Afterload reduction: ACE-inhibitor
A. Drugs for the treatment of acute myocardial infarction
Arterial hypertension (high blood pressure) generally does not impair the well-being of the affected individual; however, in the long term it leads to vascular damage and secondary complications (A). The aim of antihypertensive therapy is to prevent the latter and, thus, to prolong life expectancy.
Hypertension infrequently results from another disease, such as a cate-cholamine-secreting tumor (pheochro-mocytoma); in most cases the cause cannot be determined: essential (primary) hypertension. Antihypertensive drugs are indicated when blood pressure cannot be sufficiently controlled by means of weight reduction or a low-salt diet. In principle, lowering of either cardiac output or peripheral resistance may decrease blood pressure (cf. p. 306, 314, blood pressure determinants). The available drugs influence one or both of these determinants. The therapeutic utility of antihypertensives is determined by their efficacy and tolerability. The choice of a specific drug is determined on the basis of a benefit:risk assessment of the relevant drugs, in keeping with the patient's individual needs.
In instituting single-drug therapy (monotherapy), the following considerations apply: ß-blockers (p. 92) are of value in the treatment of juvenile hypertension with tachycardia and high cardiac output; however, in patients disposed to bronchospasm, even ß1-se-lective blockers are contraindicated. Thiazide diuretics (p. 162) are potentially well suited in hypertension associated with congestive heart failure; however, they would be unsuitable in hypo-kalemic states. When hypertension is accompanied by angina pectoris, the preferred choice would be a ß-blocker or calcium antagonist (p. 122) rather than a diuretic. As for the calcium antagonists, it should be noted that verap-amil, unlike nifedipine, possesses car-diodepressant activity. a-Blockers may be of particular benefit in patients with benign prostatic hyperplasia and im paired micturition. At present, only p-blockers and diuretics have undergone large-scale clinical trials, which have shown that reduction in blood pressure is associated with decreased morbidity and mortality due to stroke and congestive heart failure.
In multidrug therapy, it is necessary to consider which agents rationally complement each other. A p-blocker (bradycardia, cardiodepression due to sympathetic blockade) can be effectively combined with nifedipine (reflex tachycardia), but obviously not with ve-rapamil (bradycardia, cardiodepres-sion). Monotherapy with ACE inhibitors (p. 124) produces an adequate reduction of blood pressure in 50% of patients; the response rate is increased to 90% by combination with a (thiazide) diuretic. When vasodilators such as di-hydralazine or minoxidil (p. 118) are given, p-blockers would serve to prevent reflex tachycardia, and diuretics to counteract fluid retention.
Abrupt termination of continuous treatment can be followed by rebound hypertension (particularly with short t1/2 p-blockers).
Drugs for the control of hypertensive crises include nifedipine (capsule, to be chewed and swallowed), nitrogly-cerin (sublingually), clonidine (p.o. or i.v., p. 96), dihydralazine (i.v.), diazoxide (i.v.), fenoldopam (by infusion, p. 114) and sodium nitroprusside (p. 120, by infusion). The nonselective a-blocker phentolamine (p. 90) is indicated only in pheochromocytoma.
Antihypertensives for hypertension in pregnancy are p1-selective adrenoceptor-blockers, methyldopa (p. 96), and dihydralazine (i.v. infusion) for eclampsia (massive rise in blood pressure with CNS symptoms).
Systolic: blood pressure > 160 mmHg Diastolic: blood pressure > 96 mmHg
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