Calcium-channel blockers represent a major therapeutic breakthrough for patients with coronary artery disease. They are effective in patients with hypertension and peripheral vascular disease. The mechanism of action is to block calcium movement across smooth muscle, therefore promoting vessel wall relaxation. Calcium channel blockers are useful in treating concurrent hypertension and ischemic heart disease as an alternative to beta-blockers, if needed. Additionally, these drugs are particularly effective in the elderly and African Americans. Side effects noted include headache, dizziness, constipation, gastroesophageal reﬂux, and peripheral edema. The addition of long-acting calcium-channel blockers made these preparations more amenable for use in hypertension. A relative contraindication for use of these drugs is the presence of congestive heart failure or conduction disturbances.
Hydralazine is a potent vasodilator used for years in obstetrics for severe hypertension associated with preeclampsia and eclampsia. The mechanism of action is direct relaxation of vascular smooth muscle, primarily arterial. Major side effects include headaches, tachycardia, and ﬂuid (sodium) retention that may result in paradoxical hypertension. Several combinations are used to counter the side effects and enhance antihypertensive effects. Diuretics may be added to reverse ﬂuid retention caused by excess sodium. When used in combination with beta-blockers, tachycardia and headaches may be controlled without compromising the objective of lowering blood pressure. Drug-induced lupus was widely stated as a potential side effect but is rare with normal therapeutic doses of 25 to 50 mg three times daily. Minoxidil is another extremely potent drug in this class but is of limited use to the gynecologist because of its side effects in women (beard growth). Because of minoxidil’s potency, only experienced practitioners should use it.
Central-acting agents (methyldopa and clonidine) have long been used in obstetrics. The mechanism of action is to inhibit the sympathetics in the central nervous system, resulting in peripheral vascular relaxation. Side effects, including taste disorders, dry mouth, drowsiness, and the need for frequent dosing (except for the transdermal form of clonidine), limited the popularity of this group of drugs. Sudden withdrawal of clonidine may precipitate a hypertensive crisis and induce angina. Clonidine withdrawal syndrome is more likely to occur with concomitant use of beta-blockers. Compliance is always a major issue, and side-effect profiles contribute significantly to patient nonadherence. With the introduction of new classes of drugs with improved efficacy and reduced side effects, use of medications in this class is expected to decline.
Monitoring Therapy Blood pressure readings should be monitored frequently by a nurse, the patient, or in the office at 1-to 2-week intervals. If the patient has other diseases (i.e., cardiovascular, renal), therapy should be initiated earlier and directed to the target organ. If lifestyle modification alone is successful, close monitoring is necessary at 3-to 6-month intervals. When lifestyle modification is unsuccessful, a blood pressure medication should be started to decrease target organ disease.
When beginning therapy, concurrent medical conditions treatable with a common agent should be sought. Gender is not an important consideration in choosing an antihypertensive agent.
Concurrent diseases and race are important for patients who:
Have migraine headaches, for which beta-blockers or calcium channel agonists may be the best choice
Are African American and are likely to respond better to a combination of diuretics and calcium channel blockers
Have diabetes, chronic kidney disease, and heart failure, for which ACE inhibitors should be used
Have had myocardial infarctions and should receive beta-blockers because they reduce the risk for sudden death and recurrent myocardial infarctions.
A summary of the compelling indications for individual drug classes is listed in Table 9.7.