568 Unit 5 Pharmacology of the Cardiovascular System
Table 33.4 Selected Colloid IV Solutions Contraindications/Precautions: Dextran 40 is con-
traindicated in patients with severe chronic kidney disease
Drug Tonicity (CKD) because fluid overload may result. Adequate fluid
intake should be ensured in patients with severe dehy-
5% albumin Isotonic dration who receive dextran to prevent renal failure due
dextran 40 in D5W Isotonic to high urine viscosity. Other contraindications include
dextran 40 in normal saline Isotonic severe heart failure and hypervolemic disorders.
dextran 70 in normal saline Isotonic
hetastarch (Hespan) 6% in normal saline Isotonic Drug Interactions: There are no clinically significant
plasma protein fraction Isotonic interactions. Herbal/Food: Unknown.
capillary walls. It is similar to dextran 70, except dextran Pregnancy: Category C.
40 has a lower molecular weight. Given as an IV infusion,
it has the capability of doubling plasma volume within a Treatment of Overdose: For patients with normal
few minutes after administration, although its effects last renal function, discontinuing the infusion will reduce
only about 12 hours. Cardiovascular responses include adverse effects. Patients with CKD may benefit from an
increased blood pressure, increased cardiac output, and osmotic diuretic.
improved venous return to the heart. Indications include
fluid replacement for patients experiencing hypovolemic Nursing Responsibilities: Key nursing implications
shock due to hemorrhage, surgery, or severe burns. When for patients receiving dextran 40 are included in the Nurs-
given for acute shock, it is infused as rapidly as possible ing Practice Application for Patients Receiving Pharmaco-
until blood volume is restored. therapy for Fluid and Electrolyte Imbalances.
Dextran 40 also reduces platelet adhesiveness and Drugs Similar to Dextran 40
improves blood flow through capillaries by its ability to (Gentran 40, Others)
reduce blood viscosity. These antithrombotic properties
have led to its use in preventing deep vein thrombosis and The only solution similar to dextran is hetastarch.
postoperative pulmonary emboli. Dextran, however, is less
effective than heparin or low-molecular-weight heparin Hetastarch (Hespan): Hetastarch is a complex mixture of
(LMWH) in preventing thromboembolism (see Chapter 38). a nonprotein polymer of the starch amylopectin. It is a syn-
thetic colloid with properties similar to those of 5% albu-
Mechanism of Action: Dextran 40 acts by raising min, but with an extended duration of action. Hetastarch
the osmotic pressure of the blood, thereby causing fluid has a half-life of about 17 days and provides volume
to move from the interstitial spaces of the tissues to the expansion for 24 to 36 hours. It is indicated for the treat-
blood. The larger blood volume increases cardiac output, ment and prophylaxis of shock and acute edematous con-
stroke volume, blood pressure, and urinary output. Heart ditions. Hetastarch provides the same physiologic actions
rate and blood viscosity decrease. as albumin. This drug is pregnancy category C.
Pharmacokinetics: Physiology of Electrolytes
Route(s) IV 33.8 Electrolytes are charged substances
that are essential to homeostasis.
Absorption Not absorbed
Minerals are inorganic substances needed in very small
Distribution Does not leave the vascular amounts to maintain homeostasis (see Chapter 61). Miner-
als are held together by ionic bonds and dissociate or ion-
system ize when placed in water. The resulting ions have positive
or negative charges and are able to conduct electricity,
Primary metabolism Unknown hence the name electrolyte. Positively charged electrolytes
are called cations; those with a negative charge are anions.
Primary excretion Renal Electrolyte levels are measured in units of milliequivalents
per liter (mEq/L).
Onset of action Several minutes
Electrolytes are essential to many body functions,
Duration of action 12–24 h including nerve conduction, membrane permeability, mus-
cle contraction, water balance, and bone growth and
Adverse Effects: Vital signs should be monitored con- remodeling. Levels of electrolytes in body fluids are main-
tinuously during dextran 40 infusions to prevent HTN tained within very narrow ranges, primarily by the
caused by the plasma volume expansion. Signs of fluid
overload include tachycardia, peripheral edema, dis-
tended neck veins, dyspnea, or cough. A small percentage
of patients are allergic to dextran 40, with urticaria being
the most common sign. Anaphylaxis is possible.
Chapter 33 Pharmacotherapy of Fluid Imbalance, Electrolyte, and Acid–Base Disorders 569
Table 33.5 Electrolyte Imbalances
Ion Condition Abnormal Serum Value (mEq/L) Supportive Treatment*
Calcium Hypercalcemia Greater than 11 Hypotonic fluid or calcitonin
Hypocalcemia Less than 4 Calcium supplements or vitamin D
Chloride Hyperchloremia Greater than 112 Hypotonic fluid
Hypochloremia Less than 95 Hypertonic salt solution
Magnesium Hypermagnesemia Greater than 4 Hypotonic fluid
Hypomagnesemia Less than 0.8 Magnesium supplements
Phosphate Hyperphosphatemia Greater than 6 Dietary phosphate restriction
Hypophosphatemia Less than 1 Phosphate supplements
Potassium Hyperkalemia Greater than 5 Hypotonic fluid, buffers, or dietary restriction
Hypokalemia Less than 3.5 Potassium supplements
Sodium Hypernatremia Greater than 145 Hypotonic fluid or dietary restriction
Hyponatremia Less than 135 Hypertonic salt solution or sodium supplement
*For all electrolyte imbalances, the primary therapeutic goal is to identify and correct the cause of the imbalance.
kidneys and gastrointestinal (GI) tract. Because electrolytes normal range of serum sodium is 135 to 145 mEq/L of
are lost due to normal excretory functions, they must be plasma.
replaced by adequate intake; otherwise electrolyte imbal-
ances will result, as shown in Table 33.5. Although imbal- Sodium balance and water balance are intimately con-
ances can occur with any ion, sodium, potassium, and nected. As sodium levels increase in a body fluid, solute
calcium are of greatest importance. The role of calcium in particles accumulate and osmolality increases. Water will
bone homeostasis is presented in Chapter 72. move toward this area of relatively high osmolality. In sim-
plest terms, water travels toward or with sodium. The
An electrolyte imbalance is a sign of an underlying physiologic consequences of this relationship cannot be
medical condition that needs attention. Imbalances are overstated: As the sodium and water content of plasma
associated with a wide variety of acute and chronic disor- increases, so do blood volume and blood pressure. Thus,
ders, with CKD being the most common cause. In some sodium movement provides an important link between
cases, drug therapy itself can cause the electrolyte imbal- water retention, blood volume, and blood pressure.
ance. A classic example is the diuretic furosemide (Lasix),
which can cause serious potassium depletion. In all cases, In healthy individuals, sodium intake is equal to
the therapeutic goal is to quickly correct the electrolyte sodium output, which is regulated by the kidneys. High
imbalance while the underlying condition is being diag- levels of aldosterone secreted by the adrenal cortex pro-
nosed and treated. Treatments for electrolyte imbalances mote sodium and water retention by the kidneys as well as
depend on the severity of the problem and range from sim- potassium excretion. Inhibition of aldosterone promotes
ple changes in dietary intake to rapid electrolyte infusions. sodium and water excretion. When a patient ingests high
In acute cases, serum electrolyte levels must be carefully amounts of sodium, aldosterone secretion decreases, thus
monitored to prevent imbalances in the opposite direction; sending the excess sodium to the urine. This relationship is
levels can change rapidly from hypoconcentrations to illustrated in Figure 33.2.
hyperconcentrations.
Hypernatremia: Sodium excess, or hypernatremia,
Pharmacotherapy of Electrolyte occurs when the serum sodium level rises above
Imbalances 145 mEq/L. The most common cause of hypernatremia is
decreased sodium excretion due to kidney pathology.
33.9 Sodium balance is closely associated Hypernatremia may also be caused by excessive intake of
with water balance. sodium, either through dietary consumption or by over-
treatment with IV fluids containing sodium chloride or
Sodium is the major electrolyte in extracellular fluid. Due sodium bicarbonate. Overconsumption of table salt (NaCl)
to its central roles in neuromuscular physiology, acid–base or processed foods with high sodium content will quickly
balance, and overall fluid distribution, sodium imbalances exceed the daily amount needed by the body. Drinking too
can have serious consequences. Although definite sodium little water can cause hypernatremia due to the develop-
monitors or sensors have yet to be discovered in the body, ment of hypertonic plasma. Another cause of hypernatre-
the regulation of sodium balance is well understood. The mia is high net water losses, such as that occurring from
watery diarrhea, fever, or burns. High doses of glucocorti-
coids or estrogens also promote sodium retention.
570 Unit 5 Pharmacology of the Cardiovascular System
$NQQF 0C
-
Hyponatremia: Hyponatremia is the most common
electrolyte abnormality in hospitalized patients and is
QT defined as a serum sodium level of less than 135 mEq/L.
Hyponatremia may occur through excessive dilution of
+PETGCUGF the plasma caused by administration of hypotonic IV solu-
0C
KP RNCUOC tions or by high ADH secretion. Hyponatremia may also
#FTGPCN result from increased sodium loss due to disorders of the
INCPF skin, GI tract, or kidneys. Significant loss of sodium by the
skin may occur in burn patients and in those experiencing
#NFQUVGTQPG excessive sweating or prolonged fever. GI sodium losses
UGETGVKQP may occur from vomiting, diarrhea, or GI suctioning, and
renal sodium loss may occur with diuretic use and in cer-
5QFKWO tain advanced kidney disorders.
TGCDUQTRVKQP
Early symptoms of hyponatremia include nausea, vom-
-KFPG[ iting, anorexia, and abdominal cramping. Later signs include
altered neurologic function such as confusion, lethargy, con-
2QVCUUKWO vulsions, coma, and muscle twitching or tremors. Hypona-
UGETGVKQP tremia caused by excessive dilution is treated with loop
diuretics, which will remove the fluid overload that caused
+PETGCUGF -
GZETGVKQP the hyponatremia (see Chapter 32). Hyponatremia caused
by sodium loss may be treated with the administration of
Figure 33.2 Renal regulation of sodium and potassium balance. oral or parenteral sodium chloride, or with IV fluids contain-
ing salt, such as normal saline or lactated Ringer’s solution.
A high serum sodium level increases the osmolality of
the plasma, making the intravascular space hypertonic and In 2009, tolvaptan (Samsca) was approved to quickly
drawing fluid from interstitial spaces and cells, thus caus- raise serum sodium levels in hospitalized patients experi-
ing cellular dehydration. Ordinarily, a small increase in encing symptoms of hyponatremia. Tolvaptan is a vaso-
serum sodium will trigger thirst. Other manifestations of pressin (antidiuretic hormone) antagonist that enhances
hypernatremia include fatigue, weakness, muscle twitch- water excretion. As the amount of water in the blood is
ing, convulsions, altered mental status, and a decreased reduced, the serum sodium concentration is increased.
level of consciousness (LOC). For minor hypernatremia, a Tolvaptan carries several black box warnings. Therapy
low-salt diet combined with adequate water intake may be with the drug should only be conducted in a hospital where
effective in returning serum sodium to normal levels. In serum sodium levels can be monitored closely, because too
patients with acute hypernatremia, however, the treatment rapid correction of hyponatremia can result in seizures,
goal is to rapidly return the osmolality of the plasma to nor- coma, and death. In patients with advanced liver disease,
mal. If the patient is hypovolemic, infusing hypotonic fluids severe malnutrition, or alcoholism, hyponatremia should
such as 5% dextrose or 0.45% NaCl will increase plasma vol- be corrected especially slowly. Treatment should be limited
ume and at the same time reduce osmolality by diluting the to 30 days due to the risk for liver injury.
plasma. For the patient who is hypervolemic, diuretics may
be used to remove sodium and excess water from the body. CONNECTIONS: Community-
Oriented Practice
Maintaining Fluid Balance During Exercise
Hyponatremia from excessive fluid intake has been noted as a
growing problem in athletes, particularly novice athletes who
may have heard that they need to “keep drinking” to maintain
hydration. Many sports drinks contain some electrolytes but
are also high in fructose or other sugars. This creates a hyper-
tonic solution that may paradoxically cause increased water
loss. Unless exercise is extreme or prolonged, athletes, espe-
cially children, should be encouraged to drink when thirsty and
maintain urine at a color of clear yellow, not dark yellow or
colorless. Adequate fluid intake to match thirst will help ensure
normal hydration and sodium levels and prevent complica-
tions such as exercise-associated hyponatremia (EAH).
Chapter 33 Pharmacotherapy of Fluid Imbalance, Electrolyte, and Acid–Base Disorders 571
PROTOTYPE DRUG Sodium Chloride (NaCl) sodium ion and water to reduce pulmonary or peripheral
edema.
Classification Therapeutic: Drug for hyponatremia
Pharmacologic: Electrolyte, sodium Nursing Responsibilities: Key nursing implications
for patients receiving sodium chloride are included in the
supplement Nursing Practice Application for Patients Receiving Phar-
macotherapy for Fluid and Electrolyte Imbalances.
Therapeutic Effects and Uses: Sodium chloride
may be administered for hyponatremia when serum Drugs Similar to Sodium Chloride (NaCl)
levels fall below 135 mEq/L. The drug is available in
several concentrations; the decision on which NaCl con- There are no drugs similar to sodium chloride.
centration to administer is driven by the severity of the
sodium deficiency. Normal saline consists of 0.9% NaCl 33.10 Potassium imbalances must be
and is used to treat mild hyponatremia. When serum quickly corrected to prevent serious cardiac
sodium falls below 115 mEq/L, a highly concentrated 3% consequences.
NaCl solution may be infused. Other concentrations in-
clude 0.45% and 0.22%, and both hypotonic and isotonic Potassium is the most abundant intracellular cation; 98%
solutions are available. For less severe hyponatremia, 1-g of the potassium present in the body is found inside cells,
tablets are available. with the majority found in skeletal muscle. Potassium
serves critical roles in muscular contraction and the con-
Ophthalmic solutions of NaCl may be used to treat duction of nerve impulses.
corneal edema, and an over-the-counter (OTC) nasal spray
is available to relieve dry, inflamed nasal membranes. In To prevent imbalances, adequate dietary intake of
conjunction with oxytocin, 20% NaCl may be used as an potassium must be carefully balanced to potassium excre-
abortifacient late in pregnancy when instilled into the tion. Patients with normal diets consume plenty of potas-
amniotic sac. sium for bodily functions because the mineral is abundant
in fruits, vegetables, and meats.
Mechanism of Action: Sodium chloride is a replace-
ment solution for lost sodium. Insulin is a key hormone for the regulation of potas-
sium homeostasis. The uptake of potassium ion into cells is
Pharmacokinetics: Because sodium ions form natural mediated by insulin. As serum potassium levels rise, the
electrolytes, it is not possible to obtain accurate pharmaco- pancreas secretes additional insulin, which causes the ion
kinetic values. The sodium ions in the drug are widely dis- to move out of the plasma and into cells, thus preventing
tributed and excreted by the kidneys in the same manner hyperkalemia. In a typical feedback loop, as serum potas-
as endogenous sodium ions. sium levels fall, insulin secretion is diminished.
Adverse Effects: Patients receiving NaCl infusions Acid–base imbalances may also affect potassium
must be monitored frequently to avoid symptoms of homeostasis. As the blood becomes acidic, the body
hypernatremia, which include lethargy, confusion, mus- attempts to raise plasma pH by pumping hydrogen ions
cle tremor or rigidity, hypotension, and restlessness. (H1) into cells. To maintain electrical neutrality, each H1
Because some of these symptoms are also common to entering the cell is exchanged for a K1 leaving the cell. This
hyponatremia, periodic laboratory assessments must be can raise the serum potassium level, resulting in hyperka-
taken to be certain that sodium values are moving toward lemia. This is sometimes called a false hyperkalemia
the normal range. When infusing 3% NaCl solutions, the because the total body potassium is not actually increased;
nurse should continuously check for signs of pulmonary it has just shifted from intracellular to extracellular spaces.
edema.
Potassium ion is freely filtered at the glomerulus but is
Contraindications/Precautions: This drug should entirely reabsorbed as it travels along the kidney tubule. In
not be administered to patients with hypernatremia, heart the distal tubule, however, potassium is secreted back into
failure, or impaired renal function. the renal tubule and exits in the urine. Like sodium, potas-
sium excretion is influenced by the actions of aldosterone on
Drug Interactions: There are no clinically significant the kidney. In fact, the renal excretion of sodium and potas-
drug interactions. Herbal/Food: Unknown. sium ions is closely linked. For every sodium ion that is reab-
sorbed, one potassium ion is secreted into the renal tubules.
Pregnancy: Category C.
Potassium levels must be maintained within narrow
Treatment of Overdose: There is no specific treat- limits. Both hyper- and hypokalemia are associated with
ment for overdose. If excess fluid accumulation has oc- fatal dysrhythmias and serious neuromuscular disorders.
curred, diuretics may be administered to remove excess Because over 98% of potassium is intracellular, serum
potassium may not be an accurate reflection of total body
572 Unit 5 Pharmacology of the Cardiovascular System
potassium. Normal adult values for serum potassium potassium, adequate daily dietary intake is necessary. Neu-
range from 3.5 to 5 mEq/L. rons and muscle fibers are most sensitive to potassium loss,
and muscle weakness, lethargy, anorexia, dysrhythmias,
Hyperkalemia: Hyperkalemia occurs when the serum and cardiac arrest are possible consequences.
potassium level rises above 5 mEq/L. This condition may
be caused by excessive consumption of potassium-rich Mild hypokalemia is treated by increasing the dietary
foods or dietary supplements, particularly when patients intake of potassium-rich foods. The foods highest in potas-
are taking potassium-sparing diuretics such as spironolac- sium content include dried fruit, nuts, molasses, avocados,
tone (see Chapter 32). In fact, overtreatment with potas- lima beans, and bran cereals. If increasing dietary intake is
sium supplements is the most common cause of not possible, a large number of potassium products are
hyperkalemia. Excess potassium may also accumulate available for oral supplementation. The most common sup-
when renal excretion is diminished due to kidney pathol- plements are the chloride salts, because these supply both
ogy. The most serious consequences of hyperkalemia are potassium and chloride, which are lost during diuretic
related to cardiac function: dysrhythmias and heart block. therapy. Liquid preparations are very effective, although
Other symptoms are muscle twitching, fatigue, paresthe- many must be diluted with water or fruit juices prior to
sias, dyspnea, cramping, and diarrhea. Hyperkalemia is administration. Extended release (K-Dur 20, Slow-K,
much less common than hypokalemia. Micro-K) and powders (Klor-Con) are also available.
In mild cases of hyperkalemia, potassium levels may Severe hypokalemia may require parenteral potassium
be returned to normal by restricting primary dietary supplements. Caution must always be used when using IV
sources of potassium such as bananas, citrus and dried potassium because rapid administration of the drug can be
fruits, peanut butter, broccoli, and green leafy vegetables. fatal, especially for patients with CKD. Cardiac function
All potassium supplements and the use of salt substitutes should be closely monitored during IV potassium therapy.
containing potassium should be discontinued. If the patient
is taking a potassium-sparing diuretic, the dose must be PROTOTYPE DRUG Potassium Chloride (KCl)
lowered, or a thiazide or loop diuretic substituted.
Classification Therapeutic: Drug for hypokalemia
Several options are available for patients with severe Pharmacologic: Electrolyte, potassium
hyperkalemia. Administration of the diuretic furosemide
(Lasix) can significantly increase the urinary excretion of supplement
potassium within 5 to 15 minutes. Administering glucose or
dextrose concurrently with insulin temporarily lowers Therapeutic Effects and Uses: Potassium chloride
serum potassium levels by causing potassium to leave the is a preferred drug for preventing or treating hypokalemia
extracellular fluid and enter cells. In all patients who are because potassium and chloride depletion usually occur
symptomatic, calcium gluconate or calcium chloride is concurrently. It is also used to treat mild forms of alkalosis.
administered to prevent or treat potassium-induced cardio- Oral formulations of potassium chloride include tablets,
toxicity. Sodium bicarbonate is sometimes infused to correct powders, and liquids, usually heavily flavored due to its
any acidosis that may be concurrent with the hyperkalemia. unpleasant taste. Because potassium supplements can cause
peptic ulcers, the drug should be diluted with plenty of wa-
Excess potassium may also be eliminated from the ter. When given IV, potassium must be administered slowly
body by giving polystyrene sulfonate (Kayexalate) orally or because bolus injections can overload the heart and cause
rectally. This drug, which is not absorbed, exchanges Na1 cardiac arrest. Because pharmacotherapy with loop or thia-
for K1 as it travels through the intestine. The onset of action zide diuretics is the most common cause of potassium de-
is 1 hour, and the dose may be repeated every 4 hours as pletion, patients taking these drugs are usually prescribed
needed. The drug is given concurrently with a laxative such PO potassium supplements to prevent hypokalemia.
as sorbitol to promote rapid evacuation of the potassium.
Mechanism of Action: Potassium chloride is a replace
Patiromer (Veltassa) was approved in 2015 for hyperka- ment solution for lost potassium.
lemia. Like polystyrene sulfonate, it binds potassium in the
GI tract and eliminates it in the feces. This oral drug is slow- Pharmacokinetics: Because potassium chloride is
acting and is not for emergency control of hyperkalemia. a natural electrolyte, it is not possible to obtain accurate
pharmacokinetic values. The potassium ions in the drug
Hypokalemia: Hypokalemia is one of the most common are widely distributed and excreted by the kidneys in the
electrolyte imbalances and occurs when the serum potas- same manner as endogenous potassium ions.
sium level falls below 3.5 mEq/L. The most frequent cause
of hypokalemia is pharmacotherapy with loop and thiazide Adverse Effects: Nausea, vomiting, diarrhea, and
diuretics. In addition, strenuous muscular activity and abdominal pain are common, because potassium chlo-
severe vomiting or diarrhea can lead to significant potas- ride irritates the GI mucosa. The drug may be taken with
sium loss. Because the body does not have large stores of
Chapter 33 Pharmacotherapy of Fluid Imbalance, Electrolyte, and Acid–Base Disorders 573
meals or antacids to lessen gastric distress. The most seri- 33.11 Magnesium imbalances significantly
ous adverse effects of potassium chloride are related to the affect cardiovascular and neuromuscular
possible accumulation of excess potassium. Hyperkalemia function.
may occur if the patient takes potassium supplements con-
currently with potassium-sparing diuretics. Because the Magnesium is the second most abundant intracellular
kidneys perform over 90% of the body’s potassium excre- cation and, like potassium, it is essential for proper neu-
tion functions, reduced renal function can rapidly lead to romuscular function. Magnesium also serves a meta-
hyperkalemia, particularly in patients taking potassium bolic role in activating certain enzymes in the breakdown
supplements. of carbohydrates and proteins; it is a cofactor in over 300
biochemical reactions. Patients with disorders of mag-
Contraindications/Precautions: Potassium chloride nesium homeostasis generally present with cardiovas-
is contraindicated in patients with hyperkalemia, systemic cular and neuromuscular symptoms. Because the
acidosis, severe dehydration, extensive tissue breakdown majority of magnesium is found in bone, serum magne-
as in severe burns, or adrenal insufficiency. Oral potas- sium levels are not accurate indicators of total body
sium supplements are contraindicated in any condition magnesium.
for which transit through the GI tract is delayed because
prolonged contact may damage the GI mucosa. The drug Magnesium levels are primarily controlled by the kid-
should be used with extreme caution in patients with CKD ney. The ion is freely filtered and reabsorbed in the loop of
or acute renal failure because the drug may accumulate to Henle and loop diuretics such as furosemide can cause sig-
high levels. nificant magnesium loss. Magnesium imbalances may
occur in individuals with CKD. Magnesium is absorbed by
Drug Interactions: Potassium supplements should the small intestine and small amounts are secreted in intes-
not be administered to patients who are taking potas- tinal fluid.
sium-sparing diuretics because hyperkalemia may result.
Angiotensin-converting enzyme (ACE) inhibitors prevent Hypomagnesemia: Because it produces few symptoms
aldosterone secretion and cause potassium retention, thus until serum levels fall below 1 mEq/L, hypomagnesemia
increasing the risk for hyperkalemia if administered with is sometimes called the most common undiagnosed elec-
potassium supplements. Drugs that slow GI transit time, trolyte abnormality. Although the overall incidence for
such as anticholinergics, may increase the GI toxicity of magnesium deficiency is 6% to 12%, the majority of criti-
potassium supplements. Herbal/Food: Unknown. cally ill patients present with this condition. Renal causes
of hypomagnesemia include kidney failure and therapy
Pregnancy: Category C. with loop diuretics. GI causes include malabsorption dis-
orders and loss of significant amounts of body fluids due
Treatment of Overdose: Potassium-sparing diuret- to diarrhea, chronic laxative abuse, or nasogastric suction-
ics and all foods and medications containing potassium ing. Hypomagnesemia may also present in people with
should be withheld. Treatment includes IV administration alcoholism and in those receiving prolonged parenteral
of 10% dextrose solution containing 10 to 20 units of crys- feeding with magnesium-free solutions. Patients may
talline insulin. Sodium bicarbonate may be infused to cor- experience general weakness, dysrhythmias, HTN, loss of
rect acidosis. Polystyrene sulfonate may be administered deep tendon reflexes, and respiratory depression—signs
to enhance potassium elimination. and symptoms that are sometimes mistaken for hypokale-
mia. Additional signs include muscle twitches, tetany, or
Nursing Responsibilities: Key nursing implications seizures. Pharmacotherapy with magnesium sulfate can
for patients receiving potassium chloride are included in quickly reverse symptoms of hypomagnesemia (see proto-
the Nursing Practice Application for Patients Receiving type feature).
