necessary monitoring • Instruct the patient to carry a wallet identification card and wear
or precautions. (Using time during nursing care helps to optimize and medical identification jewelry indicating diabetes.
reinforce key teaching areas.)
Patient self-administration of drug therapy: • The patient, family, or caregiver is able to discuss appropriate dosing
• When administering the medication, instruct the patient, family, or and administration needs, including:
• Timing of doses: Most oral antidiabetic drugs are taken once or
caregiver in the proper self-administration of drug. (Utilizing time during twice a day. For drugs given once a day, take approximately 30
nurse administration of these drugs helps to reinforce teaching.) min before the first meal of the day. Alpha-glucosidase inhibitors
(e.g., acarbose) should be taken with meals.
• Insulin requirements: While patients with type 2 diabetes produce
some insulin, insulin injections may be required in addition to the
oral antidiabetic drug on occasion. This does not necessarily signal
a worsening of the disease condition but may be a temporary need.
Understanding Chapter 66
Key Concepts Summary 66.5 Serious complications of chronic diabetes include
neuropathy, nephropathy, retinopathy, and vascular
66.1 Serum glucose is maintained within a narrow range disease.
by the hormones insulin and glucagon.
66.6 Insulin is the cornerstone of therapy for patients
66.2 Type 1 diabetes is characterized by insufficient with type 1 and gestational diabetes.
insulin synthesis by the pancreas, whereas type 2
diabetes is characterized by insulin resistance in the 66.7 Antidiabetic drugs from multiple classes are used
target cells. to treat type 2 diabetes.
66.3 The classic signs and symptoms of diabetes include 66.8 Incretin therapies offer a different approach to
polyuria, polydipsia, and polyphagia. treating type 2 diabetes.
66.4 Acute complications of diabetes include diabetic
ketoacidosis, hyperosmolar hyperglycemic state,
and hypoglycemia.
CASE STUDY: Making the Patient Connection
Remember the patient Eileen is a 54-year-old woman who works full time as an
“Eileen Douglas” at the art teacher in a local high school. She also teaches art
beginning of the chapter? courses on the weekends at the local senior center. She vis-
Now read the remainder ited her healthcare provider last week for her annual physi-
of the case study. Based cal examination and to update her TB screening (PPD) for
on the information pre- the coming school year. The office called her back this
sented within this chapter, respond to the critical think- morning and requested that she make an appointment to
ing questions that follow. return tomorrow to discuss the results of her laboratory
1226 Unit 10 Pharmacology of the Endocrine System
tests. Her serum glucose level was elevated at 224 mg/dL Eileen’s provider will start her on glyburide (DiaBeta)
and she will need further testing to rule out type 2 and metformin (Glucophage) and will recheck her serum
diabetes. glucose in 1 month. In the meantime, she is to begin capillary
blood glucose testing before meals and at bedtime, and bring
Eileen has follow-up testing with the results of a fast- her log to the next visit. She is given dietary instructions and
ing serum glucose level at 131 mg/dL and a 2-hour 75-g you will be providing instruction on her medications.
oral glucose test of 242 mg/dL. A diagnosis of new-onset
type 2 diabetes is confirmed. Eileen expresses disbelief and Critical Thinking Questions
tells you, the nurse, “I can’t believe it! I watch what I eat; I
don’t eat a lot of sugar, cookies, or candy. I drink only diet 1. Why are two oral antidiabetic drugs prescribed for
soda. I don’t have any of the symptoms you hear about. Eileen?
And no one in my family has ever had diabetes.” A health
history and the results of Eileen’s recent physical examina- 2. What essential teaching does Eileen need about her
tion confirm overall good health. Her height is 1.7 meters glyburide (DiaBeta) and metformin (Glucophage)?
(5 ft 6 in.) and her weight is 79.5 kg (175 lb) with a BMI of
28.2 kg/m2, placing her in the “overweight” category. Vital 3. Eileen asks why she is not being started on insulin.
signs, physical examination, and all other laboratory work Why is insulin not being used at this time?
are within acceptable limits. Eileen admits that she has
been thirstier lately, “But it’s summertime and I always 4. Eileen tells you that she occasionally enjoys a glass of
drink more when it’s hot.” She has also been urinating wine with her dinner and wants to know if this is
more frequently but attributes that to her increased fluid allowed. How will you answer?
intake.
Answers to Critical Thinking Questions are available on the
faculty resources site. Please consult with your instructor.
Additional Case Study
Nicholas Jefferson is 8 years old and has just been diagnosed blood samples, and serum blood glucose samples are to be
with type 1 diabetes. After increasing symptoms during the drawn every 4 hours. The IV insulin drip is to be discontin-
past month, he was hospitalized for continuous nausea, ued when Nicholas’s blood glucose level is 240 mg/dL and
vomiting, and gradually increasing lethargy. His parents subcutaneous insulin will be started at that time.
report that during the past month or two, Nicholas has had
blurry vision and has been thirsty and hungry constantly. 1. What type of insulin do you anticipate using for the IV
He has been eating frequently but does not seem to be gain- bolus dose and IV drip?
ing any weight. They also tell you that on several occasions,
Nicholas has wet the bed, which is very unusual for him. On 2. Why do you think the insulin IV will be stopped when
admission, his serum glucose level is 420 mg/dL with a the blood glucose level is 240 mg/dL and not at the
urine sample positive for glucose and ketones. Nicholas is to normal level of 70 to 100 mg/dL?
remain NPO and will be started on an IV with 0.45 normal
saline for fluid replacement, given an IV bolus of insulin, 3. What essential teaching will Nicholas and his family
and then started on an insulin drip at 0.5 unit per hour. Glu- need at this time?
cose levels are to be checked every hour using fingerstick
Answers to Additional Case Study questions are available on
the faculty resources site. Please consult with your instructor.
Chapter Review 3. It is best to plan activities or exercise around peak
insulin times for the best utilization of glucose.
1. A patient with type 1 diabetes will use a combination
insulin that includes NPH and regular insulins. The 4. Additional insulin may be required at the peak
nurse is explaining the importance of knowing the periods to prevent hyperglycemia.
peak times for both insulins. Why is this important
information for the patient to know? 2. Before administering a morning lispro insulin
(Humalog) injection, which activity should the
1. The patient will be able to estimate the time nurse perform? (Select all that apply.)
for the next injection of insulin based on these
peaks. 1. Obtain a morning urine sample for glucose and
ketones.
2. The risk of a hypoglycemic reaction is greatest
around the peak of insulin activity. 2. Check the patient’s fingerstick glucose level.
Chapter 66 Pharmacotherapy of Diabetes Mellitus 1227
3. Ensure that breakfast trays are present on the unit 5. A young woman calls the clinic and reports that her
and the patient may eat. mother had an insulin reaction and was found
unconscious. The young woman gave her a glucagon
4. Obtain the patient’s pulse and blood pressure. injection 20 minutes ago, and her mother woke up but
5. Assess for symptoms of hypoglycemia. is still groggy and “does not make sense.” What
should the nurse tell the daughter?
3. The nurse would consider which of the following assess-
ment findings as adverse effects to metformin therapy? 1. “Let her wake up on her own, then give her
something to eat.”
1. Hypoglycemia
2. Gastrointestinal distress 2. “Place some hard candies in her mouth.”
3. Lactic acidosis
4. Weight loss 3. “Just let her sleep. People are sleepy after
hypoglycemic episodes.”
4. A patient was started on rosiglitazone for type 2
diabetes. He tells the nurse that he has been taking it 4. “Give her another injection and call the paramedics.”
for 5 days, but his glucose levels are unchanged.
What is the nurse’s best response? 6. The nurse explains the benefit of using the long-acting
insulin glargine (Lantus) over other insulins. What
1. “You should double the dose. That should help.” will the nurse tell the patient about this insulin?
2. “You need to give the drug more time. It can take
1. It does not need to be administered by injection.
several weeks before it becomes fully effective.”
3. “You will need to add a second drug since this one 2. It can be given by intramuscular or subcutaneous
injection.
has not been effective.”
4. “You most likely require insulin now.” 3. It does not require blood glucose monitoring.
4. It has no definite peak but maintains a steady state
of insulin in the body.
See Answers to Chapter Review in Appendix A.
References American Heart Association (2016). Symptoms and
diagnosis of metabolic syndrome. Retrieved from https://
American Association of Clinical Endocrinologists and www.heart.org/HEARTORG/Conditions/More/
American College of Endocrinology. (2015). Clinical MetabolicSyndrome/Symptoms-and-Diagnosis-of-
guidelines for developing a diabetes mellitus Metabolic-Syndrome_UCM_301925_Article.jsp
comprehensive care plan–2015. Endocrine Practice,
21(Suppl. 1), 1–87. Retrieved from https://www.aace. Bhavsar, A. R. (2017). Diabetic retinopathy. Retrieved from
com/files/dm-guidelines-ccp.pdf http://emedicine.medscape.com/article/
1225122-overview#a4
American Diabetes Association. (2014). Diabetes care in
the school and day care setting. Diabetes Care,
37(Suppl. 1), S91–S96. doi:10.2337/dc14-S091
American Diabetes Association. (2017). Fast facts: Data and
statistics about diabetes. Retrieved from https://
professional.diabetes.org/sites/professional.diabetes.
org/files/media/fast_facts_8-2017_pro_3.pdf
Selected Bibliography Cornell, S. (2015). Continual evolution of type 2 diabetes:
An update on pathophysiology and emerging
Centers for Disease Control and Prevention. (2017). 2017 treatment options. Therapeutics and Clinical Risk
National diabetes statistics report. Retrieved from Management, 11, 621–632. doi:10.2147/TCRM.S67387
https://www.cdc.gov/diabetes/pdfs/data/statistics/
national-diabetes-statistics-report.pdf Freeland, B., & Farber, M. S. (2015). Type 2 diabetes drugs:
A review. Home Healthcare Now, 33, 304–310.
Chaudhury, A., Duvoor, C., Dendi, V. S. R., Kraleti, S., Chada, doi:10.1097/NHH.0000000000000243
A., Ravilla, R., . . . Mirza, W. (2017). Clinical review of
antidiabetic drugs: Implications for type 2 diabetes
mellitus management. Frontiers in Endocrinology, 8, 6.
doi:10.3389/fendo.2017.00006
1228 Unit 10 Pharmacology of the Endocrine System
Gamble, J. M., Clarke, A., Myers, K. J., Agnew, M. D., Nguyen, T. (2016). Keeping up with safety warnings of
Hatch, K., Snow, M. M., & Davis, E. M. (2015). Incretin- oral antidiabetic drugs. The Journal for Nurse
based medications for type 2 diabetes: An overview of Practitioners, 12, 61–62. doi:10.1016/j.nurpra.2015.10.002
reviews. Diabetes, Obesity and Metabolism, 17, 649–658.
doi:10.1111/dom.12465 Sattar, N., Petrie, M. C., Zinman, B., & Januzzi, J. L. (2017).
Novel diabetes drugs and the cardiovascular specialist.
Gates, B. J., & Walker, K. M. (2014). Physiological changes Journal of the American College of Cardiology, 69(21),
in older adults and their effect on diabetes treatment. 2646–2656. doi.org/10.1016/j.jacc.2017.04.014
Diabetes Spectrum, 27, 20–29. doi:10.2337/
diaspect.27.1.20 Tomlinson, B., Hu, M., Zhang, Y., Chan, P., & Liu, Z. M.
(2016). An overview of new GLP-1 receptor agonists for
Krass, I., Schieback, P., & Dhippayom, T. (2015). type 2 diabetes. Expert Opinion on Investigational Drugs, 25,
Adherence to diabetes medication: A systematic review. 145–158. doi:10.1517/13543784.2016.1123249
Diabetic Medicine, 32, 725–737. doi:10.1111/dme.12651
Wang, S. S. (2017). Metabolic syndrome. Retrieved from
Lew, K. N., & Wick, A. (2015). Pharmacotherapy of type 2 http://emedicine.medscape.com/article/
diabetes mellitus: Navigating current and new 165124-overview
therapies. Medsurg Nursing, 24(6), 413–419.
“I don’t know why I’ve been
so tired lately. Maybe it’s just
my hormones starting to change,
or keeping up with the kids.
I feel like I’m cold all the time and
barely have the energy to go to work.
Maybe I should have it checked out.”
Patient “Helen Mercado”
Chapter 67
Pharmacotherapy
of Thyroid Disorders
Chapter Outline Learning Outcomes
cc Physiology of the Thyroid Gland After reading this chapter, the student should be able to:
cc Diagnosis of Thyroid Disorders
cc Pathophysiology of Hypothyroid Disorders 1. Explain the functions of thyroid hormone.
cc Pharmacotherapy of Hypothyroid Disorders 2. Explain the negative feedback control of thyroid
PROTOTYPE Levothyroxine (Levothroid, Levoxyl, function.
Synthroid, Unithroid), p. 1233 3. Explain how thyroid disorders are diagnosed.
cc Pathophysiology of Hyperthyroid Disorders 4. Describe the pathophysiology of thyroid disorders.
cc Pharmacotherapy of Hyperthyroid Disorders 5. Describe the pharmacotherapy of thyroid disorders.
PROTOTYPE Propylthiouracil (PTU), p. 1238 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 the care of patients
receiving pharmacotherapy for thyroid disorders.
1229
1230 Unit 10 Pharmacology of the Endocrine System
Key Terms myxedema coma, 1232 thyrotoxicosis, 1237
cretinism, 1232 thyroid crisis, 1237 thyrotropin-releasing hormone
exophthalmos, 1237 (TRH), 1230
goiter, 1231 thyroid-stimulating hormone
Graves’ disease, 1237 (TSH), 1231 thyroxine (T4), 1230
Hashimoto’s thyroiditis, 1232 thyroxine-binding globulin
iodism, 1239 thyroid-stimulating
myxedema, 1232 immunoglobulins (TSIs), 1237 (TBG), 1230
thyroid storm, 1237 tri-iodothyronine (T3), 1230
The thyroid gland affects the function of virtually every Most circulating thyroid hormone is in the form of T4.
organ of the body. It synthesizes and secretes hormones that Upon entering target cells, however, T4 is converted in
increase overall body metabolism and protein synthesis. peripheral tissues to T3, which is three to five times more
Adequate secretion of these hormones is also necessary for biologically active. This offers an additional level of control
normal growth and development in infants and children, (tissue level) of thyroid hormone function.
including mental development and attainment of sexual
maturity. The thyroid also affects functions of the cardiovas- The two thyroid hormones are metabolized by the
cular, respiratory, gastrointestinal (GI), and neuromuscular liver and excreted by the kidneys, with small amounts
systems. Thyroid disorders are common, affecting women excreted in the stool. Iodine is conserved in the process and
5 to 10 times more often than men. This chapter presents the returned to the thyroid gland for the production of more
pharmacotherapy of thyroid imbalances. hormone molecules. Therefore, only a small daily intake of
iodine is needed to meet the demands of the thyroid gland.
Physiology of the Thyroid Gland High amounts of iodine are found in shellfish, but the main
dietary source is the use of iodized salt. Thyroid hormones
67.1 Thyroid hormones contain iodine and are the only known use for iodine in the body.
stimulate the basal metabolic rate of nearly all
tissues. Thyroid hormone stimulates the basal metabolic rate
of all tissues except the brain, anterior pituitary, spleen,
The thyroid gland lies on both sides of the trachea just lymph nodes, testes, and lungs. In the presence of large
below the larynx. The gland contains two distinct types of amounts of thyroid hormone, the basal metabolic rate of
endocrine cell types: follicular cells and parafollicular cells. cells can increase by 60% to 100%. This increases the oxida-
Follicular cells produce, store, and secrete thyroid hor- tion of energy sources (glucose, fats, and proteins), which
mone. Parafollicular cells produce calcitonin, a hormone in turn increases oxygen consumption and generates large
totally unrelated to the structure or function of thyroid amounts of heat. The rapid metabolic rate increases the
hormone. Calcitonin regulates calcium metabolism and is body’s demands for vitamins. Thyroid hormone affects GI
used as a drug in the pharmacotherapy of osteoporosis function and motility, appetite, and body weight. Thyroid
(see Chapter 72). hormone increases the number of beta1- and beta2-adrener-
gic receptors and enhances their affinity to catecholamines
Thyroid hormone actually consists of two distinct hor- (norepinephrine, epinephrine, and dopamine). The increase
mones: tri-iodothyronine (T3) and thyroxine (T4). Both T3 in sympathetic activity leads to increased heart rate and
and T4 are synthesized from the amino acid tyrosine and force of contraction, cardiac output, and cardiac demands
iodine; the subscript numeral refers to the number of iodine for oxygen. Thyroid hormones also stimulate the secretion
molecules each hormone contains. Because the two have of growth hormone and are therefore essential for the nor-
very similar actions, they are usually considered a single mal growth and development of the skeletal and nervous
hormone. systems. Thyroid hormone affects reflexes, thought pro-
cesses, and overall level of consciousness (LOC). Signs and
When secreted into the bloodstream, more than 99% of symptoms of thyroid hormone deficiency and excess are
T3 and T4 is bound to thyroxine-binding globulin (TBG), a presented in Sections 67.3 and 67.5, respectively.
plasma protein manufactured by the liver. Any condition
that causes decreased amounts of plasma proteins, such as The secretion of thyroid hormone is regulated by the
protein malnutrition or liver impairment, can lead to a hypothalamus and anterior pituitary gland through a nega-
larger percentage of free thyroid hormone, with subse- tive feedback loop, as shown in Figure 67.1. When blood lev-
quent symptoms of hyperthyroidism. els of thyroid hormone are low, the hypothalamus secretes
thyrotropin-releasing hormone (TRH). Secretion of TRH
1 Cold Stress Chapter 67 Pharmacotherapy of Thyroid Disorders 1231
– stimulates the anterior pituitary to secrete thyroid-
stimulating hormone (TSH). TSH then stimulates the thy-
5 Neurosecretory roid to produce and secrete T3 and T4. As blood levels of free,
cells of hypothalamus unbound thyroid hormone increase, negative feedback sup-
presses the secretion of TSH and TRH. High levels of iodine
Blood Releasing can also cause a temporary decrease in thyroid activity that
Endocrine cells of hormone can last for several weeks. One of the strongest stimuli for
anterior pituitary increased thyroid hormone production is exposure to cold.
2 Thyroid-stimulating
– hormone Disorders of the thyroid result from a hypofunction
or hyperfunction of the thyroid gland. Hormonal imbal-
Negative ances may occur due to disease within the thyroid gland
feedback itself or be caused by abnormalities of the pituitary or
hypothalamus.
Thyroid
Thyroid disorders can be due to a congenital defect, or
Thyroxine they may develop later in life. They may have an insidious
or sudden onset. An increase in the size of the thyroid
3 gland is referred to as a goiter. This can occur with normal,
high, or low levels of thyroid hormone. Goiters may be dif-
4 Increased metabolic rate fuse, involving the entire gland, or nodular. When they
in most body cells become considerably enlarged, the goiter can compress the
trachea and esophagus, causing difficulty swallowing, a
Figure 67.1 Feedback mechanisms of the thyroid gland. choking sensation, and possibly inspiratory stridor (abnor-
mal high-pitched sounds when breathing). They may also
compress the superior vena cava, causing distention of the
neck veins and facial edema.
Diagnosis of Thyroid Disorders
67.2 An accurate diagnosis of thyroid hormone
dysfunction is based on the patient’s symptoms
and the results of diagnostic tests.
Because the thyroid gland is located close to the skin sur-
face, palpation of the thyroid gland is conducted for routine
screening of enlargements and nodules. Serum laboratory
tests for T3, T4, and TSH are commonly used for diagnosis,
as listed in Table 67.1. TSH is the preferred laboratory value
for diagnosing and monitoring the progression of thyroid
disease. Primary hypothyroidism is characterized by a low
serum T4 level and an elevated TSH level.
Abnormal laboratory values must be carefully evalu-
ated because a number of conditions, including stress in
Table 67.1 Serum Values for Thyroid Function Tests*
Thyroid Test Reference Value Hypothyroid Hyperthyroid
T3 (serum) 80–220 ng/dL Decreased Increased
Free T4 0.8–1.8 ng/dL Decreased Increased
Total T4 4.5–12.5 mcg/dL Decreased Increased
TSH (serum) 0.5–5.5 microinternational units/mL Increased Decreased
Antithyroglobulin antibody (TgAb) Less than 20 international units/mL – –
– –
Thyroid peroxidase antibody (TPOAb) Less than 9.0 international units/mL
* Reference values vary somewhat among different laboratories.
