Adrenergic Antagonists 31
Learning Objectives
Upon completion of this chapter, you will be able to:
1. Describe the effects of adrenergic blocking agents on adrenergic receptors, correlating these effects with their clinical effects.
2. Describe the therapeutic actions, indications, pharmacokinetics, contraindications and cautions, most common adverse reactions, and important drug–drug interactions associated with adrenergic blocking agents.
3. Discuss the use of adrenergic blocking agents across the lifespan.
4. Compare and contrast the prototype drugs labetalol, phentolamine, doxazosin, propranolol, and atenolol with other adrenergic blocking agents.
5. Outline the nursing considerations, including important teaching points, for patients receiving an adrenergic blocking agent.
Glossary of Key Terms
adrenergic-receptor-site specificity: a drug’s affinity for only adrenergic receptor sites; certain drugs may have specific affinity for only alpha- or only beta-adrenergic receptor sites
alpha1-selective adrenergic blocking agents: drugs that block the postsynaptic alpha1-receptor sites, causing a decrease in vascular tone and a vasodilation that leads to a fall in blood pressure; these drugs do not block the presynaptic alpha2-receptor sites, and therefore the reflex tachycardia that accompanies a fall in blood pressure does not occur
beta-adrenergic blocking agents: drugs that, at therapeutic levels, selectively block the beta-receptors of the sympathetic nervous system
beta1-selective adrenergic blocking agents: drugs that, at therapeutic levels, specifically block the beta1-receptors in the sympathetic nervous system while not blocking the beta2-receptors and resultant effects on the respiratory system
bronchodilation: relaxation of the muscles in the bronchi, resulting in a widening of the bronchi; an effect of sympathetic stimulation
pheochromocytoma: a tumor of the chromaffin cells of the adrenal medulla that periodically releases large amounts of norepinephrine and epinephrine into the system with resultant severe hypertension and tachycardia sympatholytic: a drug that lyses, or blocks, the effects of the sympathetic nervous system
Adrenergic antagonists or adrenergic blocking agents are also called sympatholytic drugs because they lyse, or block, the effects of the sympathetic nervous system (SNS). The therapeutic and adverse effects associated with these drugs are related to their adrenergic- receptor-site specificity; that is, the ability to react with specific adrenergic receptor sites without activating them, thus preventing the typical manifestations of SNS activation. By occupying the adrenergic receptor site, they prevent norepinephrine released from the nerve terminal or from the adrenal medulla from activating the receptor, thus blocking the SNS effects.
The adrenergic blockers have varying degrees of specificity for the adrenergic receptor sites. For example, some can interact with both alpha- and beta-receptors. Some are specific to alpha-receptors, with some being even more specific to just alpha1-receptors. Other adrenergic blockers interact with both beta1- and beta2-receptors, whereas others interact with just either beta1- or beta2-receptors. This specificity allows the clinician to select a drug that will have the desired therapeutic effects without the undesired effects that occur when the entire SNS is blocked. In general, however, the specificity of adrenergic blocking agents depends on the concentration of drug in the body. Most specificity is lost with higher serum drug levels (Figure 31.1).
FIGURE 31.1 Site of action of adrenergic receptors and resultant physiological responses.
These responses are blocked by adrenergic blockers.
The effects of the adrenergic blocking agents vary with the age of the patient (Box 31.1). Various alternative and herbal remedies also can affect these drugs (Box 31.2).
BOX 31.1
Drug Therapy Across the Lifespan
Adrenergic Blocking Agents Children
Children are at greater risk for complications associated with the use of adrenergic blocking agents, including bradycardia, difficulty breathing, and changes in glucose metabolism. The safety and efficacy for use of these drugs has not been established for children younger than 18 years of age. If one of these drugs is used the dose for these agents needs to be calculated from the child’s body weight and age. It is good practice to have a second person check the dose calculation before administering the drug to avoid potential toxic effects. Three adrenergic blocking agents have established pediatric doses, and they might be the drugs to consider when one is needed: Prazosin is used to treat hypertension, and phentolamine, which is used during surgery for pheochromocytoma. Children should be carefully monitored and supported when these drugs are given. Propranolol as an oral solution form is used for the treatment of proliferating infantile hemoangioma in children 5 weeks to 5 months of age
Adults
Adults being treated with adrenergic blocking agents should be cautioned about the many adverse effects associated with the drugs. Patients with diabetes need to be reeducated about ways to monitor themselves for hyperglycemia and hypoglycemia because the sympathetic reaction (sweating, feeling tense, increased heart rate, rapid breathing) usually alerts patients that there is a problem with their glucose levels.
