Amlodipine (am loe' di peen) besylate (Norvasc - Pfizer), a dihydropyridine calcium-channel blocker, has been approved by the US Food and Drug Administration for once-daily oral treatment of hypertension, chronic stable angina, and vasospastic (Prinzmetal's) angina.

Candesartan cilexetil (Atacand - Astra) is the fourth angiotensin II receptor antagonist to become available in the USA for oral treatment of hypertension.

Cerebral arterial spasm frequently causes ischemic neurological damage after subarachnoid hemorrhage from a ruptured intracranial aneurysm. Nimodipine (Nimotop - Miles), a 1,4-dihydropyridine calcium-entry blocker, was recently approved by the US Food and Drug Administration (FDA) for oral treatment of such patients; an intravenous preparation is available only for investigational use.

Quinupristin and dalfopristin, two streptogramin antibacterials marketed in a 30:70 combination as Synercid, have received accelerated approval from the FDA for intravenous treatment of bacteremia and life-threatening infection....

Vasodilators are widely used for treatment of congestive heart failure (CHF) that has not responded adequately to diuretics and digitalis. Vasodilator drugs redistribute blood volume in patients with heart failure, lowering pressure and reducing volume in the failing left ventricle, which leads to increased cardiac output, decreased pulmonary capillary wedge pressure, and improved exercise tolerance. Since the last Medical Letter review of this subject (Volume 26, page 115, 1984), some additional data have become available.

In a study of the interaction between alcohol and the calcium-channel blocker felodipine (Plendil), the grapefruit juice vehicle for the alcohol appeared to increase felodipine plasma concentrations. Subsequent studies have found that grapefruit juice increases plasma concentrations of several calcium-channel blockers and of some other drugs as well (DG Bailey et al, Clin Pharmacokinet, 26:91, 1994).

Many nitrates, beta-blockers, and calcium-channel blockers have now been approved by the US Food and Drug Administration for treatment of stable angina pectoris. The table beginning on page 112 lists the individual drugs, their dosage, and their cost.

Many fermented foods contain tyramine as a byproduct formed by the bacterial breakdown of the amino acid tyrosine; it can also be formed by para-hydroxylation of phenylethylamine or dehydroxylation of DOPA and dopamine. Tyramine and some other amines found in food can cause hypertensive reactions in patients taking monoamine oxidase (MAO)inhibitors.

Bosentan (Tracleer - Actelion), a non-peptide endothelin receptor antagonist, has been approved by the FDA for oral treatment of patients who have pulmonary arterial hypertension (PAH) with symptoms of dyspnea at rest or with minimal exertion.

Serious adverse interactions between drugs continue to be reported. Many of these are due to inhibition or induction of cytochrome P450 (CYP) enzymes, particularly CYP3A4. CYP3A is thought to be involved in the metabolism of more than 50 percent of currently prescribed drugs.2 CYP3A4, which is more abundantly expressed than CYP3A5, accounts for most CYP3A activity in vivo.