Figure 731

Direct-acting vasodilators. Direct-acting vasodilators may have an effect on both arterial resistance and venous capacitance vessels; however, the currently available oral drugs are highly selective for resistance vessels [6,9]. Their specific mechanism of vascular relaxation and reason for selectivity are unknown. By altering cellular calcium metabolism, they interfere with the calcium movements responsible for initiating or maintaining a contractile state. The net physiologic effect is a decrease in peripheral vascular resistance associated with increases in heart rate and cardiac output. These increases in heart rate and cardiac output are related directly to sympathetic stimulation and indirectly to the baroreceptor reflex response. ROC—receptor-operated channel; SR—sarcoplasmic reticulum; VGC—voltage-gaited channels.

Minoxidil is a substantially more potent direct-acting vasodilator than hydralazine. Absorption is greater than 95%. Peak plasma levels occur within 1 hour. Following a single oral dose, blood pressure declines within 15 minutes, reaches a nadir between 2 and 4 hours, and recovers at an arithmetically linear rate of 30% per day. Approximately 90% is metabolized by conjugation with glucuronic acid and by conversion to more polar products. Known metabolites, which are less pharmacologically active than minoxidil, are excreted in the urine. The plasma half-life of minoxidil is approximately 4 hours; dose adjustments are unnecessary in patients with renal insufficiency. Minoxidil and its metabolites are removed by hemodialysis and peritoneal dialysis; replacement therapy is required [6,9].

Generic (trade) name

First dose, mg

Usual daily dose, mg

Maximum daily dose, mg

Duration of action, h

Hydralazine (G) (Apresoline)

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