Burger's Medicinal Chemistry and Drug Discovery, by Donald A. Abraham

By Donald A. Abraham

His is quantity three: Cardiovascular brokers and Endocrines, of Burger's Medicinal Chemistry and Drug Discovery, sixth version. This new quantity comprises serious new chapters on Endogenous Vasoactive Peptides, Iron Chelators and healing makes use of, and basics of Steroid Chemistry and Biochemistry.

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Extra info for Burger's Medicinal Chemistry and Drug Discovery, Cardiovascular Agents and Endocrines

Sample text

Pharmacodynamically, combinations of ACE inhibitor plus a diuretic, 0-adrenoreceptor antagonist, or calcium channel blocker are the most promising. 4 Other Therapeutics. For the past two decades, the cardiovascular drug market has lead drug discovery efforts and sales in the pharmaceutical industry. A constant flow of new and effective drugs has kept this sector in its number one position and will continue to do so in the future. In addition to the above indicated classes of drugs, a number of highly effective drugs have been introduced and are routinely used either alone or in combination therapy.

Nilvadipine (31) (Fig. 3): Nilvadipine is marketed as a racemic mixture for < 4 Antianginal Agents and Vasodilators the treatment of hypertension and angina (164-166). Nilvadipine also provides protection against cerebral ischemia in rats having chronic hypertension. These effects are dependent on the duration of treatment (167). Results from a clinical study in the United States, during which a combination of imidapril and a diuretic, P-adrenoceptor antagonist, or a calcium channel blocker (such as nilvadipine) were administered, indicated a reasonable and safe treatment option when striving for additive pharmacodynamic effects not accompanied by relevant pharmacokinetic interactions (168).

It reversibly competes with nitrendipine and/or other calcium channel blockers for dihydropyridine binding sites and blocks voltage-dependent Ca2+ currents in vascular smooth muscle. Following oral administration, felodipine is almost completely absorbed and undergoes extensive first-pass metabolism. 1 h. Following oral administration of the immediate-release for- mulation, the plasma level of felodipine also declines polyexponentially, with a mean terminal half-life of 11-16 h. The bioavailability of felodipine is influenced by the presence of high fat or carbohydrates and increases approximately twofold when taken with grapefruit juice.

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