Patients with severe thyroid disease are also at high risk for serious adverse effects when taking these drugs, and if one of them is needed the patient should be monitored very closely. Propranolol and metoprolol are associated with more CNS adverse effects than other adrenergic blockers, and patients who have CNS complications already or who develop CNS problems while taking an adrenergic blocker might do better with a different agent.
In general, there are no adequate studies about the effects of adrenergic blockers during pregnancy and lactation, and they should be used only in those situations in which the benefit to the mother is greater than the risk to the fetus or neonate.
Adrenergic blockers can affect labor, and babies born to mothers taking these drugs
teratogenic in animal studies. Because of a similar risk of adverse reactions on the baby, nursing mothers should find another way to feed the baby if an adrenergic blocking drug is needed.
Older Adults
Older patients are more likely to experience the adverse effects associated with these drugs—CNS, CV, GI, and respiratory effects. Because older patients often also have renal or hepatic impairment, they are more likely to have toxic levels of the drug related to changes in metabolism and excretion. The older patient should be started on lower doses of the drugs and should be monitored very closely for potentially serious arrhythmias or blood pressure changes. Bisoprolol is often a drug of choice for older patients who require an adrenergic blocker for hypertension because it is not associated with as many problems in the elderly and regular dosing profiles can be used.
BOX 31.2
Herbal and Alternative Therapies
Patients who use alternative therapies as part of their daily regimen should be cautioned about potential increased adrenergic blocking effects if the following alternative therapies are combined with adrenergic blocking agents:
Ginseng, sage—increased antihypertensive effects (risk of hypotension and increased CNS effects)
Xuan shen, nightshade—slow heart rate (risk of severe bradycardia and reflex arrhythmias)
Celery, coriander, di huang, fenugreek, goldenseal, Java plum, xuan shen—lower blood glucose (increased risk of severe hypoglycemia)
Saw palmetto—increased urinary tract complications
Patients who are prescribed an adrenergic blocking drug should be cautioned about the use of herbs, teas, and alternative medicines. If a patient feels that one of these agents is needed the health care provider should be consulted and appropriate precautions should be taken to ensure that the patient is able to achieve the most therapeutic effects with the least adverse effects while taking the drug.
Nonselective Adrenergic Blocking Agents
Drugs that block both alpha- and beta-adrenergic receptors are primarily used to treat cardiac-related conditions. These drugs include amiodarone (Cordarone), carvedilol (Coreg), and labetalol (Trandate) (see Table 31.1).
Table 31.1 Drugs in Focus: Nonselective Adrenergic Blocking Agents
HF, heart failure.
Therapeutic Actions and Indications
Adrenergic blocking agents competitively block the effects of norepinephrine at alpha-and beta-receptors throughout the SNS. Subsequently, this results in lower blood pressure, slower pulse rate, and increased renal perfusion with decreased renin levels. Most of these drugs are indicated to treat essential hypertension, alone or in combination with diuretics.
Labetalol is used IV and orally to treat hypertension. It also can be used with diuretics and has been used to treat hypertension associated with pheochromocytoma (tumor of the chromaffin cells of the adrenal medulla, which periodically releases large amounts of norepinephrine and epinephrine into the system) and clonidine withdrawal. Amiodarone, which is available in oral and IV forms, is saved for serious emergencies and only used as an antiarrhythmic (see Chapter 45). Carvedilol is only available orally and is used to treat hypertension, as well as heart failure (HF) and left ventricular dysfunction after myocardial infarction (MI). Table 31.1 shows Usual Indications for each of these agents.
Pharmacokinetics
These drugs are well absorbed when given orally and are distributed throughout the body when given IV or orally. They are metabolized in the liver and excreted in feces and urine.
The half-life varies with the particular drug and preparation.
Contraindications and Cautions
The nonselective adrenergic blocking agents are contraindicated in patients with known hypersensitivity to any component of the drug to avoid potentially serious hypersensitivity reactions; with bradycardia or heart blocks, which could be worsened by the slowed heart rate and conduction; with asthma, which could be exacerbated by the loss of norepinephrine’s effect of bronchodilation; with shock or HF, which could become worse with the loss of the sympathetic reaction; and who are lactating because of the potential adverse effects on neonates.
These drugs should be used with caution in patients with diabetes because the disorder could be aggravated by the blocked sympathetic response and because the usual signs and symptoms of hypoglycemia and hyperglycemia are masked with the SNS blockade. Caution also should be used in patients with bronchospasm, which could progress to respiratory distress due to the loss of norepinephrine’s bronchodilating actions; and in pregnancy because there are no well-defined studies to evaluate the potential risk to the fetus. The drugs should only be used if the benefit to the mother clearly outweighs the potential risk to the fetus.
