Adrenergic-Blocking Drugs



Adrenergic-Blocking Drugs


Objectives


When you reach the end of this chapter, you will be able to do the following:



Drug Profiles



Key Terms


Acrocyanosis Decreased amount of oxygen delivered to the extremities, causing the feet or hands to turn blue. (p. 313)


Adrenergic receptors Specific receptor sites located throughout the body for the endogenous sympathetic neurotransmitters norepinephrine and epinephrine. (p. 313)


Agonists Drugs with a specific receptor affinity that mimic the body’s natural chemicals (e.g., hormones, neurotransmitters). (p. 313)


Angina Paroxysmal (sudden) chest pain caused by myocardial ischemia. (p. 317)


Antagonists Drugs that bind to specific receptors and inhibit or block the response of the receptors. (p. 313)


Dysrhythmias Irregular heart rhythms; almost always called arrhythmias in clinical practice. (p. 317)


Extravasation The leaking of fluid from a blood vessel into the surrounding tissues, as in the case of an infiltrated intravenous infusion. (p. 314)


First-dose phenomenon Severe and sudden drop in blood pressure after the administration of the first dose of an alpha-adrenergic blocker. (p. 314)


Intrinsic sympathomimetic activity The paradoxical action of some beta-blocking drugs (e.g., acebutolol) that mimics the action of the sympathetic nervous system. (p. 316)


Lipophilicity The chemical attraction of a substance (e.g., drug molecule) to lipid or fat molecules. (p. 317)


Orthostatic hypotension A sudden drop in blood pressure when a person stands up. Also referred to as postural hypotension or orthostasis. (p. 314)


Pheochromocytoma A vascular adrenal gland tumor that is usually benign but secretes epinephrine and norepinephrine and thus often causes central nervous system stimulation and substantial blood pressure elevation. (p. 313)


Raynaud’s disease A narrowing of small arteries that limits the amount of blood circulation to the extremities, causing numbness of the nose, fingers, toes, and ears in response to cold temperatures or stress. (p. 313)


Sympatholytics Drugs that inhibit the postganglionic functioning of the sympathetic nervous system. (p. 313)


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Anatomy, Physiology, and Pathophysiology Overview


The autonomic nervous system consists of the parasympathetic and sympathetic nervous systems. The class of drugs discussed in this chapter works primarily on the sympathetic nervous system (SNS). As discussed in Chapter 18, the adrenergic agonist drugs stimulate the SNS. Those drugs are called agonists because they bind to receptors and cause a response. Adrenergic blockers have the opposite effect and are therefore referred to as antagonists. They bind to adrenergic receptors, but in doing so inhibit or block stimulation by the SNS. They are also referred to as sympatholytics because they “lyse,” or inhibit, SNS stimulation.


Throughout the body, there are receptor sites for the endogenous sympathetic neurotransmitters norepinephrine and epinephrine. Such receptors are known as adrenergic receptors, and two basic types are found: alpha and beta. There are subtypes of the alpha- and beta-adrenergic receptors, designated 1 and 2. The alpha1– and alpha2-adrenergic receptors are differentiated by their location on nerves. The alpha1-adrenergic receptors are located on the tissue, muscle, or organ that the nerve is stimulating (postsynaptic effector cells). The alpha2-adrenergic receptors are located on the actual nerves that stimulate the presynaptic effector cells. The alpha2 receptors are inhibitory in nature. Thus, it is actually the stimulation of alpha2 receptors that causes the inhibitory effects of the SNS. Alpha2–active drugs (e.g., clonidine) are discussed in Chapter 22. The beta1-adrenergic receptors are located primarily in the heart. The beta2-adrenergic receptors are located primarily on the smooth muscles of the bronchioles and blood vessels. It is at these various receptors that adrenergic blockers act. They are classified by the type of adrenergic receptor they block—alpha or beta or, in a few cases, both. Hence, they are called alpha blockers, beta blockers, or alpha/beta blockers.


Pharmacology Overview


Alpha Blockers


Mechanism of Action and Drug Effects


The alpha-adrenergic–blocking drugs, or alpha blockers, interrupt stimulation of the SNS at the alpha1-adrenergic receptors. More specifically, alpha blockers work either by direct competition with norepinephrine or by a noncompetitive process. Figure 19-1 illustrates these two mechanisms. Alpha blockers have a greater affinity for the alpha-adrenergic receptor than norepinephrine does and therefore can chemically displace norepinephrine molecules from the receptor. Adrenergic blockade at these receptors leads to effects such as vasodilation, reduced blood pressure, miosis (pupillary constriction), and reduced smooth muscle tone in organs such as the bladder and prostate. Currently available alpha blockers are listed in Table 19-1.




Indications


The alpha blockers such as doxazosin, prazosin, and terazosin cause both arterial and venous dilation, which reduces peripheral vascular resistance and blood pressure. These drugs are used to treat hypertension (see Chapter 22). There are also alpha-adrenergic receptors in the prostate and bladder. By blocking stimulation of alpha1 receptors, these drugs reduce smooth muscle contraction of the bladder neck and the prostatic portion of the urethra. For this reason, alpha blockers are given to patients with benign prostatic hyperplasia (BPH) to decrease resistance to urinary outflow. This reduces urinary obstruction and relieves some of the effects of BPH. Tamsulosin and alfuzosin are used exclusively for treating BPH, whereas terazosin and doxazosin can be used for both hypertension and BPH.


