Overall, although the acute effects of these drugs may include a rise in peripheral resistance, chronic drug administration leads to a fall in peripheral resistance in patients with hypertension.
B. Effects on the Respiratory Tract
Blockade of the β2 receptors in bronchial smooth muscle may lead to an increase in airway resistance, particularly in patients with asthma. Beta1-receptor antagonists such as metoprolol and atenolol may have some advantage over nonselective β antagonists when blockade of β1 receptors in the heart is desired and β2-receptor blockade is undesirable. However, no currently available β1selective antagonist is sufficiently specific to completely avoid interactions with β2 adrenoceptors. Consequently, these drugs should generally be avoided in patients with asthma. However, some
TABLE 10–2 Properties of several beta-receptor–blocking drugs.
1Carvedilol and labetalol also cause α1-adrenoceptor blockade. 2β3 agonist. 3Bioavailability is dose-dependent.
patients with chronic obstructive pulmonary disease (COPD) may tolerate β1-selective blockers, and the benefits, for example in patients with concomitant ischemic heart disease, may outweigh the risks.
C. Effects on the Eye
Beta-blocking agents reduce intraocular pressure, especially in glaucoma. The mechanism usually reported is decreased aqueous humor production. (See Clinical Pharmacology and Box: The Treatment of Glaucoma.)
D. Metabolic and Endocrine Effects
Beta-receptor antagonists such as propranolol inhibit sympathetic nervous system stimulation of lipolysis. The effects on carbohydrate metabolism are less clear, although glycogenolysis in the human liver is at least partially inhibited after β2-receptor blockade.
0.5 mg/kg
FIGURE 10–6 The effect in an anesthetized dog of the injection of epinephrine before and after propranolol. In the presence of a β-receptor–blocking agent, epinephrine no longer augments the force of contraction (measured by a strain gauge attached to the ventricular wall) nor increases cardiac rate. Blood pressure is still elevated by epinephrine because vasoconstriction is not blocked. (Reproduced, with permission, from Shanks RG: The pharmacology of β sympathetic blockade. Am J Cardiol 1966;18:312. Copyright Elsevier.)
Glucagon is the primary hormone used to combat hypoglycemia; it is unclear to what extent β antagonists impair recovery from hypoglycemia, but they should be used with caution in insulin-dependent diabetic patients. This may be particularly important in diabetic patients with inadequate glucagon reserve and in pancreatectomized patients since catecholamines may be the major factors in stimulating glucose release from the liver in response to hypoglycemia. Beta1-receptor–selective drugs may be less prone to inhibit recovery from hypoglycemia. Beta-receptor antagonists are much safer in those type 2 diabetic patients who do not have hypoglycemic episodes.
The chronic use of β-adrenoceptor antagonists has been associated with increased plasma concentrations of very-low-density lipoproteins (VLDL) and decreased concentrations of HDL cholesterol. Both of these changes are potentially unfavorable in terms of risk of cardiovascular disease. Although low-density lipoprotein (LDL) concentrations generally do not change, there is a variable decline in the HDL cholesterol/LDL cholesterol ratio that may increase the risk of coronary artery disease. These changes tend to occur with both selective and nonselective β blockers, although they may be less likely to occur with β blockers possessing intrinsic sympathomimetic activity (partial agonists). The mechanisms by which β-receptor antagonists cause these changes are not understood, although changes in sensitivity to insulin action may contribute.