Pharmacotherapy for Fluid and Electrolyte Imbalances.
Hypermagnesemia: Advanced CKD is the only major
Drugs Similar to Potassium Chloride (KCl) cause of hypermagnesemia, although overtreatment with
magnesium supplements may also lead to excessive serum
Other potassium drugs include acetate, bicarbonate, magnesium levels. Clinical signs include central nervous
citrate, and gluconate salts. Potassium acetate is used as an system (CNS) depression, respiratory depression, hypo-
IV alternative to potassium chloride. Potassium bicarbon- tension, dysrhythmias, bradycardia, complete heart block,
ate supplies bicarbonate ion, which is alkaline and may be and coma. Infusions of calcium salts will immediately
useful in treating acidosis. Potassium citrate makes the reverse the neuromuscular and cardiovascular signs. If the
urine less acidic and is primarily used to reduce the forma- magnesium elevation is minor, treatment with furosemide
tion of kidney stones. Potassium gluconate is commonly to increase urinary excretion may be sufficient to reverse
available in tablet form and dissociates to potassium ion the hypermagnesemia.
and gluconate ion, a form of glucose.
574 Unit 5 Pharmacology of the Cardiovascular System
CONNECTIONS: Patient Safety Adverse Effects: Patients receiving IV infusions of
magnesium sulfate require careful observation to prevent
Control of Concentrated Electrolyte Solutions toxicity. Early signs of magnesium overdose include flush-
ing of the skin, sedation, confusion, intense thirst, and
While working with a clinical nurse preceptor, a student nurse muscle weakness. Extreme levels cause neuromuscular
asks the preceptor, “I’ve noticed that we have to wait for phar- blockade with resultant respiratory paralysis, heart block,
macy to deliver some medications and IVs. For example, we’re and circulatory collapse. Because of these potentially fatal
supposed to hang that IV with potassium for the patient in adverse effects, the use of magnesium sulfate is restricted
room 318. Wouldn’t it just be faster if nurses could mix the IV to patients with severe magnesium deficiency. Mild to
themselves on the unit?” How should the nurse respond? moderate hypomagnesemia is treated with oral forms of
magnesium such as magnesium gluconate or magnesium
Answers to Patient Safety questions are available on the faculty hydroxide. Oral magnesium sulfate often causes diarrhea.
resources site. Please consult with your instructor.
Contraindications/Precautions: Magnesium is
PROTOTYPE DRUG Magnesium Sulfate (MgSO4) contraindicated in patients with serious cardiac dis-
ease. Oral administration is contraindicated in those with
Classification Therapeutic: Drug for hypomagnesemia undiagnosed abdominal pain, intestinal obstruction, or
and seizures associated with eclampsia fecal impaction. The drug should be used cautiously in
patients with CKD because the drug may rapidly rise to
Pharmacologic: Electrolyte, magnesium toxic levels.
supplement
Drug Interactions: Use with neuromuscular blockers
Therapeutic Effects and Uses: Magnesium supple- may increase respiratory depression and apnea. Because
ments are available for both PO and parenteral routes. magnesium sulfate has CNS depression effects, patients
Severe hypomagnesemia can be rapidly reversed by the receiving other CNS depressants may experience increased
administration of intramuscular (IM) or IV magnesium sedation. Herbal/Food: Magnesium salts may decrease the
sulfate. Because IM preparations produce significant pain absorption of certain anti-infectives such as tetracycline.
at the injection site, severe cases of hypomagnesemia are
normally treated using the IV route. Parenteral formula- Pregnancy: Category A.
tions include 4%, 8%, 12.5%, and 50% solutions. After ad-
ministration, magnesium sulfate is distributed throughout Treatment of Overdose: Serious respiratory and
the body, and therapeutic effects are observed within 30 cardiac suppression may result from overdose. Calcium
to 60 minutes. Plasma magnesium levels should be moni- gluconate or gluceptate may be administered IV as an
tored frequently during therapy. antidote.
Oral forms of magnesium sulfate (Epsom salt) are used Nursing Responsibilities: Key nursing implications
as cathartics, when complete evacuation of the colon is for patients receiving magnesium sulfate are included in
desired. Epsom salt is sometimes used in bath water to ease the Nursing Practice Application for Patients Receiving
aching muscles, although the scientific basis for this use is Pharmacotherapy for Fluid and Electrolyte Imbalances.
lacking. Its action as a CNS depressant has led to its occa-
sional use as an anticonvulsant in patients with preeclamp- Drugs Similar to Magnesium
sia or eclampsia (see Chapter 22). Magnesium sulfate has Sulfate (MgSO4)
been used off-label to slow uterine contractions during pre-
term labor (see Chapter 69). Several oral magnesium salts are available OTC. Magne-
sium citrate (citrate of magnesia) and magnesium hydrox-
Mechanism of Action: Magnesium sulfate is a replace ide (milk of magnesia) are classified as laxatives or
ment solution for lost magnesium. cathartics. Magnesium oxide (Mag-Ox) is an antacid, and
magnesium salicylate (Doan’s Pills) is used as an analgesic.
Pharmacokinetics:
PharmFACT
Route(s) PO, IM, IV
Although the recommended dietary allowance for
Absorption Not absorbed magnesium is 420 mg/day in men and 320 mg/day in
women, certain patients need higher levels to maintain
Distribution Widely distributed; crosses the health. These include patients with Crohn’s disease or poorly
controlled diabetes, pregnant or lactating women, older
placenta; secreted in breast milk adults, and patients with alcoholism (National Institutes
of Health, Office of Dietary Supplements, 2016).
Primary metabolism Not metabolized
Primary excretion Renal
Onset of action PO: 1–2 h; IM: 1 h; IV: immediate
Duration of action PO and IM: 3–4 h; IV: 30 min;
half-life: unknown
Chapter 33 Pharmacotherapy of Fluid Imbalance, Electrolyte, and Acid–Base Disorders 575
Acids pH = 7.35–7.45 Bases
Normal plasma
Sodium Ammonium chloride
bicarbonate or
sodium chloride
with potassium
chloride
Bases Acids
pH < 7.35 pH > 7.45
Acids Acidosis Alkalosis Bases
CNS depression CNS stimulation
Coma Convulsions
Figure 33.3 Acid–base imbalances.
Pharmacotherapy of Acid–Base rapidly correct pH imbalances in body fluids, supporting
Imbalances the patient’s vital functions while the underlying disease is
being treated. The correction of acid–base imbalance is
33.12 The pH of body fluids must be illustrated in Figure 33.3.
maintained between very narrow limits.
33.13 The pharmacotherapy of acidosis includes
The degree of acidity or alkalinity of a solution is mea- the administration of alkaline drugs.
sured by its pH. A pH of 7.0 is defined as neutral, above 7.0
as basic or alkaline, and below 7.0 as acidic. To maintain Acidosis occurs when the pH of the plasma falls below
homeostasis, the pH of plasma and most body fluids must 7.35, which is confirmed by measuring arterial pH, partial
be kept within the narrow range of 7.35 to 7.45 because pressure of carbon dioxide (PCO2), and plasma bicarbonate
nearly all proteins and enzymes in the body function opti- levels. For proper pharmacotherapy, the diagnosis must
mally within this range. A few enzymes, most notably differentiate between respiratory etiology and metabolic
those in the digestive tract, require pH values outside the (renal) etiology. Occasionally, the cause has mixed respira-
7.35 to 7.45 range to function properly. tory and metabolic components.
The body generates significant amounts of acids dur- The most profound symptoms of acidosis affect the
ing normal metabolic processes. Without an effective CNS and include lethargy, confusion, and CNS depression
means of neutralizing these metabolic acids, the overall leading to coma. A deep, rapid respiration rate indicates an
pH of body fluids would quickly fall below the normal attempt by the lungs to rid the body of excess acid. Com-
range. Buffers are chemicals that help maintain normal mon causes of acidosis are shown in Table 33.6.
body pH by neutralizing strong acids and bases. The two
primary buffers in the body are bicarbonate ions and In patients with acidosis, the therapeutic goal is to
phosphate ions. quickly reverse the adverse effects caused by excess acids
in the blood. Mild acidosis may be treated with oral bicar-
The body uses two mechanisms to remove acid. The bonate or citrate salts or other basic substances. For acute
acidic carbon dioxide (CO2) produced during body acidosis the preferred treatment is to administer infusions
metabolism is efficiently removed by the lungs during of sodium bicarbonate. Bicarbonate ion is a base that can
exhalation. The kidneys remove excess acid in the form of quickly neutralize acids in the blood and other body fluids.
hydrogen ion (H1) by excreting it in the urine. If retained The patient must be carefully monitored during infusions
in the body, either CO2 or H1 will lower body pH. Normal because this drug can overcorrect the acidosis, causing
acid–base balance is maintained by the lungs and kid- blood pH to turn alkaline. Sodium citrate, sodium lactate,
neys. Impairment of these organs commonly leads to and sodium acetate are alternative alkaline drugs that may
change in pH. be used in place of bicarbonate.
Acidosis (excess acid) and alkalosis (excess base) are Alkalinizing drugs are also used to aid in the renal
not diseases but are symptoms of an underlying medical excretion of toxic substances through a phenomenon called
disorder. Acidic drugs and basic drugs are administered to ion trapping. Whenever a large pH gradient exists across a
576 Unit 5 Pharmacology of the Cardiovascular System
Table 33.6 Causes of Acidosis and Alkalosis alkaline. Less acid is reabsorbed, so more acid and acidic
medicine are excreted. This process is known as ion
Acidosis Alkalosis trapping.
Respiratory Origins of Acidosis Respiratory Origin of Alkalosis Mechanism of Action: The bicarbonate ion in so-
Hyperventilation due to asthma, dium bicarbonate buffers excess acid (H1) to raise the pH
Hypoventilation or shallow anxiety, or high altitude of body fluids.
breathing
Airway constriction Metabolic Origins of Alkalosis Pharmacokinetics:
Damage to respiratory center Constipation for prolonged periods
in medulla Ingestion of excess sodium Route(s) IV, PO
bicarbonate
Metabolic Origins of Acidosis Diuretics that cause potassium Absorption Rapidly absorbed
depletion
Severe diarrhea Severe vomiting Distribution Widely distributed in body fluids
Kidney failure
Diabetes mellitus Primary metabolism Not metabolized
Excess alcohol ingestion
Starvation
Primary excretion Renal
Onset of action PO: 15 min; IV: immediate
Duration of action PO: 1–3 h; IV: 8–10 min
membrane, drug molecules will accumulate on the side Adverse Effects: Most of the adverse effects of so-
where the opportunity for ionization is greatest. Recall dium bicarbonate therapy are the result of metabolic al-
from Chapter 3 that acids ionize in a basic environment; kalosis created by receiving too much bicarbonate ion.
bases ionize in acidic solutions. The infusion of an alkalin- Symptoms may include confusion, irritability, slow res-
izing drug will create an alkaline filtrate in the kidney piration rate, and vomiting. Discontinuing the sodium
tubule, a perfect environment for ionization of an acidic bicarbonate infusion often reverses these symptoms;
drug like aspirin. Rather than being absorbed back into the however, potassium chloride or ammonium chloride
body, the ionized aspirin remains trapped in the filtrate may be administered to reverse acute alkalosis. During
and is excreted in the urine. Thus, through ion trapping, sodium bicarbonate infusions, serum electrolytes should
the alkalinizing drug was able to move aspirin from the be carefully monitored because sodium levels may lead
blood to the urine. to hypernatremia and fluid retention. In addition, high
levels of bicarbonate ion passing through the kidney tu-
PROTOTYPE DRUG Sodium Bicarbonate bules increase potassium secretion, which could lead to
hypokalemia.
Classification Therapeutic: Drug to treat acidosis or
bicarbonate deficiency Contraindications/Precautions: Patients who are
vomiting, have severe diarrhea, or have continuous GI
Pharmacologic: Electrolyte, sodium, and suctioning will lose acid and chloride and may be in a
bicarbonate supplement state of metabolic alkalosis; therefore, they should not re-
ceive sodium bicarbonate because it may worsen alkalo-
Therapeutic Effects and Uses: Sodium bicarbon- sis. Due to the sodium content of this drug, it should be
ate is a preferred drug for correcting metabolic acidosis. used cautiously in patients with cardiac disease, HTN,
After dissociation, the bicarbonate ion directly raises the or CKD.
pH of body fluids. Sodium bicarbonate may be given PO
if acidosis is mild, or IV in cases of acute disease. IV con- Drug Interactions: Sodium bicarbonate may decrease
centrations range from 4.2% to 8.4%. Although sodium bi- the absorption of ketoconazole and may decrease elimina-
carbonate also neutralizes gastric acid, it is rarely used to tion of dextroamphetamine, ephedrine, pseudoephedrine,
treat peptic ulcers due to its tendency to cause uncomfort- and quinidine. The elimination of lithium, salicylates, and
able gastric distention. The PO form of sodium bicarbonate tetracyclines may be increased. Herbal/Food: Chronic use
is commonly known as baking soda. with milk or calcium supplements may cause milk-alkali
syndrome, a condition characterized by serious hypercal-
Sodium bicarbonate may also be used to alkalinize cemia and possible kidney failure.
the urine to speed the excretion of acidic medications such
as aspirin and phenobarbital and as adjunctive therapy Pregnancy: Category C.
for certain chemotherapeutic drugs such as methotrexate.
Sodium bicarbonate is also used in individuals with CKD Treatment of Overdose: Overdose results in meta-
to neutralize the metabolic acidosis that occurs when the bolic alkalosis, which is treated by administering acidic
kidneys cannot excrete hydrogen ion. When IV sodium drugs (see Section 33.14).
bicarbonate is given, it causes the urine to become more
Chapter 33 Pharmacotherapy of Fluid Imbalance, Electrolyte, and Acid–Base Disorders 577
Nursing Responsibilities: Key nursing implications also combines with bases to reduce the alkalinity of extra-
for patients receiving sodium bicarbonate are included in cellular fluids.
the Nursing Practice Application for Patients Receiving
Pharmacotherapy for Fluid and Electrolyte Imbalances. Pharmacokinetics: IV, PO
Route(s) Rapidly absorbed
Drugs Similar to Sodium Bicarbonate Absorption Unknown
Distribution Hepatic
There are no drugs similar to sodium bicarbonate. Primary metabolism Renal
Primary excretion Unknown
33.14 The pharmacotherapy of alkalosis Onset of action Unknown
includes the administration of acidic drugs. Duration of action
At plasma pH values above 7.45, alkalosis develops. Mor- Adverse Effects: Aggressive treatment with ammo-
tality can reach as high as 80% if the pH rises above 7.65. nium chloride can cause acidosis. Characteristic symptoms
Like acidosis, alkalosis may have either respiratory or meta- of acidosis include CNS depression, drowsiness, confu-
bolic causes, as shown in Table 33.6. Also like acidosis, the sion, and coma. Periods of CNS excitement may alternate
CNS is greatly affected. Symptoms of CNS stimulation occur with coma. Oral forms of the drug are irritating to the gas-
and include nervousness, hyperactive reflexes, and convul- tric mucosa and may cause nausea and vomiting.
sions. In metabolic alkalosis, slow, shallow breathing indi-
cates that the body is attempting to compensate by retaining Contraindications/Precautions: Ammonium chlo-
acid and lowering internal pH. Life-threatening dysrhyth- ride should not be administered to patients with serious
mias are the most serious adverse effects of alkalosis. hepatic impairment or severe CKD because the drug will
accumulate to toxic levels. It should not be administered to
In mild cases, alkalosis may be corrected by administer- patients with either metabolic or respiratory acidosis.
ing sodium chloride combined with potassium chloride. This
combination increases the renal excretion of bicarbonate ion, Drug Interactions: Ammonium chloride may cause
which indirectly increases the acidity of the blood. More crystalluria when taken with aminosalicylic acid. Antacids
severe alkalosis may be treated with infusions of an acidic should not be administered concurrently because they are
drug such as ammonium chloride or hydrochloric acid. alkaline and will antagonize the acidifying effects of am-
monium chloride. Ammonium chloride reduces levels of
PROTOTYPE DRUG Ammonium Chloride amphetamines, flecainide, mexiletine, methadone, ephed-
rine, and pseudoephedrine. Urinary excretion of sulfo-
Classification Therapeutic: Drug for treating metabolic nylureas and salicylates is decreased. Serum magnesium
alkalosis and hypochloremia values may decrease. Herbal/Food: Unknown.
Pharmacologic: Acidic drug Pregnancy: Category B.
Therapeutic Effects and Uses: Ammonium chlo- Treatment of Overdose: Overdose results in meta-
ride is an acidic substance that has been available as a drug bolic acidosis, which is treated by administering alkaline
to treat metabolic alkalosis for over 80 years. Ammonium drugs (see Section 33.13).
chloride acidifies the urine, which is beneficial in treating
certain urinary tract infections. Historically, it has been Nursing Responsibilities: Key nursing implica-
used as a mild diuretic, though safer and more effective tions for patients receiving ammonium chloride are
agents have made its use obsolete. By acidifying the urine, included in the Nursing Practice Application for Patients
ammonium chloride promotes the excretion of alkaline Receiving Pharmacotherapy for Fluid and Electrolyte
drugs such as amphetamines through ion trapping. Oral Imbalances.
and IV forms are available; when given for alkalosis, the
IV route is preferred. Because of the potential for causing Drugs Similar to Ammonium Chloride
acidosis, injection-site reactions, and ammonia toxicity, the
drug is infused slowly. The only similar drug is hydrochloric acid.
Mechanism of Action: During the hepatic con- Hydrochloric acid: Hydrochloric acid may be adminis-
version of ammonium chloride to urea, Cl2 and H1 are tered IV in severe cases of metabolic acidosis. A central
formed. The H1 combines with bicarbonate to form the venous catheter must be used to administer the drug.
weak acid carbonic acid, which dissociates to water and Hydrochloric acid is only used when sodium or potassium
carbon dioxide. By removing bicarbonate, ammonium chloride cannot be administered due to volume overload
chloride decreases the pH of body fluids. The chloride ion or advanced CKD. This drug can cause severe tissue necro-
sis if it extravasates into the tissues.
578 Unit 5 Pharmacology of the Cardiovascular System
CONNECTIONS: NURSING PRACTICE APPLICATION
Patients Receiving Pharmacotherapy for Fluid and Electrolyte Imbalances
Assessment
Baseline assessment prior to administration:
• Obtain a complete health history including cardiovascular (including HTN, myocardial infarction [MI]), neurologic (including stroke or head injury), burns,
endocrine, hepatic, or renal disease. Obtain a drug history including allergies, current prescription and OTC drugs, and herbal preparations. Be alert to
possible drug interactions.
• Obtain baseline weight and vital signs, LOC, breath sounds, and urinary output as appropriate.
• Evaluate appropriate laboratory findings (e.g., electrolytes, complete blood count [CBC], urine specific gravity and urinalysis, blood urea nitrogen [BUN]
and creatinine, total protein and albumin levels, activated partial thromboplastin time [aPTT], activated prothrombin time [aPT] or international normal-
ized ratio [INR], renal and liver 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., electrolyte values return to within normal range, adequate urine output).
• Continue monitoring vital signs, urinary output, and LOC as appropriate.
• Assess for and promptly report adverse effects: tachycardia, HTN, dysrhythmias, decreasing LOC, increasing dyspnea, lung congestion, pink-tinged
frothy sputum, decreased urinary output, muscle weakness or cramping, and allergic reactions.
Implementation
Interventions and (Rationales) Patient-Centered Care
Ensuring therapeutic effects: • Teach the patient to continue to consume enough liquids to remain
• Continue frequent assessments as above for therapeutic effects. adequately, but not overly, hydrated. Drinking when thirsty, avoiding
alcoholic beverages, maintaining a healthy diet, and ensuring adequate
Assist the patient as needed with obtaining fluids and eating. (Urinary but not excessive salt intake will assist in maintaining normal fluid and
output is within normal limits. Electrolyte balance is restored or within electrolyte balance.
the parameters set by the healthcare provider. Lifespan: Older adults,
infants, and patients who cannot access fluids or eat by themselves • Have the patient weigh self daily, ideally at the same time of day, and
[e.g., post-stroke] are at increased risk for fluid and electrolyte record weight along with blood pressure and pulse measurements as
imbalance.) appropriate.
• Teach the patient, family, or caregiver how to monitor pulse and blood
pressure if needed. Ensure proper use and functioning of any home
equipment obtained.
Minimizing adverse effects: • Instruct the patient to report changes in muscle strength or function;
• Monitor for signs of fluid volume excess or deficit, e.g., HTN (excess) numbness and tingling in the lips, fingers, arms, or legs; palpitations;
dizziness; nausea or vomiting; GI cramping; or decreased urination.
or hypotension (deficit), tachycardia, or changes in the quality of
pulse (bounding or thready). Notify the healthcare provider if blood • Instruct patients with hypokalemia to consume foods high in potas-
pressure or pulse exceeds established parameters. Monitor for signs sium: fresh fruits such as strawberries and bananas; dried fruits such
of potential electrolyte imbalance including nausea, vomiting, GI as apricots and prunes; vegetables and legumes such as tomatoes,
cramping, diarrhea, muscle weakness, cramping, twitching, pares- beets, and beans; juices such as orange, grapefruit, or prune; and
thesia, and irritability. Immediately report any confusion, decreasing fresh meats. Instruct patients with hyperkalemia to avoid the above as
LOC, or increasing hypotension or HTN, especially if associated with well as salt substitutes (which often contain potassium salts), and to
tachycardia, decreased urine output, or seizures. (Many fluid and consult with a healthcare provider before taking vitamin and mineral
electrolyte imbalances have similar symptoms. When assessing the supplements or specialized sports beverages. Licorice should be
patient for adverse effects, consider past health history, drug history, avoided because it causes potassium loss and sodium retention.
and current condition and medications to correlate symptoms to
possible causes.)
• Frequently monitor CBC, electrolytes, aPTT, aPT, or INR levels. (Crys- • Instruct the patient on the need to return periodically for laboratory
talloid solutions may cause electrolyte imbalances. Colloid solutions work.
may reduce normal blood coagulation. Frequent monitoring of elec-
trolyte levels while on replacement therapy may be needed to ensure
therapeutic effects.)
• Continue to monitor vital signs. Take blood pressure lying, sitting, and Teach the patient to:
standing to detect orthostatic hypotension. Lifespan: Be particularly • Rise from lying or sitting to standing slowly to avoid dizziness or falls. If
cautious with the older adult who is at increased risk for hypoten-
sion. Ensure patient safety. (Dehydration and electrolyte imbalances dizziness occurs, the patient should sit or lie down and not attempt to
may cause dizziness and hypotension. Orthostatic hypotension may stand or walk until the sensation passes.
increase the risk of falls and injury.) • Call for assistance prior to getting out of bed or attempting to
walk alone and to avoid driving or other activities requiring mental
alertness or physical coordination if dizziness or lightheadedness
occurs.
• Weigh the patient daily and report a weight gain or loss of 1 kg (2 lb) • Have the patient weigh self daily, ideally at the same time of day, and
or more in a 24-h period. (Daily weight is an accurate measure of fluid record weight along with blood pressure and pulse measurements.
status and takes into account intake, output, and insensible losses. Have the patient report a weight loss or gain of more than 1 kg (2 lb) in
Weight gain or edema may signal excessive fluid volume or electrolyte a 24-h period.
imbalances.)
• Teach the patient that excessive heat conditions contribute to exces-
sive sweating and fluid and electrolyte loss, and extra caution is war-
ranted in these conditions.
Chapter 33 Pharmacotherapy of Fluid Imbalance, Electrolyte, and Acid–Base Disorders 579
CONNECTIONS: NURSING PRACTICE APPLICATION (continued)
Implementation
Interventions and (Rationales) Patient-Centered Care
• Closely monitor for signs and symptoms of allergy if colloids are used. • Instruct the patient to report dyspnea, itching, feelings of throat tight-
(Colloids such as plasma protein fraction, dextran, and hetastarch may ness, palpitations, chest pain or tightening, or headache immediately.
cause allergic and anaphylactic reactions.)
• Closely monitor IV sites when infusing potassium or ammonium. • Instruct the patient to report any irritation, pain, redness, or swelling at
Double-check doses with another nurse before giving. (Potassium and the IV site or in the arm where the drug is infusing.
ammonium are irritating to the vessel and phlebitis may result. Potas-
sium is a “high-alert” medication and double-checking doses before
giving prevents medication errors.)
• Monitor LOC, deep tendon reflexes, urinary output, respiratory rate, • To allay anxiety, teach the patient and family the rationale for all equip-
and laboratory values frequently in patients receiving parenteral ment used and the need for frequent monitoring.
magnesium sulfate and newborns if the mother has received the drug.