Adverse Effects
The adverse effects associated with the use of nonselective adrenergic blocking agents are usually associated with the drug’s effects on the SNS. These effects can include dizziness, paresthesias, insomnia, depression, fatigue, and vertigo, which are related to the blocking of norepinephrine’s effect in the central nervous system (CNS). Nausea, vomiting, diarrhea, anorexia, and flatulence are associated with the loss of the balancing sympathetic effect on the gastrointestinal (GI) tract and increased parasympathetic dominance. Cardiac arrhythmias, hypotension, HF, pulmonary edema, and cerebrovascular accident, or stroke, are related to the lack of stimulatory effects and loss of vascular tone in the cardiovascular (CV) system.
Bronchospasm, cough, rhinitis, and bronchial obstruction are related to loss of bronchodilation of the respiratory tract and vasodilation of mucous membrane vessels (Figure 31.2). Other effects reported include decreased exercise tolerance, hypoglycemia, and rash related to the sympathetic blocking effects. Abruptly stopping these drugs after long-term therapy can result in MI, stroke, and arrhythmias related to an increased hypersensitivity to catecholamines that develops when the receptor sites have been blocked. Carvedilol has been associated with hepatic failure related to its effects on the liver.
FIGURE 31.2 Variety of adverse effects and toxicities associated with adrenergic blocking antagonists.
Clinically Important Drug–Drug Interactions
There is increased risk of excessive hypotension if any of these drugs is combined with volatile liquid general anesthetics such as enflurane, halothane, or isoflurane. The effectiveness of diabetic agents is increased, leading to hypoglycemia when such agents are used with these drugs; patients should be monitored closely and dose adjustments made as needed. In addition, carvedilol has been associated with potentially dangerous conduction system disturbances when combined with verapamil or diltiazem; if this combination is used the patient requires continuous monitoring.
Prototype Summary:Labetalol
Indications: Hypertension, alone or in combination with other drugs; off-label uses—
control of blood pressure in pheochromocytoma, clonidine withdrawal hypertension.
Actions: Competitively blocks alpha- and beta-receptor sites in the SNS, leading to lower blood pressure without reflex tachycardia and decreased renin levels.
Pharmacokinetics:
T1/2: 6 to 8 hours; metabolized in the liver; excreted in the urine.
Adverse Effects: Dizziness, vertigo, fatigue, gastric pain, flatulence, impotence, bronchospasm, dyspnea, cough, decreased exercise tolerance.
Nursing Considerations for Patients Receiving Nonselective Adrenergic Blocking Agents
Assessment: History and Examination
Assess for contraindications or cautions: Any known allergies to these to avoid hypersensitivity reactions; presence of bradycardia or heart blocks, which could be worsened by the slowing of heart rate and conduction; asthma or bronchospasm, which could be exacerbated by the loss of the bronchodilation effect of norepinephrine; shock or HF, which could worsen with the loss of the sympathetic reaction; diabetes, which could be aggravated by the blocking of the sympathetic response and the masking of the usual signs and symptoms of hypoglycemia and hyperglycemia; and pregnancy or lactation status because of the potential adverse effects on the fetus or neonate.
Perform a physical assessment to establish baseline data for determining the effectiveness of the drug and the occurrence of any adverse effects associated with drug therapy; assess the level of orientation and for any complaints of dizziness, paresthesias, or vertigo.
Monitor vital signs and assess CV status, including pulse, blood pressure, and cardiac output, to evaluate for possible cardiac effects; obtain an electrocardiogram (ECG) as ordered to assess for possible irregularities in rate or rhythm; assess respiratory rate and auscultate lungs to determine the presence of any adventitious sounds; observe for ease of breathing, and report any signs and symptoms of bronchospasm or respiratory distress; and monitor GI activity to determine the need for interventions to deal with increased activity.
Monitor the results of laboratory tests such as renal and liver function studies and electrolyte levels to determine the need for possible dose adjustment; monitor blood glucose levels to evaluate for hyperglycemia or hypoglycemia.
Nursing Diagnoses
Nursing diagnoses related to drug therapy might include the following:
Decreased cardiac output related to CV effects
Ineffective airway clearance related to lack of bronchodilating effects Risk for injury related to CNS effects
Diarrhea related to increased parasympathetic activity Deficient knowledge regarding drug therapy
Planning
The patient will receive the best therapeutic effect from the drug therapy.
The patient will have limited adverse effects to the drug therapy.
The patient will have an understanding of the drug therapy, adverse effects to anticipate, and measures to relieve discomfort and improve safety.
Implementation with Rationale
Do not discontinue abruptly after chronic therapy because hypersensitivity to catecholamines may develop and the patient could have a severe reaction; taper drug slowly over 2 weeks, monitoring the patient.
