CLINICAL PHARMACOKINETICS OF VASODILATORS - PART II

Stimulating cardiac beta(1)-adrenoceptors with oxyfedrine causes dilat ation of coronary vessels and positive inotropic effects on the myocar dium. beta(1)-adrenegic agonists increase coronary blood flow in nonst enotic and stenotic vessels. The main indication for the use of the ph osphodiesterase inhibitors pamrinone, mirinone, enoximone and piroximo ne is acute treatment of severe congestive heart failure. Theophylline is indicated for the treatment of asthma, chronic obstructive pulmona ry disease, apnea in preterm infants ans sleep apnea syndrome. Severe arterial occlusive disease associated with atherosclerosis can be bene ficially affected by elcosanoids. These drugs must be administered par enterally and have a half-life of only a few minutes. Sublingual or bu ccal preparations of nitrates are the only prompt method (within 1 or 2 min) of terminating anginal pain, except for biting nifedipine capsu les. The short half-life (about 2.5 min) of nitroglycerin (glyceryl tr initrate) makes long term therapy impossible. Tolerance is a problem e ncountered with longer-acting nitric oxide donors. Knowledge of the ph armacokinetic properties of vasodilating drugs can prevent a too sudde n and severe blood pressure decrease in patients with chronic hyperten sion. In considering the administration of a second dose, or another d rug, the time necessary for the initially administered drug to reach m aximal efficacy should be taken into account. In hypertensive emergenc ies urapidil, sodium nitroprusside, nitroglycerin, hydralazine and phe ntolamine are the drugs of choice, with the addition of beta-blockers during catecholamine crisis or dissecting aortic aneurysm. Childhood h ypertension is most often treated with angiotensin-converting enzyme ( ACE) inhibitors or calcium antagonists, primarily nifedipine. Because of the teratogenic risk involved with ACE inhibitors, extreme caution must be exercised when prescribing for adolescent females. The propaga tion of health benefits to breast-fed infants, combined with more wome n delaying pregnancy until their fourth decade, has entailed an increa se in the need for hypertension management during lactation. Low dose hydrochlorothiazide, propranolol, nifendipine and enalapril or captopr il do not pose enough of a risk to preclude breastfeeding in this grou p. The most frequently used antihypertensive agents during pregnancy a re methyldopa, labetalol and calcium channel antagonists. Methyldopa a nd beta-blockers are the drugs of choice for treating mild to moderate hypertension. Prazosin and hydralazine are used to treat moderate to severe hypertension and hydralazine, urapidil or labetalol are used to treat hypertensive emergencies. The use of overly aggressive antihype rtensive therapy during pregnancy should be avoided so that adequate u teroplacental blood flow is maintained. Methyldopa is the only drug ac cepted for use during the first trimester of pregnancy.