Keep calcium gluconate available as an antidote to magnesium toxic- • Instruct patients with hypomagnesemia to consume foods high in
ity. (Adverse effects from hypermagnesemia include respiratory and magnesium: green leafy vegetables and legumes such as peas, beans,
cardiac arrest and neuromuscular depression.) nuts, and whole grains, and to increase fluid intake.
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 the drug therapy, desired medication therapy.
therapeutic outcomes, and any necessary monitoring or precau-
tions. (Using time during nursing care helps to optimize and reinforce
supportive drug treatment and care.)
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, and administration needs.
or caregiver in proper self-administration of the drug, e.g., early • Lifespan: Assess swallowing ability before giving or taking potassium
in the day to prevent disruption of sleep from nocturia. chloride or ammonium chloride; they may cause mouth, esophageal,
(Utilizing time during nurse administration of these drugs helps or gastric irritation. Liquid forms should always be diluted with water or
to reinforce teaching.) fruit juice and tablets swallowed whole.
Understanding Chapter 33
Key Concepts Summary 33.8 Electrolytes are charged substances that are
essential to homeostasis.
33.1 Body fluids are exchanged between intracellular
and extracellular compartments. 33.9 Sodium balance is closely associated with water
balance.
33.2 Osmolality or tonicity determines the movement
of body fluids. 33.10 Potassium imbalances must be quickly corrected
to prevent serious cardiac consequences.
33.3 Overall fluid balance is regulated primarily by
hormones acting on the kidneys. 33.11 Magnesium imbalances significantly affect
cardiovascular and neuromuscular function.
33.4 Dehydration may be treated with fluid volume
expanders. 33.12 The pH of body fluids must be maintained
between very narrow limits.
33.5 Transfusions of blood products are used to treat
serious conditions that cannot be managed 33.13 The pharmacotherapy of acidosis includes the
effectively by other means. administration of alkaline drugs.
33.6 Crystalloids are intravenous solutions that closely 33.14 The pharmacotherapy of alkalosis includes the
resemble the composition of extracellular fluid. administration of acidic drugs.
33.7 Colloids are intravenous solutions containing
large molecules that remain in the blood.
580 Unit 5 Pharmacology of the Cardiovascular System
CASE STUDY: Making the Patient Connection
Remember the patient “Peggy have started the IV in her right hand. Peggy asks you why
Hoover” at the beginning of she needs it, especially since she will be returning home
the chapter? Now read the that afternoon.
remainder of the case study.
Based on the information Critical Thinking Questions
presented within this chapter,
respond to the critical thinking questions that follow. 1. Why do you think an IV was ordered for Peggy, and
what will you explain to her?
Peggy Hoover is 26 years old and has been admitted to the
short-stay surgical unit for an elective laparoscopic chole- 2. What are the two main categories of IV solutions?
cystectomy. She has been in good health except for repeated Which category was ordered for Peggy?
gallbladder attacks. It is anticipated that she will be able to
go home this afternoon after the surgery is completed. 3. Dextrose 5% in water (D5W) is a common solution.
What precautions should be taken with this
As the nurse admitting Peggy, you have orders to start fluid type?
a D5W infusion prior to surgery, to run at 15 mL/h. You
Answers to Critical Thinking Questions are available on the
faculty resources site. Please consult with your instructor.
Additional Case Study 2. What adverse effect related to potassium supplemen-
tation would you advise him to watch for?
Marvin Fields has been prescribed a loop diuretic, furose-
mide (Lasix), 40 mg daily, and a potassium supplement 3. What advice would you give Marvin about his dietary
tablet, 40 mEq daily. As you are preparing to discharge this consumption of potassium-rich foods?
patient, he states, “I understand why I need the diuretic,
but why do I have to take this potassium?” Answers to Additional Case Study questions are available on
the faculty resources site. Please consult with your instructor.
1. How would you respond to his question?
Chapter Review 3. The nurse is administering dextran 40 (Gentran 40) to
a patient with multiple traumatic injuries following a
1. The patient with a disorder causing metabolic motor vehicle crash. The nurse knows that which
acidosis is being treated with intravenous sodium adverse effect of this medication is toxic?
bicarbonate. The nurse monitors for therapeutic
effectiveness by noting which laboratory values? 1. Dehydration
2. Increased urinary output
1. Serum pH 3. Hypovolemic shock
2. Red blood cell count 4. Bleeding
3. Liver function test
4. Blood urea nitrogen 4. The patient will be receiving 5% dextrose in water
(D5W) intravenous infusion. Which statement is cor-
2. The nurse is teaching the patient about a liquid potas- rect about this therapy?
sium chloride supplement. Which statement, if made by
the patient, indicates that further teaching is necessary? 1. D5W can cause hypoglycemia in the patient who
has diabetes.
1. “I should avoid salt substitutes unless approved by
my healthcare provider.” 2. D5W may be used to dilute mixed intravenous
drugs.
2. “Liquid preparations should not be diluted with
other fluids.” 3. D5W is considered a colloid solution.
4. D5W has a sufficient number of calories to supply
3. “I should report signs of potassium deficit such as
weakness and fatigue.” metabolic needs.
4. “Persistent vomiting will result in significant losses
of potassium.”
Chapter 33 Pharmacotherapy of Fluid Imbalance, Electrolyte, and Acid–Base Disorders 581
5. The healthcare provider orders intravenous magne- 6. Which of the following nursing actions should be
sium sulfate for a pregnant patient with preeclampsia. included in the care plan for a patient receiving normal
The nurse should consult with the prescriber about serum albumin (Albuminar)? (Select all that apply.)
which patient assessment finding that may affect the
drug therapy? 1. Document past history of blood transfusion
reactions.
1. Pupil constriction to direct light
2. Restrict dietary intake of food high in potassium.
2. Chest congestion and coughing 3. Monitor blood pressure and pulse rate.
4. Measure urinary output hourly.
3. Elevated blood pressure 5. Observe for signs related to potassium deficit.
4. Decreased patellar deep tendon reflexes See Answers to Chapter Review in Appendix A.
References National Institutes of Health, Office of Dietary
Supplements. (2016). Magnesium: Fact sheet for health
American Red Cross. (n.d.). Blood facts and statistics. professionals. Retrieved from http://ods.od.nih.gov/
Retrieved from http://www.redcrossblood.org/learn- factsheets/Magnesium-HealthProfessional
about-blood/blood-facts-and-statistics
Selected Bibliography Perel, P., Roberts, I., & Ker, K. (2013). Colloids versus
crystalloids for fluid resuscitation in critically ill
Buffington, M. A., & Abreo, K. (2015). Hyponatremia A patients. Cochrane Database of Systematic Reviews, 2, Art.
review. Journal of Intensive Care Medicine, 31, 223–236. No. CD000567. doi:10.1002/14651858.CD000567.pub6
doi:10.1177/0885066614566794
Pierce, J. D., Shen, Q., & Thimmesch, A. (2016). The
Bunn, F., & Trivedi, D. (2012). Colloid solutions for fluid ongoing controversy: Crystalloids versus colloids.
resuscitation. Cochrane Database of Systematic Reviews, 7, Journal of Infusion Nursing, 39, 40–44. doi:10.1097/
Art. No. CD001319.pub4. doi:10.1002/14651858. NAN.0000000000000149
CD001319.pub4
Russell, L., & McLean, A. S. (2014). The ideal fluid. Current
Crowther, C. A., Brown, J., McKinlay, C. J., & Middleton, Opinion in Critical Care, 20, 360–365. doi:10.1097/
P. (2014). Magnesium sulphate for preventing preterm MCC.0000000000000112
birth in threatened preterm labour. Cochrane Database
of Systematic Reviews, 8, Art. No. CD001060. Salem, C. B., Badreddine, A., Fathallah, N., Slim, R., &
doi:10.1002/14651858.CD001060.pub2 Hmouda, H. (2014). Drug-induced hyperkalemia. Drug
Safety, 37, 677–692. doi:10.1007/s40264-014-0196-1
Huang, L. H. (2016). Dehydration. Retrieved from http://
emedicine.medscape.com/article/906999-overview Thomas, C. P. (2016). Metabolic alkalosis. Retrieved from
http://emedicine.medscape.com/article/
Makrides, M., Crosby, D. D., Bain, E., & Crowther, C. A. 243160-overview
(2014). Magnesium supplementation in pregnancy.
Cochrane Database of Systematic Reviews, 4, Art. No. Thompson, J. (2015). Intraoperative fluid management.
CD000937. doi:10.1002/14651858.CD000937.pub2 Critical Care Nursing Clinics of North America, 27, 67–77.
doi:10.1016/j.cnc.2014.10.012
Myburgh, J. A., & Mythen, M. G. (2013). Resuscitation
fluids. The New England Journal of Medicine, 369,
1243–1251. doi:10.1056/NEJMra1208627
“I’m doing everything my
doctor has advised me to do
to control my hypertension. My
doctor has prescribed several
different types of drugs over
the past few months. My blood
pressure is still elevated. What
else can I do?”
Patient “Elmer Foley”
Chapter 34
Pharmacotherapy of Hypertension
Chapter Outline Learning Outcomes
cc Etiology and Pathogenesis of Hypertension After reading this chapter, the student should be able to:
cc Nonpharmacologic Management of Hypertension
cc Guidelines for the Management of Hypertension 1. Summarize the long-term consequences of untreated
cc Pharmacotherapy of Hypertension hypertension.
cc Drug Classes for Hypertension
2. Compare and contrast the roles of
Diuretics nonpharmacologic and pharmacologic methods in
Calcium Channel Blockers the management of hypertension.
Drugs Affecting the Renin-Angiotensin-Aldosterone
System 3. Describe general principles guiding the
Angiotensin-Converting Enzyme Inhibitors pharmacotherapy of hypertension.
Angiotensin II Receptor Blockers
Adrenergic Antagonists 4. Identify first- and second-line drug classes used in
Beta-Adrenergic Antagonists the management of hypertension.
Alpha1-Adrenergic Antagonists
Alpha2-Adrenergic Agonists (Centrally Acting Drugs) 5. Describe the pharmacologic management of
Adrenergic Neuron Blockers hypertensive emergencies.
Direct Vasodilators
PROTOTYPE Hydralazine, p. 593 6. For each of the classes shown in the chapter outline,
cc Management of Hypertensive Emergency identify the prototype and representative drugs and
PROTOTYPE Nitroprusside Sodium explain the mechanism(s) of drug action, primary
(Nitropress), p. 595 indications, contraindications, significant drug
interactions, pregnancy category, and important
adverse effects.
7. Apply the nursing process to care for patients
receiving antihypertensive drugs.
582
Chapter 34 Pharmacotherapy of Hypertension 583
Key Terms hypertensive emergency hypertrichosis, 594
(HTN-E), 594 primary hypertension, 583
angiotensin-converting enzyme secondary hypertension, 583
(ACE) inhibitors, 590 hypertensive urgency, 594
hypertension (HTN), 584
Diseases affecting the heart and blood vessels are the most accounts for 90% of all cases. Although patients with
frequent causes of death in the United States. Hypertension primary HTN cannot be cured with medication, the disease
(HTN) or high blood pressure is the most common of the can be managed such that the risk of serious, long-term con-
cardiovascular diseases. Chronic HTN affects one in every sequences can be reduced.
three Americans and contributes to over 410,000 deaths in
the United States each year (Centers for Disease Control In some cases, a specific cause of the HTN can be iden-
and Prevention [CDC], 2016 a). Although mild HTN can be tified. This type, called secondary hypertension, accounts
controlled with lifestyle modifications, moderate to severe for 10% of all patients with HTN. Certain diseases, such as
HTN requires pharmacotherapy. Cushing’s syndrome, hyperthyroidism, chronic kidney
disease, pheochromocytoma, and arteriosclerosis, are asso-
Because nurses encounter so many patients with this ciated with elevated blood pressure. Certain drugs are also
disease, it is critical for them to understand the underlying associated with HTN, including alcohol, decongestants,
principles of antihypertensive therapy. By improving pub- caffeine, amphetamines, corticosteroids, oral contracep-
lic awareness of HTN and teaching the importance of early tives, estrogen, erythropoietin, and sibutramine. The thera-
intervention, the nurse can contribute significantly to peutic goal for secondary HTN is to treat or remove the
reducing cardiovascular mortality. underlying condition that is causing the blood pressure
elevation. In many cases, correcting the comorbid condi-
PharmFACT tion will cure the associated HTN.
Individuals whose blood pressure is higher than 140/90 mmHg Research has clearly demonstrated that failure to con-
(140 systolic or above or 90 diastolic or above) often become trol HTN can have serious consequences. Prolonged or
patients treated for serious cardiovascular problems. This improperly controlled HTN damages blood vessels, par-
includes about: ticularly small arteries and arterioles. As it progresses, the
walls of the arteries gradually thicken in an attempt to pro-
• 80% of those who experience a first stroke tect the vessels against injury from the increased pressure.
• 70% of those who have a first heart attack The injured vessel walls become inflamed, increasing the
• 70% of those with chronic heart failure (CDC, 2016b). permeability of the vessels and causing additional thicken-
ing of their walls. Eventually, the lumen of the artery per-
Etiology and Pathogenesis manently narrows, reducing blood flow to vital tissues.
of Hypertension HTN accelerates atherosclerosis and will worsen condi-
tions such as coronary artery disease (CAD).
34.1 Failure to properly manage hypertension
can lead to stroke, heart failure, or myocardial Hypertension may exist for years, indeed decades,
infarction. before becoming symptomatic. As the disease progresses,
however, the risk of target-organ damage increases.
Hypertension is a complex disease that is caused by a Because sustained HTN may affect any artery in the body,
combination of genetic and environmental factors. damage may be widespread and symptoms vary greatly
Approximately 4% of HTN cases are believed to involve according to which vessels are affected.
genetic factors. Scientists have discovered specific genes
that appear to predispose a patient to HTN. These genes The heart is a primary organ damaged by chronic
control critical activities such as renal sodium and water HTN. Hypertension increases afterload, forcing the heart
transport and the renin-angiotensin-aldosterone system. to work harder to pump blood to the tissues. The heart is
Environmental factors related to diet and exercise also subjected to chronic pressure overload, resulting in left
play an important role in the development of HTN. ventricular hypertrophy. If untreated, this excessive work-
load eventually causes the heart to fail and the lungs to fill
For the large majority of patients with HTN, no specific with fluid, a condition known as heart failure (HF). Drug
cause can be identified. HTN having no identifiable cause is therapy for HF is covered in Chapter 36. Further damaging
called idiopathic, essential, or primary hypertension and the heart is the effect of HTN on the coronary vessels.
Hypertension accelerates the deposition of atherosclerotic
584 Unit 5 Pharmacology of the Cardiovascular System
plaque, creating or worsening CAD. This places the patient plays a vital role in educating patients about controlling
at greater risk of dysrhythmias, angina pectoris, and myo- their HTN. Because all blood pressure medications have
cardial infarction (MI). Heart failure and MI are the most potential adverse effects, it is important for patients to
common causes of death in patients with HTN. attempt to control their disease through nonpharmacologic
means, to the greatest extent possible. Nonpharmacologic
The brain is also a major target organ for hypertensive methods for controlling HTN include the following:
damage. Occlusion of the small vessels supplying blood
and oxygen to the brain can cause transient ischemic • Limit intake of alcohol.
attacks and stroke. These neurologic events are common in • Restrict sodium consumption and increase potassium
patients with HTN and are a major cause of disability.
intake.
Because a large percentage of blood pumped per min- • Reduce intake of saturated fat and cholesterol, and
ute circulates through the kidneys, chronic HTN creates
major stress on these organs. As the small arteries supply- increase consumption of fruits and vegetables.
ing the kidney become injured, inflamed, and atheroscle- • Increase aerobic physical activity.
rotic, the patient’s renal function gradually declines. Poorly • Discontinue use of all tobacco products.
managed HTN is an important contributor to kidney fail- • Explore measures for dealing with excessive stress.
ure and end-stage kidney disease. • Maintain optimal weight.
Hypertension is a major cause of visual impairment, Guidelines for the Management
which can occur when vessels in the eye become athero- of Hypertension
sclerotic. Although patients may remain asymptomatic for
many years, small hemorrhages that affect vision may 34.3 Research-based guidelines have been
occur. Symptoms of retinal damage range from subtle developed to aid the healthcare provider in
vision changes to blindness. Retinopathy is particularly providing optimal treatment for patients with
serious in patients who present with diabetes mellitus hypertension.
(DM) as a comorbid condition with HTN.
Hypertension (HTN) is defined as the consistent elevation of
The importance of treating this disorder in its early systemic arterial blood pressure. When most people use the
stage cannot be overstated. The long-term damage to target word hypertension, they are referring to systemic HTN, that
organs caused by HTN will become irreversible if the dis- which is measured routinely by a conventional blood pres-
ease is allowed to progress unchecked. This is especially sure cuff on the upper arm over the brachial artery. Systemic
critical in people with DM and those with chronic kidney HTN is a general measurement of arterial blood pressure in
disease (CKD), as these patients are particularly suscepti- the body. Localized HTN may also occur. For example,
ble to the long-term consequences of HTN. patients with cirrhosis of the liver often develop portal HTN,
which occurs in the portal vein and its branches serving the
Nonpharmacologic Management liver. Pulmonary HTN occurs in the pulmonary artery and its
of Hypertension branches and is most often observed in patients with left-
sided HF. These localized types of HTN respond to many of
34.2 Therapeutic lifestyle changes can the same antihypertensive drugs used for systemic HTN.
reduce blood pressure and lessen the need
for antihypertensive medications. To develop guidelines for treatment, many attempts have
been made to define HTN and to determine when medical
When a patient is first diagnosed with HTN, a comprehen- intervention is beneficial in reducing mortality due to cardio-
sive medical history is necessary to determine if the disease vascular disease. In 2003, the National High Blood Pressure
can be controlled by nonpharmacologic means. Therapeu- Education Program Coordinating Committee of the National
tic lifestyle changes should be recommended for all patients Heart, Lung, and Blood Institute at the National Institutes of
with HTN or at risk for the development of HTN. Of great Health issued The Seventh Report of the Joint National Committee
importance is maintaining optimal weight, because obesity on Prevention, Detection, Evaluation, and Treatment of High Blood
is closely associated with hyperlipidemia and HTN. A 5- to Pressure (JNC-7), which became the standard for treating HTN
9-kg (11- to 20-lb) weight loss often produces a measurable for the following decade. The JNC-7 defined HTN as a sus-
decrease in blood pressure, even in patients who are obese. tained systolic blood pressure of greater than 140 mmHg or
Combining a medically supervised weight loss program diastolic pressure of greater than 90 to 99 mmHg.
with proper nutrition can delay the progression to HTN.
In 2013, the Eighth Joint National Committee (JNC-8)
In some cases, implementing positive lifestyle changes significantly revised the HTN guidelines, based on newer
may eliminate the need for pharmacotherapy altogether. research (James et al., 2014). The JNC-8 committee kept the
Even if medication is required to manage the HTN, positive same definition of hypertension as JNC-7: 140/90 mmHg.
lifestyle changes may allow dosages to be minimized, thus The primary difference is that research has shown that not
lowering the potential for drug adverse effects. The nurse
Chapter 34 Pharmacotherapy of Hypertension 585
CONNECTIONS: Complementary and Alternative Therapies
Grape Seed Extract
Description flavonoids, and linoleic acid. Grape skins contain resveratrol,
another antioxidant that is being studied for its anti-inflammatory
Grape seed extract is obtained from the seeds of grapes that are effects.
usually used in the process of winemaking.
History and Claims Evidence
Grapes and grape seeds have been used for medicinal purposes Thousands of studies have been conducted on the polyphenols
for thousands of years. The primary use of the extract has been contained in this supplement. Grape seed extract has antioxi-
to treat cardiovascular conditions such as venous insufficiency dant properties (University of Maryland Medical Center, 2015). In
and to generally improve circulation. Some claim that it improves general, antioxidants improve wound healing and repair cellular
wound healing and reduces inflammation. The drug is also being injury. Preliminary evidence suggests that grape seed extract
examined for its effects on Alzheimer’s disease. may have some benefit in repairing blood vessel damage that
could lead to atherosclerosis and HTN. It is also being studied in
Standardization the treatment of Alzheimer’s disease and in hereditary hemo-
chromatosis (National Center for Complementary and Integrative
Grape seeds and skins contain antioxidant oligomeric proantho- Health, 2016). Controlled, long-term studies on the effects of
cyanidins (OPCs). The grape seeds are crushed and placed into grape seed extracts on HTN have not been conducted. It has
tablet, capsule, or liquid forms. Typical doses are 50 to 300 mg/ few adverse effects. Caution should be used if taking anticoagu-
day. Standardization is based on percentage of polyphenols. lant drugs because increased bleeding may result.
The seeds also contain a high concentration of vitamin E,
all people with a blood pressure higher than 140/90 mmHg or angiotensin receptor blockers (ARBs). Blacks without
need pharmacotherapy. For example, it is now recom- CKD are more effectively treated with thiazide diuretics
mended that patients over age 60 who do not have CKD or either alone or in combination with CCBs. The therapy for
diabetes should not receive pharmacotherapy until the all patients with CKD is the same. These recommendations
150/90 mmHg threshold. Furthermore, the classes of medi- are summarized in Table 34.1.
cations recommended as first-line therapy changed in JNC-8:
Beta-adrenergic blockers are no longer considered first-line Pharmacotherapy of Hypertension
drugs, except for patients with angina.
34.4 The choice of antihypertensive medication
The latest guideline, published in 2017 by the Ameri- is determined by the degree of hypertension and
can College of Cardiology and the American Heart Associ- the presence of other medical conditions.
ation lowered the cut-off value that had previously defined
HTN (Whelton et al., 2017). The new guideline for Stage 1 The goal of antihypertensive therapy is to reduce the mor-
HTN is 130–139/80–89. It is estimated that the lower bidity and mortality associated with chronic HTN.
threshold will increase the percentage of individuals diag- Research has confirmed that keeping blood pressure
nosed with HTN from 31% to 48% of the population. within normal limits reduces the risk of hypertension-
related target-organ damage.
In the past decade, research has determined that there
are racial differences in response to antihypertensive medi- The pharmacologic management of HTN is individu-
cations. To account for these differences, the JNC-8 guide- alized to the patient’s risk factors, comorbid medical condi-
lines made a distinction between drugs used for Black and tions, and degree of blood pressure elevation. Patient
non-Black patients. First-line drugs for non-Blacks without responses to antihypertensive medications vary widely
CKD include thiazide diuretics, calcium channel blockers because of the many complex genetic and environmental
(CCBs), angiotensin-converting enzyme (ACE) inhibitors, factors affecting blood pressure.
Table 34.1 Recommendations for Treating Hypertension
FIRST-LINE DRUGS (ALONE OR IN COMBINATION)
Group Blood Pressure Goal Non-Black Black
Age 60 or greater without DM or CKD Less than150/90 mmHg Thiazide diuretic, ACEI, ARB, or CCB Thiazide diuretic or CCB
Age 59 or lower without DM or CKD Less than140/90 mmHg Thiazide diuretic, ACEI, ARB, or CCB Thiazide diuretic or CCB
All ages with DM present (no CKD) Less than140/90 mmHg Thiazide diuretic, ACEI, ARB, or CCB Thiazide diuretic or CCB
All ages with CKD present (with or without DM) Less than140/90 mmHg ACEI or ARB ACEI or ARB
DM = diabetes mellitus; CKD = chronic kidney disease; ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; CCB = calcium channel blocker.
586 Unit 5 Pharmacology of the Cardiovascular System
Pharmacotherapy Illustrated 34.1
Mechanism of Action of Antihypertensive Drugs
Alpha2 agonists
Decrease sympathetic
impulses from the CNS to
the heart and arterioles,
causing vasodilation
Arterioles
Sympathetic a2 Alpha1 blockers
nervous system Inhibit sympathetic
2 activation in
Beta blockers b1 a1 2 arterioles, causing
vasodilation
Decrease the heart 2
Direct vasodilators
Ca21 Act on the smooth
muscle of arterioles,
causing vasodilation
rate and myocardial
contractility,
reducing cardiac 2 Calcium channel
output
2 blockers
Block calcium ion
Heart channels in arterial
smooth muscle,
causing
vasodilation
Angiotensin II Angiotensin
receptor blockers
Renin Prevent angiotensin
II from reaching its
receptors, causing
vasodilation
Kidney
Diuretics ACE inhibitors
Increase urine output and Block formation of angiotensin II, causing
decrease fluid volume vasodilation, and block aldosterone
secretion, decreasing fluid volume
– = Inhibitory Effect
causing vasodilation
Eleven different drug classes are used to treat HTN, as Drugs for Initial Hypertension
shown in Table 34.2. Each class has specific benefits and Therapy
characteristic adverse effects. The mechanisms of action of
the major classes of antihypertensive drugs are summarized The JNC-7 report recommended thiazide diuretics as initial
in Pharmacotherapy Illustrated 34.1. Although many effec- drugs for the management of mild to moderate HTN.
tive drugs are available, and the data supporting the benefits Although the thiazides are still preferred by some healthcare
of therapy are strong, HTN remains a challenging disorder providers, the JNC-8 expanded this recommendation to also
to treat successfully. Choice of therapy is often based on the include ACE inhibitors, ARBs, or CCBs for most patients.
clinician’s experience. Although antihypertensive treatment Research has clearly demonstrated that these four primary
varies, several principles guide pharmacotherapy. drug classes reduce HTN-related morbidity and mortality.