1232 Unit 10 Pharmacology of the Endocrine System
critically ill adults, can affect TSH and T4 levels. In addi- growth. Almost half of normal brain development occurs
tion, these laboratory values are influenced by abnormali- during the first 6 months of life, and thyroid hormone is
ties in serum protein levels because both T3 and T4 are essential for this to occur. If thyroid replacement therapy is
heavily protein bound. Any condition that affects protein begun in the first 6 weeks of life, normal growth and devel-
levels requires careful analysis of these test results. opment take place and cretinism can be prevented. In the
United States and Canada, screening for hypothyroidism
To identify the presence of autoimmune disorders, is conducted for most neonates.
antibodies to thyroglobulin or thyroid peroxidase are mea-
sured. Individuals without thyroid disease generally have Hypothyroidism in older children and adults results in
minimal or none of these antibodies in their blood. How- a general slowing of metabolic processes and myxedema, a
ever, most patients with Hashimoto’s thyroiditis or Graves’ mucous type of edema caused by an accumulation of hydro-
disease will show elevated levels of antithyroid antibody philic substances in connective tissues. Primary hypothy-
titer. In the case of Hashimoto’s, the elevated antibodies roidism, the most common type in children and adults,
may lead to hypothyroidism; for Graves’ disease, however, results from dysfunction of the thyroid gland. Secondary
the elevated antibodies may indicate hyperthyroidism. hypothyroidism is due to pathology of the pituitary gland.
Patients with other autoimmune disorders such as sys- Tertiary hypothyroidism is a result of a disorder of the
temic lupus erythematosus or rheumatoid arthritis may hypothalamus. Causes of hypothyroidism include thyroid-
have elevated antibody values without thyroid disease. ectomy or ablation of the thyroid gland with radiation, the
use of lithium (in the treatment of bipolar disorder), or treat-
The diagnostic tool of choice for detecting malignancy ment with antithyroid drugs. Large amounts of iodine or
of a thyroid nodule is the fine needle biopsy. Ultrasonogra- substances that contain iodine, such as kelp tablets, certain
phy can be used to assess masses, cysts, and enlargement cough syrups, the cardiac drug amiodarone, or iodine-
of the thyroid gland. The radioactive iodine uptake test containing radiographic contrast media, can block thyroid
measures the rate of iodine uptake by the thyroid gland hormone production and cause goiter and hypothyroidism.
after administration of 123I tracer. This test can detect areas Iodine deficiency is rarely a cause of hypothyroidism in the
of increased and decreased function. Computed tomogra- United States due to the widespread use of iodized salt.
phy (CT) and magnetic resonance imaging (MRI) scans
can be used to determine tracheal compression or pressure The most common cause of hypothyroidism is an auto-
on neighboring structures caused by thyroid gland immune disorder known as Hashimoto’s thyroiditis. This
enlargement. disease affects women 5 to 10 times more often than men.
An accurate diagnosis of thyroid hormone dysfunction Hypothyroidism affects nearly all major organ sys-
is essential. Proper treatment of the disorder will depend tems, with manifestations arising from two factors: a
on whether the abnormality lies within the thyroid gland hypometabolic state and myxedematous changes in body
itself or is the result of a defect in the negative feedback tissues. The hypometabolic state is marked by a gradual
control by the hypothalamus or pituitary. onset of weakness and fatigue, a tendency to gain weight
despite a decreased appetite, and cold intolerance. Hypo-
PharmFACT tension, bradycardia, hypoventilation, and subnormal
temperature may occur. In time, the skin becomes rough
The demands on the mother’s thyroid gland increase during and dry and may have a yellowish cast; the hair becomes
pregnancy. If women have too little iodine during pregnancy, coarse and brittle; and GI motility slows, causing chronic
the damage to the nervous system of the fetus may be constipation, flatulence, and abdominal distention. Men-
irreversible (Harding et al., 2017). tal dullness, lethargy, slowed reflexes, and memory prob-
lems may occur. Because of the importance of thyroid
Pathophysiology of Hypothyroid hormone to fetal development, women experiencing
Disorders hypothyroidism should be treated with thyroid hormone
during pregnancy. Women also experience a high inci-
67.3 Hypothyroidism, or thyroid deficiency, can dence of postpartum thyroiditis, which occurs following
occur as a congenital or acquired disorder. about 10% of pregnancies.
Hypothyroidism may occur as a congenital disorder, or it As fluid accumulates in tissues, the face takes on a
may be acquired in adulthood. Congenital hypothyroid- puffy look, especially around the eyes; the tongue enlarges;
ism is a common, preventable cause of mental retardation. and the voice may be husky. Fluid can accumulate in the
The infant appears normal at birth due to hormones sup- pericardial or pleural spaces, causing effusions, cardiac
plied by the mother while in utero. If untreated, congenital dilation, and bradycardia. Myxedema coma or crisis is a
hypothyroidism results in a condition known as cretinism, life-threatening end-stage condition of hypothyroidism,
marked by profound mental retardation and impaired characterized by coma, hypothermia, cardiovascular col-
lapse, hypoventilation, hyponatremia, hypoglycemia, and
Chapter 67 Pharmacotherapy of Thyroid Disorders 1233
Table 67.2 Signs and Symptoms of Thyroid Emergencies CONNECTIONS: Community-
Oriented Practice
Thyroid Storm Myxedema Coma
The Effects of Soy Intake
Tachycardia Bradycardia
Hyperthermia Hypothermia Over the years, claims about the benefits and risks accruing
Tachypnea Hypoventilation from the use of soy and soy products have varied widely.
Hypercalcemia Hyponatremia
Hyperglycemia Hypoglycemia Based on a comprehensive literature review, D’Adamo
Metabolic acidosis Respiratory and metabolic acidosis and Sahin (2014) investigated claims as to the health ben-
Cardiovascular collapse: cardiogenic Cardiovascular collapse: decreased efits and risks of soy supplementation. Health benefits of
shock, hypovolemia, arrhythmias vascular tone soy that were reviewed included relief of menopausal symp-
Depressed LOC Depressed LOC toms and prevention of heart disease, breast cancer, pros-
Emotional lability Seizures, coma tate cancer, and osteoporosis. Health risks of soy that were
Psychosis Hyporeflexia reviewed included increased risk of breast cancer, male
Tremors, restlessness hormonal and fertility problems, and effects on thyroid func-
– tion. This literature review revealed evidence that soy foods
and supplements may provide relief from menopausal
lactic acidosis. This condition occurs most often in older symptoms and protect against breast cancer and heart dis-
women. Even with early detection and treatment, the mor- ease, but they do not appear to offer protection against
tality rate is 30% for those who develop myxedema coma. osteoporosis. Soy supplementation also appears to affect
Treatment consists of supportive measures, correction of thyroid function in an inconsistent manner, with both
electrolyte and acid–base imbalances, treatment of hypo- increases and decreases of thyroid activity noted. The evi-
tension, and immediate thyroid replacement therapy. If dence on male fertility and reproductive issues was mixed,
hypothermia is present, active rewarming is contraindi- with some studies demonstrating a harmful impact and oth-
cated, because this may precipitate vasodilation and lead to ers showing no effect.
cardiovascular collapse. Features of thyroid emergencies
are described in Table 67.2. Because some patients may consume soy as a supple-
ment to or a substitute for animal proteins in their diet, nurses
CONNECTION Checkpoint 67.1 should include a dietary assessment, especially for infants; for
adult patients on thyroid hormone replacement therapy, par-
Patients with hypothyroidism tend to have low rates of angina and ticularly those who are experiencing hypothyroidism after a
myocardial infarction. From what you learned in Chapter 35, explain period of a euthyroid (normal) state; and for postmenopausal
this link. Answers to Connection Checkpoint questions are available on women. Currently, the use of soy and soy products warrants
the faculty resources site. Please consult with your instructor. caution in infants and postmenopausal women where thyroid
function may be disrupted. Nurses should also assess whether
Pharmacotherapy of Hypothyroid vegetarians are following a varied diet to ensure that all essen-
Disorders tial amino acids are consumed because soy is low in the nec-
essary amino acid methionine.
67.4 Hypothyroidism is treated by replacement
therapy with thyroid hormone. adults, the precaution is to “go low and go slow,” because
there is a risk for inducing acute coronary syndromes in
Hypothyroidism is treated by replacement therapy with T3 susceptible individuals. Table 67.3 lists the doses of the
or T4. The standard replacement regimen consists of levo- drugs used to treat hypothyroidism.
thyroxine (T4), although combined therapy with levothy-
roxine plus liothyronine (T3) is an option. Although T4 is PROTOTYPE DRUG Levothyroxine (Levothroid,
less biologically active than T3, it is readily converted to T3 Levoxyl, Synthroid, Unithroid)
in peripheral tissues. In most cases, thyroid replacement
therapy is lifelong. Classification Therapeutic: Thyroid hormone
Pharmacologic: Thyroid hormone
In children with cretinism, therapy with levothyroxine
should continue for 3 years, after which it should be replacement
stopped for 1 month. During this time, thyroid hormone
levels are monitored to assess the status of the deficiency Therapeutic Effects and Uses: Levothyroxine is a
and to determine if further treatment is needed. synthetic form of T4, with actions identical to endogenous
thyroid hormone. It is used for primary or secondary hypo-
In adults, serum TSH levels are used to evaluate the thyroidism, congenital hypothyroidism, hypothyroid state
progress of therapy. When initiating therapy in older resulting from the surgical removal of the thyroid gland,
radiation or antithyroid drugs, management of thyroid
1234 Unit 10 Pharmacology of the Endocrine System
Table 67.3 Drugs for Hypothyroidism
Drug Name Dose for Adults Adverse Effects
(Maximum Dose Where Indicated)
Weight loss, headache, tremors, nervousness,
levothyroxine (Levothroid, Levoxyl, Synthroid, PO: 100–400 mcg/day heat intolerance, irritability, sweating, insomnia,
Unithroid) menstrual irregularities
IV: initial loading dose of 300–500 mcg followed
by maintenance doses of 50–100 mcg Dysrhythmias, hypertension, palpitations, angina
liothyronine (Cytomel, Triostat) PO: 25–75 mcg/day
IV: 25–100 mcg/day
liotrix (Thyrolar) PO: 12.5–30 mcg/day
thyroid, desiccated (Armour thyroid, Thyroid USP) PO: 60–180 mg/day
Note: Italics indicate common adverse effects. Underline indicates severe adverse effects.
cancer, or treatment of myxedema coma. The drug is given aspirin. Black Box Warning: Use of thyroid hormone for
by the oral (PO) route for routine replacement therapy and weight loss or the treatment of obesity is contraindicated.
intravenously (IV) for myxedema coma.
Contraindications/Precautions: The use of levothy-
To avoid adverse effects, doses of thyroid hormone are roxine is contraindicated if the patient is hypersensitive
highly individualized for each patient. When given by the to the drug, is experiencing thyrotoxicosis, or has severe
PO route, 1 to 3 weeks may be required to obtain full thera- cardiovascular conditions or acute myocardial infarction
peutic benefits. Doses for patients with preexisting cardiac (MI). If thyroid hormone is given to patients with adrenal
disease are usually increased at 4- to 6-week intervals to insufficiency, it may cause a serious adrenal crisis; thus,
avoid the possibility of dysrhythmias or angina attacks. the insufficiency should be corrected prior to administra-
tion of levothyroxine. It should be used with caution in
Mechanism of Action: The actions of levothyroxine patients with cardiac disease, angina pectoris, cardiac dys-
are identical to those of endogenous thyroid hormone. rhythmias, hypertension, and impaired kidney function,
The drug increases the metabolic rate, thereby increasing and in older adults. Symptoms of diabetes mellitus may
oxygen consumption, respiration, and heart rate; increases be worsened with administration of thyroid hormone, and
the rate of fat, protein, and carbohydrate metabolism; and doses of antidiabetic drugs may require adjustment.
promotes growth and maturation. Because levothyroxine
is converted to T3, it is not necessary to also give T3. Drug Interactions: A large number of medications
can interact with thyroid hormone and result in either
Pharmacokinetics: increased or decreased effects. Drugs that decrease the
absorption of levothyroxine include cholestyramine,
Route(s) PO, IV colestipol, calcium- or aluminum-containing antacids,
sucralfate, and iron supplements. Several drugs are known
Absorption Variable; partial absorption from to accelerate the metabolism of levothyroxine, including
phenytoin, carbamazepine, rifampin, phenobarbital, and
the GI tract (50% to 80%) sertraline. Levothyroxine increases the effects of warfa-
rin, resulting in an increased risk of bleeding. Digoxin
Distribution Gradually released to peripheral decreases the effectiveness of levothyroxine. Thyroid hor-
mone sensitizes cardiac responsiveness to catecholamines;
tissues; crosses the placenta; therefore, administration of epinephrine or norepineph-
rine must be carefully monitored in these patients to pre-
secreted in breast milk; more vent dysrhythmias. Herbal/Food: Soybean flour (infant
formula), cottonseed meal, walnuts, and dietary fiber may
than 99% bound to protein bind and decrease the absorption of levothyroxine sodium
from the GI tract. Calcium or iron supplements should be
Primary metabolism Hepatic taken at least 4 hours after taking levothyroxine to prevent
interference with drug absorption. The patient should also
Primary excretion Kidneys, with some secreted in avoid consuming large amounts of foods that can inhibit
thyroid secretion, such as strawberries, peaches, pears,
bile and excreted in feces cabbage, turnips, spinach, kale, Brussels sprouts, cauli-
flower, radishes, and peas.
Onset of action PO: Slow; IV: 6–8 h
Pregnancy: Category A.
Duration of action 1–3 weeks; half-life: 6–7 days
Adverse Effects: At therapeutic doses, adverse effects
of levothyroxine therapy are rare. At high doses, treat-
ment may cause central nervous system (CNS) excitabil-
ity such as tremors, headache, nervousness, or insomnia.
Cardiovascular adverse effects include palpitations,
tachycardia, angina, and cardiac arrest. Other possible
adverse events include allergic skin reactions, diarrhea,
nausea, and vomiting. Synthroid 100-mcg and 300-mcg
tablets contain tartrazine, which may cause an allergic
reaction in some patients, especially those sensitive to
Chapter 67 Pharmacotherapy of Thyroid Disorders 1235
Treatment of Overdose: The treatment of levothy- liotrix over levothyroxine. Its actions, adverse effects, and
roxine overdose is the same as the treatment of thyroid contraindications are similar to those for endogenous thy-
crisis or thyroid storm, as discussed later in Section 67.6. roid hormone. This drug is pregnancy category A.
Treatment is directed at reducing the level of circulating
thyroid hormone with antithyroid drugs and decreasing Thyroid, desiccated (Armour thyroid, Thyroid USP): Des-
sympathetic stimulation with corticosteroids and beta- iccated thyroid is an older formulation, approved in 1939,
adrenergic blockers. obtained from the dried thyroid glands of pigs. The drug
contains T3 and T4 in their natural proportions. Desiccated
Nursing Responsibilities: Key nursing implications thyroid is less pure and has less reliable content than syn-
for patients receiving levothyroxine are included in the thetic formulations and has been replaced by levothyrox-
Nursing Practice Application for Patients Receiving Phar- ine. It is used only for patients who have taken it for
macotherapy with Thyroid Hormone Replacements. years—newly diagnosed cases of hypothyroidism are
treated with synthetic thyroid hormone.
Drugs Similar to Levothyroxine (Levothroid,
Levoxyl, Synthroid, Unithroid) CONNECTIONS: Treating the
Diverse Patient
Other thyroid replacement medications include liothyro-
nine, liotrix, and desiccated thyroid. All thyroid drugs Improved Kidney Function from Thyroid
carry a black box warning stating they should not be used Hormone Replacement
for weight loss or to treat obesity.
Because thyroid hormones affect nearly all body systems,
Liothyronine (Cytomel, Triostat): Approved in 1954, lio- even slight changes in the amount of circulating hormones
thyronine is a synthetic form of T3 used in replacement may have profound effects, especially in the very young and
therapy for hypothyroidism. Its actions, adverse effects, the older adult populations. Recent research suggests that
and contraindications are similar to those for endogenous thyroid hormone therapy may help preserve renal function in
thyroid hormone. It has a shorter onset, half-life, and dura- older patients (Lu, Guo, Liu, & Zhao, 2016). Subclinical hypo-
tion of action than levothyroxine and is more expensive. thyroidism may have significant effects on chronic kidney dis-
Liothyronine is readily converted to T3 in the bloodstream. ease. Several theories exist as to why thyroid replacement
The injectable form of liothyronine is a preferred drug for improves renal function, including improvement in cardiac
the treatment of myxedema coma. It is available in oral status, improvement in dyslipidemias, or the effect on vascu-
and IV formulations. This drug is pregnancy category A. lar endothelium (Hataya, Igarashi, Yamashita, & Komatsu,
2013; Rhee et al., 2015; Shin et al., 2013). Individualized
Liotrix (Thyrolar): Liotrix is a synthetic mixture of T4 and treatment for subclinical hypothyroidism should be consid-
T3, in a 4:1 ratio, available in PO form only for the treat- ered in older patients.
ment of hypothyroidism. Because levothyroxine is readily
converted to T3, there is no apparent advantage in using
CONNECTIONS: NURSING PRACTICE APPLICATION
Patients Receiving Pharmacotherapy with Thyroid Hormone Replacements
Assessment
Baseline assessment prior to administration:
• Obtain a complete health history including cardiovascular, GI, hepatic, and kidney disease; pregnancy; or breastfeeding. Obtain a drug history
including allergies, current prescription and over-the-counter (OTC) drugs, herbal preparations, alcohol use, and smoking. Be alert to possible
drug interactions.
• Evaluate appropriate laboratory findings (e.g., T3, T4, and TSH levels; complete blood count [CBC]; platelets, electrolytes, glucose, and lipid levels).
• Obtain baseline height, weight, and vital signs. Obtain an electrocardiogram (ECG) as needed.
• Assess the patient’s ability to receive and understand instructions. Include family and caregivers as needed.
Assessment throughout administration:
• Assess for desired therapeutic effects (e.g., T3, T4, and TSH levels return to normal, associated symptoms ease).
• Continue periodic monitoring of T3, T4, and TSH levels and glucose levels.
• Continue monitoring height, weight, and vital signs. Monitor ECG as needed.
• Assess for adverse effects: nausea, vomiting, diarrhea, epigastric distress, skin rash, itching, headache, tachycardia, palpitations, dysrhythmia,
sweating, nervousness, paresthesia, tremors, insomnia, heat intolerance, and angina. Hypo- or hypertension, tachycardia, especially associated with
dysrhythmia, or angina should be immediately reported to the healthcare provider.
(continued )
1236 Unit 10 Pharmacology of the Endocrine System
CONNECTIONS: NURSING PRACTICE APPLICATION (continued)
Implementation
Interventions and (Rationales) Patient-Centered Care
Ensuring therapeutic effects: • Advise the patient that the drug will help to stabilize thyroid hormone
• Monitor vital signs, appetite, weight, sensitivity to heat or cold, sleep levels quickly, but full effects may take a week or longer to occur.
patterns, and ability to perform activities of daily living (ADLs). (As • Instruct the patient to maintain consistent dosing to allow the drug to
metabolic activity controlled by thyroid hormones stabilizes, the patient reach therapeutic levels.
should return to normal weight, ADLs, and feelings of wellness.)
• Instruct the patient to weigh self 2 to 3 times per week, record the find-
ings, and bring the record to each clinic visit.
• Avoid iodine-containing foods (e.g., iodized salt, soy sauce, tofu, yogurt, • Provide dietary instruction on foods to avoid. Provide for a dietitian
milk, strawberries, eggs) unless approved by the healthcare provider. consultation as needed.
(Iodine is necessary for the synthesis of thyroid hormone. Increasing or
decreasing normal intake may result in adverse drug effects.)
• Monitor thyroid function tests. (Results help determine the effective- • Instruct the patient on the need to return periodically for laboratory
ness of the drug therapy and the need for dosage changes.) work.