Other alpha blockers can inhibit responses to adrenergic stimulation. These drugs noncompetitively block alpha-adrenergic receptors on smooth muscle and various exocrine glands. Because of this action, they are very useful in controlling or preventing hypertension in patients who have a pheochromocytoma, a tumor that forms on the adrenal gland on top of the kidney and secretes norepinephrine, thus causing SNS stimulation. The alpha blockers are also useful in the treatment of patients who have increased endogenous alpha-adrenergic agonist activity, which results in vasoconstriction. Three conditions in which this occurs are Raynaud’s disease, acrocyanosis, and frostbite. Phenoxybenzamine, in particular, is an alpha blocker that is beneficial in the treatment of these syndromes, although its use is uncommon.


Still other alpha blockers (e.g., phentolamine) are effective at counteracting the effects of injected epinephrine and norepinephrine. They do this by causing peripheral vasodilation and reducing peripheral resistance by blocking catecholamine-stimulated vasoconstriction. Because of their potent vasodilating properties and their fast onset of action, they are used to prevent skin necrosis and sloughing after the extravasation of vasopressors such as norepinephrine or epinephrine. When these drugs extravasate (leak out of the blood vessel into the surrounding tissue), they cause vasoconstriction and ultimately tissue death, or necrosis. If the vasoconstriction is not reversed quickly, the entire limb can be lost. Phentolamine, in particular, can reverse this potent vasoconstriction and restore blood flow to the ischemic tissue.


Contraindications


Contraindications to the use of alpha-blocking drugs include known drug allergy and peripheral vascular disease and may include hepatic and renal disease, coronary artery disease, peptic ulcer, and sepsis.


Adverse Effects


The primary adverse effects of alpha blockers are those related to their effects on the vasculature. First-dose phenomenon, which is a severe and sudden drop in blood pressure after the administration of the first dose of an alpha-adrenergic blocker, can cause patients to fall or pass out. All patients must be warned about this adverse effect before they take their first dose of an alpha blocker. Orthostatic hypotension can occur with any dose of an alpha blocker, and patients must be warned to get up slowly from a supine position. The primary adverse effects of the alpha blockers are listed by body system in Table 19-2.



Toxicity and Management of Overdose


In an acute oral overdose, activated charcoal is administered to bind the drug and remove it from the stomach and the circulation. With overdoses of both oral and injectable forms, symptomatic and supportive measures are to be instituted as needed. Blood pressure support with the administration of fluids, volume expanders, and vasopressor drugs and the administration of anticonvulsants such as diazepam for the control of seizures are examples of such measures.


Interactions


The most severe drug interactions with alpha blockers are the ones that potentiate the effects of the alpha blockers. The alpha blockers are very highly protein bound and compete for binding sites with other drugs that are highly protein bound (see Chapter 2). Because of the limited sites for binding on proteins and the increased competition for these sites, more free alpha blocker molecules circulate in the bloodstream. More active drug results in a more pronounced drug effect. Some of the common drugs that interact with alpha blockers and the results of these interactions are listed in Table 19-3.



Dosages


For dosage information on alpha blockers, see the table on p. 315.



Drug Profiles


The alpha blockers are commonly used to treat hypertension and/or benign prostatic hyperplasia. They include phentolamine, phenoxybenzamine, terazosin, alfuzosin, tamsulosin, silodosin, and prazosin. Prazosin is discussed in Chapter 22.


♦ phentolamine


Phentolamine (Regitine) is an alpha blocker that reduces peripheral vascular resistance and is also used to treat hypertension. Like phenoxybenzamine, it is used to treat the high blood pressure caused by pheochromocytoma, but phentolamine can also be used in the diagnosis of this catecholamine-secreting tumor. To help establish a diagnosis of pheochromocytoma, a single intravenous dose of phentolamine is given to the hypertensive patient. If the blood pressure declines rapidly, it is highly likely that the patient has a pheochromocytoma. Phentolamine is available only as an injectable preparation. It is most commonly used to treat the extravasation of vasoconstricting drugs such as norepinephrine, epinephrine, and dopamine, which when given intravenously can leak out of the vein, especially if the intravenous tube is not correctly positioned. If such a drug is allowed to extravasate into the surrounding tissue, the result is intense vasoconstriction, decreased blood flow, necrosis, and potential loss of the limb. When phentolamine is injected subcutaneously in a circular fashion around the extravasation site, it causes alpha-adrenergic receptor blockade and vasodilation, which in turn increases blood flow to the ischemic tissue and thus prevents permanent damage. Its use is contraindicated in patients who have shown a hypersensitivity to it, those who have experienced a myocardial infarction (MI), and those with coronary artery disease. Adverse effects include tachycardia, dizziness, gastrointestinal upset, and others listed in Table 19-2. Drugs with which phentolamine interacts include alcohol (a disulfiram-like reaction; see Chapter 17) and erectile dysfunction medications such as sildenafil (additive hypotensive effects; see Chapter 35). Epinephrine and ephedrine can counteract the desired effects of phentolamine. The recommended dosages are given in the table on p. 315.


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May 9, 2017 | Posted by in NURSING | Comments Off on Adrenergic-Blocking Drugs

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