Chapter 34 Pharmacotherapy of Hypertension 587
Table 34.2 Drug Classes for Hypertension Table 34.3 Selected Combination Medications
Type Class for Hypertension
First-line drugs Angiotensin-converting enzyme (ACE) inhibitors Thiazide Diuretic with ACE Inhibitor
Second-line drugs Angiotensin receptor blockers (ARBs)
Calcium channel blockers (CCBs) Accuretic HCTZ and quinapril
Thiazide diuretics
Lotensin HCT HCTZ and benazepril
Alpha1-adrenergic blockers
Alpha2-adrenergic agonists Vaseretic HCTZ and enalapril
Beta-adrenergic blockers
Centrally acting alpha and beta blockers Zestoretic HCTZ and lisinopril
Direct-acting vasodilators
Direct renin inhibitors Thiazide Diuretic with Angiotensin II Blocker
Peripherally acting adrenergic neuron blockers
Atacand HCT HCTZ and candesartan
Avalide HCTZ and irbesartan
Benicar HCT HCTZ and olmesartan
In most cases, low doses of an initial drug are pre- Diovan HCT HCTZ and valsartan
scribed and the patient is reevaluated after an appropriate
time period. As therapy continues, dosage is adjusted to Edarbyclor chlorthalidone and azilsartan
maintain optimal blood pressure.
Hyzaar HCTZ and losartan
Adding Drugs to the
Antihypertensive Regimen Thiazide Diuretic with Autonomic Drug
If the patient does not respond to the initial medication, a Corzide HCTZ with bendroflumethiazide and nadolol (beta blocker)
drug from a different antihypertensive class may be added
to the regimen. Prescribing two antihypertensives concur- Inderide HCTZ and propranolol (beta blocker)
rently results in additive or synergistic blood pressure
reduction and is common practice when managing resis- Lopressor HCTZ and metoprolol (beta blocker)
tant HTN. The use of two drugs allows lower doses, HCT
resulting in fewer adverse effects and better patient adher-
ence. Drug manufacturers sometimes combine two drugs Minizide polythiazide and prazosin (alpha blocker)
into a single pill or capsule for dosing convenience. The
majority of these combinations include a thiazide diuretic, Tenoretic chlorthalidone and atenolol (beta blocker)
usually hydrochlorothiazide, sometimes abbreviated as
HCTZ, combined with an ACE inhibitor or ARB. ACE Timolide HCTZ and timolol (beta blocker)
inhibitors and ARBs are not used in combination with
each other because they act by very similar mechanisms. Ziac HCTZ and bisoprolol (beta blocker)
Selected combination antihypertensives are shown in
Table 34.3. Thiazide Diuretic with Potassium-Sparing Diuretic
Certain antihypertensive classes cause a higher inci- Aldactazide HCTZ and spironolactone
dence of adverse effects and are generally prescribed when
drugs from the four primary classes do not produce a satis- Dyazide HCTZ and triamterene
factory response. In some cases, research studies have not
demonstrated a firm link between drug use and lowered Other Combinations
morbidity or mortality. The alternative antihypertensive
drug classes include the following: Amturnide HCTZ with amlodipine (CCB) and aliskiren (renin inhibitor)
• Alpha1-adrenergic antagonists Apresazide HCTZ and hydralazine (direct vasodilator)
• Alpha2-adrenergic agonists
• Beta-adrenergic antagonists Azor olmesartan and amlodipine
• Direct-acting vasodilators
• Peripheral adrenergic antagonists. Byvalson valsartan and nebivolol
Enhancing Patient Adherence Edarbyclor azilsartan and chlorthalidone
Because chronic HTN may produce no identifiable symp- Exforge valsartan and amlodipine
toms for as long as 10 to 20 years, many people are not
Lexxel enalapril and felodipine (CCB)
Lotrel benazepril and amlodipine
Prestalia perindopril and amlodipine
Tarka trandolapril and verapamil (CCB)
Tekturna HCT HCTZ and aliskiren
Tribenzor HCTZ with olmesartan and amlodipine
aware of their condition. Convincing patients to change
established lifestyle habits, spend money on medication,
and take drugs on a regular basis when they are feeling
healthy can be a challenging task for the nurse. Patients
with limited income or who do not have health insurance
are at high risk for not purchasing the drugs after receiving
a prescription. The prescriber should consider generic
forms of these drugs to reduce costs and increase
adherence.
588 Unit 5 Pharmacology of the Cardiovascular System
Further reducing adherence to the regimen is the Drug Classes for Hypertension
occurrence of adverse drug effects. Some of the antihyper-
tensive drugs cause embarrassing adverse effects such as 34.5 Diuretics are often preferred drugs for
impotence, which may go unreported. Others cause fatigue treating mild to moderate hypertension.
and generally make patients feel sicker than they were
before therapy was initiated. The nurse should teach the Diuretics were the first class of medications used to treat
patient the importance of treating the disease to avoid seri- HTN in the 1950s. Despite the many advances in drug
ous long-term consequences. Furthermore, the nurse therapy, diuretics are still considered first-line drugs for
should teach patients to report adverse effects so that dos- this disease because they are very effective at controlling
age can be adjusted, or the drug changed, so the treatment mild to moderate HTN with few serious adverse effects.
can continue without interruption. Simple adjustments to Although sometimes used as monotherapy, diuretics are
the dosage or changing the selected drug can often elimi- frequently prescribed with other antihypertensive medica-
nate the causes of nonadherence. tions to enhance their effectiveness. Because this class of
drugs was presented in detail in Chapter 32, this section is
Antihypertensives in African a summary of their application to the treatment of HTN.
Americans
Although dozens of diuretics are available for the
The incidence of HTN is significantly higher in African Amer- treatment of HTN, all produce a similar result: the reduc-
icans than in other ethnic groups. As expected from this high tion of blood volume through the urinary excretion of
incidence, African Americans experience greater target-organ water and electrolytes. Reducing blood volume places
damage than other populations. In an effort to reduce the less pressure on the arterial walls, thereby decreasing
high morbidity and mortality risks, aggressive antihyperten- peripheral resistance and lowering systemic blood pres-
sive therapy may be necessary to overcome resistant HTN. sure. The mechanism by which diuretics increase the
excretion of water and electrolytes, specifically where and
Some research studies have suggested that certain how the kidney is affected, differs among the various
antihypertensive drug classes are less effective in African classes of diuretics.
Americans. Monotherapy with ACE inhibitors, ARBs, or
beta-adrenergic antagonists does not reduce blood pres- Whenever a medication changes urine flow or compo-
sure as much in African Americans compared to other eth- sition, dehydration and electrolyte depletion are possible.
nic groups. Thiazide diuretics and CCBs seem to provide Dehydration may manifest as increased thirst or poor skin
the greatest blood pressure reduction in this population. turgor. Excessive sodium loss (hyponatremia) is a concern
The JNC-8 report recommends initiating therapy with two for all diuretics. Potassium loss (hypokalemia) is of particu-
drugs to ensure an adequate response. lar concern for loop and thiazide diuretics. The potassium-
sparing diuretics such as triamterene (Dyrenium) have less
tendency to cause hypokalemia.
CONNECTIONS: Community-Oriented Practice
Self-Monitoring Blood Pressure for Better Control
With the availability of small devices to self-monitor blood pres- The USPSTF recommendation for self-monitoring blood
sure that are easily used outside of the healthcare provider’s pressure included the use of ambulatory or home blood pressure
office setting, better blood pressure control may be achieved. monitoring. Ambulatory monitoring takes place throughout the
The U.S. Preventive Services Task Force (USPSTF, 2016) recom- day and night, and readings are commonly taken every 15 to
mends that ambulatory blood pressure monitoring and home 30 minutes. Home monitoring may be accomplished through
monitoring may be the best methods for detecting HTN, above brachial artery or wrist devices, although wrist readings may be
and beyond a single value obtained in the healthcare provider’s less accurate. Recommended use may be two readings each in
office. Values obtained in the provider’s office may be affected by the morning and evening for up to 7 consecutive days (Shimbo
“white coat syndrome,” that is, a higher than usual reading due to et al., 2015). Cost, adequate calibration of the device, and the
the stress or anxiety of the visit. It is estimated that up to 30% of need for further information about the timing of the blood pres-
the population may experience white coat syndrome (Piper et al., sure measurement (e.g., at rest, after exercise) are also impor-
2015). A corollary, “masked hypertension,” where blood pressure tant items to consider (Cohen & Townsend, 2015). Patient use of
appears normal in a provider’s office but is higher throughout the the devices allows for a collaborative approach to treatment and,
day, is also estimated to occur in up to 30% of patients (Shimbo, combined with office-based measurements, a fuller assessment
Abdalla, Falzon, Townsend, & Muntner, 2015). Clearly, accurate of blood pressure fluctuations is possible, which allows the pro-
blood pressure readings are necessary to treat HTN and to avoid vider to make better decisions about drug therapy (Campos-
unnecessary treatment (Piper et al., 2015). Outcalt, 2016; Goldstein, Zullig, Bosworth, & Oddone, 2016).
Chapter 34 Pharmacotherapy of Hypertension 589
Thiazide and thiazide-like diuretics: Thiazide and diuretic in widespread use, is presented as a prototype
thiazide-like diuretics have been the mainstay for the phar- drug in Chapter 32. In addition to furosemide, other loop
macotherapy of HTN for decades. The thiazide diuretics diuretics indicated for HTN include bumetanide (Bumex),
are inexpensive, and most are available in generic formula- ethacrynic acid (Edecrin), and torsemide (Demadex).
tions. They are safe drugs, with excessive urinary potas-
sium loss being the primary adverse effect. Because CONNECTION Checkpoint 34.1
hypokalemia can induce serious dysrhythmias in suscepti-
ble patients, regular laboratory monitoring of serum potas- From what you learned in Chapter 32, why must the thiazide diuretics be
sium is necessary. Patients should increase their amount of used with great caution in patients taking digoxin (Lanoxin)? Answers
dietary potassium, and potassium supplements may be to Connection Checkpoint questions are available on the faculty resources
prescribed. These diuretics may also cause hyperglycemia; site. Please consult with your instructor.
therefore, blood glucose levels should be monitored in
patients with diabetes. Because thiazides may increase 34.6 Calcium channel blockers have emerged as
blood lipids, these drugs should be used cautiously in important drugs in the treatment of hypertension.
patients with existing hyperlipidemia. Hydrochlorothia-
zide, or HCTZ (Microzide), is featured as the prototype Calcium channel blockers (CCBs) are widely used in the
drug in this class in Chapter 32. In addition to HCTZ, thia- treatment of HTN, angina pectoris, and dysrhythmias, as
zides indicated for HTN include chlorothiazide (Diuril), presented in Chapter 30. This section summarizes their
chlorthalidone (Hygroton), indapamide (Lozol), methyclo- application to the treatment of HTN.
thiazide (Enduron), and metolazone (Zaroxolyn).
CCBs exert beneficial effects on the heart and blood ves-
Potassium-sparing diuretics: Although potassium- sels by blocking calcium ion channels in cardiac and arterio-
sparing diuretics such as spironolactone (Aldactone) and lar smooth muscle. The flow of calcium ions into muscle cells
triamterene (Dyrenium) produce only a modest diuresis, is inhibited, limiting the degree of muscular contraction. At
their primary advantage is they do not cause potassium low doses, CCBs relax arterial smooth muscle, thus decreas-
depletion. They are especially beneficial when the patient is ing peripheral resistance and lowering blood pressure. Some
at risk of developing hypokalemia due to a medical condi- CCBs such as nifedipine (Adalat CC, Procardia XL) are selec-
tion or the use of thiazide or loop diuretics. The primary tive for arterioles, whereas others such as verapamil (Calan,
concern when using potassium-sparing diuretics is the pos- Isoptin, Verelan) affect channels in both arterioles and the
sibility of retaining too much potassium, which can cause myocardium. CCBs vary in potency and in the frequency and
serious dysrhythmias. Patients with diabetes and those types of adverse effects produced. Nifedipine and verapamil
with CKD are particularly susceptible to hyperkalemia. are highlighted as drug prototypes in Chapter 30.
Patients should be instructed to avoid excess potassium in
their diet, including salt substitutes containing KCl, and Due to their potent vasodilating effects, CCBs can
not to use potassium supplements during therapy. Concur- cause reflex tachycardia, especially with those CCBs that
rent use with an ACE inhibitor or ARB significantly are selective for arterioles. Because CCBs can slow myocar-
increases the potential for development of hyperkalemia. dial conduction, they are contraindicated in patients with
Spironolactone is presented as a prototype drug for this certain types of heart conditions such as sick sinus syn-
class in Chapter 32. In addition to spironolactone and tri- drome or third-degree atrioventricular (AV) block without
amterene, other potassium-sparing diuretics indicated for the presence of a pacemaker. The CCBs that reduce myo-
HTN are amiloride (Midamor) and eplerenone (Inspra). cardial contractility can worsen HF.
Loop (high-ceiling) diuretics: The loop diuretics such CCBs are usually not used as monotherapy for chronic
as furosemide (Lasix) cause greater diuresis and have the HTN. They are, however, useful in combination therapy for
potential to produce a higher reduction in blood pressure treating certain populations such as older adults and Afri-
than the thiazides or potassium-sparing diuretics. Although can Americans who are sometimes less responsive to drugs
this makes them very effective at reducing blood pressure, in other antihypertensive classes. In addition to nifedipine
they are not ideal drugs for maintenance therapy. The risk and verapamil, other CCBs indicated for HTN include
of adverse effects such as hypokalemia and dehydration is amlodipine (Norvasc), clevidipine (Cleviprex), diltiazem
great because of their ability to remove large amounts of (Cardizem, Dilacor, others), felodipine, isradipine
fluid from the body in a short time period. Loop diuretics (DynaCirc), nicardipine (Cardene), and nisoldipine (Sular).
are ototoxic, an effect more likely to occur in patients with
CKD or when high doses are administered. Because of their CONNECTION Checkpoint 34.2
greater toxicity, loop diuretics are sometimes reserved for
patients with resistant HTN. Furosemide, the only loop Verapamil and nifedipine are both calcium channel blockers used
for HTN. From what you learned in Chapter 30, why would a beta
blocker be used concurrently with nifedipine but be contraindicated
with verapamil? Answers to Connection Checkpoint questions are avail-
able on the faculty resources site. Please consult with your instructor.
590 Unit 5 Pharmacology of the Cardiovascular System
34.7 Blocking the renin-angiotensin-aldosterone are often combined with drugs from other classes in the
system leads to a decrease in blood pressure and management of HTN. A drug prototype feature for losar-
improved kidney function. tan (Cozaar) is included in Chapter 31. Other ARBs indi-
cated for HTN include candesartan (Atacand), eprosartan
As discussed in Chapter 31, the renin-angiotensin-aldoste- (Teveten), irbesartan (Avapro), olmesartan (Benicar),
rone system (RAAS) is one of the primary homeostatic telmisartan (Micardis), and valsartan (Diovan).
mechanisms controlling blood pressure and fluid balance.
Drugs inhibiting the RAAS are widely used in the treatment Aliskiren (Tekturna) was the first in a new class of anti-
of cardiovascular disease. Clinical research suggests ACE hypertensives called direct renin inhibitors approved for
inhibitors are as effective as the diuretics in reducing HTN- HTN. They act by interfering with part of the RAAS sys-
related morbidity and mortality. The following section sum- tem. The combination of aliskiren with HCTZ (Tekturna
marizes their applications to HTN pharmacotherapy. ACT) is also approved for treating HTN. The most com-
mon adverse effects of aliskiren are diarrhea, cough, flulike
Angiotensin-converting enzyme (ACE) inhibitors: symptoms, and rash. The direct renin inhibitors are not
Angiotensin-converting enzyme (ACE) inhibitors block the considered first-line medications for HTN.
formation of angiotensin II, decreasing blood pressure
through two mechanisms. First, ACE inhibitors block 34.8 Adrenergic antagonists are commonly used
the intense vasoconstriction of arterioles caused by to treat hypertension.
angiotensin II, which decreases blood pressure due to dimin-
ished peripheral resistance. Second, these drugs block the The adrenergic antagonists, or blockers, are used for a wide
effects of angiotensin II on the secretion of aldosterone, variety of cardiovascular disorders, including HTN, angina
which lowers blood pressure by decreasing blood volume. pectoris, dysrhythmias, and MI prophylaxis. Blocking
Through their inhibition of aldosterone secretion, ACE inhib- adrenergic receptors in the sympathetic nervous system has
itors enhance the effects of the thiazide diuretics; thus drugs a number of beneficial effects on the heart and vessels. For
from these two classes may be used concurrently in the man- example, by blocking the “fight-or-flight” responses, heart
agement of HTN. Lisinopril (Prinivil, Zestril) is the proto- rate slows, blood pressure declines, and the bronchi dilate.
type drug for the ACE inhibitors in Chapter 31. Other ACE
inhibitors indicated for HTN include benazepril (Lotensin), Adrenergic blockers affect the sympathetic division
captopril (Capoten), enalapril (Vasotec), fosinopril (Mono- through a number of distinct mechanisms, although all
pril), moexipril (Univasc), perindopril (Aceon), quinapril have in common the effect of lowering blood pressure.
(Accupril), ramipril (Altace), and trandolapril (Mavik). These mechanisms include the following:
Adverse effects of ACE inhibitors are usually minor • Blockade of beta1-adrenergic receptors
and include persistent cough and orthostatic hypotension, • Blockade of alpha1-adrenergic receptors
particularly following the first few doses of the drug. • Nonselective blockade of both alpha1- and beta-
Hyperkalemia may occur and can be a major concern for
patients with diabetes, those with CKD, and patients tak- adrenergic receptors
ing potassium-sparing diuretics. Though rare, the most • Stimulation of centrally acting alpha2-adrenergic
serious adverse effect of ACE inhibitors is the development
of angioedema. When it does occur, angioedema most receptors in the brainstem
often develops within days after beginning ACE inhibitor • Blockade of peripheral adrenergic neurons.
therapy. Cough and angioedema arise more frequently in
African Americans than in other ethnic groups. The earliest drugs for HTN were nonselective drugs
that blocked nerve transmission at the ganglia or at both
Angiotensin receptor blockers (ARBS) and direct alpha- and beta-adrenergic receptors. Although the nonse-
renin inhibitors: The ARBs afford a second method for lective medications revolutionized the treatment of HTN,
altering the RAAS pathway. ARBs such as losartan they caused a high incidence of adverse effects. These drugs
(Cozaar) block receptors for angiotensin II in arteriolar are rarely used today because selective agents are more effi-
smooth muscle and in the adrenal gland, thus causing cacious and better tolerated by patients. Of the five sub-
blood pressure to fall. Their actions are similar to those of classes of adrenergic antagonists, the beta-adrenergic
the ACE inhibitors. blockers are the most widely used group. All of the adrener-
gic inhibitors are considered second-line drugs for HTN.
Angiotensin II receptor blockers have the lowest inci-
dence of serious adverse effects of any of the antihyperten- Beta-adrenergic antagonists: In this section, the discus-
sive classes. Most ARB adverse effects are related to sion of beta-adrenergic antagonists is limited to their use
hypotension. Unlike the ACE inhibitors, they do not cause in treating HTN. The student should refer to Chapter 16
cough, and angioedema is rare. Medications in this class for a detailed discussion of the basic pharmacology of this
drug class. Other important therapeutic applications of the
beta blockers include angina pectoris and MI, dysrhyth-
mias, HF, and migraines.
Chapter 34 Pharmacotherapy of Hypertension 591
Beta-adrenergic antagonists may be cardioselective The alpha1-adrenergic antagonists lower blood pres-
(beta1) or nonspecific (beta1 and beta2). Cardioselective beta sure directly by blocking sympathetic receptors in arteri-
blockers decrease heart rate, myocardial contractility, and oles, causing the vessels to dilate. They also dilate veins,
cardiac conduction velocity. Nonspecific beta blockers pro- which lowers blood pressure indirectly by decreasing
duce the same effects but also act on the respiratory system venous return to the heart and reducing cardiac output.
to cause bronchoconstriction. Decreasing the heart rate and The alpha blockers are not first-line drugs for HTN because
contractility also reduces cardiac output and lowers sys- long-term clinical trials have shown them to be less effec-
temic blood pressure. Some of their antihypertensive effect tive at reducing the incidence of serious HTN-related car-
is also caused by the blockade of beta1 receptors in the jux- diovascular events than diuretics. When used to treat HTN,
taglomerular apparatus, which inhibits the secretion of the alpha blockers are used concurrently with other classes
renin and the formation of angiotensin II. Although they of antihypertensives, such as diuretics.
are not recommended by the JNC-8 report as first-line
drugs for HTN, the beta-adrenergic antagonists are still The alpha1-adrenergic blockers may cause significant
widely used for this condition. orthostatic hypotension. It is particularly serious with the ini-
tial doses of these medications and is referred to as the
At low doses, beta blockers are well tolerated and serious first-dose phenomenon, although orthostatic hypotension
adverse events are uncommon. As the dosage is increased, may persist throughout treatment. In severe cases, syncope
however, adverse effects can become numerous and poten- can occur. Blood pressure should be assessed regularly during
tially serious in certain patients. Because nonselective beta therapy to maintain patient safety. Other common adverse
blockers will slow the heart rate and cause bronchoconstric- effects include weakness, dizziness, dry mouth, headache,
tion, they should be used with caution in patients with and gastrointestinal (GI) complaints such as nausea and vom-
asthma or HF. Heart rate and rhythm should be regularly iting. Less common, though sometimes a major cause for non-
monitored during beta-blocker therapy. Many patients report adherence, are adverse effects on male sexual function that
fatigue and activity intolerance at higher doses because the include decreased libido and erectile dysfunction.
reduction in heart rate causes the heart to become less respon-
sive to exertion. When discontinuing a beta blocker, drug Nonselective alpha1- and beta-adrenergic antago-
doses should be tapered over a several week period. Abrupt nists: Carvedilol (Coreg) and labetalol (Trandate) are
cessation of beta-blocker therapy can result in rebound HTN, unique in that they block both alpha1- and beta-adrenergic
angina, MI, and even death in patients with CAD. receptors. These drugs act by a combination of effects:
They reduce cardiac output, inhibit renin secretion, and
Prototype features for beta-adrenergic antagonists can block vasoconstriction of arterioles and veins. As expected,
be found for propranolol (Inderal, InnoPran XL) and meto- their adverse effects are a combination of alpha and beta
prolol (Lopressor, Toprol XL) in Chapter 16, atenolol blockade and include orthostatic hypotension, bradycar-
(Tenormin) in Chapter 35, and timolol in Chapter 74. In dia, and bronchoconstriction. The applications of
addition to atenolol, metoprolol, propranolol, and timolol, carvedilol in treating HF are presented in Chapter 36.
other beta blockers approved for HTN include betaxolol
(Kerlone), bisoprolol (Zebeta), nadolol (Corgard), and Alpha2-adrenergic agonists: If an alpha antagonist
nebivolol (Bystolic). such as prazosin lowers blood pressure, it might be pre-
dicted that the administration of an alpha2-adrenergic ago-
CONNECTION Checkpoint 34.3 nist would raise blood pressure. This is not the case. The
answer to this contradiction lies in the different locations
From what you learned in Chapter 16, should a patient with hyper- of the two subtypes of alpha receptors. The alpha1 recep-
tension and asthma receive a selective beta1 blocker or a nonse- tors blocked by prazosin lie in the peripheral nervous sys-
lective beta blocker for HTN? Answers to Connection Checkpoint tem (PNS) at arterioles. The alpha2 receptors reside in the
questions are available on the faculty resources site. Please consult with central nervous system (CNS).
your instructor.
When alpha2 receptors are activated, the outflow of
Alpha1-adrenergic antagonists: The alpha1-adrenergic sympathetic nerve impulses from the CNS to the heart and
antagonists have several clinical applications, which were arterioles is inhibited. In effect, this produces the same
presented in Chapter 16. In addition to their use in HTN, responses as inhibition of the alpha1 receptor: slowing the
they are prescribed for benign prostatic hyperplasia (BPH) heart rate and conduction velocity and dilating the arteri-
because their ability to relax smooth muscle in the prostate oles. Thus, activating alpha2 receptors (in the CNS) produces
and bladder neck reduces urethral resistance. A prototype similar actions as inhibiting alpha1 receptors (in the PNS).
drug feature for prazosin (Minipress) is included in
Chapter 16, and the use of tamsulosin (Flomax) in treating The centrally acting alpha2 agonists are used less fre-
BPH is discussed in Chapter 71. Terazosin is another quently than the alpha1 antagonists. The alpha2 agonists have
alpha1-adrenergic antagonist used for HTN. a tendency to cause excessive sedation, dizziness, and ortho-
static hypotension, which can be especially troublesome in
592 Unit 5 Pharmacology of the Cardiovascular System
older adults. Extended use results in sodium and water sedation, fatigue, drowsiness, and dizziness are common.
retention, which increases blood volume and counteracts the Transdermal clonidine produces fewer serious adverse
antihypertensive action of these drugs. Alpha2 agonists are effects, although the patches can cause skin irritation and
usually reserved for treating resistant HTN that cannot be itching. The patient should be warned not to abruptly dis-
managed by safer medications. The two drugs in this class continue the drug, as severe rebound HTN, agitation, ner-
are methyldopa (Aldomet) and clonidine (Catapres, Dura- vousness, and anxiety may result.
clon, Kapvay, Nexiclon XR).