Minimizing adverse effects: • Teach the patient that small daily fluctuations may occur, especially
• Monitor for return of original symptoms and report consistent occur- during periods of stress or illness. Any significant or increasing changes
in pulse rate, weight, nervousness or fatigue, intolerance to heat or
rence. (Daily fluctuations in symptoms may occur because hormone cold, and diarrhea or constipation should be reported to the healthcare
replacement therapy does not precisely approximate the body’s own provider.
levels. Significant increases in original symptoms may signal less-than-
optimal therapeutic results. Dramatic “opposite” effect and hypo- or
hyperthyroid symptoms may signal drug toxicity.)
• Lifespan: Monitor symptoms in older adults more frequently. (Older • Teach the patient, family, or caregiver that the lowest dose will be
patients are more sensitive to thyroid replacement therapy. Minor started and gradually increased to find the optimal level. Any significant
changes in daily thyroid levels may cause a significant change in symp- change in symptoms should be promptly reported to the healthcare
toms.) provider.
• Lifespan: Monitor height, weight, and developmental growth in infants • Teach the parents or caregivers to weigh the child weekly and record.
and young children. (Infants and children receiving thyroid replacement Bring the record to each healthcare visit.
therapy should continue to display normal growth and development
curves.) • Encourage the parents or caregivers to discuss concerns or any unusual
findings that would suggest developmental or growth delays with the
healthcare provider if they are noted in the child between healthcare visits.
• Monitor serum glucose levels, especially in patients with diabetes. • Teach patients with diabetes to monitor capillary glucose levels more
Patients with diabetes should monitor capillary levels more frequently. frequently during therapy. Report any consistent changes to the health-
(Thyroid replacement therapy may cause changes in glucose levels care provider.
and an adjustment in antidiabetic medications may be needed.)
• Ensure patient safety. Observe for lightheadedness or dizziness. • Instruct the patient to call for assistance prior to getting out of bed or
Monitor ambulation until the effects of the drug are known. (Dizziness attempting to walk alone if dizziness occurs. When dizziness occurs,
may be secondary to changes in pulse or blood pressure and should the patient should sit or lie down and not attempt to stand or walk until
be assessed by the healthcare provider. Lifespan: The older adult is the sensation passes.
especially at risk for falls related to dizziness. Effects of thyroid hor-
mone on bone remodeling may place the patient at risk for fractures.) • Assess the safety of the home environment and discuss needed modi-
fications with the family or caregiver.
• Continue to monitor the effectiveness of all other medications the • Teach the patient to report any unusual symptoms of concern to the
patient is taking. Teach patients to take thyroid replacement 1 h before healthcare provider.
or 4 h after foods high in fiber or medications such as cholestyramine,
calcium or aluminum antacids, or iron supplements. (Thyroid replace-
ment drugs interact with many drugs and may cause suboptimal or
excessive responses. Drugs such as calcium and aluminum antacids
decrease absorption of thyroid hormone.)
Patient understanding of drug therapy: • The patient should be able to state the reason for the drug, appropriate
• Use opportunities during administration of medications and during dose and scheduling, what adverse effects to observe for, and when to
report them.
assessments to discuss the rationale for drug therapy, desired thera-
peutic outcomes, commonly observed adverse effects, parameters
for when to call the healthcare provider, and any necessary monitoring
or precautions. (Using time during nursing care helps to optimize and
reinforce key teaching areas.)
Patient self-administration of drug therapy: • Teach the patient to take the drug following appropriate guidelines:
• When administering the medication, instruct the patient, family, or • Take the drug at the same time each morning to approximate nor-
mal body hormone levels. If night shift hours are worked, consult
caregiver in proper self-administration of the drug, e.g., take the drug with the healthcare provider about scheduling appropriate time of
in the morning at the same time each day. (Utilizing time during nurse drug administration.
administration of these drugs helps to reinforce teaching.) • Avoid foods high in iodine unless approved by the healthcare provider.
• To ensure optimal therapeutic response, take the same brand of
drug and request the same manufacturer each time the prescrip-
tion is filled. If the same drug is unavailable, consult with the health-
care provider about dosage or observe for adverse drug effects.
Do not switch trade names until the provider has been consulted.
Chapter 67 Pharmacotherapy of Thyroid Disorders 1237
Pathophysiology of Hyperthyroid diabetic ketoacidosis, trauma, or manipulation of the thy-
Disorders roid gland during surgery. Manifestations include high
fever, cardiovascular effects (tachycardia, heart failure,
67.5 Hyperthyroidism, or Graves’ disease, angina, and MI), and CNS effects (agitation, restlessness,
is an autoimmune disorder accompanied by delirium, progressing to coma). It is treated with support-
ophthalmopathy and goiter. ive measures, efforts to reduce body temperature without
causing shivering, fluid, glucose and electrolyte replace-
Symptoms of hyperthyroidism have been recorded in ment, and beta-adrenergic blockers. Aspirin should not be
medical documents dating back to the 12th century. The used to lower the body temperature of an individual in
most common cause of hyperthyroidism is Graves’ dis- thyroid storm because it displaces thyroid hormone from
ease, named after the Irish doctor Robert Graves who its protein-binding sites in the serum, increasing the level
described the disorder in 1835. The condition is character- of free, or active, thyroid hormone, which worsens the con-
ized by the excessive secretion of thyroid hormone. dition. Antithyroid drugs may be used to decrease thyroid
hormone production.
The two most visible signs of Graves’ disease are goiter
and exophthalmos, an outward bulging of the eyes. Up to PharmFACT
one third of those with Graves’ disease develop ophthal-
mopathy, leading to severe eye problems. These include Although Graves’disease most commonly occurs in adults, it
paralysis of the ocular muscles, damage to the optic also occurs in children. About 10% of infants born to women
nerve with some vision loss, and corneal ulceration due to with Graves’disease have hyperthyroidism, but most are
the inability of the eyelids to close. These eye problems are asymptomatic. Concordance for Graves’ disease is 30% to
aggravated by smoking, which should be strongly discour- 50% in identical twins (Levitsky, 2016).
aged in patients with Graves’ disease. The ophthalmopa-
thy usually stabilizes with treatment but not all eye changes Pharmacotherapy of Hyperthyroid
are reversible with therapy. A rare skin disorder, pretibial Disorders
myxedema, may also occur, with thickening of the skin,
plaques, and nodules over the shins and dorsal surface of 67.6 Hyperthyroidism is treated with surgery
the feet. Like the ophthalmic changes, these skin changes or drugs that reduce the production of thyroid
may persist despite effective treatment of the disease. hormone.
Causes of Graves’ disease include adenoma and exces- Treatment of hyperthyroidism often requires surgical
sive intake of thyroid hormone. The onset is usually removal of all or part of the thyroid gland. In less serious
between the ages of 20 and 40 years, and it occurs five times cases of the disorder, pharmacotherapy can be used to
more often in women than in men. Graves’ disease is an diminish the secretion of thyroid hormone.
autoimmune disorder in which the thyroid gland is stimu-
lated by thyroid-stimulating immunoglobulins (TSIs). It One strategy to lower thyroid hormone secretion is to
may occur concurrently with other autoimmune disorders, destroy part of the gland (ablation) by administering radio-
and there is a familial tendency to the condition. active iodide (131I). The goal of thyroid ablation is to use the
ionizing radiation from the drug to destroy just enough of
The manifestations of hyperthyroidism are caused by the thyroid gland to return the patient to a normal thyroid
the hypermetabolic state and the increase in sympathetic state. This therapy is preferred by many endocrinologists
nervous system activity. The symptoms include nervous- because it results in a permanent, long-term solution to
ness, irritability, fatigue, insomnia, weight loss despite a hyperthyroidism. This therapy is contraindicated during
large appetite, tachycardia, palpitations, hypertension, pregnancy due to the risk of exposing the fetus to ionizing
shortness of breath, increased sweating, muscle cramps, radiation.
hyperthermia, and heat intolerance. A fine muscle tremor
may occur. Approximately 15% of older adults with new- Antithyroid drugs may be administered to manage
onset atrial fibrillation, a common cardiac dysrhythmia, hyperthyroidism. Propylthiouracil (PTU) and methima-
have thyrotoxicosis. zole (Tapazole) prevent the incorporation of iodine into the
thyroid hormone molecule and block the conversion of T4
Very high levels of circulating thyroid hormone may to T3 in peripheral tissues. Doses of the antithyroid drugs
cause thyrotoxicosis. Thyroid crisis, or thyroid storm, is a are listed in Table 67.4.
rare, life-threatening form of thyrotoxicosis. If untreated, it
is associated with mortality rates of 80% to 90%. Even with Treatment of thyroid storm is a medical emergency.
treatment, mortality from thyroid storm exceeds 20%. It Methimazole or propylthiouracil are administered to pre-
occurs most often in teenage and young adult women with vent further synthesis of thyroid hormone. Propylthioura-
undiagnosed or untreated cases of hyperthyroidism and cil also blocks the conversion of T4 to T3 in peripheral
can be precipitated by the stress of an acute infection,
1238 Unit 10 Pharmacology of the Endocrine System
Table 67.4 Antithyroid Drugs
Drug Name Dose for Adults (Maximum Dose Where Indicated) Adverse Effects
methimazole (Tapazole) PO: 5–15 mg tid (max: 60 mg/day)
Nausea, rash, pruritus, urticaria, fever, numbness in
potassium iodide and iodine PO: 125 mg daily fingers, peripheral neuropathy, leukopenia,
(Lugol’s solution, Thyro-Block) hypothyroidism
propylthiouracil (PTU) PO: 300–450 mg tid Agranulocytosis, bradycardia, hepatotoxicity
radioactive iodide (131I) PO: 0.8–150 millicurie (a curie is a unit of radioactivity) Diarrhea, nausea, vomiting, stomach pain, fever,
weakness, irregular heartbeat, hypothyroidism
Angioneurotic edema, iodine poisoning
Nausea, rash, pruritus, headache, fever, numbness in
fingers, diarrhea, myelosuppression, hypothyroidism
Agranulocytosis
Adverse effects are uncommon
Thyroiditis, hypothyroidism, hypersensitivity
Note: Italics indicate common adverse effects. Underline indicates severe adverse effects.
tissues and is preferred for pregnant patients. Potassium Therapeutic Effects and Uses: Approved in 1947,
iodide solution can be given to immediately block the propylthiouracil decreases thyroid hormone levels in
release of thyroid hormone but should not be given until hyperthyroid states that are caused by the overproduction
1 hour after the administration of antithyroid medications. of thyroid hormone. It is also used to establish the normal
thyroid state prior to surgery or radioactive iodine treat-
Several drugs are used as adjuncts in the therapy of ment and for palliative control of toxic nodular goiter. Pro-
thyroid storm. During hyperthyroid states, beta-adrenergic pylthiouracil is not effective in treating thyroiditis because
blocking drugs such as propranolol (Inderal), esmolol (Bre- this condition is due to overrelease, not overproduction, of
vibloc), or metoprolol (Toprol) are given to block the effects thyroid hormone.
of the thyroid hormones on sympathetic receptors in the
heart. The actions include a decrease in heart rate and Mechanism of Action: Propylthiouracil inhibits the
strength of contraction, thereby decreasing myocardial first step in the synthesis of thyroid hormone and sup-
oxygen demands. These effects occur quickly, while the presses the peripheral conversion of T4 to T3. It does not
actions of antithyroid drugs take longer to occur. Refer to affect thyroid hormone that has already been synthesized,
Chapter 16 for the specific pharmacology of beta-adrenergic so therapeutic response may be delayed by 3 to 12 weeks,
blockers. until existing supplies of thyroid hormone have been
depleted.
IV corticosteroids such as hydrocortisone (Solu-Cortef)
or dexamethasone (Decadron) may be ordered to treat Pharmacokinetics:
acute hyperthyroid states. Corticosteroids block the con-
version of T4 to T3 in peripheral tissues. In addition, severe Route(s) PO
hyperthyroid states create high levels of stress that deplete
adrenal corticosteroids in the body, and administration of Absorption Rapidly absorbed
replacement doses is necessary. The pharmacology of the
corticosteroids is presented in Chapter 68. Distribution Concentrated by the thyroid
CONNECTION Checkpoint 67.2 gland; crosses the placenta;
Patients with Graves’ disease have increased hepatic gluconeo- secreted in breast milk; 60–80%
genesis, rapid glucose absorption, and increased insulin resistance.
From what you learned in Chapter 66, what insulin dosage adjust- bound to plasma protein
ment is necessary for these patients who also have diabetes mel-
litus? Answers to Connection Checkpoint questions are available on the Primary metabolism Hepatic
faculty resources site. Please consult with your instructor.
Primary excretion Kidneys
PROTOTYPE DRUG Propylthiouracil (PTU)
Onset of action Absorbed within 30 min, but
Classification Therapeutic: Antithyroid drug
Pharmacologic: Thyroid hormone therapeutic effects may take up
inhibitor to 3 weeks
Duration of action Half-life: 1–2 h; peak: 1–1.5 h
Adverse Effects: Approximately 15% to 20% of
patients taking this drug will experience leukopenia,
which is normally asymptomatic. Serious hypersensitiv-
ity reactions are rare but may include agranulocytosis,
aplastic anemia, thrombocytopenia, rash, urticaria, and
glomerulonephritis. Arthralgias and joint swelling occur
Chapter 67 Pharmacotherapy of Thyroid Disorders 1239
in 5% of patients. CNS effects include headache, vertigo, inhibit both the synthesis and release of thyroid hormone.
neuritis, and paresthesias. Propylthiouracil can also cause Chronic use can result in toxicity known as iodism, which
hypothyroidism and goiter at high doses. Black Box Warn- is characterized by burning in the mouth and throat, a
ing: Severe liver injury and acute hepatic failure have been metallic taste, sore teeth and gums, increased salivation
reported in patients taking propylthiouracil. This drug and nasal discharge, swollen eyelids, gastric irritation, and
should be reserved for those unable to tolerate methima- diarrhea. The distribution of Lugol’s solution is now regu-
zole and in whom radioactive iodine therapy or surgery lated by the U.S. Drug Enforcement Administration
are not appropriate treatments for hyperthyroidism. because strong iodine solutions are used in the manufac-
ture of crystal methamphetamine. Potassium iodide is
Contraindications/Precautions: The use of pro- pregnancy category D.
pylthiouracil is contraindicated if the patient has a hyper-
sensitivity to the drug. Although contraindicated during Methimazole (Tapazole): Approved in 1950, methimazole
pregnancy, the drug occasionally must be administered is given by the oral route to correct hyperthyroidism by
to women who experience a thyrotoxic crisis during preg- inhibiting the synthesis of thyroid hormone. Like PTU, it
nancy, and it is preferred over methimazole because less does not affect existing stores of thyroid hormone; thus it
of the drug crosses the placenta. It should be used with may take many weeks before a normal thyroid state is
caution during active infection, lactation, and bone mar- achieved. Its uses, contraindications, and adverse effects
row depression. Because propylthiouracil can cause liver are similar to those for PTU, except that methimazole does
impairment, caution should be used when treating patients not induce hypothyroidism or cause serious liver injury.
with preexisting hepatic disease. Other important differences are that methimazole does not
inhibit conversion of T4 to T3; therefore, its effects may take
Drug Interactions: Propylthiouracil increases the longer to occur. Methimazole has a longer half-life, allow-
actions of anticoagulants, which creates an increased risk ing for once-a-day dosing, while PTU must be taken
of bleeding. Iodine-containing drugs (amiodarone, potas- 3 times a day. Methimazole is usually administered for 12
sium iodide, sodium iodide, radioactive iodine) and thy- to 18 months, then tapered or discontinued if TSH levels
roid hormones can inhibit the effectiveness of this drug. are normal. This drug is pregnancy category D.
Altered serum levels of metoprolol, propranolol, and
digoxin can occur as the patient moves from a hyper- Potassium iodide (Thyro-Block): Potassium iodide is
thyroid to a normal thyroid state. Cross hypersensitivity given orally prior to thyroid surgery to reduce the vascu-
occurs in about 50% of patients who have experienced a larity (risk of bleeding), fragility, and size of the thyroid
hypersensitivity reaction to methimazole, the other major gland. It may also be used alone for hyperthyroidism or in
antithyroid medication. Propylthiouracil should not combination with antithyroid drugs and beta-adrenergic
be used with carbamazepine or clozapine because this blockers in the treatment of thyroid storm. Like other
may increase the risk of agranulocytosis. Herbal/Food: forms of iodide, it suppresses the synthesis and release of
Unknown. thyroid hormone. It is also used to protect the thyroid
gland in instances of radiation exposure secondary to a
Pregnancy: Category D. nuclear incident. It is taken up by the thyroid gland,
thereby blocking the uptake of radioactive iodide in the
Treatment of Overdose: When propylthiouracil is thyroid gland, reducing the risk for developing thyroid
taken in high doses, it can induce hypothyroidism; the cancer. As a protective agent, it must be given immediately
administration of thyroid hormone may be necessary. prior to, or within 3 hours following, radiation exposure.
This drug is pregnancy category D.
Nursing Responsibilities: Key nursing implications
for patients receiving propylthiouracil are included in the Radioactive iodide (131I): Radioactive iodide is an isotope
Nursing Practice Application for Patients Receiving Phar- of iodine used for hyperthyroidism. Like all iodine, 131I is
macotherapy with Antithyroid Drugs. taken up by the thyroid gland, where its radioactivity
destroys thyroid tissue. The goal is to destroy part of the
Drugs Similar to Propylthiouracil (PTU) gland, thereby decreasing the amount of thyroid hor-
mone produced and secreted. In some patients, too much
Drugs similar to propylthiouracil include Lugol’s solution, thyroid gland is destroyed and hypothyroidism results,
methimazole, potassium iodide, and radioactive iodide. which is then treated with levothyroxine. Approximately
two thirds of patients treated with 131I respond to a sin-
Lugol’s solution (5% elemental iodine and 10% potassium gle treatment, whereas the rest require two or more
iodide): This strong iodine solution is given orally to treat treatments. Therapeutic effects develop slowly over 2 to
hyperthyroidism, as adjunctive therapy 10 to 14 days prior 3 months, and the tissue damage is limited to the thyroid
to thyroid surgery, or for the treatment of thyrotoxicosis. It
has been used as a topical antiseptic. Although iodine is
necessary for the synthesis of thyroid hormone, high levels
1240 Unit 10 Pharmacology of the Endocrine System
gland with no surrounding structures affected. Although patients wishing to avoid surgery or those who do not
it is contraindicated during pregnancy and breastfeed- tolerate antithyroid drugs. It is administered PO and is
ing, and usually not used in children, 131I has not been also used to treat thyroid cancer (in high doses) and for
known to cause cancer or other serious adverse effects to the diagnosis of thyroid disorders. This drug is preg-
the thyroid gland or elsewhere in the body. It is used in nancy category X.
CONNECTIONS: NURSING PRACTICE APPLICATION
Patients Receiving Pharmacotherapy with Antithyroid Drugs
Assessment
Baseline assessment prior to administration:
• Obtain a complete health history including cardiovascular, GI, hepatic, or kidney disease; pregnancy; or breastfeeding. Obtain a drug history including
allergies, current prescription and OTC drugs, herbal preparations, alcohol use, and smoking. Be alert to possible drug interactions.
• Evaluate appropriate laboratory findings (e.g., T3, T4, and TSH levels, CBC, and glucose).
• Obtain baseline height, weight, and vital signs. Obtain ECG as needed.
• Assess the patient’s ability to receive and understand instructions. Include family and caregivers as needed.
Assessment throughout administration:
• Assess for desired therapeutic effects (e.g., T3, T4, and TSH levels return to normal, associated symptoms of hyperthyroidism ease).
• Continue periodic monitoring of T3, T4, and TSH levels, CBC, and glucose.
• Continue monitoring height, weight, and vital signs. Monitor ECG as needed.
• Assess for adverse effects: nausea, vomiting, diarrhea, epigastric distress, skin rash, itching, headache, vertigo, and paresthesias.
