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  • Title: Antihypertensive compounds with combined actions.
    Author: Rahn KH.
    Journal: J Cardiovasc Pharmacol; 1987; 10 Suppl 11():S18-22. PubMed ID: 2454363.
    Abstract:
    In the treatment of hypertension, drugs with different mechanisms of action are frequently combined. The rationale for this procedure is that lowering blood pressure via one mechanism often leads to the activating of processes that tend to increase blood pressure. Thus, during antihypertensive treatment with vasodilating agents, reflex stimulation of the heart occurs with increase of cardiac output. By this, the blood pressure lowering effect of the vasodilator is antagonized. Combination of several drugs may complicate therapy because of differences in the onset and the duration of action. Sometimes, there are pharmacokinetic drug interactions. By combining several blood pressure lowering mechanisms in one drug molecule, one tries to prevent these difficulties. There are now several drugs with a dual mode of action available for the treatment of hypertension. Labetalol combines alpha- and beta-receptor blocking activities. Meanwhile, there is ample experience with the use of this drug in the treatment of hypertensive patients. Labetalol can be used for acute decrease of blood pressure in hypertensive emergencies. Most often, the drug is given for chronic treatment of hypertension. The overall incidence of side effects from labetalol compares favorably with that from other drugs. In addition to side effects caused by beta-blockade, the use of labetalol may result in postural hypotension due to the alpha-receptor blocking activity. Carvedilol is a new compound that combines beta-receptor blockade and vasodilation in one molecule. The drug can be used to acutely and chronically reduce blood pressure. Carvedilol is now undergoing clinical investigation. The same is true for celiprolol, a beta 1-receptor blocking agent with alpha 2-receptor blocking activity.
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