Adrenergic neuron blockers: The adrenergic neuron-
Methyldopa is an older drug approved in 1962. Its only blocker class consists of two drugs that inhibit the synthesis
indication is HTN that has not responded adequately to or release of norepinephrine (NE) in sympathetic neurons.
safer antihypertensives. The drug is normally administered With less NE available to cross the synapse, sympathetic
by the oral (PO) route, although an intravenous (IV) form activity is diminished at both alpha- and beta-adrenergic
known as methyldopate is available for hypertensive crises. receptors. In effect, the actions of these drugs are the same
Compared to other antihypertensives given by the IV route, as the nonselective alpha1- and beta-adrenergic antagonists:
methyldopa has a relatively slow onset of action because it reduced heart rate and cardiac output (beta effects) com-
must first be metabolized inside neurons to an active metab- bined with dilation of arterioles (alpha effect).
olite, methyl norepinephrine. Methyldopa is sometimes
used to treat HTN occurring during pregnancy because it The adrenergic neuron blockers have mostly historical
maintains stable blood flow to the uterus, and its safety to interest, as they are rarely prescribed today due to the
the fetus has been demonstrated in long-term studies. availability of safer medications. Reserpine (Serpalan),
approved in 1952, was one of the earliest drugs used for
Because methyldopa is a centrally acting drug, CNS HTN. Unfortunately, reserpine can cause profound depres-
effects such as drowsiness, depression, headache, sedation, sion and sedation, and cardiovascular adverse effects such
and bizarre dreams are relatively common. Orthostatic as bradycardia and orthostatic hypotension can be severe.
hypotension may occur, but it is less severe than that pro- Reserpine is only prescribed when patients are unable to
duced by the alpha1 antagonists. Peripheral edema due to tolerate safer antihypertensives.
sodium retention may occur, which can be managed by
administration of a thiazide diuretic. A significant number Guanethidine (Ismelin) is also an adrenergic neuron–
of patients develop a positive Coombs’ test, which detects blocking drug. The limiting adverse effects of guanethidine
antibodies against the patient’s own red blood cells. are severe diarrhea and orthostatic hypotension, which
Because tolerance develops after 3 to 4 months of therapy, occur frequently and can be serious enough to cause syn-
a dosage increase may be required to manage HTN. This cope. Guanethidine is rarely prescribed due to the potential
drug is pregnancy category B. for serious adverse effects.
Approved in 1974, clonidine (Catapres, Duraclon, 34.9 Direct-acting vasodilators lower blood
Kapvay, Nexiclon XR) activates alpha2-adrenergic recep- pressure by relaxing arteriolar smooth muscle.
tors in the cardiovascular control centers in the brainstem.
The reduced sympathetic outflow causes vasodilation and The ability to cause vasodilation is a property shared by
slows the heart rate. As an antihypertensive, it is available many different classes of drugs, as shown earlier in Pharma-
as regular oral tablets, extended release tablets or suspen- cotherapy Illustrated 34.1. Most vasodilators are used to
sion (Nexiclon), or a transdermal patch (Catapres) that treat HTN, and some are also used for the pharmacotherapy
releases the drug at a constant rate over 7 days. A second of HF, angina pectoris, and MI. Some of the drugs presented
approved indication for clonidine (Duraclon) is intractable in previous sections of this chapter produce vasodilation
pain in patients with cancer that is not relieved by opiates. indirectly by affecting autonomic nerves or by influencing
Pain control is achieved by a continuous epidural infusion the renin-angiotensin-aldosterone pathway. The drugs pre-
of the drug. To assist in pain management, transdermal sented in this section affect the vascular smooth muscle
clonidine may be used to provide some degree of analgesia itself; thus, they are called direct vasodilators.
so that the dose of opiate can be reduced. An extended
release form of clonidine (Kapvay) is approved to treat Direct relaxation of arteriolar smooth muscle is an
attention-deficit/hyperactivity disorder. effective way to reduce blood pressure. Indeed, the direct
vasodilator sodium nitroprusside (Nitropress) is used in
Clonidine has many off-label indications. These hypertensive emergencies to lower blood pressure almost
include dysmenorrhea, menopausal flushing, migraine instantaneously. Unfortunately, the medications in this
prophylaxis, smoking cessation, opiate and benzodiaze- class have the potential to produce serious adverse effects.
pine withdrawal, and Tourette’s syndrome. In the pharmacotherapy of HTN, these drugs are generally
reserved for hypertensive emergencies and for HTN that
The most common adverse effect of clonidine is dry has not been successfully managed with medications from
mouth, which occurs in about 40% of the patients taking safer drug classes.
the drug. Like methyldopa, CNS adverse effects such as
Chapter 34 Pharmacotherapy of Hypertension 593
All direct vasodilators cause reflex tachycardia, a com- Hydralazine is also available by the intramuscular
pensatory increase in heart rate due to the sudden decrease (IM) and IV routes for hypertensive emergencies, espe-
in blood pressure. The baroreceptor reflex is an essential cially those associated with preeclampsia, although it is not
component of the normal physiologic control of blood a preferred drug for this indication. It is sometimes admin-
pressure. However, when reflex tachycardia occurs as the istered to patients with acute HF because the drug reduces
result of vasodilator drugs, the heart is forced to work the workload on the heart due to its antihypertensive
harder and the resultant blood pressure increase counter- action. ACE inhibitors have largely replaced hydralazine
acts the effect of the antihypertensive drug. Patients with for patients with HF. A fixed-dose combination therapy of
CAD may experience an acute angina attack due to the isosorbide dinitrate and hydralazine (BiDil) is available for
sudden increase in cardiac workload. Fortunately, reflex the treatment of HF in African American patients.
tachycardia can be prevented by administering a beta-
adrenergic blocker, such as propranolol (Inderal). Beta Mechanism of Action: By causing peripheral vaso-
blockers are often administered concurrently with direct dilation, hydralazine acts directly to relax arterial smooth
vasodilators for this reason. muscle. The decreased peripheral resistance is accompa-
nied by an increase in heart rate and cardiac output. The
A second potentially serious adverse effect of direct overall result is a reduction in afterload. Because the drug
vasodilator therapy is salt and water retention. The reduc- is selective for arterioles and does not cause dilation of
tion in blood pressure from the vasodilator causes a com- veins, orthostatic hypotension is not a major adverse effect.
pensatory increase in aldosterone secretion by the adrenal
gland. The increased aldosterone level signals the kidney Pharmacokinetics:
to retain more sodium and water. Blood volume increases,
thus raising blood pressure and canceling the antihyper- Route(s) PO, IM, IV
tensive action of the vasodilator. A diuretic may be admin-
istered concurrently with a direct vasodilator in order to Absorption Rapidly absorbed PO and well
prevent fluid retention.
absorbed IM
Other adverse effects are drug specific. Hydralazine can
induce a lupus-like syndrome characterized by myalgia, Distribution Widely distributed; crosses the
arthralgia, fever, and the presence of antinuclear antibodies.
Although rare, symptoms may persist for 6 months or lon- placenta and is secreted in breast
ger and antinuclear antibodies may be present for 9 years.
The occurrence of this lupus-like syndrome is more common milk; 87% bound to plasma
in Whites who are slow acetylators (see Chapter 11). Anti-
nuclear antibody titers should be determined prior to initiat- protein
ing therapy and periodically thereafter to identify the
development of this syndrome. Primary metabolism GI mucosa and liver; extensive
PROTOTYPE DRUG Hydralazine first-pass metabolism
Classification Therapeutic: Antihypertensive Primary excretion 90% renal, 10% feces
Pharmacologic: Direct vasodilator
Onset of action PO: 20–30 min; IM: 10–30 min;
Therapeutic Effects and Uses: In 1952, hydralazine
was one of the first oral antihypertensive medications mar- IV: 5–20 min
keted in the United States. It is most commonly adminis-
tered in tablet form for moderate to severe HTN, usually in Duration of action 3–8 h (PO); 1–4 h (IV)
combination with other antihypertensives. Apresazide is a
fixed-dose combination of hydralazine with HCTZ. When Adverse Effects: Hydralazine may cause several
given PO, hydralazine is administered 2 to 4 times per day, a dverse effects that have the potential to prompt discon-
usually with food because this increases its bioavailabil- tinuation of therapy. Headache, tachycardia, palpitations,
ity. Therapy is generally begun with low doses, which are flushing, nausea, and diarrhea are common but may
gradually increased until the desired therapeutic response r esolve as therapy progresses. Orthostatic hypotension,
is obtained. After several months of therapy, tolerance to fluid retention, and peripheral edema may also occur.
the drug develops and a dosage increase may be necessary. Patients who are slow acetylators and those with CKD or
Although it produces an effective reduction in blood pres- who are receiving high doses of hydralazine are suscepti-
sure, drugs in other antihypertensive classes have largely ble to experiencing a lupus-like syndrome. Symptoms may
replaced hydralazine. include rash, urticaria, myalgia, fever, chills, and fatigue.
Blood dyscrasias such as agranulocytosis and leukopenia
are rare, though potentially serious, adverse effects.
Contraindications/Precautions: Patients with lupus
should not receive hydralazine, as the drug can worsen
symptoms. The drug is contraindicated in patients with
cerebrovascular disease or rheumatic heart disease. P atients
should discontinue hydralazine gradually because abrupt
withdrawal may cause severe rebound HTN and anxiety.
Because it is excreted primarily by the kidneys, the drug
should be used with caution in patients with CKD. Caution
594 Unit 5 Pharmacology of the Cardiovascular System
must be used when administering hydralazine to patients baldness. The topical form of the drug is not absorbed into
who are known slow acetylators because plasma drug lev- the systemic circulation; thus Rogaine produces none of the
els will be significantly higher in these patients. Caution serious cardiovascular effects observed with Loniten.
should be used when treating patients with CAD, because
hydralazine can precipitate angina attacks and an acute MI. Management of Hypertensive
Emergency
Drug Interactions: Administering hydralazine with
other antihypertensives or monoamine oxidase inhibitors 34.10 Hypertensive crisis is a medical
(MAOIs) may cause severe hypotension. This includes emergency that is treated by the intravenous
all drug classes used as antihypertensives. Nonsteroidal administration of antihypertensive medications.
anti-inflammatory drugs (NSAIDs) may decrease the an-
tihypertensive action of hydralazine. Beta blockers are A hypertensive emergency (HTN-E), also called hyperten-
usually used concurrently with hydralazine to block reflex sive crisis, is defined as a diastolic pressure of greater than
tachycardia, and heart rate should be carefully monitored 120 mmHg, with evidence of target-organ system damage.
to avoid bradycardia. Hydralazine may produce false- HTN-E requires aggressive treatment, usually within min-
positive Coombs’ tests. Herbal/Food: Hawthorn should be utes to hours, to prevent further organ damage. A related
avoided because it may cause additive hypotensive effects. condition, hypertensive urgency, is when a patient pres-
ents with severe HTN but has no evidence of target-organ
Pregnancy: Category C. damage.
Treatment of Overdose: Treatment includes gastric Target-organ damage from extreme HTN most often
lavage, activated charcoal, and administration of a plasma occurs in the cardiovascular system, the kidneys, or the
volume expander to raise blood pressure. Tachycardia may CNS. In the cardiovascular system, the increased workload
require treatment with a beta blocker. on the heart leads to acute left HF with pulmonary edema,
sometimes accompanied by myocardial ischemia or infarc-
Nursing Responsibilities: Key nursing implica- tion. Chest pain and dyspnea are the most common symp-
tions for patients receiving hydralazine are included in the toms in patients with HTN-E. Renal function is diminished,
Nursing Practice Application for Patients Receiving Phar- as evidenced by oliguria, hematuria, and proteinuria.
macotherapy with Direct Vasodilators. Acute renal failure may occur, or preexisting CKD may
worsen. In the brain, thrombotic or hemorrhagic stroke
Drugs Similar to Hydralazine may occur. The capillaries in the brain become leaky, pro-
ducing hypertensive encephalopathy, with resulting head-
Other direct vasodilators used for HTN include minoxidil ache, paralysis, seizures, or coma. In addition, retinal
and nitroprusside. Nitroprusside is a drug for hyperten- hemorrhages and edema of the retina (papilledema) are
sive emergencies and is presented in Section 34.10. signs of severe HTN.
Minoxidil (Loniten): Minoxidil is a direct vasodilator The most common cause of HTN-E is untreated or
with profound vasodilation activity that is selective for poorly controlled essential HTN. In some cases, the patient
arterioles: It does not dilate veins. It is administered PO has abruptly discontinued use of the antihypertensive
for severe HTN that is unresponsive to drugs from other medication. There are, however, a large number of possible
classes. Because of its efficacy and the potential for serious secondary causes of HTN-E, including the following
effects on the cardiovascular system, initial doses are very conditions:
low, and the amount is increased gradually. It is a preg-
nancy category C drug. • Renovascular hypertension
• Pheochromocytoma
Minoxidil is considerably more toxic than hydralazine. • Cocaine use
The most serious adverse effects are cardiovascular in • Eclampsia or preeclampsia
nature, including reflex tachycardia and plasma volume • Head injuries
expansion due to sodium and water retention. Beta block- • Primary hyperaldosteronism
ers are usually administered concurrently to minimize • Coarctation of the aorta
tachycardia, and diuretics to prevent fluid retention. • Hyperthyroidism or thyroid storm.
Although rare, pericardial effusion has been reported with
minoxidil use. Minoxidil causes hypertrichosis, the elon- In the management of HTN-E, the therapeutic goal is
gation, thickening, and increased pigmentation of body to rapidly lower blood pressure. Care must be taken, how-
hair. This is normal and will reverse when the drug is dis- ever, to not decrease blood pressure too quickly because
continued. The drug’s effect on hair growth is used to the rapid and intense vasodilation can result in serious hypo-
patient’s advantage in Rogaine, a topical form of minoxidil perfusion of the cerebral, coronary, or renal vascular
used to stimulate hair growth in patients with male-pattern
Chapter 34 Pharmacotherapy of Hypertension 595
capillaries. This can cause ischemia or infarction, worsen- Mechanism of Action: Nitroprusside dilates both
ing target-organ damage to the brain, heart, kidneys, or arteries and veins; therefore, the hypotensive action of
retina. It is recommended that the pretreatment blood pres- nitroprusside is due to direct relaxation of arteriolar
sure be progressively reduced by 20% to 25%, over 30 to smooth muscle and to blood pooling in the veins. In most
60 minutes. Additional, gradual reductions are made over patients, heart rate is mildly increased, while cardiac out-
a 12- to 48-hour period until blood pressure is reduced to a put is decreased. In patients with severe left ventricular
value within the normal range. Parenteral antihyperten- hypertrophy, however, cardiac output may increase.
sives are preferred over PO medications due to their rapid
onset of action and because infusions offer more precise Pharmacokinetics: IV
control during the gradual pressure reduction. Route(s) N/A
Absorption Unknown
In patients with hypertensive urgencies, target-organ Distribution Metabolized to thiocyanates in
damage has not yet developed. These patients are treated Primary metabolism erythrocytes and other tissues
more conservatively by increasing the dose of their cur- Renal
rent antihypertensive drug, or by adding a second drug to Primary excretion 1–2 min
the regimen. Oral medications are used to lower blood Onset of action 1–10 min
pressure because these drugs are less toxic than paren- Duration of action
teral antihypertensives. Oral drugs with a relatively rapid
onset of action that may be used for hypertensive urgency Adverse Effects: Signs and symptoms of vasodilation
include clonidine (Catapres), captopril (Capoten), or such as hypotension, headache, dizziness, and flushing of
labetalol (Trandate). The patient should be monitored for the skin are expected adverse effects. With extended ther-
several hours, and doses may be repeated at frequent apy, thiocyanate toxicity may manifest. Thiocyanate poi-
intervals, as needed, to lower pressure to acceptable lev- soning is characterized by hypotension, lethargy, blurred
els. All patients with hypertensive urgency should receive vision, metabolic acidosis, faint heart sounds, and loss of
follow-up assessments after 1 to 3 days on the new consciousness. Irritation may occur at the infusion site.
regimen. Black Box Warning: Nitroprusside requires dilution prior
to infusion and is not suitable for direct injection. The drug
PROTOTYPE DRUG Nitroprusside Sodium can cause irreversible ischemic injury and death due to sig-
(Nitropress) nificant drops in blood pressure. Accumulation of cyanide
ion may occur.
Classification Therapeutic: Drug for hypertensive
emergency Contraindications/Precautions: Patients with
inadequate cerebral circulation or who have compensa-
Pharmacologic: Direct vasodilator tory HTN should not receive nitroprusside. Because the
kidneys excrete the toxic thiocyanate metabolite of the
Therapeutic Effects and Uses: Nitroprusside is a drug, patients with serious CKD should be treated cau-
first-line drug for patients with aggressive, life-threatening tiously. Nitroprusside is contraindicated in patients with
HTN because it has the ability to lower blood pressure high intracranial pressure because the drug may worsen
almost instantaneously upon IV administration. Indications this condition.
include hypertensive crisis, acute HF, and promotion of
controlled hypotension to reduce bleeding during surgery. Drug Interactions: Antihypertensive drugs, etha-
The drug has a short half-life, and the hypotensive effects nol, general anesthetics, and ganglionic blockers should
disappear approximately 3 minutes after the infusion is dis- be used with caution with nitroprusside because additive
continued. Unlike most direct vasodilators, nitroprusside hypotension could result. Sympathomimetics such as epi-
causes very little reflex tachycardia. Although discovered nephrine will block the antihypertensive actions of nitro-
in 1850, the drug was not approved by the U.S. Food and prusside. Dobutamine (Dobutrex) and nitroprusside are
Drug Administration (FDA) until 1974. sometimes administered concurrently because this inter-
action results in a beneficial synergistic increase in cardiac
Patients must be continuously monitored while receiv- output and decrease in pulmonary capillary wedge pres-
ing nitroprusside to prevent hypotension due to overtreat- sure. Herbal/Food: Hawthorn may cause additive hypo-
ment. Therapy is limited to 72 hours because the drug is tensive effects.
metabolized to toxic thiocyanate and cyanide compounds.
This is of special concern to patients with CKD who are Pregnancy: Category C.
unable to excrete the cyanide. If serum thiocyanate exceeds
12 mg/dL, the nitroprusside infusion should be discontin- Treatment of Overdose: Extreme hypotension may
ued. As a general rule, patients are switched from nitro- be treated with a vasopressor. Cyanide toxicity caused by
prusside to an oral antihypertensive as soon as blood
pressure has stabilized.
596 Unit 5 Pharmacology of the Cardiovascular System
the overdose may require the use of a cyanide antidote kit, hypertensive crisis. Diazoxide is a rapid-acting vasodilator
which contains amyl nitrate, sodium nitrite, and sodium that is no longer marketed for blood pressure control. An
thiosulfate. The purpose of these drugs is to convert toxic oral form of diazoxide (Proglycem) is available to treat vari-
cyanide into nontoxic thiocyanate. ous hypoglycemic states, usually caused by the presence of
excessive insulin (hyperinsulinism).
Nursing Responsibilities: Key nursing implications
for patients receiving nitroprusside are included in the PharmFACT
Nursing Practice Application for Patients Receiving Phar-
macotherapy with Direct Vasodilators. Hypertensive crisis is a common condition, affecting 1% of
the patients with primary HTN. The most common
Drugs Similar to Nitroprusside Sodium presentation, occurring in 25% of patients, is stroke. The
(Nitropress) 1-year survival rate for a patient presenting with a HTN crisis
has improved from only 20% prior to 1950 to more than 90%
Other vasodilators for HTN-E are shown in Table 34.4, which with current medical treatment (Hopkins, 2017).
summarizes their applications to the pharmacotherapy of
Table 34.4 Drugs for Hypertensive Emergency
Drug Class Applications
clevidipine (Cleviprex) Calcium channel blocker Onset of action is 2–4 min with a short duration, allowing for rapid blood pressure reduction
enalaprilat (Enalapril IV) ACE inhibitor
Onset of action is 15–30 min; useful in HTN-E associated with HF or high plasma levels of
esmolol (Brevibloc) Beta-adrenergic angiotensin II
antagonist
fenoldopam (Corlopam) Dopamine agonist Onset of action is 1–5 min; useful for patients with severe left ventricular dysfunction or with
peripheral vascular disease
hydralazine Direct vasodilator
Onset of action is 5 min; useful for patients with CKD because the drug increases renal
labetalol (Trandate) Alpha- and beta- blood flow
adrenergic antagonist
nicardipine (Cardene IV) Calcium channel blocker Onset of action is 5–20 min; useful in HTN-E due to eclampsia and preeclampsia because
it increases uterine blood flow
nitroprusside sodium (Nitropress) Direct vasodilator
phentolamine (Regitine) Alpha-adrenergic Onset of action is 2–5 min; reduces incidences of MI and death
antagonist
Onset of action is 1 min; rapid and effective for most HTN-E, with fewer adverse effects
than some other HTN-E drugs
Onset of action is 1 min; preferred drug for many HTN-E
Onset of action is 1–5 min; rarely used due to high incidence of reflex tachycardia and
myocardial ischemia; useful for HTN-E due to pheochromocytoma
CONNECTIONS: NURSING PRACTICE APPLICATION
Patients Receiving Pharmacotherapy with Direct Vasodilators
Assessment
Baseline assessment prior to administration:
• Obtain a complete health history: cardiovascular (including MI, HF), cerebrovascular and neurologic (including level of consciousness [LOC], history of
stroke, head injury, increased intracranial pressure), respiratory, and the possibility of autoimmune diseases, especially systemic lupus erythematosus.
Obtain a drug history including allergies, current prescription and over-the-counter drugs, and herbal preparations. Be alert to possible drug
interactions.
• Evaluate appropriate laboratory findings: electrolytes, especially sodium and potassium levels, hepatic and renal function studies, and lipid profiles.
• Obtain baseline weight, vital signs, pulse oximetry, breath and heart sounds, and cardiac monitoring (e.g., electrocardiogram [ECG], cardiac output).
Assess location and character of peripheral edema if present.
• 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., lowered blood pressure within established limits).
• Continue frequent and careful monitoring of vital signs, pulse oximetry, urinary and cardiac output, and daily weight, especially if IV administration is
used. Blood pressure and pulse must be monitored every 5 minutes or as ordered while on IV infusion of the drug. (Invasive monitoring, such as
arterial lines, is often used for this purpose.)
• Continue periodic monitoring of electrolytes, especially potassium.
• Continue frequent physical assessments, particularly neurologic, cardiac, and respiratory systems.
• Assess for and promptly report adverse effects: excessive hypotension, dysrhythmias, reflex tachycardia (from too rapid decrease in blood pressure or
significant hypotension), headache, decreased urinary output, peripheral edema, and priapism (prolonged erection in the absence of sexual
stimulation). Severe hypotension, seizures, dysrhythmias, or palpitations may signal drug toxicity and are immediately reported.
Chapter 34 Pharmacotherapy of Hypertension 597
CONNECTIONS: NURSING PRACTICE APPLICATION (continued)
Implementation
Interventions and (Rationales) Patient-Centered Care
Ensuring therapeutic effects: • To allay possible anxiety, teach the patient, family, or caregiver the
• Continue frequent assessments as above for therapeutic effects. IV rationale for all equipment used and the need for frequent monitoring.
infusion of vasodilators may be titrated frequently to achieve desired • Teach the patient, family, or caregiver how to monitor pulse and blood
effects. Vital signs, cardiac and urinary output, and daily weights should pressure as appropriate if the patient is on oral therapy at home.
remain within the limits set by the healthcare provider. (Pulse, blood Ensure proper use and functioning of any home equipment obtained.
pressure, and respiratory rate should be within normal limits or acceptable
parameters. An increase in weight of more than 1 kg [2 lb] per day may • Have the patient weigh self daily along with blood pressure and pulse
indicate excessive fluid gain, and may require judicious diuretic therapy.) measurements. Report a weight gain or loss of more than 1 kg (2 lb) in
a 24-h period.
Minimizing adverse effects: • Instruct the patient, family, or caregiver to report angina-like symptoms
• Continue to monitor vital signs frequently. Lifespan: Be particularly (e.g., chest, arm, back, or neck pain), palpitations, faintness, dizziness,
drowsiness, or headache.
cautious with older adults who are at increased risk for hypotension,
patients with a preexisting history of cardiac or cerebrovascular
ischemia, which may be worsened by decreased blood pressure,
patients with dehydration, and patients with lupus erythematosus.