Consult with the physician about withdrawing the drug before surgery because withdrawal is controversial; effects on the sympathetic system after surgery can cause problems.
Encourage the patient to adopt lifestyle changes, including diet, exercise, smoking cessation, and stress reduction, to aid in lowering blood pressure.
Assess heart rate for changes that might suggest arrhythmias. Obtain blood pressure in various positions to assess for orthostatic hypotension.
Institute safety precautions especially if the patient complains of dizziness, fatigue, or vertigo or if orthostatic hypotension occurs to prevent injury to the patient.
Monitor GI function and need for increased access to bathroom facilities and need for increased fluid intake related to diarrhea.
Monitor for any sign of liver failure to arrange to discontinue the drug if this occurs (this effect is more likely to happen with carvedilol).
Offer support and encouragement to help the patient deal with the drug regimen.
Provide thorough patient teaching, including drug name, dosage, and schedule for administration; measures to prevent adverse effects and warning signs of problems; the need to avoid herbal or alternative therapies unless allowed by the prescriber; and safety measures, such as changing position slowly and avoiding driving or operating hazardous machinery; and the need for monitoring and evaluation to enhance patient knowledge about drug therapy and to promote compliance.
Evaluation
Monitor patient response to the drug (improvement in blood pressure and HF).
Monitor for adverse effects (CV changes, headache, GI upset, bronchospasm, liver failure).
Evaluate the effectiveness of the teaching plan (patient can name drug, dosage, adverse effects to watch for, specific measures to avoid adverse effects).
Monitor the effectiveness of comfort measures and compliance with the regimen.
KEY POINTS
Adrenergic blocking agents block the effects of the SNS.
The nonselective adrenergic blocking agents block all receptors; that is, both alpha- and beta-receptors. Selective adrenergic blocking agents have specific affinity for alpha- or beta-receptors or for specific alpha1-, beta1-, or beta2-receptor sites.
Blocking all of the receptor sites within the SNS results in a lowering of blood pressure.
Nonselective Alpha-Adrenergic Blocking Agents
Some adrenergic blocking agents have a specific affinity for alpha-receptor sites. Their use is somewhat limited because of the development of even more specific and safer drugs. Only one of these drugs, phentolamine (Regitine), is still used (Table 31.2).
Table 31.2 Drugs in Focus: Nonselective Alpha-Adrenergic Blocking Agent
Therapeutic Actions and Indications
Phentolamine blocks the postsynaptic alpha1-adrenergic receptors, decreasing sympathetic tone in the vasculature and causing vasodilation, which leads to a lowering of blood pressure. It also blocks presynaptic alpha2-receptors, preventing the feedback control of norepinephrine release. The result is an increase in reflex tachycardia that occurs when blood pressure is lowered. Phentolamine is most frequently used to prevent cell death and tissue sloughing after extravasation of intravenous norepinephrine or dopamine, causing a local vasodilation and a return of blood flow to the area. Table 31.2 shows Usual Indications for each of these agents.
Pharmacokinetics
Phentolamine is rapidly absorbed after IV or IM injection and is excreted in the urine.
There are few data on its metabolism and distribution.
Contraindications and Cautions
Phentolamine is contraindicated in the presence of allergy to this or similar drugs and in the presence of coronary artery disease or MI because of the potential exacerbation of these conditions; it should be used cautiously in pregnancy or lactation because of the potential adverse effects on the fetus or neonate.
Adverse Effects
Patients receiving phentolamine often experience extensions of the therapeutic effects, including hypotension, orthostatic hypotension, angina, MI, cerebrovascular accident, flushing, tachycardia, and arrhythmia—all of which are related to vasodilation and decreased blood pressure. Headache, weakness, and dizziness often occur in response to hypotension.
Nausea, vomiting, and diarrhea may also occur.
Clinically Important Drug–Drug Interactions
Ephedrine and epinephrine may have decreased hypertensive and vasoconstrictive effects if they are taken concomitantly with phentolamine because these agents work in opposing ways in the body. Increased hypotension may occur if this drug is combined with alcohol, which is also a vasodilator.
Prototype Summary:Phentolamine
Indications: Prevention or control of hypertensive episodes associated with pheochromocytoma; test for diagnosis of pheochromocytoma; prevention and treatment of dermal necrosis and sloughing associated with IV extravasation of norepinephrine or dopamine.
Actions: Competitively blocks postsynaptic alpha1- and presynaptic alpha2-receptors, causing a vasodilation and lowering of blood pressure, accompanied by increased reflex tachycardia.
Pharmacokinetics:
T1/2: Metabolism and excretion are unknown.
Adverse Effects: Acute and prolonged hypotensive episodes, MI, tachycardia, arrhythmias, nausea, flushing.