Implementation
Interventions and (Rationales) Patient-Centered Care
Ensuring therapeutic effects: • Advise the patient that the drug will help to stabilize thyroid hormone
• Monitor vital signs, appetite, weight, sensitivity to heat or cold, sleep levels quickly, but other methods (e.g., surgery, radioactive iodine) may
be required for long-term management.
patterns, and ability to perform ADLs. (As metabolic activity controlled
by thyroid hormones stabilizes, the patient should return to more • Instruct the patient to maintain consistent dosing to allow the drug to
normal weight, ADLs, and feelings of wellness. Weight and pulse rate reach therapeutic levels.
are measured to assist in the assessment of the therapeutic response
to drug therapy.) • Instruct the patient to weigh self 2 to 3 times per week, record the find-
ings along with the pulse rate, and bring the record to each healthcare
provider visit.
• Avoid iodine-containing foods (e.g., iodized salt, soy sauce, tofu, yogurt, • Provide dietary instruction on which foods to avoid to reduce excessive
milk, strawberries, eggs) unless approved by the healthcare provider. intake of foods with high iodine content. Provide for dietitian consulta-
(Iodine is necessary for the synthesis of thyroid hormone. Increasing or tion as needed.
decreasing normal intake may result in adverse drug effects.)
• Monitor thyroid function tests. (Results help determine the effective- • Instruct the patient on the need to return periodically for laboratory
ness of the drug therapy and need for dosage changes.) work.
Minimizing adverse effects: • Teach the patient that small daily fluctuations in symptoms may occur,
• Monitor for the return of original symptoms and report consistent especially during periods of stress or illness. Any significant changes
in pulse rate, weight, nervousness, or fatigue, intolerance to heat or
occurrence. (Significant return of hyperthyroid symptoms may indicate cold, and diarrhea or constipation should be reported to the healthcare
that inadequate therapeutic levels are being maintained; symptoms of provider.
hypothyroidism may signal drug toxicity.)
• Monitor for signs of infection: fever, rashes, sore throat, malaise, • Instruct the patient to report fever, rashes, sore throat, chills, malaise,
fatigue, or weakness. Monitor CBC and platelet counts. (Antithyroid or weakness to the healthcare provider.
drugs may cause agranulocytosis.)
• Continue to monitor the effectiveness of all other medications the • Review the patient’s medication list at each health visit. Instruct the
patient is taking. (Antithyroid replacement drugs interact with many patient to report any unusual symptoms of concern to the healthcare
drugs, particularly those containing iodine such as amiodarone. As provider.
a more normal thyroid state is reached, doses of cardiac drugs may
need to be adjusted.)
• Lifespan: Monitor symptoms in older adults more frequently. (Older • Teach the patient, family, or caregiver that the lowest dose will be
patients are more sensitive to thyroid hormone levels and minor started and gradually increased to find the optimal level. Any significant
changes in daily thyroid levels may cause a significant change in change in symptoms should be promptly reported to the healthcare
symptoms.) provider.
• Monitor serum glucose levels, especially in patients with diabetes. • Teach patients with diabetes to monitor capillary glucose levels more
Patients with diabetes should monitor capillary glucose levels more frequently during therapy. Report any consistent changes to the health-
frequently. (Antithyroid drugs may cause changes in glucose levels.) care provider.
• Ensure patient safety. Observe for lightheadedness or dizziness. • Instruct the patient to call for assistance prior to getting out of bed or
Monitor ambulation until the effects of the drug are known. (Dizziness attempting to walk alone if dizziness occurs. When dizziness occurs,
may be secondary to changes in pulse or blood pressure or related the patient should sit or lie down and not attempt to stand or walk until
to adverse drug effects and should be assessed by the healthcare the sensation passes.
provider. Lifespan: The older adult is especially at risk for falls related
to dizziness.) • Assess the safety of the home environment and discuss needed modi-
fications with the family or caregiver.
Chapter 67 Pharmacotherapy of Thyroid Disorders 1241
CONNECTIONS: NURSING PRACTICE APPLICATION (continued)
Implementation
Interventions and (Rationales) Patient-Centered Care
• Ensure patient and caregiver safety if radioactive iodine is used. (Even • Teach the patient to limit contact with family to 1 h per day per person
though radioactive iodine provides just low-dose radiation, prolonged until the treatment period is over. Young children and pregnant women
contact by care providers or visitors should be avoided.) should avoid contact with the patient.
• Advise the patient to increase fluid intake up to 2 L/day as allowed and
to void frequently to avoid irradiation to gonads from radioactivity in
urine excretion.
• Instruct the patient not to expectorate and to cover the mouth when
coughing. Any contaminated tissues should be disposed of per the
protocol of the agency or healthcare provider.
Patient understanding of drug therapy: • The patient should be able to state the reason for the drug, appropriate
• Use opportunities during administration of medications and during dose and scheduling, what adverse effects to observe for, and when to
report them.
assessments to discuss the rationale for drug therapy, desired thera-
peutic outcomes, commonly observed adverse effects, parameters
for when to call the healthcare provider, and any necessary monitoring
or precautions. (Using time during nursing care helps to optimize and
reinforce key teaching areas.)
Patient self-administration of drug therapy: • Teach the patient to take the drug following appropriate guidelines:
• When administering the medication, instruct the patient, family, or • Take the drug at the same time each day.
• Take the drug 1 h before or 2 h after breakfast.
caregiver in proper self-administration of the drug, e.g., take the drug • Avoid foods high in iodine unless approved by the healthcare
in the morning at the same time each day. (Utilizing time during nurse provider.
administration of these drugs helps to reinforce teaching.)
Understanding Chapter 67
Key Concepts Summary 67.4 Hypothyroidism is treated by replacement therapy
with thyroid hormone.
67.1 Thyroid hormones contain iodine and stimulate the
basal metabolic rate of nearly all tissues. 67.5 Hyperthyroidism, or Graves’ disease, is
an autoimmune disorder accompanied by
67.2 An accurate diagnosis of thyroid hormone ophthalmopathy and goiter.
dysfunction is based on the patient’s symptoms
and the results of diagnostic tests. 67.6 Hyperthyroidism is treated with surgery or drugs
that reduce the production of thyroid hormone.
67.3 Hypothyroidism, or thyroid deficiency, can occur as
a congenital or acquired disorder.
CASE STUDY: Making the Patient Connection
Remember the patient she feels cold all the time. Acting on her feelings that some-
“Helen Mercado” at the thing might be wrong, she goes to her healthcare provider.
beginning of the chapter? Her vital signs at that time are as follows: blood pressure,
Now read the remainder 94/60 mmHg; heart rate, 58 beats/min; temperature,
of the case study. Based 36.3°C (97.4°F). Her weight has increased 13.6 kg (30 lb)
on the information pre- from when she was last seen 6 months ago. She confirms
sented within this chap- that her appetite has decreased. After completing a physi-
ter, respond to the critical thinking questions that cal examination, the healthcare provider orders some labo-
follow. ratory tests including T3, T4, and TSH.
Helen is a 38-year-old mother of three young children, Critical Thinking Questions
who works full time in a department store. She has been
feeling extremely tired, has been gaining weight, and says 1. Based on the patient’s symptoms, what test results
would you anticipate?
1242 Unit 10 Pharmacology of the Endocrine System 4. What symptoms should Helen report to the provider
while she is taking the Synthroid?
2. The healthcare provider orders levothyroxine (Syn-
throid) 200 mcg PO daily for Helen. What will you Answers to Critical Thinking Questions are available on the
teach Helen about this drug and when to take it? faculty resources site. Please consult with your instructor.
3. Helen asks you if she will need to be on the medi-
cation for very long. How will you answer her?
Additional Case Study 1. What diagnostic tests do you expect to see ordered for
this patient?
The nurse receives a new patient admission onto a cardiac
unit: Carolyn James, a 72-year-old woman, with new-onset 2. What drug therapy do you anticipate for this patient?
atrial fibrillation with rapid ventricular response. The nurse
connects the patient to a cardiac monitor and obtains the 3. What long-term therapy do you believe is appro-
following vital signs: blood pressure, 168/96 mmHg; respi- priate for this patient?
rations, 28 breaths/min; heart rate, 162 beats/min; temper-
ature 38.7°C (101.6°F). The nurse learns from the patient’s Answers to Additional Case Study questions are available
daughter that Carolyn was recently diagnosed with Graves’ on the faculty resources site. Please consult with your
disease, but she has not been taking her medications. instructor.
Chapter Review drug, which symptoms will the nurse teach the
patient to report to the healthcare provider?
1. The patient on replacement therapy with levothyrox-
ine (Synthroid) reports feeling nervous and is having 1. Sore throat, low-grade fever, chills
occasional palpitations and tremors. The nurse recog- 2. Increase in appetite and caloric intake
nizes that these symptoms may indicate what effect is 3. Tinnitus, altered taste, thickened saliva
occurring? 4. Insomnia, nightmares, and night sweats
1. The patient is still experiencing hypothyroidism 4. Which assessment finding would cause the nurse to
and the dose may need to be increased. withhold a regularly scheduled dose of levothyroxine?
2. The patient now has normal thyroid function 1. A 1-kg (2-lb) weight gain
and the levothyroxine (Synthroid) is no longer 2. A blood pressure reading of 100/70 mmHg
needed. 3. A heart rate of 110 beats/min
4. A temperature of 37.9°C (100.2°F)
3. The patient has developed diabetes and needs
further evaluation. 5. A patient is taking a solution of 5% iodine and 10%
potassium iodide (Lugol’s solution) prior to a thy-
4. The patient is experiencing symptoms of roidectomy. The patient asks why iodine solution is
hyperthyroidism and the drug dosage may need used since iodine is needed to make thyroid hormone.
to be decreased. What is the nurse’s best answer?
2. Which of the following assessment findings 1. “The symptoms you were having indicate you
would the nurse expect to observe in an adult were not receiving enough iodine.”
patient experiencing therapeutic effects
from levothyroxine (Synthroid)? (Select all 2. “High levels of iodine can temporarily reduce the
that apply.) amount of thyroid hormone your body makes and
secretes.”
1. Constipation and weight gain
3. “High levels of iodine are always used prior to
2. Decreased blinking and exophthalmos thyroidectomy to make up for the loss of iodine
when the thyroid is removed.”
3. Decreased reports of fatigue
4. “The high levels of iodine help prevent diabetes
4. Decreased blood cholesterol levels from developing.”
5. Pulse rate between 60 and 100 beats/minute
3. A patient will be treated with propylthiouracil (PTU)
for hyperthyroidism. While the patient is taking this
6. What should the nurse teach the patient who is newly Chapter 67 Pharmacotherapy of Thyroid Disorders 1243
diagnosed with hypothyroidism and will start taking
levothyroxine (Synthroid)? 3. Take the dose in the morning before breakfast, as
close to the same time each day as possible.
1. Take the pill in the afternoon with a high-fiber
snack to prevent stomach upset. 4. The drug may be taken every other day if diarrhea
occurs.
2. Eat plenty of fruits and vegetables such as
strawberries, spinach, and kale to replace vital See Answers to Chapter Review in Appendix A.
nutrients.
References Lu, Y., Guo, H., Liu, D., & Zhao, Z. (2016). Preservation of
renal function by thyroid hormone replacement in
D’Adamo, C. R., & Sahin, A. (2014). Soy foods and elderly persons with subclinical hypothyroidism.
supplementation: A review of commonly perceived Archives of Medical Science, 12, 772–777. doi:10.5114/
health benefits and risks. Alternative Therapies in Health aoms.2016.60965
and Medicine, 20(Suppl. 1), 39–51.
Rhee, C., Kalantar-Zadeh, K., Streja, E., Carrero, J., Ma,
Harding, K. B., Pena-Rosas, J. P., Webster, A. C., Yap, C. M. J. Z., Lu, J. L., & Kovesdy, C. P. (2015). The relationship
Y., Payne, B. A., Ota, E., & De-Regil, L. M. (2017). Iodine between thyroid function and estimated glomerular
supplementation for women during the preconception, filtration rate in patients with chronic kidney disease.
pregnancy and postpartum period. Cochrane Database of Nephrology Dialysis Transplantation, 30, 282–287.
Systematic Reviews, 3, Art. No. CD011761. doi:10.1093/ndt/gfu303
doi:10.1002/14651858.CD011761.pub2
Shin, D. H., Lee, M. J., Lee, H. S., Oh, H. J., Ko, K. I., Kim,
Hataya, Y., Igarashi, S., Yamashita, T., & Komatsu, C. H., . . . Kang, S.-W. (2013). Thyroid hormone
Y. (2013). Thyroid hormone replacement therapy for replacement therapy attenuates the decline of renal
primary hypothyroidism leads to significant function in chronic kidney disease patients with
improvement of renal function in chronic kidney subclinical hypothyroidism. Thyroid, 23, 654–661.
disease patients. Clinical and Experimental Nephrology, doi:10.1089/thy.2012.0475
17, 525–531. doi:10.1007/s10157-012-0727-y
Levitsky, L. L. (2016). Pediatric Graves’ disease. Retrieved
from http://emedicine.medscape.com/article/
920283-overview
Selected Bibliography Kilpatrick, S. J. (2015). ACOG guidelines at a glance: Thyroid
disease in pregnancy. Retrieved from http://
Antonelli, A., Ferrari, S. M., Corrado, A., Di contemporaryobgyn.modernmedicine.com/
Domenicantonio, A., & Fallahi, P. (2015). Autoimmune contemporary-obgyn/news/acog-guidelines-
thyroid disorders. Autoimmunity Reviews, 14, 174–180. glance-thyroid-disease-pregnancy?page=full
doi:10.1016/j.autrev.2014.10.016
Leung, A. M. (2016). Thyroid emergencies. Journal of
Dunn, D., & Turner, C. (2016). Hypothyroidism in women. Infusion Nursing, 39, 281–286. doi:10.1097/
Nursing for Women’s Health, 20, 93–98. doi:10.1016/j. NAN.0000000000000186
nwh.2015.12.002
Maraka, S., Ospina, N. M. S., O’Keeffe, D. T., Espinosa De
Eledrisi, M. S. (2016). Myxedema coma or crisis. Retrieved Ycaza, A. E., Gionfriddo, M. R., Erwin, P. J., . . .
from http://emedicine.medscape.com/article/ Montori, V. M. (2016). Subclinical hypothyroidism in
123577-overview pregnancy: A systematic review and meta-analysis.
Thyroid, 26, 580–590. doi:10.1089/thy.2015.0418
Fatourechi, V. (2014). Hyperthyroidism and thyrotoxicosis.
In F. Bandeira et al. (Eds.), Endocrinology and diabetes: A
problem-oriented approach (pp. 9–21). New York, NY:
Springer. doi:10.1007/978-1-4614-8684-8_2
1244 Unit 10 Pharmacology of the Endocrine System Ross, D. S., Burch, H. B., Cooper, D. S., Greenlee, M. C.,
Laurberg, P., Maia, A. L., . . . Walter, M. A. (2016). 2016
Mendes, A. (2015). Recognising hypothyroidism in the American Thyroid Association guidelines for diagnosis
community: What can nurses and patients do? British and management of hyperthyroidism and other causes
Journal of Community Nursing, 20(4), 200–202. of thyrotoxicosis. Thyroid, 26, 1343–1421. doi:10.1089/
doi:10.12968/bjcn.2015.20.4.200 thy.2016.0229
Misra, M. (2017). Thyroid storm. Retrieved from http:// Walsh, J. P. (2016). Managing thyroid disease in general
emedicine.medscape.com/article/925147-overview practice. The Medical Journal of Australia, 205, 179–184.
doi:10.5694/mja16.00545
Ramdath, D. D., Padhi, E. M. T., Sarfaraz, S., Renwick,
S., & Duncan, A. M. (2017). Beyond the cholesterol- Zimmermann, M. B., & Boelaert, K. (2015). Iodine
lowering effect of soy protein: A review of the effects of deficiency and thyroid disorders. The Lancet Diabetes
dietary soy and its constituents on risk factors for & Endocrinology, 3, 286–295. doi:10.1016/
cardiovascular disease. Nutrients, 9, 324. doi:10.3390/ S2213-8587(14)70225-6
nu9040324
“I don’t think this is poison ivy.
I’ve never had a problem with it and
I’ve been around it a lot.
But man, does this itch!”
Patient “Charlie Harness”
Chapter 68
Corticosteroids and Drugs
Affecting the Adrenal Cortex
Chapter Outline Learning Outcomes
cc Physiology of the Adrenal Gland After reading this chapter, the student should be able to:
cc Overview of Corticosteroid Pharmacotherapy
cc Adverse Effects of Corticosteroids 1. Identify the functions of the three classes of
cc Replacement Therapy with Corticosteroids hormones secreted by the adrenal gland.
PROTOTYPE Hydrocortisone (Cortef, Solu-Cortef, 2. Diagram the negative feedback regulation of
Others), p. 1252 corticosteroid secretion.
cc Corticosteroids for Nonendocrine Conditions
cc Mineralocorticoids 3. Identify common properties of the corticosteroid
PROTOTYPE Fludrocortisone, p. 1257 medications.
cc Antiadrenal Drugs
4. Describe the potential adverse effects of long-term
corticosteroid therapy.
5. Compare and contrast the pharmacotherapy of acute
and chronic adrenocortical insufficiency.
6. Explain how corticosteroids affect the inflammatory
and immune responses.
7. Recognize nonendocrine disorders that respond to
corticosteroid therapy.
8. Describe indications for pharmacotherapy with
mineralocorticoids.
9. Explain the pharmacotherapy of Cushing’s syndrome.
10. Describe the nurse’s role in the pharmacologic
management of adrenal disorders.
11. 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.
12. Apply the nursing process to the care of patients
receiving pharmacotherapy with corticosteroids and
mineralocorticoids.
1245
1246 Unit 10 Pharmacology of the Endocrine System
Key Terms adrenocorticotropic hormone gonadocorticoids, 1247
(ACTH), 1247 hyperaldosteronism, 1257
Addison’s disease, 1250 hypoaldosteronism, 1257
adrenal atrophy, 1250 Cushing’s syndrome, 1258 mineralocorticoids, 1246
adrenal crisis, 1250
adrenocortical insufficiency, 1250 glucocorticoids, 1246
Though small, the adrenal glands secrete hormones that Glucocorticoids: More than 30 different glucocorticoids
affect every body tissue. The primary secretions of the are secreted from the adrenal cortex. Cortisol, also called
adrenal glands, the corticosteroids, are some of the most hydrocortisone, is secreted in the highest amount and is
widely used drugs in medicine. They can be delivered by the most important pharmacologically. The liver converts
any route to treat conditions as diverse as dermatitis, hydrocortisone into cortisone, an active metabolite that is
lymphoma, ulcerative colitis, allergic rhinitis, and arthri- also available as a drug. Corticosterone is an additional
tis. This chapter examines the pharmacologic properties steroid secreted by the adrenal cortex.
of corticosteroids that make them so important to
pharmacotherapy. Glucocorticoids prepare the body for long-term stress
and affect the metabolism of nearly every cell. The effects
Physiology of the Adrenal Gland of glucocorticoids are diverse, and include the following:
68.1 The adrenal glands secrete • Increase the level of blood glucose (hyperglycemic
gonadocorticoids, mineralocorticoids, and effect) by inhibiting insulin secretion and promoting
corticosteroids. gluconeogenesis, which is the synthesis of carbohy-
drates from lipid and protein sources. This decreases
Weighing only two tenths of an ounce, each pyramid- glucose utilization by tissues and promotes the stor-
shaped adrenal gland sitting atop each kidney is divided age of glycogen in the liver.
into two major portions: an inner medulla and an outer
cortex. The secretions from these two portions have very • Increase the breakdown of proteins to amino acids.
different functions. Amino acids are then converted to glucose and glyco-
gen in the liver, resulting in protein depletion.
