Use of alpha1-adrenergic drugs became popular in men because of their minimal effects on potency and unique relationship to lipids. They may contribute to stress urinary incontinence in women because of altered urethral tone. As single agents, they decrease total cholesterol and low-density lipoprotein (LDL) cholesterol while increasing HDL cholesterol, in contrast to the metabolic effects of beta-blocking agents. Their mode of action is to promote vascular relaxation by blocking postganglionic norepinephrine vasoconstriction in the peripheral vascular smooth muscle. Prazosin and doxazosin are two preparations available in this class. A serious side effect of these drugs, which is commonly described in the elderly patients, is called the “first-dose effect.” In susceptible individuals, severe orthostasis was reported when therapy was initiated but subsided after several days. When alpha1-adrenergic drugs are used in combination with diuretics, hypotension may be further exacerbated. Therapy should begin with small doses taken at bedtime followed by incremental increases. Other side effects that may limit the usefulness of these agents in some patients include tachycardia, weakness, dizziness, and mild ﬂuid retention.
The angiotensin-converting enzyme (ACE) inhibitors are first-line drugs in the treatment of hypertension. Their rapid rise in popularity results from the introduction of new formulations, which allow dosing once or twice a day with a good therapeutic response. There are relatively few side effects; chronic cough is the most worrisome and is a common reason of discontinuing the use of this group of drugs. Other side effects are occasional first-dose hypotension and blood dyscrasias. Occasionally, patients will suffer from rashes, loss of taste, fatigue, or headaches. Other agents should be considered for patients at risk for pregnancy (a strict contraindication). ACE inhibitors can be used in combination with other agents, including diuretics, calcium channel antagonists, and beta-blocking agents. In contrast to beta-blocking agents, these medications can be used in patients with asthma, depression, and peripheral vascular disease. For unknown reasons, they are less effective in African Americans unless a diuretic is used concomitantly. Use with diuretics increases the effectiveness of both drugs, but hypovolemia may result. If renal failure is present, hyperkalemia may result from potassium supplementation and altered tubular metabolism. Any NSAID, including aspirin, may decrease the antihypertensive effectiveness. Use of NSAIDs, volume depletion, and renal artery stenosis may precipitate acute renal failure when administration of an ACE inhibitor is initiated. Creatinine levels should be measured at the start of therapy and 1 week after initiation of any ACE inhibitor. An increase of up to 35% of the baseline creatinine value is acceptable, and treatment should be continued unless hyperkalemia develops.
The angiotensin-receptor blockers such as losartan and valsartan interfere with the binding of angiotensin II to AT1 receptors. As with ACE inhibitors, they are effective in lowering blood pressure without causing the side effect of coughing. Angiotensin-receptor blockers have favorable effects on the progression of kidney disease in individuals who have diabetes, and on those without diabetes and congestive heart failure.