Panel Cites Advantages of New Calcium Antagonist

Drug Topics, February 18, 1991 | Go to article overview
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Panel Cites Advantages of New Calcium Antagonist


Filodipine, a new calcium antagonist, appears to offer a number of advantages over conventional agents in the treatment of high blood pressure, according to a panel of hypertension experts at the 12th Congress of the European Society of Cardiology. They were speaking at a symposium sponsored by Astra Pharmaceuticals, the firm that licensed the drug to Merck Sharp & Dohme for marketing once the product has received Food & Drug Administration approval.

"Changes in calcium antagonists are bringing changes in the therapeutic approach to hypertension," noted Ronald Campbell, M.D., consultant cardiologist, Freeman Hospital, Newcastle-upon-Tyne, England.

The World Health Organization classifies the calcium antagonists into two broad classes. Class A includes those that selectively block slow calcium channels, such as verapamil, nifedipine, and felodipine; Class B includes those that do not, such as flunarizine (under investigation in this country by Ortho Pharmaceutical Corp.).

However, recent research highlighting the different types of Class A calcium antagonists and the receptors they interact with have brought new appreciation for the differences among drugs in the phenylalkylamine class (verapamil), the benzothiazepine class (diltiazem), and the 1,4- dihydropyridine class (nifedipine, felodipine.)

"These agents act at distinct sites. Just as they are heterogeneous chemically, they also have a therapeutic heterogeneity. While all of them are effective against hypertension, there are quantitative and qualitative therapeutic differences among them," commented Dr. David Triggle, professor of pharmacy at the School of Pharmacy, State University of New York, Buffalo.

The chief advantage of felodipine appears to be its high vascular selectivity. In contrast to other agents, the drug appears to act specifically on resistance vessels to control hypertension, without causing negative effects on cardiac conduction or contractility.

Calcium antagonists with poor vascular selectivity may be more likely to have cardiac effects. The ratio of vascular to cardiac selectivity for nifedipine is 15 times greater than verapamil. Felodipine is more than 10 times more vascularly selective than nifedipine, said Alberto Zanchetti, M.D., professor of cardiology, University of Milan, Italy.

"The reason these agents have become increasingly popular for antihypertensive therapy has to do with their vasodilatory properties. Since this is a vasoconstrictive condition, there are significant reasons for using vasodilators that are tissue selective," added Zanchetti.

Other factors favoring more selective calcium antagonists include better compliance, better control of systolic blood pressure, and better control of isolated systolic hypertension, he noted.

The primary cardiac effects of felodipine include a reduction in afterload, an improvement in coronary perfusion without any sign of "steal syndrome," and a lack of inotropic effects.

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