The adrenal medulla secretes 75% to 80% epinephrine,
with the remainder of the secretion being norepinephrine. • Increase the breakdown of lipids (lipolysis). The fatty
Adrenal release of epinephrine is triggered by activation acids are then utilized as energy sources.
of the sympathetic division of the autonomic nervous sys-
tem. Symptoms of the fight-or-flight response resulting • Suppress the inflammatory and immune responses.
from the secretion of these hormones are described in • Increase the sensitivity of vascular smooth muscle to
Chapters 12 and 15.
the actions of norepinephrine and angiotensin II, thus
The adrenal cortex secretes three essential classes of modifying smooth muscle tone.
steroid hormones: mineralocorticoids, glucocorticoids, and • Influence the central nervous system (CNS) by affect-
gonadocorticoids. Collectively, the mineralocorticoids and ing mood and maintaining normal nerve excitability.
glucocorticoids are called corticosteroids or adrenocortical • Increase the breakdown of bony matrix, resulting in
hormones. Although the terms corticosteroid and glucocorti- bone demineralization.
coid are sometimes used interchangeably in clinical prac- • Promote bronchodilation by making bronchial smooth
tice, the term corticosteroid technically refers to a hormone muscle more responsive to sympathetic nervous sys-
or drug that has both glucocorticoid and mineralocorticoid tem activation.
activity. The hormones secreted by the adrenal gland are • Stabilize mast cells, inhibiting the release of inflamma-
illustrated in Figure 68.1. tory mediators.
Mineralocorticoids: Aldosterone accounts for more As this list confirms, the glucocorticoids are essential
than 95% of the mineralocorticoids secreted by the adre- hormones for maintaining homeostasis. When given as
nal glands. The primary function of aldosterone is to con- medications, some of the physiologic actions of glucocorti-
serve sodium and water and promote the excretion of coids are considered therapeutic effects, while others are
potassium by the renal tubule, thus regulating plasma vol- adverse effects. Unfortunately, it is impossible to totally
ume. Pharmacotherapy with mineralocorticoids is pre- separate therapeutic effects from adverse effects when
sented in Section 68.6. drugs with such widespread actions are used in
pharmacotherapy.
The physiologic levels of glucocorticoids vary based on
a circadian rhythm. The lowest serum levels occur during
Chapter 68 Corticosteroids and Drugs Affecting the Adrenal Cortex 1247
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Figure 68.1 Hormonal secretions of the adrenal gland.
early sleep. Secretion rises during the night, with levels women (see Chapter 69). Tumors of the adrenal cortex can
peaking at awakening and declining during the day, cause hypersecretion of gonadocorticoids, resulting in hir-
depending on the needs of the body. Stress can cause a rapid sutism and masculinization, signs that are more noticeable
increase in glucocorticoid levels; when faced with internal in women than men. The physiologic effects of androgens
inflammatory or stressful conditions, the secretion of gluco- are discussed in Chapter 71.
corticoids can increase to 10 times their baseline level.
Overview of Corticosteroid
Regulation of glucocorticoid levels begins with cortico- Pharmacotherapy
tropin-releasing factor (CRF), secreted by the hypothalamus.
CRF travels to the pituitary where it causes the release of 68.2 Corticosteroids are widely used, and all
adrenocorticotropic hormone (ACTH). ACTH then travels drugs in the class have similar indications,
via the blood to reach the adrenal cortex, causing it to release actions, and adverse effects.
glucocorticoids. When the serum level of cortisol rises, it
provides negative feedback to the hypothalamus and pitu- Corticosteroids are some of the most widely prescribed
itary to shut off further release of glucocorticoids. This nega- medications because they are useful in treating conditions
tive feedback mechanism is illustrated in Figure 68.2. affecting nearly every body system. Furthermore, some of
their indications are for diseases common to all age groups
Gonadocorticoids: The gonadocorticoids or sex hor- and for diseases that occur frequently in the population.
mones secreted by the adrenal cortex are mostly androgens, Some are available over the counter (OTC).
though small amounts of estrogens are also produced. The
amounts of adrenal sex hormones are far less than the lev- Corticosteroids can be classified in many different
els secreted by the testes or ovaries during the reproductive ways. One method is based on pathophysiology, such as
years. Though their amount is small, the adrenal gonado- grouping corticosteroids used for the treatment of inflam-
corticoids contribute to the onset of puberty and are the pri- mation, allergies, or neoplasias. Another method is to
mary source of endogenous estrogen in postmenopausal
1248 Unit 10 Pharmacology of the Endocrine System
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Pharmacologic Action Indications
%4( 2 Inhibit cell division Lymphomas and other neoplasms
Reduce joint inflammation Rheumatoid arthritis, osteoarthritis,
1 0GICVKXG bursitis, tendonitis
HGGFDCEM Reduce lung inflammation Asthma, chronic obstructive
#PVGTKQT RKVWKVCT[ pulmonary disease (COPD)
#%6* 2 Reduce skin inflammation Dermatitis, psoriasis
Supply exogenous corticosteroids Replacement therapy
1 Suppress allergic response Allergic rhinitis; anaphylaxis
Suppress gastrointestinal (GI) Inflammatory bowel disease
inflammation
Suppress general inflammatory Systemic lupus erythematosus
response
Suppress immune response Prophylaxis of transplant rejection
Autoimmune hemolytic anemia
Suppress ocular inflammation Conjunctivitis
#FTGPCN EQTVGZ More than 20 corticosteroids are available as medica-
tions, and the choice of a particular drug depends primar-
)NWEQEQTVKEQKFU ily on its pharmacokinetic properties. The duration of
action, which is sometimes used to classify these drugs,
1 5VKOWNCVKQP ranges from short to long acting. Some, such as hydrocorti-
sone, also have mineralocorticoid activity and may cause
$KQNQIKECN GHHGEVU 0GICVKXG sodium and fluid retention; others, such as prednisone,
HGGFDCEM have no such effect. Some corticosteroids are available by
only one route, such as topical for dermal conditions or
Figure 68.2 Feedback control of the adrenal cortex. intranasal for allergic rhinitis. An overview of the indica-
tions for corticosteroid therapy is given in Table 68.1.
group the drugs by body system, such as corticosteroids
used for skin conditions, immune disorders, or lung dis- Adverse Effects of Corticosteroids
eases. A third method is to look at corticosteroid use based
on their pharmacologic actions, as listed in Table 68.1. In 68.3 Long-term therapy with corticosteroids has
clinical practice, all methods are used. the potential to cause serious adverse effects in
multiple body systems.
Regardless of the method of classification, several gen-
eral statements can be made about the corticosteroid Low-dose or brief-duration regimens of corticosteroids
medications: produce few clinically significant adverse effects. How-
ever, high doses taken for prolonged periods offer a signif-
• They act by the same mechanism. icant risk for serious adverse effects. These adverse effects
• All have the same basic adverse effects, which are of corticosteroid therapy are well documented and can
impact nearly any body system. The following list includes
dose dependent. the most significant adverse events from long-term corti-
• Indications and adverse effects vary by the dose, costeroid therapy:
length of use, and route of administration. • Immune response. Suppression of inflammation and
• They are well absorbed when administered orally or immune responses increases patients’ susceptibility to
infections. Latent infections, such as herpesvirus or
parenterally, and they are widely distributed to all tuberculosis, may be reactivated during corticosteroid
body tissues. Topical administration (intra-articular, therapy. In addition, the anti-inflammatory actions of
inhalation, skin products, and ocular drops) results in the corticosteroids may mask the signs of an existing
systemic absorption, although at a slow rate. infection.
• Most are highly bound to plasma proteins.
• All are metabolized by the liver and excreted by the • Peptic ulcers. Prolonged corticosteroid use is asso-
kidneys. ciated with the development of peptic ulcers,
• All have the potential to cross the placenta (pregnancy
category C) and are secreted in breast milk. Use should
be avoided during pregnancy and lactation.
Chapter 68 Corticosteroids and Drugs Affecting the Adrenal Cortex 1249
CONNECTIONS: Complementary and Alternative Therapies
Fish Oils for Inflammation
Description Evidence
Fish oils, also known as marine oils, are lipids found primarily in Omega-3 fatty acids are known for their triglyceride-lowering activity
coldwater fish such as salmon, mackerel, tuna, and herring, as and their anti-inflammatory actions (National Center for Complemen-
well as in algae oils, green leafy vegetables, beans, and nuts. tary and Integrative Health, 2017). Several mechanisms are believed
These oils are rich sources of long-chain polyunsaturated fatty to account for the anti-inflammatory activity of EPA and DHA. The
acids of the omega-3 type. The two most studied fatty acids two competitively inhibit the conversion of arachidonic acid to the
found in fish oils are eicosapentaenoic acid (EPA) and docosa- proinflammatory prostaglandins, thus reducing their synthesis.
hexaenoic acid (DHA).
Many studies have examined a proposed relationship
History and Claims between cognitive ability and high intake of omega-3 fatty acids,
and no benefit has been demonstrated in patients with Alzheimer’s
Fish oils are sometimes used for their anti-inflammatory, anti- disease. Randomized clinical trials have not shown statistically
thrombotic, antidysrhythmic, and antihyperlipidemic properties. significant improvement in cognitive function related to intake of
omega-3 fatty acids, although changes in aortic blood pressure
Standardization were noted (Chew et al., 2015; Pase et al., 2015). Aerobic exer-
cise combined with the use of omega-3 fatty acids demonstrated
Fish oils are standardized by the amount of omega-3 fatty acids positive effects that prevented the decline of gray matter, and
they contain. There is no standard dose; capsules may range omega-3s seemed to benefit cognition in those patients who
from 300 to 2000 mg. were less active (Köbe et al., 2016; Leckie et al., 2014).
especially when these drugs are combined with non- • Myopathy. Muscle wasting induced by corticosteroids
steroidal anti-inflammatory drugs (NSAIDs). Both may cause weakness and fatigue. The myopathy may
classes of drugs reduce prostaglandin synthesis in involve ocular or respiratory muscles.
the gastric mucosa, which normally provides protec-
tion from the high acidity in the stomach. Use of pro- CONNECTION Checkpoint 68.1
ton pump inhibitors may reduce the incidence of
peptic ulcers in patients who are taking corticoste- From what you learned in Chapter 41, what drug class includes the
roids (see Chapter 59). preferred drugs for treating mild to moderate inflammation? Answers
• Osteoporosis. Corticosteroids inhibit calcium absorp- to Connection Checkpoint questions are available on the faculty
tion, suppress bone formation, and accelerate bone resources site. Please consult with your instructor.
resorption—all actions that weaken the bony matrix.
Up to 50% of patients on long-term corticosteroid ther- Corticosteroids also interact with many drugs. Their
apy will sustain a fracture due to osteoporosis. Treat- hyperglycemic effects may decrease the effectiveness of
ment with a bisphosphonate may reduce the incidence antidiabetic medications. Combining glucocorticoids with
of fractures in these patients (see Chapter 72). other ulcerogenic drugs such as aspirin and other NSAIDs
• Behavioral changes. By an unknown mechanism, cor- markedly increases the risk of peptic ulcer disease. Admin-
ticosteroids can induce psychologic changes. These istration with certain diuretics may lead to hypocalcemia
may be minor, such as nervousness or moodiness, or and hypokalemia. Vaccines will have a diminished effect if
may involve hallucinations and increased suicidal administered during corticosteroid therapy. The nurse
tendencies. should always check for potential drug interactions when
• Eye changes. Cataracts and open-angle glaucoma are a patient is receiving prolonged corticosteroid therapy.
potential adverse events of long-term corticosteroid
therapy. An important goal during long-term corticosteroid
• Metabolic changes. Corticosteroids have a hypergly- therapy is to prevent the development of serious adverse
cemic action that raises serum glucose and can cause effects. The following strategies are often used to minimize
glucose intolerance, especially in patients with diabe- the incidence of serious adverse effects:
tes. Mobilization of lipids may cause hyperlipidemia
and abnormal fat deposits. Electrolyte changes include • Doses are kept to the lowest amount that will achieve
hypocalcemia, hypokalemia, and hypernatremia. the therapeutic goal. In some cases, concurrent drug
Fluid retention, weight gain, hypertension (HTN), and therapy with a noncorticosteroid may be implemented
edema are other possible effects. to produce additive therapeutic effects, while keeping
the corticosteroid dose low. Careful monitoring of the
effectiveness of the drug is necessary.
1250 Unit 10 Pharmacology of the Endocrine System
• Corticosteroids are sometimes administered every receiving ACTH stimulation. Secondary adrenocortical
other day (alternate-day dosing) to minimize adrenal insufficiency is much more common than primary and
atrophy (see Section 68.4). This prevents constant, neg- can occur when corticosteroids are suddenly withdrawn
ative feedback on the pituitary and forces the patient’s during pharmacotherapy. Symptoms of primary and sec-
adrenal glands to secrete endogenous corticosteroids ondary adrenocortical insufficiency are the same because
every other day. both are characterized by inadequate corticosteroid
secretion.
• For acute conditions, patients are administered large
doses of corticosteroids for a few days and then the The onset of chronic adrenocortical insufficiency is
drug dose is gradually decreased until discontinued. gradual, and it may take several months or even years
This prevents the severe symptoms of adrenal atrophy before an accurate diagnosis is made. Symptoms include
from developing. For example, methylprednisolone hypoglycemia, fatigue, muscle weakness, hypotension,
(Medrol Dosepak) consists of twenty-one 4-mg tablets, increased skin pigmentation, and GI disturbances such as
taken over 6 days. Six tablets are taken on day 1, five anorexia, vomiting, and diarrhea. Replacement therapy
on day 2, four on day 3, three on day 4, two on day 5, with corticosteroids is indicated. The goal of replacement
and one on day 6. therapy is to achieve the same physiologic level of hor-
mones in the blood that would be present if the adrenal
• Whenever possible, corticosteroids should be admin- glands were functioning properly. Patients requiring
istered locally by inhalation, intra-articular injections, replacement therapy usually must take corticosteroids
or topical applications to the skin, eyes, or ears to their entire lifetime, and concurrent therapy with a miner-
diminish the extent of systemic effects. Local adminis- alocorticoid such as fludrocortisone is necessary.
tration rarely produces systemic adverse effects.
Acute adrenocortical insufficiency has a sudden onset
Replacement Therapy with and usually occurs when corticosteroids are abruptly with-
Corticosteroids drawn from a patient who has been on long-term therapy.
This is because constant, high amounts of corticosteroid
68.4 Adrenocortical insufficiency is treated medications provide continuous negative feedback to the
by administering physiologic levels of hypothalamus and pituitary, shutting down the secretion
corticosteroids. of ACTH. Without stimulation by ACTH, the adrenal cor-
tex shrinks and stops secreting endogenous corticosteroids,
Lack of adequate secretion by the adrenal cortex, or adre- a condition known as adrenal atrophy. If the corticosteroid
nocortical insufficiency, involves a lack of both glucocor- medication is abruptly withdrawn, the shrunken adrenal
ticoids and mineralocorticoids. When pathology of the glands will not be able to secrete sufficient corticosteroids,
adrenal glands is the cause of the hyposecretion, it is called and symptoms of adrenal crisis will appear. Symptoms of
primary adrenocortical insufficiency, or Addison’s dis- this condition include nausea, vomiting, lethargy, confu-
ease. The most common etiology of primary adrenocorti- sion, myalgia, arthralgia, fever, asthenia, acute abdominal
cal insufficiency is the autoimmune destruction of both pain, hypotension, seizures, kidney failure, and coma.
adrenal glands. Hemorrhage, infections, or metastases in Immediate administration of IV hydrocortisone is essential
the adrenal glands are other potential causes. Addison’s because shock may quickly result if symptoms remain
disease is rare and includes a deficiency of both glucocorti- untreated. To prevent adrenal crisis, corticosteroids should
coids and mineralocorticoids. be discontinued gradually. The mechanism by which adre-
nal atrophy is induced by corticosteroid use is illustrated in
PharmFACT Pharmacotherapy Illustrated 68.1.
One of the earliest symptoms of Addison’s disease is The most frequently prescribed corticosteroids for
hyperpigmentation of the oral and vaginal mucosas and the treating adrenal insufficiency are hydrocortisone, predni-
sun-exposed areas of the skin. This occurs because high sone, and dexamethasone. Doses of these drugs are indi-
ACTH levels stimulate melanocytes to produce excessive vidualized to the specific amount of replacement therapy
amounts of melanin (Griffing, 2017). needed by the patient, and doses will need to be increased
during periods of high stress. Hydrocortisone and dexa-
Secondary adrenocortical insufficiency occurs when methasone can be administered by the intramuscular (IM)
the adrenal glands are normal, but they are not receiving or intravenous (IV) routes for acute disease, or orally (PO)
adequate stimulation due to lack of sufficient ACTH from for maintenance doses. Prednisone is administered PO.
the pituitary. Low serum levels of both ACTH and cortisol Because dexamethasone and prednisone have little or no
are diagnostic of secondary adrenocortical insufficiency mineralocorticoid activity, concurrent fludrocortisone ther-
because this indicates that the adrenal gland is not apy is necessary. Hydrocortisone has some intrinsic miner-
alocorticoid activity; therefore, concurrent administration
Chapter 68 Corticosteroids and Drugs Affecting the Adrenal Cortex 1251
Pharmacotherapy Illustrated 68.1
Corticosteroids and Adrenal Atrophy
1. Normal adrenal glands
Corticosteroid Therapy
2. Adrenal gland atrophy following Sudden Discontinuation
corticosteroid therapy
Gradual Discontinuation
3. Gradual withdrawal of 4. Sudden withdrawal of
corticosteroids allows adrenal corticosteroids leads to acute
glands to resume normal • adrenal insufficiency
function • hypotension
• lethargy
• renal failure
• asthenia
• nausea/vomiting
of fludrocortisone may not be necessary. Doses for selected fail to rise after the injection, the pathology is at the level of
corticosteroids are listed in Table 68.2. the adrenal gland (primary adrenocortical insufficiency).
Cosyntropin (Cortrosyn) is a drug structurally similar CONNECTION Checkpoint 68.2
to ACTH that is used as a simple diagnostic test for adreno-
cortical deficiency. For this test, cosyntropin is injected IV From what you learned in Chapter 43, explain why immunizations
and the plasma levels of cortisol are measured 30 to 60 min- are sometimes contraindicated in patients receiving high-dose cor-
utes later. If the adrenal gland responds by secreting corti- ticosteroid therapy. Answers to Connection Checkpoint questions
costeroids after the cosyntropin injection, the pathology are available on the faculty resources site. Please consult with your
lies at the level of the pituitary or hypothalamus (second- instructor.
ary adrenocortical insufficiency). If plasma cortisol levels
1252 Unit 10 Pharmacology of the Endocrine System
Table 68.2 Selected Corticosteroids
Drug Route and Adult Dose Adverse Effects
(Maximum Dose Where Indicated)
Mood swings, weight gain, acne, facial
betamethasone (Celestone, Diprolene) PO: 0.6–7.2 mg/day flushing, nausea, insomnia, sodium and
IM: 0.5–9 mg/day fluid retention, impaired wound healing,
menstrual abnormalities
budesonide (Entocort EC, Pulmicort, Rhinocort) Intranasal (Rhinocort): 1–2 sprays in each nostril/day
(each spray: 32 mcg) Peptic ulcer, hypocalcemia,
osteoporosis with possible bone
PO (Entocort): 9 mg/day fractures, loss of muscle mass,
decreased growth in children, possible
cortisone PO: 20–300 mg/day in divided doses masking of infections
dexamethasone PO: 0.25–9 mg/day in divided doses
hydrocortisone (Cortef, Solu-Cortef, others) PO: 10–320 mg/day in 3–4 divided doses
IV/IM: 15–800 mg/day in 3–4 divided doses
(max: 2 g/day)
methylprednisolone (Depo-Medrol, Medrol, others) PO: 4–48 mg/day in divided doses
prednisolone PO: 5–60 mg 1–4 times/day
prednisone PO: 5–60 mg 1–4 times/day
triamcinolone (Aristospan, Kenalog, others) PO: 4–48 mg 1–4 times/day
Note: Italics indicate common adverse effects. Underline indicates serious adverse effects.
PROTOTYPE DRUG Hydrocortisone Pharmacokinetics:
(Cortef, Solu-Cortef,
Others) Route(s) PO, IV, IM, subcutaneous, rectal,
Classification Therapeutic: Adrenal hormone intra-articular, topical
Pharmacologic: Corticosteroid
Absorption Rapid
Therapeutic Effects and Uses: Structurally identical
to the natural hormone cortisol, hydrocortisone is a syn- Distribution Widely distributed when given
thetic corticosteroid that is the preferred drug for treating
adrenocortical insufficiency. When used for replacement PO or parenterally; crosses the
therapy, it is given at physiologic doses. Once proper dos-
ing has been achieved, its therapeutic effects should mimic placenta; secreted in breast milk;
those of endogenous corticosteroids. Hydrocortisone is
also available for the treatment of inflammation, allergic extensively bound to plasma protein
disorders, and many other conditions. Intra-articular injec-
tions may be given to decrease severe inflammation in Primary metabolism Hepatic
affected joints.
