ABlocking Drugs

Phenoxybenzamine and phentolamine have been available for a number of years and are sometimes referred to as classical «-blockers. The frequency of their use for the treatment of primary hypertension has greatly diminished in recent years because of the development of drugs such as prazosin that are relatively selective for «j-receptors. «j-Receptor-selective antagonists will not potentiate the release of norepinephrine from sympathetic nerves. Thus, the stimulation of the heart and renin release, actions that limit the usefulness of classical «-blockers, are less with «1-selective antagonists.

Unlike the vasodilators, which have a more prominent effect on arterial beds than on venous beds, the «blockers prevent vasoconstriction in both vascular beds. Because of the venous dilation, postural hypotension is a feature of «-blockade, although less so with prazosin than with the classical «-blockers.

Prazosin and its derivatives that are selective for «1-adrenoceptors are quite useful for the management of primary hypertension. The «1-receptor-selective antagonists can be used alone in mild hypertension.When hypertension is moderate or severe, prazosin is generally administered in combination with a thiazide and a ß-blocker. The antihypertensive actions of prazosin are considerably potentiated by coadministration of thi-azides or other types of antihypertensive drugs.

Prazosin may be particularly useful when patients cannot tolerate other types of antihypertensive agents or when blood pressure is not well controlled by other drugs. Since prazosin does not significantly influence blood uric acid or glucose levels, it can be used in hypertensive patients whose condition is complicated by gout or diabetes mellitus. Prazosin treatment is associated with favorable effects on plasma lipids. Thus, it may be of particular importance in managing patients with hyperlipidemia.

Further information about the pharmacokinetics, adverse reactions, and preparations of «-blockers is given in Chapter 11.

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