Immediately notify the healthcare provider if the blood pressure or
pulse decrease beyond established parameters or if hypotension is
accompanied by reflex tachycardia. (Direct-acting vasodilators cause
significant vasodilation, resulting in the potential for dramatically and
rapidly lowered blood pressure accompanied by reflex tachycardia.
Reflex tachycardia may require treatment with beta-blocking drugs.)
• Continue cardiac monitoring (e.g., ECG) and invasive monitoring (e.g., • To allay possible anxiety, teach the patient, family, or caregiver the
cardiac output, arterial line pressures) as ordered in the hospitalized rationale for all equipment used and the need for frequent monitoring.
patient. (Monitoring devices assist in detecting early signs of adverse
effects as well as monitoring for therapeutic effects. Diverse Patients:
Hydralazine is known to metabolize in patients who are slow acetylators,
and because this cannot always be predicted, ensure that frequent
monitoring continues, especially in the early stages of drug therapy.)
• Continue frequent physical assessments, particularly neurologic, • When on oral therapy at home, the patient, family, or caregiver should
cardiac, and respiratory. Immediately report any changes in LOC, immediately report changes in mental status or LOC, palpitations,
headache, or changes in heart or lung sounds. (Vasodilator therapy dizziness, dyspnea, increasing productive cough, especially if frothy
may worsen preexisting neurologic, cardiac, or respiratory conditions sputum is present, and seek medical attention.
as blood pressure drops and perfusion to vital organs diminishes.)
• Weigh the patient daily and report weight gain or loss of 1 kg (2 lb) or • When on oral therapy at home, have the patient weigh self daily, ideally
more in a 24-h period or significant peripheral edema. (Daily weight is at the same time of day, and record weight along with blood pressure
an accurate measure of fluid status and takes into account intake, and pulse measurements. Have the patient report a weight gain or
output, and insensible losses. Weight gain or edema may signal blood loss of more than 1 kg (2 lb) in a 24-h period, or peripheral edema,
pressure has lowered too quickly, stimulating renin release, and may especially if increasing.
require judicious use of diuretic therapy to treat.)
• Continue to monitor IV infusion sites frequently. (Direct-acting • Instruct the patient to report any burning or stinging pain, swelling,
vasodilators may cause tissue damage if the drug extravasates.) warmth, redness, or tenderness at the IV insertion site.
• Observe for signs and symptoms of lupus in patients taking • Instruct the patient to report symptoms such as a butterfly-shaped
vasodilators, particularly hydralazine. (Hydralazine has been linked to rash over the nose and cheeks, muscle aches, and fatigue when
drug-induced or drug-related lupus. Other direct vasodilators are used taking oral vasodilators, particularly hydralazine.
with caution for this reason.)
• Monitor for the development of priapism and notify the healthcare • Instruct the patient to report a sustained erection that lasts more than 4 h
provider. (Priapism may result in tissue damage if unrelieved and is if on vasodilator therapy at home and to seek immediate medical care.
considered a medical emergency.)
• For oral drug therapy, give the first dose of the drug at bedtime. • Instruct the patient to take the first dose of the medication at bedtime,
(A first-dose response may result in a greater initial drop in blood immediately before going to bed, and to avoid driving or other
pressure than subsequent doses.) substantial activities for 12–24 h after the first dose or when the
dosage is increased until effects are known.
• Do not abruptly stop medication. (Rebound HTN and tachycardia may • Teach the patient, family, or caregiver not to stop the medication
occur.) abruptly and to call the healthcare provider if the patient is unable to
take the medication for more than 1 day due to illness.
• Encourage appropriate lifestyle changes: lowered fat intake, gradual • Encourage the patient, family, or caregiver to adopt a healthy lifestyle
increase in exercise, limited alcohol intake, smoking cessation. (Healthy of low-fat food choices, reduced sodium intake, increased exercise,
lifestyle changes will support and minimize the need for drug therapy. decreased alcohol consumption, and smoking cessation.
Direct vasodilators decrease blood pressure substantially, and concurrent
beta-blocker use may decrease heart rate. Given alone or together, this • Provide for dietitian consultation as needed.
may lead to exercise intolerance. Activity levels should be increased • Caution the patient about sudden increases in activity level. Report
gradually to patient tolerance. If dizziness or shortness of breath occurs,
decrease exercise levels to a comfortable level. Alcohol consumption may dizziness, palpitations, or shortness of breath that occurs while
increase the risk of blood pressure–related adverse effects.) exercising.
(continued )
598 Unit 5 Pharmacology of the Cardiovascular System
CONNECTIONS: NURSING PRACTICE APPLICATION (continued)
Implementation
Interventions and (Rationales) Patient-Centered Care
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 medication therapy.
therapeutic outcomes, commonly observed adverse effects,
parameters for when to call the healthcare provider, and any
necessary monitoring or precautions. (Using time during nursing care
helps to optimize and reinforce key teaching areas.)
Patient self-administration of drug therapy: • Instruct the patient in proper administration techniques, followed by
• When administering medications, instruct the patient, family, or return demonstration.
caregiver in proper self-administration techniques. (Utilizing time • The patient, family, or caregiver is able to discuss appropriate dosing
during nurse administration of these drugs helps to reinforce teaching.) and administration needs.
Understanding Chapter 34
Key Concepts Summary 34.6 Calcium channel blockers have emerged as
important drugs in the treatment of hypertension.
34.1 Failure to properly manage hypertension can lead
to stroke, heart failure, or myocardial infarction. 34.7 Blocking the renin-angiotensin-aldosterone
system leads to a decrease in blood pressure and
34.2 Therapeutic lifestyle changes can reduce blood improved kidney function.
pressure and lessen the need for antihypertensive
medications. 34.8 Adrenergic antagonists are commonly used to
treat hypertension.
34.3 Research-based guidelines have been developed
to aid the healthcare provider in providing 34.9 Direct-acting vasodilators lower blood pressure
optimal treatment for patients with hypertension. by relaxing arteriolar smooth muscle.
34.4 The choice of antihypertensive medication is 34.10 Hypertensive crisis is a medical emergency that
determined by the degree of hypertension and the is treated by the intravenous administration of
presence of other medical conditions. antihypertensive medications.
34.5 Diuretics are often preferred drugs for treating
mild to moderate hypertension.
CASE STUDY: Making the Patient Connection
Remember the patient 168/102 mmHg. Next, Elmer’s healthcare provider added
“Elmer Foley” at the an ACE inhibitor, captopril (Capoten), to the regimen. Still,
beginning of the Elmer’s blood pressure remained above normal limits.
chapter? Now read Lastly, the healthcare provider discontinued the captopril
the remainder of the and started Elmer on PO hydralazine. With this visit, his
case study. Based on blood pressure is 146/90 mmHg.
the information
presented within this When Elmer was first told he had HTN, he began
chapter, respond to the critical thinking questions that many of the suggested lifestyle changes encouraged by
follow. his healthcare provider. He has lost a total of 15 kg (33 lb)
since starting his diet 10 months ago. Elmer started walk-
Elmer Foley is a 72-year-old White man with a 10-month ing daily for exercise and can now walk up to 1 mile with-
history of uncontrolled HTN. Initially, Elmer was pre- out fatigue. He avoids all salty foods and diligently checks
scribed the thiazide diuretic HCTZ (Microzide). However, food labels for fat and salt content. Elmer occasionally
after 1 week of therapy, his blood pressure remained at drinks a glass of wine, although never more than 1 to
2 glasses per month. Although it was difficult for Elmer to
Chapter 34 Pharmacotherapy of Hypertension 599
stop smoking, he proudly claims he has been smokeless 2. Elmer wants to know why the previous therapies were
for 8 months. unsuccessful. What would you say as his nurse?
Critical Thinking Questions 3. As the nurse, how can you support Elmer before he
leaves the clinic?
1. How would you respond to Elmer’s question, “What
else can I do?” Is there anything else he can do to Answers to Critical Thinking Questions are available on the
reduce his blood pressure? faculty resources site. Please consult with your instructor.
Additional Case Study Helen is started on an infusion of nitroprusside
(Nitropress) 50 mg in 250 mL in D5W. The dose will be
Helen Edwards is a 44-year-old African American woman titrated between 0.5 and 10 mcg/kg/min to maintain the
who presents to the emergency department (ED) with head- patient’s diastolic pressure at less than 100 mmHg.
ache and shortness of breath. Helen has a long-standing his-
tory of HTN. She has never consistently adhered to any 1. Describe the mechanism of action related to nitroprus-
HTN management strategies and has been nonadherent side (Nitropress).
with her medication regimen for the past 8 months. On
arrival at the ED her blood pressure is 192/126 mmHg. 2. For what adverse effects should you monitor in
patients receiving this drug therapy?
When you assess the patient, you note that she is
approximately 1.7 m (5′6″) in height and the self-reported 3. What factors does this patient have that predispose her
weight is 107 kg (235 lb). She is slightly lethargic and to hypertensive crises?
reports having left arm numbness and tingling. Other
physical assessment parameters are normal. Answers to Additional Case Study questions are available on the
faculty resources site. Please consult with your instructor.
Chapter Review 4. Angioedema
5. Hypotension
1. Methyldopa (Aldomet) is being initiated for a patient
with hypertension. Which health teaching would be 4. A patient with hypertensive crisis is started on nitroprus-
most appropriate for this drug? side (Nitropress) therapy. The nurse would perform what
priority intervention during the course of this treatment?
1. Avoid hot baths and showers and prolonged
standing in one position. 1. Monitor for the presence or absence of bowel sounds.
2. Obtain urine samples for specific gravity
2. This drug may discolor the urine a pinkish-brown
color. measurements and glucose levels.
3. Observe skin pressure points for turgor and
3. You may experience bloating and weight gain.
4. The tablet should be taken only with food or milk. integrity.
4. Titrate intravenous infusion rate according to the
2. A patient is receiving hydralazine for elevated blood
pressure levels. The nurse would include in the care blood pressure response.
plan to monitor the patient for which adverse effects?
5. A 65-year-old White patient has been newly diagnosed
1. Atelectasis with hypertension, with an average blood pressure of
2. Crystalluria 164/92 mmHg. Which of the following drug groups will
3. Photosensitivity potentially be ordered initially? (Select all that apply.)
4. Orthostatic hypotension
1. Beta blockers
3. The nurse is preparing to administer the first dose of 2. Calcium channel blockers
enalapril (Vasotec). Identify the potential adverse 3. Thiazide diuretics
effects of this medication. (Select all that apply.) 4. Angiotensin-converting enzyme inhibitors (ACEIs)
1. Reflex hypertension or angiotensin receptor blockers (ARBs)
2. Hyperkalemia 5. Direct-acting vasodilators
3. Persistent cough
600 Unit 5 Pharmacology of the Cardiovascular System 3. Past history of alcohol use
4. Level of consciousness
6. A patient is receiving nitroprusside (Nitropress) and 5. Skin color and turgor
is being monitored in the intensive care unit. Because
of toxic cyanide metabolites that develop, which of See Answers to Chapter Review in Appendix A.
the following should the nurse evaluate in the
patient? (Select all that apply.)
1. Cardiac status and cardiac output
2. Renal function and creatinine levels
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and Blood Institute, National High Blood Pressure
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express.pdf
Campos-Outcalt, D. (2016). USPSTF urges extra step
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patients have ambulatory blood pressure monitoring
performed to validate the diagnosis of hypertension? University of Maryland Medical Center. (2015). Grape seed.
Journal of Clinical Hypertension, 17, 412–413. Retrieved from http://umm.edu/health/medical/
doi:10.1111/jch.12527 altmed/herb/grape-seed
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E. Z. (2016). Consideration of out-of-office blood recommendation statement, high blood pressure in adults:
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pressure-in-adults-screening
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1952052-overview Collins, K. J., Dennison Himmelfarb, . . . Wright, J. T.
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Dennison-Himmelfarb, C., Handler, J., . . . Ortiz, E. guideline for the prevention, detection, evaluation, and
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Perlini, S., Semplicini, A., . . . Pedrinelli, R. (2015). An
Adebayo, O., & Rogers, R. L. (2015). Hypertensive update on hypertensive emergencies and urgencies.
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doi:10.1016/j.emc.2015.04.005
Qaseem, A., Wilt, T. J., Rich, R., Humphrey, L. L., Frost,
Axon, R. N., Turner, M., & Buckley, R. (2015). An update J., & Forciea, M. A. (2017). Pharmacologic treatment of
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doi:10.1002/2327-6924.12262
“I was simply sitting and
reading the newspaper, when
suddenly my chest felt tight, I
felt weak, and I had difficulty
breathing.”
Patient “Michael Graff”
Chapter 35
Pharmacotherapy of Angina Pectoris
and Myocardial Infarction
Chapter Outline Learning Outcomes
cc Pathophysiology of Myocardial Ischemia After reading this chapter, the student should be able to:
cc Etiology of Coronary Artery Disease
cc Pathophysiology of Angina Pectoris 1. Describe factors that affect myocardial oxygen
cc Nonpharmacologic Therapy of Coronary supply and demand.
Artery Disease 2. Explain the relationship between atherosclerosis and
cc Pharmacologic Management of Angina Pectoris coronary artery disease.
cc Drug Classes for Angina Pectoris
3. Explain the pathophysiology of angina pectoris and
Organic Nitrates myocardial infarction.
PROTOTYPE Nitroglycerin (Nitrostat, Nitro-Bid,
Nitro-Dur, Others), p. 609 4. Discuss the role of therapeutic lifestyle changes in
Beta-Adrenergic Antagonists the management of coronary artery disease.
PROTOTYPE Atenolol (Tenormin), p. 611
Calcium Channel Blockers 5. Describe the pharmacologic management of the
cc Pathophysiology of Myocardial Infarction different types of angina.
cc Pharmacologic Management of Myocardial
Infarction 6. Describe the pharmacologic management of
Thrombolytics and Adjunct Medications for myocardial infarction.
Myocardial Infarction
7. For each of the classes shown in the chapter outline,
identify the prototype and representative drugs and
explain the mechanism(s) of drug action, primary
indications, contraindications, significant drug
interactions, pregnancy category, and important
adverse effects.
8. Apply the nursing process to care for patients
receiving pharmacotherapy for angina and
myocardial infarction.
602
Chapter 35 Pharmacotherapy of Angina Pectoris and Myocardial Infarction 603
Key Terms nitric oxide, 607 silent ischemia, 605
stable angina, 605
angina pectoris, 604 partial fatty-acid oxidation unstable angina, 605
coronary artery disease (CAD), 604 inhibitors, 606 variant (Prinzmetal’s) angina, 605
myocardial infarctions (MIs), 612
myocardial ischemia, 603 plaque, 604
The tissues of the body depend on a continuous supply of as in acute shock, it could be life threatening. Immediate
oxygen and vital nutrients to support life and health. The restoration of blood pressure is required to reestablish an
heart is particularly demanding of a steady source of oxy- adequate oxygen supply to the myocardium as well as to
gen. Insufficient arterial blood supply to cardiac muscle other vital tissues. Other hemodynamic factors contrib-
may result in angina pectoris, acute myocardial infarction uting to the myocardial oxygen supply include changes
(heart attack), and possibly death. This chapter focuses on in blood volume (e.g., hemorrhage) and disorders that
the pharmacologic interventions related to angina pectoris reduce the oxygen content or carrying capacity of the
and myocardial infarction (MI). blood (e.g., anemia).
Pathophysiology of The narrowing of a coronary artery resulting from ath-
Myocardial Ischemia erosclerosis or coronary artery disease (CAD) deprives
cells of needed oxygen and nutrients. If the narrowing
35.1 Myocardial ischemia develops when develops over a long period of time, the heart compensates
there is inadequate blood supply to meet the for its inadequate blood supply and the patient may be
metabolic demands of cardiac muscle. asymptomatic. Indeed, coronary arteries may be occluded
as much as 50% or more and cause no symptoms.
Myocardial ischemia is a condition in which the heart is
receiving an insufficient amount of oxygen to meet its met- Myocardial Oxygen Demand
abolic demands. This occurs when there is an imbalance
between oxygen supply and oxygen demand in myocar- As CAD progresses, cardiac muscle does not receive
dial cells. Knowledge of factors affecting myocardial oxy- enough oxygen to meet the body’s metabolic demands.
gen supply and demand is necessary for understanding The physiologic demands on the heart are highly variable
the pharmacotherapy of the diseases associated with myo- and depend on a large number of hemodynamic and life-
cardial ischemia. style factors.
Myocardial Oxygen Supply Basically, anything that increases the workload of the
heart will increase myocardial oxygen demand. It is not
The heart, from the moment it begins to function in utero difficult to think of the many daily activities that increase
until death, works to distribute oxygen and nutrients by cardiac workload. Exercise, for example, will cause the
means of its nonstop pumping action. It is the hardest work- heart to beat faster in order to pump more blood to mus-
ing organ in the body, functioning continuously during both cles. This physical activity need not be extreme: Simply
activity and rest. Because the heart is a muscle, it needs a walking at a normal pace will increase cardiac workload
steady supply of nourishment to sustain itself and maintain over resting levels.
the systemic circulation in a balanced state of equilibrium.
Any disturbance in blood flow to the myocardium—even In some patients, the increased cardiac workload can
for brief episodes—can result in life-threatening conse- be the result of mental, rather than physical, stressors.
quences. A review of basic coronary circulation is provided Think of the first time (or last time) you had to give a speech
in Chapter 28. in front of a group, or became angry with a child, spouse, or
coworker. These activities resulted in your heart pumping
As with other arteries in the body, the amount of harder or faster, even though there was no physical activity
blood flow through the coronary arteries is dependent involved. What factors do physical exercise and mental
on a number of hemodynamic factors. Of these, blood stress have in common that produced the increased cardiac
pressure is the most important. When systolic blood workload?
pressure falls, the quantity of blood flowing to the coro-
nary arteries is diminished. If this occurs suddenly, such The answer is simple. Anything that increases heart
rate, contractility, or tension on the ventricular walls causes
the heart to work harder and affect cardiac oxygen con-
sumption. For example, if heart rate increases due to
604 Unit 5 Pharmacology of the Cardiovascular System Platelets and fibrin deposit
on plaque and initiate clot
exercise or hyperthyroidism, it is easy to understand why formation
the heart needs more oxygen because it must beat more
times per minute. Similarly, the heart will need more oxy- Smooth muscle
gen if it beats more forcefully (increased contractility). A
patient with heart failure (HF) has a thickened myocar- Plaque
dium (increased tension) that will require more work to
contract. The heart of a patient with hypertension will have
to work harder to overcome resistance and eject blood. It is
important to remember that anything that makes the heart
beat faster or contract with more force will increase myo-
cardial oxygen demand. Drugs that diminish these factors
are of value in the treatment of angina, MI, and HF.
Etiology of Coronary Moderate Thrombus Thrombus
Artery Disease narrowing partially completely
of lumen occluding lumen occluding lumen
35.2 Coronary artery disease is the major cause
of myocardial ischemia. Figure 35.1 Atherosclerosis in the coronary arteries.
Coronary artery disease (CAD) is one of the leading CONNECTION Checkpoint 35.1
causes of mortality in the United States. The primary
defining characteristic of CAD is narrowing or occlusion From what you learned in Chapter 28, predict what would happen to
of one or more coronary arteries. Narrowing can result in the cardiac workload when plasma volume is increased by a rapid
symptoms of angina pectoris, whereas occlusion results infusion of normal saline. What effect might this have on a patient
in MI. The two disorders are closely related, as most with CAD? Answers to Connection Checkpoint questions are available
patients who experience an MI have narrowing of the on the faculty resources site. Please consult with your instructor.
coronary vessels.
Pathophysiology
The most common etiology of CAD in adults is athero- of Angina Pectoris
sclerosis, the presence of plaque—a fatty, fibrous material—
within the walls of the coronary arteries. Plaque develops 35.3 Angina pectoris is characterized by severe
progressively over time, producing varying degrees of chest pain brought on by physical exertion or
intravascular narrowing that results in partial or total block- emotional stress.
age of the vessel. During periods of rest, demands on the
heart are reduced and a partially occluded artery may be Angina pectoris is acute chest pain caused by myocardial
able to provide adequate oxygen. During exercise (or a ischemia. The classic presentation of angina pectoris is steady,
pharmacology test), however, workload on the heart intense pain, sometimes with a crushing sensation in the
increases, the cardiac muscle distal to the obstruction anterior chest. Typically, the discomfort radiates to the left
receives insufficient oxygen supply, and ischemia results. shoulder and proceeds down the left arm. It may also extend
to the posterior thoracic region or move upward to the jaw,
A healthy heart responds to stress by changing the and in some patients the pain is experienced in the epigas-
diameter of the coronary arteries. When the oxygen trium or abdominal area. Accompanying the discomfort is
demands of the heart increase, the vessels will immediately severe emotional distress—a feeling of panic with fear of
dilate to bring more oxygen to the myocardium. Plaque impending death. There is usually pallor, dyspnea with cya-
impairs normal elasticity, and the coronary vessels are nosis, diaphoresis, tachycardia, and elevated blood pressure.
unable to dilate properly when the myocardium demands
additional oxygen. Myocardial ischemia occurs when car- Anginal pain is usually precipitated by physical exer-
diac demands exceed the amount of oxygen that can be tion or emotional excitement—events associated with
supplied through the narrowed, inelastic vessels character- increased myocardial oxygen demand. Angina pectoris
istic of CAD. episodes are of short duration. With physical rest and men-
tal relaxation, the workload demands on the heart diminish
Plaque accumulation occurs gradually, over periods of and the discomfort subsides within 5 to 10 minutes.
40 to 50 years in some individuals, but actually begins to Descriptions of the four basic types of angina follow.
accrue very early in life. The development of atherosclero-
sis is illustrated in Figure 35.1.
Chapter 35 Pharmacotherapy of Angina Pectoris and Myocardial Infarction 605
When angina occurrences are fairly predictable in fre- Nonpharmacologic Therapy of
quency, intensity, and duration, the condition is described Coronary Artery Disease
as classic or stable angina. Rest usually relieves the pain
associated with stable angina in about 5 minutes or less. 35.4 Therapeutic lifestyle changes can
decrease the frequency of anginal
Variant (Prinzmetal’s) angina occurs when the episodes and reduce the risk of coronary
decreased myocardial blood flow is caused by spasms of the artery disease.
coronary arteries. This type is sometimes called vasospastic
angina. The vessels undergoing spasms may or may not A combination of variables influences the development
contain atherosclerotic plaque. Thus, the primary cause of and progression of angina, including dietary patterns
the narrowing and subsequent angina pain is vasoconstric- and lifestyle choices. The nurse is instrumental in teach-
tion of the artery, rather than plaque buildup. Variant angina ing patients the means of preventing CAD as well as
pain occurs most often during periods of rest, although it how to lower the rate of recurrence of anginal episodes.
may occur unpredictably, unrelated to rest or activity. Such support includes the formulation of a comprehen-
sive plan of care that incorporates psychosocial support
Although most people equate angina with chest pain, and an individualized teaching plan. The patient needs
this is not always the case. When myocardial ischemia to understand the causes of angina, identify the condi-
occurs in the absence of pain, it is called silent ischemia. tions and situations that trigger it, and develop the moti-
Although one or more coronary arteries are partially vation to modify behaviors associated with their
occluded, the patient is asymptomatic. Some patients diag- disease.
nosed with stable angina also experience silent ischemia.
Although the mechanisms underlying silent ischemia are Listing therapeutic lifestyle changes that modify the
not completely understood, the condition is associated development and progression of cardiovascular disease
with a high risk for acute MI and sudden death. (CVD) may seem repetitious, as these same factors have
been included in chapters on hypertension (HTN) and
Unstable angina occurs when episodes of angina hap- heart disease. However, the importance of prevention
pen suddenly, have added intensity, and occur during peri- and management of CVD through nonpharmacologic
ods of rest. Unstable angina is a type of acute coronary means cannot be overemphasized. Making healthy life-
syndrome in which an atherosclerotic plaque within a coro- style choices can prevent CAD and slow the progression
nary artery ruptures. A thrombus quickly builds on the dis- of the disease in those who have existing plaque. The fol-
placed plaque, and the artery becomes at serious risk of lowing interventions have been shown to reduce the inci-
occlusion. This condition is a medical emergency requiring dence of CAD:
aggressive intervention because of the associated increased
risk for MI. • Limit alcohol consumption to small or moderate
amounts.
Anginal pain often parallels the signs and symptom-
atology of MI. It is extremely important for the nurse to be • Eliminate foods high in cholesterol or saturated fats.
able to accurately identify the characteristics that differenti- • Keep blood cholesterol and other lipid indicators
ate the two conditions, since the pharmacologic interven-
tions related to angina differ considerably from those of within the normal ranges.
MI. Angina, while aggravating and uncomfortable, rarely • Keep blood pressure within the normal range.
leads to a fatal outcome and the chest pain is usually imme- • Maintain blood glucose levels within the normal
diately relieved by nitroglycerin. MI, however, carries with
it a high mortality rate if appropriate treatment is delayed range.