Primary excretion Renal
Hydrocortisone is available in six different salts: base,
acetate, cypionate, sodium phosphate, sodium succinate, Onset of action PO: 1–2 h; IM: 20 min
and valerate. Some of the salts, such as hydrocortisone ace-
tate, are designed for topical use, whereas others such as Duration of action 1–1.5 days (PO or IM)
hydrocortisone sodium succinate are for parenteral use
only. When administering hydrocortisone, care should be Adverse Effects: When used at low doses for replace-
taken to use the correct route for the prescribed formula- ment therapy, or by the topical or intranasal routes, adverse
tion of this drug. effects of hydrocortisone are uncommon. However, signs
of Cushing’s syndrome can develop with high doses
Mechanism of Action: The actions of hydrocortisone or with prolonged use. Hydrocortisone possesses some
are complex and the drug is thought to act by multiple mineralocorticoid activity, so sodium and fluid retention
mechanisms in different tissues. As a replacement drug, it may be observed. A wide range of CNS effects have been
restores deficient levels of glucocorticoids and, to a lesser reported, including insomnia, anxiety, headache, vertigo,
extent, mineralocorticoids. As an anti-inflammatory drug, confusion, and depression. Cardiovascular effects may
it blocks the actions of various chemical mediators in the include HTN and tachycardia. Long-term therapy may
inflammatory and allergic responses, including histamine, result in peptic ulcer disease, osteoporosis, hyperglycemia,
prostaglandins, and kinins. cataracts, HTN, and impaired wound healing.
Contraindications/Precautions: Hydrocortisone
is contraindicated in patients who are hypersensitive
to the drug or who have known infections, unless the
patient is being treated concurrently with anti-infectives.
Patients with diabetes, osteoporosis, psychosis, liver dis-
ease, or hypothyroidism should be treated with caution.
Patients with heart failure (HF) or HTN should be treated
with caution due to the possibility of fluid retention with
Chapter 68 Corticosteroids and Drugs Affecting the Adrenal Cortex 1253
hydrocortisone. If taken for longer than 2 weeks, hydrocor- Prednisone: Prednisone is rapidly absorbed and is the
tisone should be discontinued gradually. Caution should most frequently prescribed corticosteroid for oral adminis-
be used in treating children because the drug may delay tration. It is about 4 times more potent than hydrocortisone
normal growth and development. PO corticosteroids must and has a longer duration of action. It has little mineralocor-
be used with caution in patients with preexisting GI dis- ticoid activity. Prednisone is a synthetic corticosteroid
ease such as peptic ulcers or ulcerative colitis because they whose actions are the result of being metabolized to an
may worsen these conditions. Use with potassium-wasting active form, which is also available as the drug predniso-
drugs such as thiazide or loop diuretics may increase the lone. Although prednisone is available only by the PO route,
risk of hypokalemia. Anticholinesterase drugs may produce prednisolone may be administered PO, parenterally, or topi-
severe weakness. Hydrocortisone may cause a decrease in cally and may be of value in patients with liver impairment
immune response to vaccines and toxoids. Patients on high because it does not require hepatic activation. Oral solutions
doses of hydrocortisone should not receive live vaccines (Prelone) and an orally disintegrating tablet (Orapred ODT)
due to the possibility of infection. Because hydrocortisone are primarily prescribed for treating childhood asthma.
can cause hyperglycemia, doses of insulin and oral hypo- When used for inflammation, duration of prednisone ther-
glycemic drugs may require adjustment. Vitamin D supple- apy is commonly 4 to 10 days. For long-term therapy, alter-
ments are recommended to prevent corticosteroid-induced nate-day dosing is used. Prednisone is occasionally used to
osteoporosis. Herbal/Food: Chronic use of aloe, senna, cas- terminate acute bronchospasm in patients with asthma and
cara, or buckthorn may cause potassium deficiency. as an antineoplastic drug for cancers such as Hodgkin’s dis-
ease, acute childhood leukemias, and lymphomas. Predni-
Pregnancy: Category C. sone has the same adverse effects and contraindications as
hydrocortisone. This drug is pregnancy category C.
Treatment of Overdose: Hydrocortisone has no
acute toxicity and deaths are rare. No specific therapy is Corticosteroids for Nonendocrine
available and patients are treated symptomatically. Conditions
Nursing Responsibilities: Key nursing implications 68.5 Corticosteroids are frequently used
for patients receiving hydrocortisone are included in the to suppress the inflammatory and immune
Nursing Practice Application for Patients Receiving Phar- responses.
macotherapy with Systemic Corticosteroids.
One of the most important physiologic effects of cortico-
Drugs Similar to Hydrocortisone steroids is their natural ability to dampen the immune
response and inhibit the synthesis of inflammatory media-
(Cortef, Solu-Cortef, Others) tors. When used to treat conditions characterized by
hyperactive body defenses, the anti-inflammatory effects
There are many other corticosteroids, all having the same of the corticosteroids are therapeutic. When the drugs are
actions. In addition to hydrocortisone, dexamethasone and administered as replacement therapy, however, suppres-
prednisone are most frequently used for adrenocortical sion of the immune response can result in an increased
insufficiency. incidence of infections.
Dexamethasone: Dexamethasone is a synthetic corticoste- Part of the reason for the effectiveness of the corticoste-
roid that has almost no mineralocorticoid activity. It is 20 to roids in reducing inflammation and the immune response
30 times more potent than hydrocortisone and is available by is that they act by multiple mechanisms. These mechanisms
PO, IV, IM, topical, aerosol, and ophthalmic routes. The par- include the following:
enteral formulations (dexamethasone sodium phosphate)
are used for serious disorders such as anaphylaxis, reduction • Decreased numbers of circulating lymphocytes, eosin-
of cerebral edema, or acute adrenocortical insufficiency, or ophils, monocytes, and basophils
when PO therapy is not possible. Dexamethasone may be
injected intra-articularly for the short-term therapy of • Inhibited movement of macrophages and leukocytes
inflamed joints, or intralesionally into acute inflamed lesions to areas of inflammation
associated with discoid lupus, psoriatic plaques, and granu-
lomatous disorders. It is also indicated for the palliative • Decreased production of inflammatory cytokines,
management of leukemias and lymphomas. Dexamethasone including histamine, bradykinin, interferons, interleu-
is sometimes found in fixed-dose combinations with antibi- kins, and granulocyte-macrophage colony-stimulating
otics such as ciprofloxacin to treat otic or ocular infections factor
that have significant inflammation. Systemic forms of the
drug are metabolized by the liver to inactive metabolites. • Decreased formation of prostaglandins.
Dexamethasone has one of the longest durations of action of
any corticosteroid. This drug is pregnancy category C. It is important to note that the doses necessary to treat
inflammatory and other nonendocrine diseases are much
1254 Unit 10 Pharmacology of the Endocrine System
CONNECTIONS: Lifespan Considerations
Corticosteroid Use by Mothers at Risk for Preterm Labor
Giving corticosteroids to mothers at risk for preterm labor helps follow-up assessments between children whose mothers had
to develop the baby’s lungs and reduces the chance for serious received repeated corticosteroids and those who had not
complications such as infant respiratory distress syndrome if the received the drug. The authors concluded that the research
baby is born preterm. However, the benefit does not last long, supports the use of repeated corticosteroids for women at risk
approximately 7 days. Due to concerns about effects on birth for preterm birth to reduce the incidence of respiratory distress
weight and later childhood disabilities related to repeated corti- and serious health problems in the infant.
costeroid use, repeated doses may not be ordered. Crowther,
McKinlay, Middleton, and Harding (2015) conducted an analysis Recently, research seems to suggest that optimal timing of
of 10 randomized controlled trials found in the Cochrane drug administration, generally accepted as 7 days before deliv-
Pregnancy and Childbirth Group’s Trials Register to assess the ery, may be difficult to plan when the outcome of preterm labor is
effect of repeated corticosteroid use prior to preterm labor. not clear. Rupture of the membranes, cervical dilation over 2 cm,
Repeated dosages were found to have positive effects in reduc- and changes in cervical length have been used to time drug
ing the risk for respiratory distress syndrome in the newborn. administration (Adams, Kinzler, Chavez, Fazzari, & Vintzileos,
Although slight reductions in mean birth weight were noted in 2015; Aghajanian, Nguyen, Greene, & Gregory, 2016).
these babies, when adjusted for gestational age, these differ- Corticosteroids used in preterm labor may also increase the risk
ences were insignificant. And no statistically significant differ- of neonatal death due to infection, especially when healthcare
ences in disability outcomes were noted at early childhood resources are suboptimal, and special care and observation of
the newborn are crucial (Althabe et al., 2016).
higher than those used to treat adrenocortical insufficiency. large intestine (ulcerative colitis). Various drugs, includ-
For example, a daily maintenance dose of prednisone for a ing the 5-aminosalicylic acid drugs, are used to control
patient with Addison’s disease is 7.5 mg/day. This amount inflammation, cramping, and diarrhea. Exacerbations are
approximates what would normally be secreted by the treated with corticosteroids for brief time periods.
adrenal glands. Daily doses of prednisone for nonendo- Budesonide (Entocort-EC, Uceris) is a corticosteroid that
crine disorders range from 5 to 30 mg for transplant pro- has a delayed release and remains in the intestine to treat
phylaxis; 80 mg for chronic lymphocytic leukemia; 40 to the inflammation locally, without causing significant
60 mg for Crohn’s disease; and 20 to 300 mg for systemic systemic effects. IBD pharmacotherapy is presented in
lupus erythematosus. At these high doses, the adverse Chapter 60.
effects of corticosteroids will quickly manifest and the
adrenal gland will begin to atrophy in only 2 to 4 weeks. Asthma: Asthma is characterized by chronic inflamma-
Interventions should be planned to prevent anticipated tion that causes bronchoconstriction in the respiratory pas-
adverse effects. sages. Inhaled corticosteroids are preferred drugs for the
prevention of asthmatic attacks and the management of
Arthritis: Arthritis is one of the most common diseases chronic asthma. The inhaled drugs produce few systemic
affecting older adults. Rheumatoid arthritis (RA) is a adverse effects. Oral corticosteroids are used for the short-
chronic autoimmune disease that causes inflammation of term management of acute asthma exacerbations. Asthma
joints and is characterized by disfigurement and inflam- pharmacotherapy is presented in Chapter 44.
mation of multiple joints. Osteoarthritis is also a progres-
sive joint disease, but it occurs with more advanced age Allergies: Allergic rhinitis is inflammation of the nasal
and is characterized by less inflammation than RA. Both mucosa caused by exposure to allergens. Corticosteroids
types of arthritis are treated with NSAIDs early in the are applied directly to the nasal mucosa to prevent symp-
course of the disease. Corticosteroids are administered toms of allergic rhinitis. They have largely replaced anti-
when inflammation becomes severe, with therapy being histamines as preferred drugs for this condition. When
limited to 1 to 2 weeks, or until the pain and inflammation administered intranasally, the corticosteroids do not
subside. If the pain and inflammation are localized to one exhibit systemic adverse effects. For acute allergies, corti-
or two joints, intra-articular injections may be used. Corti- costeroids may be administered parenterally. Because their
costeroids offer only symptomatic treatment and do not onset of action is slow, however, they are always adminis-
alter the course of either type of arthritis. Arthritis phar- tered concurrently with other drugs, such as epinephrine,
macotherapy is presented in Chapter 72. for this indication. The pharmacotherapy of allergic rhini-
tis is presented in Chapter 45.
Inflammatory bowel disease: Inflammatory bowel
disease (IBD) is characterized by ulceration in the distal Transplant rejection prophylaxis: Successful tissue
portion of the small intestine (Crohn’s disease) or in the transplantation requires the use of immunosuppressant
Chapter 68 Corticosteroids and Drugs Affecting the Adrenal Cortex 1255
drugs; otherwise, the patient’s immune system would followed by moderate- to low-potency corticosteroids for
reject the transplant. One or more immunosuppressants maintenance therapy. The pharmacotherapy of dermato-
are administered at the time of transplantation and are logic diseases is presented in Chapter 73.
continued for several months following surgery. Corti-
costeroids are part of most therapeutic regimens to pre- Neoplasms: Corticosteroids such as prednisone and
vent transplant rejection. They may be used for several dexamethasone are used as adjuncts in the treatment of
weeks or maintained for 3 to 6 months following sur- certain neoplasms, especially acute childhood leukemias
gery. The prophylaxis of transplant rejection is pre- and Hodgkin’s disease. They are always used in combina-
sented in Chapter 42. tion with other antineoplastics. The pharmacotherapy of
cancer is presented in Chapter 57.
Dermatologic conditions: Topical corticosteroids are the
most effective therapy for treating the inflammation and Edema: Corticosteroids are occasionally used to treat
itching of dermatitis. These corticosteroids are specially for- disorders characterized by edema. They have been used
mulated to penetrate deep into the skin layers. Topical corti- for many years to reduce intracranial edema associated
costeroids such as betamethasone and hydrocortisone with trauma, tumors, and cerebral ischemia. These hor-
acetate are also the primary, initial treatment for psoriasis. mones tend to stabilize capillary membranes. Their effec-
High-potency corticosteroids are used for 1 to 2 weeks, tiveness in treating edema is controversial.
CONNECTIONS: NURSING PRACTICE APPLICATION
Patients Receiving Pharmacotherapy with Systemic Corticosteroids
Assessment
Baseline assessment prior to administration:
• Obtain a complete health history including cardiovascular, respiratory, neurologic, hepatic, or kidney disease; pregnancy; or breastfeeding. Obtain a
drug history including allergies, current prescription and OTC drugs, herbal preparations, caffeine, nicotine, and alcohol use. Be alert to possible drug
interactions.
• Obtain baseline vital signs and weight.
• Evaluate appropriate laboratory findings (e.g., complete blood count [CBC], platelets, electrolytes, glucose, lipid profile, hepatic or renal function
studies).
• Assess the patient’s ability to receive and understand instructions. Include family and caregivers as needed.
Assessment throughout administration:
• Assess for desired therapeutic effects (e.g., signs and symptoms of inflammation such as redness or swelling are decreased).
• Continue periodic monitoring of CBC, platelets, electrolytes, glucose, lipid profile, hepatic or renal function studies.
• Assess vital signs and weight periodically or if symptoms warrant. Obtain weight daily and report any gain over 1 kg (2 lb) in a 24-h period or more
than 2 kg (5 lb) in 1 week. Obtain height and weight of children on long-term corticosteroid therapy.
• Assess for and promptly report adverse effects: nausea, vomiting, symptoms of GI bleeding (dark or tarry stools, hematemesis, coffee-ground emesis,
blood in the stool), abdominal pain, dizziness, lightheadedness, confusion, agitation, euphoria or depression, palpitations, tachycardia, HTN, increased
respiratory rate and depth, pulmonary congestion, significant weight gain, edema, blurred vision, fever, or infections.
Implementation
Interventions and (Rationales) Patient-Centered Care
Ensuring therapeutic effects: • Teach the patient to report any return of original symptoms or an
• Continue assessments as above for therapeutic effects. (Diminished increase in inflammation, allergic response, or generalized malaise to
the healthcare provider.
inflammation, allergic response, and increased feelings of wellness
should begin after taking the first dose and continue to improve.) • Teach the patient how to monitor pulse and BP. Ensure proper use
and functioning of any home equipment obtained. Immediately report
Minimizing adverse effects: tachycardia, palpitations, or increased BP to the healthcare provider.
• Continue to monitor vital signs, especially blood pressure (BP) and
pulse. Immediately report tachycardia or BP over 140/90 mmHg, or
per parameters as ordered, to the healthcare provider. (Corticosteroids
may cause increased BP, HTN, and tachycardia due to increased
retention of fluids.)
• Continue to monitor periodic laboratory work: CBC, electrolytes, glu- • Instruct the patient on the need to return periodically for laboratory
cose, lipid levels, and hepatic and renal function tests. (Corticosteroids work.
have effects on the CBC and may cause hyperglycemia, hyperna-
tremia, hyperlipidemia, and hypokalemia. Patients with diabetes may • Advise the patient taking corticosteroids long term to carry a wallet
require a change in antidiabetic medication if the glucose remains identification card and wear medical identification jewelry indicating
elevated.) corticosteroid therapy.
• Teach the patient with diabetes to test for blood glucose more
frequently, notifying the healthcare provider if a consistent elevation is
noted.
• Lifespan: Monitor symptoms in older adults more frequently. (Older • Teach the patient, family, or caregiver to follow administration guide-
patients are at increased risk of adverse effects in all body systems due lines. Any significant change in symptoms should be promptly reported
to normal physiologic changes related to aging.) to the healthcare provider.
(continued )
1256 Unit 10 Pharmacology of the Endocrine System
CONNECTIONS: NURSING PRACTICE APPLICATION (continued)
Implementation
Interventions and (Rationales) Patient-Centered Care
• Monitor for and report abdominal pain, black or tarry stools, blood in • Instruct the patient to immediately report any signs or symptoms of GI
the stool, hematemesis, coffee-ground emesis, dizziness, lightheaded- bleeding.
ness, and hypotension, especially if associated with tachycardia. (GI
bleeding is an adverse drug effect.) • Teach the patient to take the drug with food or milk to decrease GI
irritation. Alcohol use should be eliminated.
• Monitor for signs and symptoms of infection in patients taking corti- • Instruct the patient to report any signs or symptoms of infection (e.g.,
costeroids. (Corticosteroids suppress the body’s normal immune and increasing temperature or fever, sore throat, redness or swelling at the
inflammatory response and may mask the signs and symptoms of site of injury, white patches in the mouth, vesicular rash).
infection.)
• Monitor for osteoporosis (e.g., bone density testing) periodically in • Teach the patient to maintain adequate calcium in the diet, avoid car-
patients on long-term corticosteroids. Encourage adequate calcium bonated sodas, and do weight-bearing exercises at least 3–4 times per
intake, weight-bearing exercise, and avoidance of carbonated week.
sodas. (Corticosteroids affect bone metabolism and may cause
osteoporosis and fractures. Weight-bearing exercise stresses bone • Teach postmenopausal women and patients on prolonged corticoste-
and encourages normal bone remodeling. Excessive or long-term roid therapy to consult with their provider about the need for vitamin D
consumption of carbonated sodas has been linked to an increased or additional drug therapy (e.g., bisphosphonates) for osteoporosis
risk of osteoporosis.) prevention.
• Monitor for unusual changes in mood or affect. (Corticosteroids may • Teach the patient, family, or caregiver to promptly report excessive
cause increased or decreased mood, euphoria, depression, or severe mood swings or unusual changes in mood.
mental instability.)
• Weigh the patient daily and report a gain of 1 kg (2 lb) or more in a • Instruct the patient to weigh self daily, ideally at the same time of day.
24-h period, or more than 2 kg (5 lb) per week, or increasing peripheral The patient should report weight gain of more than 1 kg (2 lb) in a 24-h
edema. Measure intake and output in the hospitalized patient. (Daily period, or more than 2 kg (5 lb) per week, or increasing peripheral
weight is an accurate measure of fluid status and takes into account edema to the healthcare provider.
intake, output, and insensible losses. Patients will experience some
fluid retention but should report weight gain, as above, or edema to the
healthcare provider.)
• Lifespan: Monitor height and weight in children. (Children receiving • Teach the parents or caregivers to weigh the child periodically at home
long-term corticosteroid therapy should continue to display normal and record. Bring the record to each healthcare visit.
growth and development curves.)
• Encourage the parents or caregivers to discuss concerns or any
unusual findings that would suggest developmental or growth delays
with the healthcare provider if they are noted in the child between
healthcare visits.
• Monitor vision periodically in patients taking corticosteroids. (Cortico- • Teach the patient to have eye examinations twice yearly or more
steroids may cause increased intraocular pressure and an increased frequently as instructed by the healthcare provider. Immediately report
risk for glaucoma, and may cause cataracts.) any eye pain, rainbow halos around lights, diminished vision, blurring,
and inability to focus.