(see Section 35.9). In the event of MI, pharmacologic inter- • Exercise regularly and maintain optimal weight.
vention must be initiated immediately and systematically • Do not use tobacco.
maintained. When a patient presents with chest pain, the
foremost objective for the healthcare provider is to quickly When the patient is unable or unwilling to adopt
determine the cause of the pain so that proper, effective healthy lifestyle choices, preventive drug therapy may
interventions can be delivered. be used to lower CAD risk factors. For example, antihy-
pertensives are often used to manage blood pressure,
PharmFACT statins to lower blood lipids, and insulin or oral hypo-
glycemics to keep blood glucose within the normal
About 9.8 million Americans experience angina each year. range. The nurse should teach patients that therapeutic
The risk of angina increases with age and is more common lifestyle changes should be incorporated into their daily
in women. Only 18% of coronary attacks are preceded by routine, even if medications are necessary to control
angina (Alaeddini, 2016). major risk factors.
606 Unit 5 Pharmacology of the Cardiovascular System
Pharmacologic Management of • Causing the heart to contract with less force (reduced
Angina Pectoris contractility)
35.5 The pharmacologic management of angina • Lowering blood pressure (reduced afterload).
includes organic nitrates, beta-adrenergic
antagonists, and calcium channel blockers. The pharmacotherapy of angina uses three primary
classes of drugs: organic nitrates, beta-adrenergic antago-
There are several desired therapeutic goals for a patient nists, and calcium channel blockers (CCBs). Rapid-acting
receiving pharmacotherapy for angina. A primary goal is organic nitrates are preferred drugs for terminating an acute
to reduce the frequency and intensity of angina episodes. angina episode. Beta-adrenergic antagonists or blockers are
Additionally, successful pharmacotherapy should improve first-line drugs for prophylactic treatment. CCBs are used
exercise tolerance and allow the patient to actively partici- when beta blockers are not tolerated well by a patient.
pate in activities of daily living. Long-term goals include Long-acting nitrates, given by the oral (PO) or transdermal
extending the patient’s lifespan by preventing the serious routes, are alternatives for prophylaxis. Persistent angina
consequences of ischemic heart disease such as dysrhyth- requires drugs from two or more classes, such as a beta
mias, HF, and MI. Pharmacotherapy alone, however, can- blocker combined with a long-acting nitrate or a CCB. Phar-
not usually achieve all these outcomes; the patient must be macotherapy Illustrated 35.1 illustrates the mechanisms of
willing to implement therapeutic lifestyle changes that action of medications used to prevent and treat angina.
promote a healthy heart.
Should the patient be unable to tolerate beta blockers
Medications for angina are sometimes placed into two or CCBs, ranolazine may be considered as another option.
categories: those that terminate an acute angina episode in Approved in 2006, ranolazine (Ranexa) is the only medica-
progress, and those that decrease the frequency of angina tion in a class called partial fatty-acid oxidation inhibitors.
episodes. The primary means by which antianginal medica- Ranolazine reduces the flow of sodium and calcium ions
tions act is by reducing the myocardial demand for oxygen. into the myocardium, which decreases the metabolic rate
This may be accomplished by the following mechanisms: and oxygen demands of myocardial cells. Thus, it is the
only antianginal that acts through its metabolic effects,
• Slowing the heart rate rather than hemodynamic effects; effects on heart rate and
• Dilating veins so that the heart receives less blood blood pressure are minimal. The drug is approved only for
chronic angina that has not responded to other drugs.
(reduced preload)
CONNECTIONS: Complementary and Alternative Therapies
Omega-3 Fatty Acids
Description much as 10 to 25 times more omega-6 than omega-3, due in
large part to the consumption of meats that are higher in omega-
Omega-3 fatty acids are unsaturated fats found in fatty fish 6. Doses of less than 3 g/day of omega-3 fatty acids are usually
such as salmon, mackerel, and tuna; vegetable oils such as recommended to prevent GI side effects such as diarrhea. The
canola and soybean; seeds such as flaxseed and flaxseed oil; recommended dose is up to 4 g/day for patients with high lipid
and nuts, green leafy vegetables, and beans. Omega-3 fatty levels and 1 g/day for patients with coronary artery disease (Uni-
acids are essential to the body and necessary for regulating versity of Maryland Medical Center, 2015).
muscle function, blood clotting, digestion, cell growth, and
other functions (National Center for Complementary and Inte- Evidence
grative Health, 2015).
Research has shown that omega-3 fatty acids may reduce the
History and Claims incidence of cardiovascular disease. In some research studies,
patients have shown improvement in lipid levels and in inflamma-
Claims have been made that omega-3 fatty acids can reduce tory conditions such as rheumatoid arthritis or inflammatory
inflammation and prevent or treat conditions such as heart dis- bowel disease. Larger studies need to be conducted, however,
ease, high blood pressure, rheumatoid arthritis, lupus, asthma, to determine the extent of such benefits. While obtaining
inflammatory bowel disease, and cancer. omega-3 fatty acids through dietary means is highly recom-
mended, concern about mercury and other toxic metals in fatty
Standardization fish has been raised, and it is recommended that pregnant
women and young children avoid eating more than one 2-ounce
There are different types of omega-3 fatty acids: alpha-linolenic serving per week of fatty fish (mackerel, shark, swordfish, or tile-
acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic fish), but may eat up to 12 ounces of other types (University of
acid (DHA). While a balance of omega-3 and omega-6 fatty acids Maryland, 2015).
in the diet is important, the average U.S. diet tends to contain as
Chapter 35 Pharmacotherapy of Angina Pectoris and Myocardial Infarction 607
Pharmacotherapy Illustrated 35.1
Mechanisms of Action of Drugs Used to Treat Angina
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CONNECTION Checkpoint 35.2 reduced and the workload on the heart is decreased,
thereby lowering myocardial oxygen demand. The thera-
Many patients take HMG-CoA reductase inhibitors (statins) concurrently peutic outcome is that chest pain is alleviated and episodes
with antianginal medications. From what you learned in Chapter 29, of angina become less frequent.
what is the rationale for prescribing drugs from this class for a patient
with CAD? Answers to Connection Checkpoint questions are available on Organic nitrates also have the ability to dilate coronary
the faculty resources site. Please consult with your instructor. arteries, which was once thought to be their primary mech-
anism of action. It seems logical that dilating a partially
Drug Classes for Angina Pectoris occluded coronary vessel would allow more oxygen to
reach ischemic tissue. Although this effect does indeed
35.6 Organic nitrates may be used to terminate occur, it is no longer considered the primary mechanism of
or prevent angina episodes. nitrate action in the treatment of stable angina. Coronary
artery vasodilation, however, is crucial in treating variant
After their medicinal properties were discovered in 1879, angina, in which the chest pain is caused by coronary artery
the organic nitrates became the mainstay for the treatment spasm. The organic nitrates relax these spasms, allowing
of angina for the next 100 years. The mechanism of action more oxygen to reach the myocardium, thereby terminat-
results from the formation of nitric oxide in vascular ing the pain.
smooth muscle. Nitric oxide is an important cell-signaling
molecule and a potent vasodilator, causing relaxation of Organic nitrates are classified by their onset and dura-
both arterial and venous smooth muscle. Dilation of veins tion of action. The short-acting nitrates, such as nitroglyc-
reduces the amount of blood returning to the heart (pre- erin, may be taken sublingually (SL) or as an oral spray or
load), and the chambers contain a smaller volume. With buccal tablet to quickly terminate an acute anginal episode.
less blood for the ventricles to pump, cardiac output is Long-acting nitrates, such as isosorbide dinitrate (Isordil),
are taken orally or are absorbed slowly through a
608 Unit 5 Pharmacology of the Cardiovascular System
Table 35.1 Administration of Organic Nitrates
Route Administration
Sublingual (SL) tablet • Give 1 tablet. If pain is unrelieved, may give additional tablets at 5-min intervals up to 3 tablets in a 15-min period.
Sustained release buccal tablet • Moisture on SL tissue is necessary for the SL tablet to dissolve. A patient may be unresponsive to SL nitroglycerin,
Sustained release tablet or capsule
Translingual spray as the anxiety caused by chest pain typically leads to dry mouth.
Transdermal ointment
• Place 1 tablet between lip and gum above incisors or between cheek and gum. Allow to slowly dissolve over 3–5 h.
Transdermal unit • Avoid touching tongue to tablet or drinking hot fluids, as these can increase dissolution of the tablet, decrease the
Intravenous (IV)
duration of the medicinal effect, and lead to the onset of angina pain.
• Avoid chewing, crushing, or swallowing the tablet.
• Give on an empty stomach with a full glass of water 1 h before, or 2 h after, meals. The tablet should be swallowed
whole.
• Note that the sustained release form helps to prevent angina attacks but is not intended for immediate relief of
angina.
• Avoid chewing or crushing the tablet.
• Avoid shaking medicine canister. Spray on or under the tongue. Never inhale spray.
• Repeat spray every 5 min if needed for a maximum of 3 metered doses.
• Teach the patient to avoid swallowing for at least 10 sec.
• Avoid touching ointment with fingers. Squeeze the prescribed dosage onto the dose-determining applicator (paper
application patch) in the medication package. Spread ointment in a thin, even layer to premarked 5.5- by 9-cm
(2 1/4- by 3 1/2-in.) square. Place patch with ointment side down onto nonhairy skin surface such as the forearm,
chest, abdomen, or anterior thigh. Cover with transparent wrap and secure with tape.
• Rotate application sites to prevent skin inflammation and sensitization. Remove any residual ointment before
reapplication.
• Keep medication container closed and stored in a cool place.
• Apply transdermal patch at the same time each day to nonhairy or closely trimmed area without excessive
movement.
• Avoid application on irritated or scarred skin.
• Rotate application site each time to prevent skin irritation and sensitization.
• Verify with healthcare provider the correct IV concentration and rate of infusion, and use the supplied IV tubing for
administration.
• Remove any existing transdermal unit or ointment in place on the patient before starting IV infusion to prevent
overdosage.
• Note that IV nitroglycerin can cause hypotension, so give with extreme caution to patients with preexisting
hypotension or hypovolemia.
• Monitor patient closely for any change in levels of consciousness and for dysrhythmias, because IV nitroglycerin
contains a substantial amount of ethanol as a diluent. Ethanol intoxication with symptoms of nausea, vomiting,
coma, lethargy, and alcohol breath can occur with high doses of IV nitroglycerin. Stop infusion if intoxication
occurs. The patient should recover immediately when drug administration is discontinued.
transdermal patch to decrease the frequency and severity Most adverse effects of organic nitrates are extensions
of angina episodes. Long-acting organic nitrates are occa- of their hypotensive action. Flushing of the face and head-
sionally used to treat symptoms of HF; their role in the ache are common effects, related to vasodilation. Ortho-
treatment of that disease is presented in Chapter 36. The static hypotension is a frequent adverse effect of this drug
various routes of administration are listed in Table 35.1. class, and patients should be advised to change positions
Doses for the organic nitrates, along with other medica- gradually to prevent lightheadedness. Blood pressure
tions for treating angina and MI, are listed in Table 35.2. should be carefully monitored, and the nurse should hold
nitrates and remove topical forms if serious hypotension is
Tolerance is a common and potentially serious prob- discovered. Taking organic nitrates concurrently with
lem with the long-acting organic nitrates. The magnitude alcohol may cause severe hypotension and even cardio-
of the tolerance depends on the dosage and frequency of vascular collapse.
drug administration. Although tolerance develops
rapidly—as quickly as 24 hours after the initiation of ther- An additional adverse effect that can be limiting in
apy in some patients—it also disappears rapidly when the some patients is reflex tachycardia. When the organic
drug is withheld. Patients are often instructed to remove nitrates dilate vessels and blood pressure falls, the barore-
the transdermal patch for 6 to 12 hours each day or with- ceptor reflex is triggered. Sympathetic stimulation of the
hold a nighttime dose of the oral medications in order to heart increases heart rate and contractility, which are unde-
delay the development of tolerance. Because the oxygen sirable effects in a patient with angina. This adverse effect
demands during sleep are diminished, the patient with is often transient and asymptomatic. Patients who report
stable angina experiences few angina episodes during this significant palpitations may be administered a beta blocker,
drug-free interval. which will prevent the reflex cardiac stimulation.
Chapter 35 Pharmacotherapy of Angina Pectoris and Myocardial Infarction 609
Table 35.2 Selected Drugs for Angina and Myocardial Infarction
Drug Route and Adult Dose Adverse Effects
Organic Nitrates (Maximum Dose Where Indicated)
isosorbide dinitrate (Dilatrate SR, Isordil) Headache, orthostatic hypotension, flushing of the
PO (regular release): 2.5–30 mg qid (max: 480 mg/day) face, dizziness, rash (transdermal patch),
isosorbide mononitrate (Imdur, Ismo, PO: (sustained release): 40 mg bid–qid (max: 160 mg/day) tolerance
Monoket) SL: 2.5–5 mg taken 15 min before exercise Anaphylaxis, circulatory collapse due to
PO (regular release: Ismo, Monoket): 20 mg bid hypotension, syncope due to orthostatic
nitroglycerin (Nitrostat, Nitro-Bid, Nitro- (max: 40 mg/day) hypotension
Dur, others) PO (extended release: Imdur): 30–60 mg each morning
Beta-Adrenergic Antagonists (max: 240 mg/day) Fatigue, insomnia, drowsiness, impotence or
atenolol (Tenormin) SL: 1 tablet (0.3–0.6 mg) or 1 spray (0.4–0.8 mg) every decreased libido, depression, bradycardia, and
metoprolol (Lopressor, Toprol XL) 3–5 min (max: 3 doses in 15 min) confusion
propranolol (Inderal, Inderal LA, Agranulocytosis, laryngospasm, Stevens–Johnson
InnoPran XL) PO: 25–50 mg daily (max: 100 mg/day) syndrome, anaphylaxis; if the drug is abruptly
PO (for HTN or angina): 100 mg/day (max: 400 mg/day) withdrawn, palpitations, rebound HTN, life-
timolol PO (immediate release): 40–420 mg bid (max: 640 mg/day) threatening dysrhythmias or myocardial ischemia
PO (extended release): 80–160 mg/day (max: 120 mg/day may occur
for InnoPran XL; 640 mg/day for Inderal LA)
PO (for MI): 10 mg bid (max: 60 mg/day) Flushed skin, headache, dizziness, peripheral
edema, lightheadedness, nausea, constipation
Calcium Channel Blockers PO: 5–10 mg daily (max: 10 mg/day) Hepatotoxicity, MI, HF, confusion, mood changes
amlodipine (Norvasc) PO (regular release): 30 mg tid–qid (max: 360 mg/day)
diltiazem (Cardizem, Cartia XT, Dilacor PO: (extended release): 120–240 mg bid (max: 540 mg/day) Dizziness, constipation, headache, nausea
XR, others) PO (regular release): 20–40 mg tid QT interval prolongation, bradycardia
nicardipine (Cardene) PO (sustained release): 30–60 mg bid (max: 120 mg/day)
PO (regular release): 10–20 mg tid (max: 180 mg/day)
nifedipine (Adalat CC, Procardia XL, PO (extended release): 30–90 mg once daily
others) PO (immediate release): 80–120 mg 3–4 times daily (max:
verapamil (Calan, Covera-HS, Isoptin 480 mg/day)
SR, Verelan) PO (extended release): 180–540 mg/day
Miscellaneous Drug PO: 500–1000 mg bid (max: 2000 mg/day)
ranolazine (Ranexa)
Note: Italics indicate common adverse effects. Underline indicates serious adverse effects.
PROTOTYPE DRUG Nitroglycerin (Nitrostat, services (EMS) should be contacted. The transdermal and
Nitro-Bid, Nitro-Dur, Others) oral sustained release forms are for prophylaxis only, since
they have a relatively slow onset of action. The long-acting
Classification Therapeutic: Antianginal drug forms should be discontinued gradually because vaso-
Pharmacologic: Organic nitrate, spasm may result if they are abruptly withheld.
vasodilator Nitroglycerin is also used for indications other than
angina. When administered by the IV route, the drug is
Therapeutic Effects and Uses: Nitroglycerin, the approved for controlled hypotension induction during
oldest and most widely used organic nitrate, can be deliv- anesthesia and the treatment of HF, acute pulmonary
ered by a number of different routes: sublingual, lingual edema, acute MI, severe HTN, or hypertensive emergency.
spray, PO, intravenous (IV), transmucosal, transdermal, Off-label indications include use as a uterine relaxant to aid
topical, and extended release forms. The rapid-acting in the extraction of a retained placenta and for pain associ-
forms may be taken while an acute angina episode is in ated with anal fissures or hemorrhoids.
progress or just prior to physical activity. When given
sublingually, it reaches peak plasma levels within min- Mechanism of Action: Upon reaching vascular
utes, thus quickly terminating angina pain. Chest pain smooth muscle, nitroglycerin forms nitric oxide, which
that does not resolve within 5 minutes after a dose of SL triggers a cascade resulting in the release of calcium ions
nitroglycerin may indicate MI, and emergency medical in smooth muscle. Nitroglycerin relaxes both arterial and
610 Unit 5 Pharmacology of the Cardiovascular System
venous smooth muscle. The venous dilation decreases the before or after taking these drugs. Concurrent use with
amount of blood returning to the heart, reducing preload. ethanol, CCBs, antidepressants, phenothiazines, or
With less blood for the ventricles to pump, myocardial antihypertensive drugs may cause additive hypotension.
oxygen demand is decreased. In addition, direct vasodi- Sympathomimetics such as epinephrine will antagonize
lation of coronary arteries enhances the blood supply to the vasodilation effects of nitroglycerin. Herbal/Food: Use
the myocardium and is partially responsible for its thera- with hawthorn may result in additive hypotension.
peutic effects.
Pregnancy: Category C.
Pharmacokinetics:
Treatment of Overdose: During overdose, hypoten-
Route(s) PO: SL tablets, SL spray, buccal sion may be reversed with the IV administration of nor-
mal saline. If methemoglobinemia is suspected, methylene
tablets; transdermal patch; topi- blue may be administered.
cal ointment Nursing Responsibilities: Key nursing implications
for patients receiving nitroglycerin are included in the
Absorption Rapid Nursing Practice Application for Patients Receiving Phar-
macotherapy with Organic Nitrates for Angina and Myo-
Distribution Widely distributed; 60% bound cardial Infarction.
to plasma protein Drugs Similar to Nitroglycerin (Nitrostat,
Nitro-Bid, Nitro-Dur, Others)
Primary metabolism Hepatic; extensive first-pass
Other organic nitrates include isosorbide dinitrate and iso-
metabolism sorbide mononitrate.
Primary excretion Renal Isosorbide dinitrate (Dilatrate SR, Isordil): Approved in
1961, isosorbide dinitrate is an organic nitrate used to ter-
Onset of action SL: 1–3 min; buccal: 2–5 min; minate anginal attacks (SL) and for the prophylaxis of
angina (extended release tablets). It is occasionally used to
transdermal patch: 40–60 min; treat HF. The dosing schedule must allow for a drug-free
period of at least 14 hours to prevent tolerance to the drug’s
topical ointment: 20–60 min effects. The PO forms of the drug should not be used to ter-
minate angina attacks in progress because it takes as long
Duration of action SL: 30–60 min; buccal: 2 h; trans- as 60 minutes to reach therapeutic drug levels. The SL dos-
age forms may be taken 15 minutes prior to activities likely
dermal patch: 18–24 h; topical to precipitate angina. Adverse effects are similar to those of
nitroglycerin. Like other nitrates, isosorbide dinitrate
ointment: 12 h should not be administered within 24 hours of taking erec-
tile dysfunction medications such as sildenafil. A fixed-
Adverse Effects: Most patients experience flushing of dose combination of isosorbide dinitrate with hydralazine
the face and a throbbing, transient headache, which result (BiDil) is available to reduce morbidity and mortality asso-
from the drug’s vasodilation action. Orthostatic hypoten- ciated with HF. This drug is pregnancy category C.
sion and syncope may occur. Stinging and rash may occur
with ointments and transdermal patches. Methemoglo- Isosorbide mononitrate (Imdur, Ismo, Monoket): Approved
binemia is a rare adverse effect that can cause shock and in 1991, isosorbide mononitrate is an active, long-acting
coma. Anaphylaxis leading to circulatory collapse due to metabolite of isosorbide dinitrate. The mononitrate is only
severe hypotension is rare. Tolerance develops with con- used for prophylaxis: Its 30- to 60-minute onset of action
tinuous therapy or large doses of the drug. makes it unacceptable for termination of acute anginal
pain. The dosing schedule must allow for a drug-free
Contraindications/Precautions: Nitrates are con- period of at least 7 hours to prevent the development of tol-
traindicated in patients with preexisting hypotension, erance to the drug’s effects. It is available as regular release
shock, head injury with increased intracranial pressure, or or extended release tablets, which should be taken on an
head trauma because additive vasodilation would worsen empty stomach at least 30 minutes before a meal. Imdur is
these conditions. Drugs in this class are contraindicated an extended release form of the drug that permits once-
in pericardial tamponade and constrictive pericarditis daily dosing. Adverse effects are the same as the other
because the heart is unable to increase cardiac output to organic nitrates. This drug is pregnancy category C.
maintain blood pressure when the drug causes vasodila-
tion. Sustained release forms of the medicine should not
be given to patients with glaucoma because the drug may
increase intraocular pressure. Nitroglycerin should be
used cautiously in patients with severe liver or renal dis-
ease, as the drug could build to toxic levels. Dehydration
or hypovolemia should be corrected before nitroglycerin is
administered; otherwise serious hypotension may result.
Drug Interactions: Concurrent use with sildenafil
(Viagra) or other phosphodiesterase-5 inhibitors may
cause life-threatening hypotension and cardiovascular
collapse. Nitrates should not be taken within 24 hours
Chapter 35 Pharmacotherapy of Angina Pectoris and Myocardial Infarction 611
35.7 Beta-adrenergic antagonists are sometimes becomes more sensitive to catecholamines, which are
preferred drugs for stable angina. blocked by these medications. When withdrawn abruptly,
adrenergic receptors are activated and rebound excitation
Beta-adrenergic antagonists decrease cardiac workload by occurs. In patients with CAD, this can exacerbate angina,
lowering blood pressure, slowing heart rate, and reducing precipitate tachycardia, or cause an MI.
contractility. These actions on the heart are particularly
beneficial during exercise. Beta blockers are as effective as PROTOTYPE DRUG Atenolol (Tenormin)
the organic nitrates in decreasing the frequency and sever-
ity of anginal episodes caused by exertion. For the phar- Classification Therapeutic: Antianginal drug
macotherapy of CAD, cardioselective beta1 antagonists Pharmacologic: Beta-adrenergic antagonist
are preferred over nonselective beta antagonists because
they are less likely to cause bronchoconstriction (a beta2 Therapeutic Effects and Uses: Atenolol is one of
response). Beta-adrenergic antagonists are not effective the most frequently prescribed drugs in the United States,
for treating variant angina and may, in fact, worsen this due to its relative safety and effectiveness in treating a
condition. number of chronic disorders, including HF, HTN, stable
angina, and post-acute MI. Approved in 1981, it is given by
Beta-adrenergic antagonists offer several advantages the PO route and has a long duration of action that allows
over the organic nitrates. Tolerance does not develop to the for once-daily dosing. Off-label indications for atenolol
antianginal effects of the beta blockers during prolonged include ethanol withdrawal, migraine prophylaxis, and
therapy. They possess antidysrhythmic properties, which unstable angina.
help prevent cardiac conduction abnormalities that are
common complications of patients with ischemic heart dis- Mechanism of Action: Atenolol selectively blocks
ease. Beta blockers are ideal for patients who have both beta1-adrenergic receptors in the heart. Its effectiveness in
HTN and CAD due to their antihypertensive action. They angina is attributed to its ability to slow the heart rate and
have also been shown to reduce the incidence of MI. reduce contractility, both of which lower myocardial oxy-
Because of these cardioprotective actions, beta blockers are gen demand.
considered preferred drugs for the prophylaxis of chronic
angina. The beta blockers used for angina are listed in Table Pharmacokinetics:
35.2. Beta blockers have a variety of indications and addi-
tional details may be found in chapters on adrenergic Route(s) PO, IV
antagonists (see Chapter 16), HTN (see Chapter 34), HF
(see Chapter 36), and dysrhythmias (see Chapter 37). A Absorption 50% absorbed from the gastroin-
Nursing Practice Application for patients receiving beta
blockers is included in Chapter 16. testinal (GI) tract
Beta-adrenergic antagonists are well tolerated by most Distribution Distributed to most tissues
patients. In some patients, fatigue, lethargy, and depression
are reasons for discontinuation of beta-blocker therapy. At including the placenta; secreted
high doses, drugs in this class can cause shortness of breath
and respiratory distress due to bronchoconstriction, and in breast milk; does not readily
they should be used cautiously in patients with asthma or
chronic obstructive pulmonary disease (COPD). Because cross the blood–brain barrier;
beta blockers slow the heart rate and myocardial conduc-
tion velocity, they are contraindicated in patients with bra- 5–15% bound to protein
dycardia and greater than first-degree heart block. Heart
rate should be closely monitored so that it does not fall Primary metabolism Not metabolized
below 50 to 60 beats/min at rest or 100 beats/min during
exercise. Beta blockers are also contraindicated in cardio- Primary excretion Renal (50%), feces (50%)
genic shock and overt cardiac failure.