• Do not stop the drug abruptly. Drug dosages must be tapered off if • Teach patients to not stop corticosteroids abruptly and to notify the
used for longer than 1–2 wk. (Adrenal insufficiency and crisis may healthcare provider if unable to take medication for more than 1 day
occur with profound hypotension, tachycardia, and other adverse due to illness.
effects if the drug is stopped abruptly.)
• Patients taking corticosteroids as replacement therapy for adrenal • Instruct patients on replacement therapy to obtain and carry replace-
insufficiency should obtain and carry PO and injectable medication ment doses in both PO and parenteral forms for emergency use.
forms, especially when traveling. (In an emergency, replacement medi-
cation may not be readily available and the patient may be unable to
take an oral dose. Having doses readily available ensures that the drug
can be taken or given if another replacement is not available.)
Patient understanding of drug therapy: • The patient, family, or caregiver should be able to state the reason for
• Use opportunities during administration of medications and during the drug, appropriate dose and scheduling, what adverse effects to
observe for and when to report them, and the anticipated length of
assessments to discuss the rationale for drug therapy, desired thera- medication therapy.
peutic outcomes, commonly observed adverse effects, parameters
for when to call the healthcare provider, and any necessary monitoring
or precautions. (Using time during nursing care helps to optimize and
reinforce key teaching areas.)
Patient self-administration of drug therapy: • The patient, family, or caregiver is able to discuss appropriate dosing
• When administering the medication, instruct the patient, family, or and administration needs, including:
• Take the drug in the morning at the same time each day.
caregiver in proper self-administration of the drug, e.g., with food or • Take the drug with food, milk, or a meal to prevent GI upset.
milk, followed by teach-back. (Utilizing time during nurse administra- • Do not use household measuring spoons to measure liquid or
tion of these drugs helps to reinforce teaching. Household measuring pediatric doses. Use the measuring device included with the drug
devices such as teaspoons differ significantly in size and amount and or obtain a dose syringe or other device from a pharmacy or the
should not be used for pediatric or liquid doses.) healthcare provider.
Chapter 68 Corticosteroids and Drugs Affecting the Adrenal Cortex 1257
Mineralocorticoids CONNECTION Checkpoint 68.3
68.6 Patients with adrenal insufficiency From what you learned in Chapter 31, name the two drugs classified
often require replacement therapy with as aldosterone antagonists and give their indications. Answers to
mineralocorticoids. Connection Checkpoint questions are available on the faculty resources
site. Please consult with your instructor.
Aldosterone is the primary hormone regulating sodium
and potassium balance in the body. Regulation of aldo- PROTOTYPE DRUG Fludrocortisone
sterone secretion is through activation of the renin-
angiotensin-aldosterone system. When plasma volume Classification Therapeutic: Drug for
falls, the kidney secretes renin, which results in the pro- hypoaldosteronism
duction of angiotensin II. Angiotensin II then promotes
aldosterone secretion, which in turn acts on the renal Pharmacologic: Mineralocorticoid
tubules to promote sodium and water retention and
increased excretion of potassium. Therapeutic Effects and Uses: Approved by the
U.S. Food and Drug Administration (FDA) in 1954, fludro-
Lack of adequate aldosterone secretion, or hypoaldo- cortisone is an oral corticosteroid that possesses a high
steronism, may be caused by a number of disorders. The degree of mineralocorticoid activity that mimics aldoste-
three broad categories of hypoaldosteronism are as rone. Although it has some glucocorticoid activity, this
follows: action is minimal at therapeutic doses. It is approved for
the treatment of Addison’s disease and for salt-losing
• Decreased stimulation of the adrenal cortex. Beta forms of adrenogenital syndrome, a life-threatening con-
blockers, NSAIDs, and calcium channel blockers may genital disorder that occurs during the first few weeks of
reduce renin serum levels and suppress the stimula- life. It has been used off-label to treat neurogenic ortho-
tion of aldosterone secretion. Angiotensin-converting static hypotension.
enzyme (ACE) inhibitors block the formation of angio-
tensin II, which is the normal signal for aldosterone Mechanism of Action: Fludrocortisone has the same
secretion. pharmacologic actions as aldosterone. It acts on the distal
renal tubule to promote sodium and water reabsorption
• Hyposecretion of aldosterone. Low aldosterone secre- and increased urinary potassium excretion.
tion may result from primary adrenal insufficiency
(Addison’s disease), which is usually a deficiency in Pharmacokinetics:
the secretion of both glucocorticoids and mineralocor-
ticoids. Heparin can also suppress aldosterone synthe- Route(s) PO
sis and secretion.
Absorption Rapidly absorbed
• Aldosterone resistance. The renal tubules may become
resistant to the actions of aldosterone. Aldosterone Distribution Distributed to most tissues;
resistance occurs during diseases of the renal tubules
and may also result from therapy with spironolactone crosses the placenta; secreted
(Aldactone) or progestins.
in breast milk; highly bound to
Whenever possible, the cause of hypoaldosteronism is
identified and treated. In some cases, replacement therapy plasma protein
with fludrocortisone is necessary.
Primary metabolism Hepatic to inactive metabolites
Excessive secretion of aldosterone, or hyperaldoste-
ronism, is usually caused by a benign tumor of the adre- Primary excretion Renal
nal gland. Also known as Conn’s syndrome, symptoms
include HTN caused by fluid retention and muscle Onset of action Peak plasma level: 1.5 h
weakness due to hypokalemia. Surgical excision of the
adrenal tumor is the preferred treatment for most Duration of action Half-life: 3.5 h
patients; however, pharmacotherapy with spironolac-
tone (Aldactone) may benefit patients whose surgical Adverse Effects: Most adverse effects of fludrocorti-
risk is high. Spironolactone is a potassium-sparing sone are the result of excessive mineralocorticoid activity:
diuretic that blocks the actions of aldosterone in the sodium and fluid retention, edema, cardiomegaly, HTN,
renal tubule. Spironolactone is featured as a drug proto- and HF. Excessive urinary loss of potassium may result in
type in Chapter 32. symptoms of hypokalemia: nausea, vomiting, prolonga-
tion of the QT interval, muscle cramps, and fatigue.
Contraindications/Precautions: Fludrocortisone
must be used with caution if the patient has any disorders
in which fluid accumulation could be hazardous, such as
HF, HTN, chronic kidney disease (CKD), or hepatic impair-
ment. Because the drug has glucocorticoid properties that
1258 Unit 10 Pharmacology of the Endocrine System
could lead to immunosuppression, it should not be admin- spreading. This could result in a delay in the initiation of
istered to patients with a known systemic fungal infection. antibiotic therapy.
Drug Interactions: If used with drugs that cause potas- PharmFACT
sium loss, fludrocortisone use will result in additive hypo-
kalemia. Potassium-wasting drugs include thiazide and Cushing’s syndrome caused by adrenal or pituitary tumors is
loop diuretics and amphotericin B. Fludrocortisone should quite rare, has a peak incidence between the ages of 25 and
be used with caution in patients taking digoxin due to the 40 years, and afflicts 5 times as many women as men
potential for hypokalemia-induced digoxin toxicity. Con- (Nguyen, 2017).
current use with androgens may cause additive sodium
retention and edema. Fludrocortisone may affect glyce- Because Cushing’s syndrome has a high mortality
mic control in patients with diabetes; doses of antidiabetic rate, medical intervention is necessary. The primary thera-
drugs may need to be increased. Herbal/Food: Sodium peutic goal is to identify and treat the cause of the excess
intake should be monitored because high levels may lead corticosteroids. If the patient is receiving high doses of a
to sodium retention. corticosteroid medication, gradual discontinuation of the
drug is usually sufficient to reverse the syndrome. When
Pregnancy: Category C. the cause of the hypersecretion is an adrenal tumor or an
ectopic tumor secreting ACTH, surgical removal is
Treatment of Overdose: Overdosage results in HTN, indicated.
edema, and hypokalemia. Treatment is symptomatic.
Potassium supplements may be beneficial. When removal of the tumor is not possible, a second-
ary option is to administer medications to reduce the excess
Nursing Responsibilities: Key nursing implications cortisol secretion. The antifungal drug ketoconazole has
for patients receiving fludrocortisone are included in the been the traditional drug for long-term therapy of Cush-
Nursing Practice Application for Patients Receiving Phar- ing’s syndrome. Used off-label for this indication, ketocon-
macotherapy with Systemic Corticosteroids. azole rapidly blocks the synthesis of glucocorticoids,
lowering serum levels. Unfortunately, the falling glucocor-
Drugs Similar to Fludrocortisone ticoid level signals the pituitary to release more ACTH.
Eventually, the very high levels of ACTH may overcome
Fludrocortisone is the only drug in its class. ketoconazole’s inhibition of glucocorticoid synthesis.
Although effective, ketoconazole carries a black box warn-
Antiadrenal Drugs ing that it should be used only for fungal infections that
have not responded to other medications due to the poten-
68.7 Antiadrenal drugs may be administered tial for serious hepatotoxicity.
to lower serum corticosteroid levels in patients
with Cushing’s syndrome. A newer approach is the drug pasireotide (Signifor),
which was approved in 2012 to treat Cushing’s syndrome
Cushing’s syndrome occurs when high levels of cortico- in patients for whom pituitary surgery is not an option.
steroids are present in the body over a prolonged time Pasireotide is closely related to somatostatin (growth
period. Although hypersecretion of these hormones can hormone–inhibiting hormone). Binding of pasireotide to
occur due to pituitary or adrenal tumors, the most com- somatostatin receptors causes inhibition of ACTH secretion
mon cause of Cushing’s syndrome is long-term therapy by the pituitary and subsequently corticosteroid secretion
with high doses of systemic corticosteroids. Signs and from the adrenals. Given by the subcutaneous route, sev-
symptoms include adrenal atrophy, osteoporosis, HTN, eral weeks or months of therapy may be needed for opti-
increased risk of infections, delayed wound healing, acne, mal suppression of corticosteroid secretion. The drug is
peptic ulcers, general obesity, and a redistribution of fat pregnancy category C.
around the face (moon face), shoulders, and neck (buffalo
hump). Mood and personality changes are common, and Mitotane (Lysodren) is an antineoplastic drug that is
the patient may become psychologically dependent on the specific for cells of the adrenal cortex. It is approved to
drug. Some corticosteroids, including hydrocortisone, also treat inoperable tumors of the adrenal gland. Although not
have mineralocorticoid activity and can cause retention of specifically approved for Cushing’s syndrome, it will
sodium and water. Because of their anti-inflammatory and reduce symptoms of this disorder if they are caused by an
immunosuppressant properties, corticosteroids may mask adrenal cancer. Gastrointestinal symptoms such as
signs of infection. It is important to note that corticoste- anorexia, nausea, and vomiting will occur in 80% of
roids do not have anti-infective properties. Even though patients. CNS adverse effects, including depression, leth-
the patient may not exhibit signs and symptoms of infec- argy, and dizziness, occur in 40% of patients. The drug is
tions, the microorganisms continue duplicating and pregnancy category C.
Chapter 68 Corticosteroids and Drugs Affecting the Adrenal Cortex 1259
Understanding Chapter 68
Key Concepts Summary 68.4 Adrenocortical insufficiency is treated by
administering physiologic levels of corticosteroids.
68.1 The adrenal glands secrete gonadocorticoids,
mineralocorticoids, and corticosteroids. 68.5 Corticosteroids are frequently used to suppress the
inflammatory and immune responses.
68.2 Corticosteroids are widely used, and all drugs
in the class have similar indications, actions, and 68.6 Patients with adrenal insufficiency often require
adverse effects. replacement therapy with mineralocorticoids.
68.3 Long-term therapy with corticosteroids has 68.7 Antiadrenal drugs may be administered to lower
the potential to cause serious adverse effects in serum corticosteroid levels in patients with
multiple body systems. Cushing’s syndrome.
CASE STUDY: Making the Patient Connection
Remember the patient rash as allergic dermatitis caused by poison ivy and pre-
“Charlie Harness” from scribed prednisone 60 mg/day for 4 days, then tapering by
the beginning of the 10 mg every 2 days for a 14-day treatment regimen.
chapter? Now read the
remainder of the story. Critical Thinking Questions
Based on the information
presented within this 1. Why has Charlie reacted to the poison ivy now when
chapter, answer the critical thinking questions that he has had no reaction to previous exposures?
follow.
2. Why would the nurse practitioner use a 14-day pred-
Charlie Harness is a 36-year-old man who, while clearing nisone taper and not a Medrol Dosepak for Charlie?
out weeds and brush in his yard, pulled up a patch of poi-
son ivy. He was not concerned about the incident because 3. What would you teach Charlie about not abruptly dis-
he had never reacted to poison ivy in the past. Later that continuing this medication before completing the
afternoon, he experienced intense itching, first on his hands entire taper? Why?
and arms, which then spread to his chest, shoulder, and
back. A macular rash appeared on his arms and small blis- 4. Charlie asks you if there are any additional precau-
ters erupted on his hands. He is seen in the local urgent tions that he should take related to his exposure. How
care clinic by the nurse practitioner, who diagnosed the would you respond?
Answers to Critical Thinking Questions are available on the
faculty resources site. Please consult with your instructor.
Additional Case Study abdominal and underarm areas. Her blood pressure is also
elevated, measuring 162/100 mmHg. The healthcare pro-
Monica Hamric, a 53-year-old woman, is referred to the vider has diagnosed Monica with Cushing’s syndrome
endocrinologist for evaluation after being seen by the related to her prednisone use. Monica will be withdrawn
advanced practice nurse. She has a history of systemic lupus from the prednisone and started on immunosuppressant
erythematosus, managed with corticosteroids, and has therapy. Because she has taken the prednisone for some time,
begun to experience weight gain, facial hirsutism with thin- how do you anticipate the drug will be stopped and why?
ning of the hair on her head, spontaneous bruising, muscle
weakness, and a recent diagnosis of diabetes. She has been Answers to Additional Case Study questions are available on
taking prednisone (Deltasone) for the past 3 months. The the faculty resources site. Please consult with your instructor.
physical examination reveals that Monica has developed a
“buffalo hump” on her shoulder and red striae on her
1260 Unit 10 Pharmacology of the Endocrine System
Chapter Review 4. A patient with adrenocortical insufficiency has started
therapy with fludrocortisone. What important inter-
1. A patient has been given a few prescriptions for acute vention related to this drug therapy should the nurse
bronchitis. One of the prescriptions is for methylpred- teach the patient?
nisolone (Medrol Dosepak). The nurse will teach the
patient to report which adverse effects to the health- 1. “Report any abdominal pain or changes in your
care provider? (Select all that apply.) stool color.”
1. Edema 2. “Return monthly for laboratory work to assess
blood lipid levels.”
2. Tinnitus
3. “Report any unusual changes in your mood.”
3. Eye pain or vision changes
4. “Weigh yourself daily, ideally at the same time
4. Dizziness upon standing each day.”
5. Abdominal pain 5. A patient who has been taking dexamethasone for
rheumatoid arthritis was unable to take the drug for
2. A patient has been taking a thiazide diuretic for treat- several days due to an intestinal virus. The patient
ment of hypertension and has been prescribed hydro- seeks treatment in the emergency department for
cortisone (Cortef) for a significant allergic reaction to complaints of severe nausea, vomiting, lethargy, fever,
shellfish. Which symptom should be immediately and hypotension. What drug does the nurse antici-
reported to the provider? pate will be given to this patient?
1. Irregular heart rate and rhythm 1. Fludrocortisone
2. Delayed wound healing 2. Ketoconazole (Nizoral)
3. Weight gain of 2 to 3 pounds in 1 week 3. Hydrocortisone (Solu-Cortef)
4. Elevated serum lipid levels 4. Mitotane (Lysodren)
3. An older adult patient with chronic bronchitis has 6. A patient with chronic adrenal insufficiency taking
been receiving low-dose therapy with dexamethasone hydrocortisone (Cortef) and fludrocortisone is plan-
for several months to reduce the inflammation occur- ning a family vacation. What essential teaching does
ring secondary to the bronchitis. What teaching this patient need prior to taking this trip?
should this patient receive to reduce the risk of osteo-
porosis related to dexamethasone use? (Select all that 1. “Take your blood pressure once or twice while
apply.) you’re gone.”
1. Perform weight-bearing exercises at least 3 to 2. “Avoid crowded indoor areas to avoid infections.”
4 times weekly.
3. “Have your vision checked before you leave.”
2. Increase dietary intake of calcium and vitamin D–
rich foods. 4. “Carry an oral and injectable form of both drugs
with you on your trip.”
3. Remain sedentary except during periods of
exercise. See Answers to Chapter Review in Appendix A.
4. Increase fluid intake, including carbonated sodas,
but avoid alcohol.
5. Request a prescription for a bisphosphonate drug
from the provider.
References and Gynecology International, 2016, Art. ID 5054037, 5 pp.
doi:10.1155/2016/5054037
Adams, T. M., Kinzler, W. L., Chavez, M. R., Fazzari, M. J., Althabe, F., Thorsten, V., Klein, K., McClure, E. M.,
& Vintzileos, A. M. (2015). Practice patterns in the Hibberd, P. L., Goldenberg, R. L., . . . Belizán, J. M.
timing of antenatal corticosteroids for fetal lung (2016). The antenatal corticosteroids trial (ACT)’s
maturity. Journal of Maternal–Fetal & Neonatal Medicine, explanations for neonatal mortality—a secondary
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s12978-016-0175-3
Aghajanian, P., Nguyen, Q. T., Greene, N. H., & Gregory,
K. D. (2016). Can we accurately time the administration
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Chew, E. Y., Clemons, T. E., Agrón, E., Launer, L. J., cognitive impairment. Neuroimage, 131, 226–238.
Grodstein, F., & Bernstein, P. S. (2015). Effect of omega-3 doi:10.1016/j.neuroimage.2015.09.050
fatty acids, lutein/zeaxanthin, or other nutrient Leckie, R. L., Manuck, S. B., Bhattacharjee, N., Muldoon,
supplementation on cognitive function: The AREDS2 M. F., Flory, J. M., & Erickson, K. I. (2014). Omega-3
randomized clinical trial. JAMA, 314, 791–801. doi:10. fatty acids moderate effects of physical activity on
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Crowther, C. A., McKinlay, C. J. D., Middleton, P., & National Center for Complementary and Integrative
Harding, J. E. (2015). Repeat doses of prenatal Health. (2017). Omega-3 fatty acids. Retrieved from
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improving neonatal health outcomes. Cochrane Database Nguyen, H. C. T. (2017). Endogenous Cushing syndrome.
of Systematic Reviews, 7, Art. No. CD003935. doi:10.1002/ Retrieved from http://emedicine.medscape.com/
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Pase, M. P., Grima, N., Cockerell, R., Stough, C., Scholey,
Griffing, G. T. (2017). Addison disease clinical presentation. A., Sali, A., & Pipingas, A. (2015). The effects of long-
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article/116467-clinical and cardiovascular function: A randomized, controlled
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Köbe, T., Witte, A. V., Schnelle, A., Lesemann, A., Fabian, 34, 21–31. doi:10.1080/07315724.2014.880660
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fatty acids, aerobic exercise and cognitive stimulation
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parietal and cingulate cortex in patients with mild
Selected Bibliography Lau, D., Rutledge, C., & Aghi, M. K. (2015). Cushing’s
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Wauchope, A., Hammer, G. D., . . . Torpy, D. J. (2016). 38(2), E11. doi:10.3171/2014.10.FOCUS14700
Diagnosis and treatment of primary adrenal
insufficiency: An Endocrine Society clinical practice Lonser, R. R., Nieman, L., & Oldfield, E. H. (2016).
guideline. The Journal of Clinical Endocrinology & Cushing’s disease: Pathobiology, diagnosis, and
Metabolism, 101, 364–389. doi:10.1210/jc.2015-1710 management. Journal of Neurosurgery, 126, 404–417.
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Feelders, R. A., & Hofland, L. J. (2013). Medical treatment
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“I get fatigued so easily. I’m having
mood swings, headaches, bouts of
depression, and irritability; but my
main concern is that I have absolutely
no desire to have sexual intercourse.
What’s happening to me, and what
can I do about it?”
Patient “Maureen John”
Chapter 69
Estrogens, Progestins, and Drugs
Modifying Uterine Function
Chapter Outline Learning Outcomes
cc Hormonal Regulation of Female Reproductive After reading this chapter, the student should be able to:
Function
1. Describe the roles of the hypothalamus, pituitary,
cc Estrogens and ovaries in maintaining female reproductive
function.
PROTOTYPE Conjugated Estrogens
(Cenestin, Enjuvia, Premarin), p. 1265 2. Identify indications for estrogen pharmacotherapy.
cc Progestins
3. Identify indications for progestin pharmacotherapy.
PROTOTYPE Medroxyprogesterone (Depo-Provera,
Depo-SubQ-Provera, Provera), p. 1269 4. Compare and contrast the advantages and
cc Hormone Replacement Therapy disadvantages of hormone replacement therapy
cc Uterine Stimulants: Oxytocics during menopause.
Ergot Alkaloids
Prostaglandins 5. Explain the use of uterine stimulants to promote
labor and delivery.
PROTOTYPE Oxytocin (Pitocin), p. 1274
cc Uterine Relaxants: Tocolytics 6. Discuss the use of uterine relaxants in suppressing
cc Pharmacotherapy of Female Infertility and Female preterm labor.
Sexual Desire Disorder 7. Explain how drug therapy may be used to treat
female infertility.
PROTOTYPE Clomiphene (Clomid, Serophene), p. 1281
8. Describe the nurse’s role in the pharmacologic
management of disorders and conditions of the
female reproductive system.
9. 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.
10. Apply the nursing process to the care of patients
receiving pharmacotherapy for disorders and
conditions of the female reproductive system.
1262
Chapter 69 Estrogens, Progestins, and Drugs Modifying Uterine Function 1263
Key Terms hormone replacement therapy ovulatory dysfunction, 1279
(HRT), 1271 oxytocics, 1273
anovulatory cycles, 1268 polycystic ovary syndrome, 1279
climacteric, 1271 infertility, 1278 preterm labor, 1277
corpus luteum, 1263 progestins, 1267
dysfunctional uterine menopause, 1271 tocolytics, 1277
bleeding, 1268 ovarian hyperstimulation
endometriosis, 1281 syndrome (OHS), 1281
estrogen, 1263
ovulation, 1263
The steroid hormones estrogen and progesterone are respon- the lining of the uterus (uterine cycle). Both cycles are con-
sible for the growth, development, and reproductive health trolled by hormones from the hypothalamus and pituitary.
of females throughout the lifespan. Deficiencies or excesses The first day of menstruation is considered day 1 of the
of these hormones can result in profound changes that extend cycle. The hormonal changes that occur during the ovarian
beyond the reproductive system. These hormones impact and uterine cycles are illustrated in Figure 69.1.
virtually every body system including effects on coagulation,
blood vessels, bone, muscles, overall body metabolism, and The hypothalamus secretes gonadotropin-releasing
behavior. Stimulating hormones from the pituitary also affect hormone (GnRH), which travels a short distance to the
reproductive function, including fertility, labor, delivery, and pituitary to stimulate the secretion of the gonadotropins:
the production and ejection of breast milk. This chapter follicle-stimulating hormone (FSH) and luteinizing hor-
examines hormones and drugs used to treat conditions asso- mone (LH). Both of these anterior pituitary hormones act
ciated with the female reproductive system. on the ovary and promote the development of immature
ovarian follicles. Under the influence of FSH and LH, sev-
Hormonal Regulation of Female eral ovarian follicles begin the maturation process each
Reproductive Function month during the reproductive lifespan. As ovarian folli-
cles mature, they secrete increasing amounts of estrogen.
69.1 Regulation of the female reproductive On approximately day 14 of the ovarian cycle, a surge of
system is achieved by hormones from the LH (and to a lesser extent FSH) secretion causes one follicle
hypothalamus, pituitary gland, and ovary. to expel its oocyte (egg), a process called ovulation. The LH
surge is an absolute requirement for ovulation and, thus,
The two primary hormones of the female reproductive conception. The oocyte begins its journey through the uter-
system are estrogen and progesterone. During a woman’s ine tube and eventually reaches the uterus.
childbearing years, nearly all estrogen and progesterone is
secreted by the ovaries. Small amounts of estrogen are The ruptured follicle, minus the oocyte, remains in the
secreted by nonreproductive organs, including the adrenal ovary and is transformed into the corpus luteum, an endo-
glands, liver, kidney, skeletal muscle, and adipose tissue. crine tissue that secretes steadily increasing amounts of
In postmenopausal women, nearly all estrogen and pro- progesterone for the next 12 days. Progesterone thickens
gesterone is secreted by these nonreproductive tissues. In the uterine mucosa, readying this organ for implantation
men, estrogen and progesterone are also secreted in small and potential pregnancy.
amounts by the testes.
High progesterone and estrogen levels in the final third
Unlike men, who secrete steady and continuous levels of the uterine cycle provide negative feedback to shut off
of testosterone throughout adult life, secretion of the female GnRH, FSH, and LH secretion, as illustrated in Figure 69.2.
sex hormones is variable and complex. Knowledge of these Without stimulation from FSH and LH, estrogen and pro-
complexities is essential to understanding the pharmaco- gesterone levels fall sharply, the endometrium is shed, and
therapy of the female reproductive system. Although this menstrual bleeding begins a new monthly cycle.
section reviews physiology that is relevant to drug therapy,
the student should refer to an anatomy and physiology Estrogens
textbook for more detailed information.
69.2 Estrogens are administered as replacement
Secretion of female reproductive hormones varies on a therapy, to prevent conception, and for certain
28-day menstrual cycle. The menstrual cycle is described neoplasms.
by changes that occur in the ovaries (ovarian cycle) and in
Estrogen is a general term for three different steroid hor-
mones: estradiol, estrone, and estriol. Estradiol is present in
1264 Unit 10 Pharmacology of the Endocrine System LH
FEMALE REPRODUCTIVE CYCLE
Gonadotropic
hormone
cycle
hormone levels FSH
Ovarian Follicle growth Ovulation Corpus luteum degeneration
cycle Progestins
Ovarian Estrogens
hormone hormone levels menstruation
cycle
Menstrual thickness of uterine lining
(uterine)
cycle
Menstrual flow Proliferative Secretory phase
phase phase
Days: 0 7 14 28
Figure 69.1 Hormonal changes during the ovarian and uterine cycles.
the body in the largest amount. Estrogens are responsible the risk of myocardial infarction (MI) in premenopausal
for the maturation of the reproductive organs and for women. By blocking resorption of the bony matrix, estrogen
the appearance of the secondary sex characteristics of causes bones to grow longer and stronger in younger women.
the female during puberty. When women enter menopause As estrogen levels decrease in postmenopausal women, the
around ages 50 to 55, the secretion of estrogen by the ova- risk of osteoporosis and bone fractures dramatically increases.
ries diminishes and eventually stops.
Estrogens are used as contraception and to treat meno-
Apart from its reproductive functions, estrogen also pausal symptoms, female hypogonadism, and primary
affects the heart, liver, blood vessels, and bones. Estrogen ovarian failure. When used as replacement therapy follow-
decreases the levels of low-density lipoprotein (LDL) and ing surgical removal of the ovaries, estrogen is usually
increases the amount of high-density lipoprotein (HDL) in combined with a progestin. The purpose of the progestin is
the blood. These effects are cardioprotective and help lower to counteract some of the adverse effects of estrogen on the
Chapter 69 Estrogens, Progestins, and Drugs Modifying Uterine Function 1265
PROTOTYPE DRUG Conjugated Estrogens
(Cenestin, Enjuvia, Premarin)
– Hypothalamus Classification Therapeutic: Hormone
– Pituitary Pharmacologic: Estrogen
GnRH Therapeutic Effects and Uses: Conjugated estro-
gen, equine (Premarin) was approved by the U.S. Food and
+ Drug Administration (FDA) in 1938 and contains a mixture
of different natural estrogens, traditionally obtained from
Negative LH FSH pregnant mares’ urine. Conjugated estrogen A (Cenestin)
feedback and conjugated estrogen B (Enjuvia) contain a mixture of
9 to 10 different synthetic plant estrogens.
++
The primary indication for conjugated estrogens has
Ovaries been to treat moderate to severe vasomotor symptoms of
Maturation of follicles menopause, such as hot flashes and night sweats, caused
• Secretion of estrogens by diminished estrogen secretion by the ovaries. Topical
• Ovulation preparations may be used to treat symptoms associated
Development of corpus luteum with menopause such as vulvar or vaginal atrophy and
• Secretion of progestins dyspareunia (pain during intercourse). Replacement thera-
pies include treatment of female hypogonadism and use
+ following oophorectomy. Premarin is approved for the pal-
liative treatment of prostate cancer and certain types of
Uterus breast cancer. Conjugated estrogens have been used in the
Stimulation past for osteoporosis prophylaxis in postmenopausal
of endometrium women, but safer therapies have replaced these drugs for
this indication.
Figure 69.2 Negative feedback control of the female reproductive
hormones. Conjugated estrogens are usually administered by the
oral (PO) route. For dysfunctional uterine bleeding, they
uterus. Estrogen drugs are listed in Table 69.1. The contra- may be administered by the intramuscular (IM) or intrave-
ceptive uses of estrogen are presented in Chapter 70. nous (IV) routes.
High doses of estrogens are sometimes used to treat Mechanism of Action: Conjugated estrogens bind to
advanced prostate and breast cancer. Prostate cancer is intracellular estrogen receptors that stimulate deoxyribonu-
usually dependent on androgens for growth, and adminis- cleic acid (DNA) and ribonucleic acid (RNA) to synthesize
tration of estrogens will suppress androgen secretion. In proteins responsible for the biologic effects of estrogens.
the treatment of cancer, estrogen is nearly always used in
combination with other antineoplastics. Pharmacokinetics:
Route(s) PO, IM, IV, intravaginal
Absorption Rapid absorption from the
gastrointestinal (GI) tract, readily
absorbed through the skin
and mucous membranes, slow
absorption through IM injections
Distribution Widely distributed; crosses the
placenta; secreted in breast milk;
bound primarily to albumin
Primary metabolism Hepatic metabolism by CYP3A4
to estrone, estradiol, and estriol
Primary excretion Renal
Onset of action PO: 30–60 min; IM: 15–30 min
Duration of action Half-life: 4–18 h
Adverse Effects: The most frequently reported
adverse effects of conjugated estrogens include headache,
1266 Unit 10 Pharmacology of the Endocrine System
Table 69.1 Selected Estrogens and Progestins
Drug Route and Adult Dose (Maximum Dose Where Indicated) Adverse Effects
Estrogens Breakthrough bleeding, spotting, breast
tenderness, libido changes
estradiol (Alora, Climara, Divigel, PO (Estrace): 0.5–2 mg daily Hypertension (HTN), gallbladder disease,
Elestrin, Estrace, Estraderm, others) MI, deep vein thrombosis, increased
Transdermal patch: 1 patch (0.025–0.1 mg/day) once weekly (Climara) endometrial cancer risk, hypercalcemia,
or twice weekly (Alora, Estraderm, Minivelle) dementia, fetal toxicity (PO and
parenteral forms)
Topical gel (Divigel, Elestrin): 0.25–1.0 g/day applied to skin of upper
thigh or arm Breakthrough bleeding, spotting, breast
tenderness, weight gain
Vaginal cream (Estrace): 1 g 1–3 times/wk maintenance dose Amenorrhea, dysmenorrhea, depression,
thromboembolic disorders, fetal toxicity
Vaginal ring (Estring, Femring): 1 ring every 90 days (PO and parenteral forms)
estradiol valerate (Delestrogen) IM: 10–20 mg q4wk Breakthrough bleeding, spotting, breast
tenderness, weight gain
estrogen, conjugated PO: 0.3–1.25 mg daily for 21 days each month Amenorrhea, dysmenorrhea, depression,
(Cenestin, Enjuvia, Premarin) thromboembolic disorders, HTN
estropipate (Ogen) PO: 0.75–6 mg daily for 21 days each month
Vaginal cream (Ogen): 2–4 g/day
Progestins
medroxyprogesterone (Depo-Provera, PO (Provera): 5–10 mg daily on days 1–12 of menstrual cycle
Depo-SubQ-Provera, Provera)
IM (Depo-Provera): 400–1000 mg/wk
Subcutaneous (Depo-SubQ-Provera): 104 mg every 3 months.
Give first dose during the first 5 days of the menstrual period
progesterone (Crinone, Endometrin, IM (amenorrhea or uterine bleeding): 5–10 mg/day
Prochieve, Prometrium)
Vaginal (assisted reproductive technology): 90-mg gel once daily
or 100-mg tablets bid–tid
Estrogen–Progestin Combinations
conjugated estrogens with PO (Premphase): Estrogen 0.625 mg/daily on days 1–28; add 5 mg
medroxyprogesterone medroxyprogesterone daily on days 15–28
(Premphase, Prempro)
PO (Prempro): Estrogen 0.3 mg and medroxyprogesterone 1.5 mg daily
Vaginal cream: Insert 0.5–2 g daily for 3–6 months
estradiol with norgestimate PO: 1 mg estradiol for 3 days, followed by 1 mg estradiol combined
with 0.09 mg norgestimate for 3 days
ethinyl estradiol with norethindrone PO: 0.5–0.1 mg of estradiol and 0.5–1 mg norethindrone
acetate (Activella) Transdermal patch: 1 patch, twice weekly
Note: Italics indicate common adverse effects. Underline indicates serious adverse effects.
infections, abdominal cramps and bloating, breast tender- in patients with lipid disorders because they may increase
ness, and vaginal bleeding. Other less common adverse HDL cholesterol and triglycerides. They are contraindi-
effects may include thromboembolic events, fluid reten- cated in patients with undiagnosed abnormal vaginal
tion, edema, acute pancreatitis, appetite changes, skin bleeding. Because estrogens are classified as category X,
eruptions, mental depression, decreased or increased pregnancy and lactation are contraindications for this drug.
libido, fatigue, nervousness, and weight gain. The risks of
adverse effects increase in patients over age 35. Effects are Drug Interactions: Estrogen is metabolized by CYP450
dose dependent. Black Box Warnings: Estrogens have been enzymes and may interact with other drugs metabolized
associated with a higher risk of endometrial cancer in post- in the liver. The following drugs will decrease the effects of
menopausal women (see Section 69.4). Using conjugated conjugated estrogens: corticosteroids, erythromycin, heparin,
estrogens with medroxyprogesterone increases the risk of rifampin, tetracycline, and warfarin. Use with azole antifun-
breast cancer. Estrogens when used alone increase the risk gals, diltiazem, or statins may increase the effects of conju-
of stroke, deep vein thrombosis (DVT), MI, and pulmonary gated estrogens. Herbal/Food: St. John’s wort, red clover, and
emboli. They may increase the risk for dementia. black cohosh have weak estrogenic effects and may interfere
with estrogen therapy. Effects of estrogen may be enhanced if
Contraindications/Precautions: Estrogens should combined with ginseng. Estrogen may decrease the absorp-
be avoided in patients who have a history of breast cancer, tion of folic acid. If allergic to soy products, patients should
cervical cancer, endometrial cancer or hyperplasia, pros- not take Cenestin because it contains soy estrogens.
tate cancer, and hepatic diseases or cancer. Additionally,
because estrogens have been associated with thromboem- Pregnancy: Category X.
bolic disorders, hypercalcemia, and lupus, they should
not be prescribed without a thorough investigation of Treatment of Overdose: Overdose will cause nausea,
these conditions. Estrogens should be used with caution vomiting, and breakthrough bleeding, which are treated
symptomatically.
Chapter 69 Estrogens, Progestins, and Drugs Modifying Uterine Function 1267
Nursing Responsibilities: Key nursing implications Progestins
for patients receiving conjugated estrogens are included
in the Nursing Practice Application for Patients Receiving 69.3 Progestins are administered to treat
Pharmacotherapy with Estrogen. dysfunctional uterine bleeding, to prevent
conception, and for certain neoplasms.
Drugs Similar to Conjugated Estrogens
(Cenestin, Enjuvia, Premarin) Progestins are synthetic hormones that have actions iden-
tical to natural, endogenous progesterone. In combination
Other estrogens are listed in Table 69.1. These drugs have with estrogen, progesterone promotes breast development
the same actions, adverse effects, and contraindications as and regulates the monthly changes of the uterine cycle.
those of conjugated estrogens. Under the influence of estrogen and progesterone, the
uterine endometrium becomes more vascular and thickens
CONNECTION Checkpoint 69.1 in preparation for receiving a fertilized egg. If implanta-
tion does not occur, levels of progesterone fall dramatically
The majority of drugs in this chapter are pregnancy category X. From and menses begins. If pregnancy does occur, the ovary will
what you learned in Chapter 2, what is the difference between a continue to secrete progesterone, maintaining a healthy
category D drug and a category X drug? Answers to Connection endometrium until the placenta develops sufficiently to
Checkpoint questions are available on the faculty resources site. begin producing the hormone.
Please consult with your instructor.
CONNECTIONS: NURSING PRACTICE APPLICATION
Patients Receiving Pharmacotherapy with Estrogen
Assessment
Baseline assessment prior to administration:
• Obtain a complete health history including cardiovascular, peripheral vascular, thyroid, hepatic, or kidney disease; migraine headaches; diabetes;
pregnancy; or breastfeeding. Note personal or family history of thromboembolic disorders (e.g., MI, stroke, peripheral vascular disease) and of
reproductive cancers (e.g., breast, uterine, or ovarian cancer).
• Obtain a drug history including allergies, current prescription and over-the-counter (OTC) drugs, herbal preparations, alcohol use, and smoking. Be
alert to possible drug interactions.
• Evaluate appropriate laboratory findings (e.g., complete blood count [CBC], platelets, electrolytes, glucose, lipid, and thyroid function levels), Pap test,
human papilloma virus (HPV) screening, and pregnancy test.
• Obtain baseline height, weight, and vital signs.
• Assess the patient’s ability to receive and understand instructions. Include family and caregivers as needed.
Assessment throughout administration:
• Assess for desired therapeutic effects (e.g., symptoms of menopause or ease of dysfunctional uterine bleeding).
• Continue periodic monitoring of CBC, platelets, and thyroid function studies.
• Monitor vital signs and weight at each healthcare visit.
• Assess for adverse effects: nausea, vomiting, headache, weight gain, breast tenderness, skin rash, acne, fluid retention, changes in mood, and
midcycle breakthrough bleeding. Immediately report tachycardia, palpitations, HTN, especially associated with angina, severe headache, cramping in
calves, chest pain, or dyspnea.
Implementation
Interventions and (Rationales) Patient-Centered Care
Ensuring therapeutic effects: • Instruct the patient to take the drug at the same time daily to help with
• Monitor appropriate medication administration for optimal results. remembering to take the pill. Do not omit, increase, or decrease doses
without consulting the healthcare provider. Omitting doses increases
(Maintaining consistent daily doses for treatment of menopausal the chance of breakthrough bleeding.
symptoms or dysfunctional uterine bleeding will ensure that hormone
levels stay stable and symptoms ease.)
Minimizing adverse effects: • Instruct the patient to immediately report:
• Monitor for symptoms of cardiopulmonary, cerebrovascular, and • Dyspnea, chest pain, or blood in sputum (possible pulmonary embolism)
• Heaviness, chest pain, or overwhelming feeling of fatigue and
peripheral vascular thromboembolism. Monitor blood pressure at each weakness accompanied by nausea and diaphoresis (possible MI)
clinical visit. (Thromboembolic events are a possible adverse effect of • Sudden, severe headache, especially if associated with a
estrogen drugs. The risk increases with age over 35, in women with a preheadache aura, dizziness, difficulty with speech, numbness in
previous history of cardiovascular disease, and in women who smoke. arm or leg, and difficulty with vision (possible stroke)
Monitor for symptoms of peripheral thrombophlebitis, pulmonary • Warmth, redness, swelling, or tenderness in calf or pain on walking
embolism, MI, stroke, or other complications related to blood clots.) (possible thrombophlebitis).
• Teach the patient to monitor blood pressure periodically and report any
blood pressure above 140/90 mmHg or per parameters set by the
healthcare provider.
• Encourage smoking cessation and provide information about smoking • Advise the patient of the risk of smoking while using estrogens and
cessation programs. (Smoking greatly increases the risk of adverse discuss smoking cessation programs, providing referrals to appropriate
effects of hormone therapy.) support groups and literature on smoking cessation programs.
(continued )
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