Onset of action PO: 1 h; IV: immediate
Patients with diabetes who are prescribed beta block-
ers should be aware that the actions of beta blockers can Duration of action PO/IV: 24 h; half-life: 6–7 h
obscure the initial symptoms of hypoglycemia (palpita-
tions, diaphoresis, and nervousness). Because of this, blood Adverse Effects: Oral atenolol is well tolerated by
glucose levels should be monitored more frequently, and most patients. Beta-blocking effects can result in bradycar-
insulin doses may need to be adjusted accordingly. dia and hypotension. Fatigue, weakness, and dizziness are
other potential adverse effects. Nausea and vomiting occur
Beta-adrenergic antagonists should never be abruptly in some patients. Black Box Warning: Abrupt discontinua-
discontinued. With long-term beta-blocker use, the heart tion should be avoided in patients with ischemic heart dis-
ease because this may worsen angina or cause an MI. Doses
should be gradually reduced over a 1- to 2-week period if
possible. If angina worsens during the withdrawal period,
the drug should be reinstituted, at least temporarily.
Contraindications/Precautions: Because atenolol
slows heart rate, it should not be used by patients with
severe bradycardia, advanced atrioventricular (AV) heart
block, cardiogenic shock, or decompensated HF. Due to its
612 Unit 5 Pharmacology of the Cardiovascular System
vasodilation effects, it is contraindicated in patients with ischemic heart disease are discussed in this section. The
severe hypotension. Patients with severe chronic kidney CCBs used for angina are listed in Table 35.2.
disease (CKD) should receive reduced doses or have lon-
ger time intervals between doses to prevent drug accumu- CCBs have several actions on the cardiovascular sys-
lation. Because atenolol reduces cardiac output, patients tem that benefit a patient with angina. Most importantly,
with stroke or low cerebrovascular blood flow should not CCBs relax arteriolar smooth muscle, thus reducing blood
receive this drug. Patients with major depression should pressure. This reduction in afterload decreases myocardial
not receive beta blockers because these drugs can worsen oxygen demand. Some of the CCBs also slow cardiac con-
this condition. duction velocity through the AV node, thereby decreasing
heart rate and contributing to the reduced cardiac work-
Drug Interactions: Anticholinergics may decrease the load. An additional effect of the CCBs is their ability to
absorption of atenolol from the GI tract. Use with digoxin dilate the coronary arteries, bringing more oxygen to the
or other antidysrhythmic drugs that depress myocardial myocardium. This vasodilation is especially important in
conduction may cause AV heart block. Concurrent use of patients with variant angina. CCBs are considered pre-
atenolol with other antihypertensives may result in addi- ferred drugs for that condition. For stable, exertional
tive hypotension. Although CCBs are often used concur- angina, they may be used as monotherapy in patients
rently with beta blockers for their additive therapeutic unable to tolerate beta blockers. In patients with persistent
actions, patients must be monitored carefully due to the symptoms, CCBs may be administered concurrently with
possibility of excessive cardiac suppression. Herbal/Food: organic nitrates or beta blockers.
Use with hawthorn may result in additive hypotension.
Adverse effects of CCBs are generally not serious and
Pregnancy: Category D. are related to vasodilation: headache, dizziness, and edema
of the ankles and feet. CCBs should be used with caution in
Treatment of Overdose: The most serious symptoms patients taking other cardiovascular medications that slow
of atenolol overdose are hypotension and bradycardia. conduction through the AV node, particularly digoxin or
Atropine or isoproterenol may be used to reverse brady- beta-adrenergic antagonists. The combined effects of these
cardia, or a cardiac pacemaker may be used to stabilize drugs may cause partial or complete AV heart block, HF, or
cardiac rhythm. Atenolol can be removed from the sys- dysrhythmias. Some CCBs worsen HF by reducing myo-
temic circulation by hemodialysis. cardial contractility.
Nursing Responsibilities: Key nursing implications CONNECTION Checkpoint 35.3
for patients receiving atenolol are included in the Nursing
Practice Application for Patients Receiving Pharmacother- For patients with asthma, calcium channel blockers are generally
apy with Adrenergic Antagonists in Chapter 16. the preferred antianginal drugs, rather than beta-adrenergic antag-
onists. From what you learned in Chapter 16, why would calcium
Drugs Similar to Atenolol (Tenormin) channel blockers be preferred for patients with this comorbid condi-
tion? Answers to Connection Checkpoint questions are available on the
Atenolol, metoprolol, propranolol, and timolol are equally faculty resources site. Please consult with your instructor.
effective in treating chronic angina. Information on these
beta-adrenergic antagonists is presented in other chapters. Pathophysiology
The student should review the general information on beta of Myocardial Infarction
blockers in Chapter 16. Several are featured as prototype
drugs: metoprolol (Lopressor, Toprol XL) and propranolol 35.9 Early diagnosis and pharmacotherapy
(Inderal, InnoPran XL) in Chapter 16 and timolol is fea- of myocardial infarction increase chances of
tured as an antiglaucoma medication in Chapter 74. survival.
35.8 Calcium channel blockers are effective Myocardial infarctions (MIs), blood clots that block coro-
at reducing myocardial oxygen demand and nary arteries, are responsible for a substantial number of
treating stable and variant angina. deaths each year. Many patients die before reaching a
medical facility for treatment, or within 48 hours following
Blockade of calcium channels has a number of effects on the initial MI, due to complications of the disorder. Clearly,
the heart, most of which are similar to those of beta block- MI is a serious and frightening disease and one responsi-
ers. Although the first approved indication for CCBs was ble for a large percentage of sudden deaths.
for the treatment of angina, these medications are also
used for HTN and dysrhythmias. The mechanisms of cal- The primary cause of MI is advanced CAD: atheroscle-
cium channel blockade by drugs in this class are presented rotic plaque accumulation in the endothelial wall of one or
in detail in Chapter 30. The actions of CCBs relevant to more branches of the coronary arteries. Pieces of unstable
Chapter 35 Pharmacotherapy of Angina Pectoris and Myocardial Infarction 613
Table 35.3 Changes in Blood Test Values with Acute Myocardial Infarction
Blood Test Initial Elevation Peak Elevation Duration Normal Range
After MI After MI of Elevation
Males: 5–35 mcg/L
CK: total creatine kinase (also called 3–8 h 12–24 h 2–4 days Females: 5–25 mcg/L
creatine phosphokinase) 0–3% of CK
Males: 15–20 mm/h
CK-MB 4–6 h 10–24 h 3–4 days Females: 20–30 mm/h
ESR (erythrocyte sedimentation rate) 2–3 days 4–5 days Several weeks 70–250 units/L
12–90 ng/mL
LDH: total (lactate dehydrogenase) 12–24 h 2–5 days 6–12 days 0.1–0.5 mcg/L
Myoglobin 2–6 h 8–12 h 1–2 days less than 0.2 mcg/L
Troponin I 1–3 h 24–36 h 5–9 days
Troponin T 1–3 h 24–36 h 10–14 days
plaque in a coronary artery can ulcerate or rupture and • Restore blood supply (reperfusion) to the damaged
lodge in a small vessel serving a portion of the myocar- myocardium as quickly as possible through the use of
dium. Exposed plaque activates the clotting cascade, result- thrombolytics.
ing in platelet aggregation. A new clot quickly builds on
the existing plaque, making obstruction of the vessel immi- • Reduce myocardial oxygen demand with organic
nent. A detailed discussion of coagulation and clot forma- nitrates, beta blockers, or CCBs to lower the risk of
tion is included in Chapter 38. additional infarctions.
Deprived of adequate oxygen supply, the obstructed • Control or prevent MI-associated dysrhythmias with
region of the myocardium becomes ischemic. The myo- amiodarone (Cordarone), beta blockers, or other
cytes shift to anaerobic metabolism after only 8 to 10 sec- antidysrhythmics.
onds of oxygen loss. Anaerobic metabolism, however, is
inefficient and cannot produce enough ATP to keep the • Reduce post-MI mortality with aspirin, beta blockers,
heart beating efficiently for prolonged periods. Lactic acid and ACE inhibitors.
accumulates, causing acidosis, which affects contractility
and suppresses normal conduction across the myocardium. • Manage severe MI pain and associated anxiety with
As contractility diminishes, the patient may experience HF. narcotic analgesics.
Myocytes will begin to die in about 20 minutes unless the
blood supply is quickly restored. The necrosis of myocar- Pharmacologic Management of
dial tissue, which may be irreversible, releases certain Myocardial Infarction
“marker” enzymes, such as creatine kinase (CK) or cardiac-
specific troponin (cTn), which can be measured in the blood 35.10 Thrombolytic drugs can restore perfusion
to confirm the patient has experienced an MI. to ischemic regions of the myocardium if
administered soon after a myocardial infarction.
Extreme chest pain is often the first symptom of MI and
the one that drives most patients to seek medical attention. An Thrombolytic therapy is administered to dissolve clots
electrocardiogram (ECG) can give important clues as to the obstructing the coronary arteries in order to restore circu-
extent and location of the MI because the infarcted region of lation to the ischemic region of the myocardium. Clinical
the myocardium is nonconducting, producing abnormal Q research has confirmed that quick restoration of coronary
waves, T waves, and ST segments. Patients showing elevation circulation reduces mortality following an acute MI. After
of the ST segment on the ECG are at highest risk for death and the clot is successfully dissolved, anticoagulant or anti-
require immediate treatment. Laboratory test results are used platelet therapy is initiated to prevent additional thrombus
to aid in diagnosis and monitor progress after an MI. Table 35.3 formation. Dosages and descriptions of the various throm-
describes some of these important laboratory values. bolytics are listed in Chapter 38 where alteplase (Activase)
is presented as a drug prototype for this class. A Nursing
Early diagnosis and prompt pharmacotherapy of MI Practice Application feature for thrombolytics is also
can significantly reduce the mortality and long-term dis- included in Chapter 38.
ability associated with MI. Drugs used in the management
of MI are shown in Table 35.2. The pharmacologic goals for Thrombolytics are most effective when administered
treating a patient with an acute MI are as follows: from 20 minutes to 12 hours after the onset of MI symp-
toms. Ideally, the time from presentation in the emergency
• If cardiac arrest has occurred, restart the heart and department (ED) to administration of the thrombolytic
restore normal blood pressure with vasopressors. should be 30 minutes or less. Research has demonstrated
little or no therapeutic benefit if the drugs are administered
614 Unit 5 Pharmacology of the Cardiovascular System
24 hours or more after the MI onset. In addition, research formation of C-reactive protein, which is associated with
suggests that patients over age 75 do not experience an increased risk of MI.
reduced mortality from these drugs. Because thrombolytic
therapy is expensive and has the potential to produce seri- The major concern over aspirin use is its tendency to
ous adverse effects, it is important to identify circumstances promote GI bleeding in some patients. This could be a seri-
that contribute to successful therapy. The development of ous adverse effect, given that some post-MI patients receive
clinical practice guidelines for thrombolytic therapy anticoagulants. However, the benefits of taking aspirin fol-
remains an area of active research. Pharmacotherapy Illus- lowing an acute MI generally outweigh the risks for most
trated 35.2 illustrates this reperfusion process. patients. Aspirin maintenance therapy can cut the risk of
death due to a subsequent MI by as much as 50% in some
Thrombolytics exhibit a narrow margin of safety populations. Furthermore, the low doses used in mainte-
between dissolving clots and producing serious adverse nance therapy (75–150 mg/day) rarely cause GI bleeding.
effects. Although therapy is usually targeted to a single Additional discussion of aspirin may be found in
thrombus in a specific artery, once infused in the blood the Chapter 41, where it is featured as a prototype drug.
drugs travel to all vessels and may cause adverse effects
anywhere in the body. The primary risk of thrombolytics is Anticoagulants and
excessive bleeding from interference with the clotting pro- Antiplatelet Drugs
cess. Vital signs must be monitored continuously and signs
of bleeding call for discontinuation of therapy. Because Drugs from several classes are routinely used to prevent
these medications have a brief half-life and are rapidly MIs by altering the coagulation properties of the blood. The
destroyed in the blood, stopping the infusion normally primary goal for using these coagulation modifiers is to pre-
results in the rapid termination of adverse effects. Physical vent new thrombi from being formed or from enlarging.
and laboratory assessment for the possibility of abnormal
bleeding should continue for 2 to 4 days after therapy is CONNECTIONS: Treating the
discontinued. Diverse Patient
Thrombolytic therapy is contraindicated for many con- The Effect of the CYP2C19 Genotype on
ditions, including recent trauma or surgery, internal bleed- Therapeutic Treatment Outcomes for
ing (other than menses), active peptic ulcer, postpartum Cardiovascular Patients
(within 10 days), history of intracranial hemorrhage, sus-
pected ischemic stroke within the past 3 months, bleeding Recall from Chapter 11 that genetic polymorphisms in the
disorders, severe liver disease, or thrombocytopenia. Cau- CYP450 enzyme system have an effect on the metabolism of
tion should be used when administering thrombolytics to drugs, potentially rendering them less useful due to slowed
patients taking anticoagulants or antiplatelet drugs. metabolism. Genetic CYP450 variations also have other
effects, such as on platelet activity (Sun et al., 2016; Wang,
35.11 Drugs are used to treat the symptoms and Cai, Zhou, Zhang, & Liu, 2016). People of Asian descent and
complications of acute myocardial infarction. some African Americans are known to carry the CYP2C19
genotype variant.
The most immediate needs of the patient with MI are to
ensure that the heart continues to function adequately and In several recent studies, patients with the CYP2C19 gen-
that permanent damage from the infarction is minimized. otype were found to have higher platelet activity and less
In addition to restoring perfusion to the myocardium with response to clopidogrel and similar drugs after stenting proce-
thrombolytic therapy, drugs from several other classes are dures for coronary and carotid artery blockage (Arima et al.,
administered soon after the onset of symptoms to prevent 2015; González et al., 2016; Sun et al., 2016; Tabata et al.,
reinfarction and to ultimately reduce mortality from the 2016). The risk for additional cardiovascular events was noted
episode. to be higher in those with the variation, especially in the acute
stage (Arima et al., 2015).
Aspirin
Further study is needed to determine whether patients
Unless contraindicated, 160 to 325 mg of aspirin is given as with the CYP2C19 genotype would benefit from higher doses
soon as an MI is suspected. Research has determined that of clopidogrel or similar drugs, or whether combining those
aspirin use in the weeks following an acute MI dramati- drugs with aspirin would be beneficial. At this time, routine
cally reduces mortality. These effects from aspirin are screening for CYP2C19 is not recommended (Bhopalwala,
believed to be due to several mechanisms. Clearly, aspirin Hong, Khan, Valentin, & Badawi, 2015), but at-risk patients
has antiplatelet action that reduces platelet aggregation who may be carriers of the genotype should be carefully
and thus the formation or enlargement of thrombi. Addi- assessed post-stent, especially in the acute phase, for subop-
tionally, its anti-inflammatory properties decrease the timal response to clopidogrel and for additional cardiovascular
complications.
Chapter 35 Pharmacotherapy of Angina Pectoris and Myocardial Infarction 615
Pharmacotherapy Illustrated 35.2
Thrombolytic Pharmacotherapy
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616 Unit 5 Pharmacology of the Cardiovascular System
Anticoagulants: Upon diagnosis of MI in the ED, Nitrates
patients may be placed on the anticoagulant heparin to
prevent the formation of additional thrombi. Unfraction- The value of nitrates in treating myocardial ischemia was
ated heparin therapy is sometimes continued for 48 hours, presented in Section 35.6. Nitrates have additional uses in
or until percutaneous coronary intervention (PCI) is com- the patient with a suspected MI. At the initial onset of chest
pleted, at which time the patients are switched to warfarin pain, sublingual nitroglycerin is administered to assist in the
(Coumadin) or an antiplatelet drug. An alternative is to diagnosis, and three doses may be taken 5 minutes apart.
administer a low-molecular-weight heparin, such as Pain that persists 5 to 10 minutes after the initial dose may
enoxaparin (Lovenox). A comparison of these different indicate an MI, and the patient should seek medical assis-
anticoagulants is presented in Chapter 38, along with pro- tance. Thus, nitrates serve a diagnostic role for MI patients.
totype drug features for heparin and warfarin.
Patients with persistent pain, HF, or severe HTN may
Some patients may remain on anticoagulant therapy receive IV nitroglycerin for 24 hours following the onset of
after hospital discharge. These include patients at high risk pain. The arterial and venous dilation produced by the
for thromboembolic disease and those with chronic atrial drug reduces myocardial oxygen demand. Organic nitrates
fibrillation. Research has not shown that the use of warfa- also relieve coronary artery vasospasm, which may be
rin lowers mortality in post-MI patients; however, it does present during the acute stage of MI. On patient discharge
increase the risk of bleeding. For most patients, anticoagu- from the hospital, organic nitrates are discontinued, unless
lation with aspirin or antiplatelet drugs is sufficient for the patient needs them for relief of stable anginal pain.
protection from thromboembolic events. The long-term use
of heparin in post-MI patients is limited unless other condi- Beta-Adrenergic Antagonists
tions are present that warrant the use of the drug.
Beta blockers have the ability to slow heart rate, decrease con-
Adenosine diphosphate receptor blockers: Clopido- tractility, and reduce blood pressure. These three factors
grel (Plavix), ticlopidine (Ticlid), ticagrelor (Brilinta), and reduce myocardial oxygen demand, which is critical for
prasugrel (Effient) are antiplatelet drugs approved for the patients experiencing a recent MI. In addition, they slow
prevention of thrombotic stroke and MI. Research has dem- impulse conduction through the heart, suppressing dys-
onstrated that these drugs reduce mortality associated with rhythmias, which are serious and sometimes fatal complica-
thromboembolic events. They are considered for antiplate- tions following an MI. Research has clearly demonstrated
let therapy in patients who are allergic to aspirin or at high that beta blockers can reduce MI-associated mortality if
risk for GI bleeding from aspirin. Some protocols call for administered within 8 hours of MI onset. These drugs may be
combination therapy with clopidogrel and aspirin. Clopi- initially administered IV, and then switched to oral dosing for
dogrel is one of the most frequently used drugs for preven- chronic therapy. Unless contraindicated, beta-blocker therapy
tion of MI, and is featured as a prototype in Chapter 38. continues for the remainder of the patient’s life. For patients
unable to tolerate beta blockers, CCBs are an alternative. The
Glycoprotein IIb/IIIa inhibitors: Glycoprotein IIb/IIIa beta blockers most often used for MI are listed in Table 35.2.
is a receptor found on the surface of platelets. Glycopro-
tein IIb/IIIa inhibitors are sometimes indicated to prevent Angiotensin-Converting
thrombi from forming in patients with unstable angina or Enzyme Inhibitors
MI or for those undergoing PCI procedures such as angio-
plasty. The most common drug in this class, abciximab Clinical research has demonstrated increased survival for
(ReoPro), is infused at the time of PCI and continued for 12 patients administered the angiotensin-converting enzyme
hours after the procedure is completed to prevent reinfarc- (ACE) inhibitors captopril (Capoten) or lisinopril (Prinivil,
tion. These drugs may be used in combination therapy Zestoretic) following an acute MI. These drugs are most
with aspirin and heparin, thus increasing the need for effective when therapy is started within 24 hours after the
careful monitoring for bleeding. Doses for the glycoprotein onset of symptoms. Oral doses are normally begun after
IIb/IIIa inhibitors and a prototype feature for abciximab thrombolytic therapy is completed and the patient’s condi-
are found in Chapter 38. tion has stabilized. IV therapy may be used during the
early stages of MI pharmacotherapy.
Other antiplatelet drugs: In 2014 the Food and Drug
Administration (FDA) approved the first in a new class of The benefit of ACE inhibitors is believed to be due to
antiplatelet drugs called the protease-activated receptor-1 their ability to prevent cardiac remodeling and their ability
antagonists. Vorapaxar (Zontivity) is administered to to suppress dysrhythmias. Unless otherwise contraindi-
reduce the incidence of thrombotic events in patients with cated, post-MI patients should receive an ACE inhibitor
a history of MI or other clotting disorders. It is usually indefinitely to prevent HF and future ischemic develop-
given in combination with aspirin or clopidogrel. ment. The mechanisms of action and prototype features for
several ACE inhibitors may be found in Chapter 31.
Chapter 35 Pharmacotherapy of Angina Pectoris and Myocardial Infarction 617
Pain Management Cardiopulmonary resuscitation (CPR) must be initi-
ated as quickly as possible to restore ventilation and blood
The pain associated with an MI can be debilitating and circulation to avoid hypoxic injury to the tissues. Electrical
stressful, creating an increased workload for the myocar- defibrillation is used to restore normal cardiac rhythm.
dium. Pain control is essential in order to ensure patient
comfort and to reduce stress. Narcotic analgesics such as Pharmacotherapy is an important component of CPR.
morphine sulfate or meperidine (Demerol) are given to The primary drugs used in the initial phase of resuscitation
ease extreme pain, sedate the anxious patient, and decrease are sympathomimetics, and epinephrine is the preferred
the workload of the heart. Pharmacology of the analgesics drug. Sympathomimetics cause vasoconstriction, immedi-
was presented in Chapter 25. ately raising cerebral, coronary, and systemic blood pres-
sure. Vasopressin, also called antidiuretic hormone, is an
PharmFACT alternative therapy.
About 1.5 million Americans experience a new or recurrent MI Following restoration of cardiac function and venti-
each year. About one third of the patients experiencing an MI lation, it is critical that the heart maintain normal conduc-
will die within 24 hours of the onset of the attack (Zafari, 2017). tion in order to prevent the recurrence of ventricular
fibrillation or the establishment of other serious
35.12 Vasopressors are used following dysrhythmias. Historically, lidocaine has been the pre-
cardiopulmonary arrest to reestablish coronary ferred drug for ventricular dysrhythmias associated with
and cerebral blood flow. MI. Clinical research, however, has shown that the
administration of amiodarone (Cordarone) may result in
Cardiopulmonary arrest is a complete stoppage of heart improved patient survival. If the risk of dysrhythmia is
and lungs activity, usually resulting from a dysrhythmia high, a loading dose of amiodarone is given by infusion,
such as ventricular fibrillation or pulseless ventricular and the patient is switched to oral forms after a therapeu-
tachycardia. Most patients who experience cardiopulmo- tic plasma level of the drug has been achieved.
nary arrest have underlying CAD. Amiodarone is featured as an antidysrhythmic drug pro-
totype in Chapter 37.
CONNECTIONS: NURSING PRACTICE APPLICATION
Patients Receiving Pharmacotherapy with Organic Nitrates for Angina and Myocardial Infarction
Assessment
Baseline assessment prior to administration:
• Obtain a complete health history: cardiovascular (including previous MI, HF, valvular disease), cerebrovascular and neurologic (including level of con-
sciousness, history of stroke, head injury, increased intracranial pressure), renal or hepatic dysfunction, dysrhythmias, pregnancy, or lactation. Obtain
a drug history including allergies, current prescription and over-the-counter (OTC) drugs, herbal preparations, and alcohol use. Be aware that use of
erectile dysfunction drugs (e.g., sildenafil [Viagra], vardenafil [Levitra], or tadalafil [Cialis]) within the past 24–48 h may cause profound and prolonged
hypotension when nitrates are administered. Be alert to possible drug interactions.
• Obtain baseline weight, vital signs (especially blood pressure and pulse), and ECG. Assess for location and character of angina if currently present.
• Evaluate appropriate laboratory findings, electrolytes, renal function studies, and lipid profiles. Troponin and/or CK-MB laboratory values may be
ordered to rule out MI.
• 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., chest pain has subsided or has significantly lessened), heart rate and blood pressure remain within normal
limits, ECG remains within normal limits without signs of ischemia or infarction.
• Continue periodic monitoring of ECG for ischemia or infarction.
• Continue frequent monitoring of blood pressure and pulse whenever IV nitrates are used or when giving rapid-acting (e.g., SL) nitrates. With
SL nitrates, take blood pressure before and 5 min after giving dose and hold the drug if blood pressure is less than 90/60 mmHg, pulse over
100 beats/min, or parameters as ordered, and check with the healthcare provider before continuing to give the drug.
• Assess for and promptly report adverse effects: severe hypotension, dysrhythmias, reflex tachycardia (from too rapid decrease in blood pressure or
severe hypotension), headache that does not subside within 15–20 min, or when accompanied by neurologic changes or decreased urinary output.
Immediately report severe hypotension, seizures, dysrhythmias, or palpitations. Chest pain remaining present after three sublingual nitroglycerin tablets
given 5 min apart should be reported immediately, even if pain has lessened, as this may be a sign of impending ischemia or infarction.
Implementation
Interventions and (Rationales) Patient-Centered Care
Ensuring therapeutic effects: • Ask the patient to briefly describe the location and character of pain
• Continue frequent assessments as above for therapeutic effects.
(use a pain rating scale for rapid assessment) prior to and after giving
(Because nitrates cause vasodilation, preload and afterload diminish,
decreasing myocardial oxygenation needs, and chest pain diminishes.) nitrates to assess for extent of relief. Correlate with objective assess-
ment findings. Lifespan and Diverse Patients: Due to differences
in reporting pain, use subjective and objective data in evaluating pain
relief in ethnically diverse or older adult patients. (continued )
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