Calcium antagonists angina treatment

Knight CJ et al. Different effects of calcium antagonists, nitrates and beta blockers on platelet function Possible importance for the treatment of unstable angina. Circulation 1997 95 125-132. 

Application of part of the classical Hantzsch pyridine synthesis leads to nifedipine (87) (81 AG(E)762, 68SAP6801482), a calcium antagonist useful in the treatment of angina. The pharmacology of a chemically related drug, nisoldipine (88), has recently been studied (80AF2144). Both compounds inhibit the transmembrane movement of calcium into activated smooth and cardiac muscle. Nisoldipine, however, is characterized by a high potency and uniqueness of action and may well prove to be of considerable therapeutic value. 

Calcium antagonists can cause serious toxicity or death with relatively small overdoses. These channel blockers depress sinus node automaticity and slow AV node conduction (see Chapter 12 Vasodilators the Treatment of Angina Pectoris). They also reduce cardiac output and blood pressure. Serious hypotension is mainly seen with nifedipine and related dihydropyridines, but in severe overdose all of the listed cardiovascular effects can occur with any of the calcium channel blockers. 

Exertional angina calcium antagonists are useful in the treatment of exercise-induced angina, through their ability to increase coronary dilatation and blood flow. 

Diltiazem hydrochloride is a calcium ion influx inhibitor (slow channel blocker or calcium antagonist). It has generally been indicated for the treatment of angina and, more recently (2), hypertension. Diltiazem hydrochloride is a potent dilator of coronary arteries and has been shown to increase exercise tolerance in man. It is available for dosing as immediate release tablets and as extended or sustained release capsules and is usually well-tolerated. While some adverse reactions have been reported during diltiazem hydrochloride therapy, it is generally considered to be well-tolerated. In most cases, no causal relationship between the events and diltiazem hydrochloride use has yet to be established (1). 

Certain aryl-dihydropyridines [e.g. (12)], prepared by conventional Hantzsch synthesis, have been found to be highly effective calcium antagonists and are used to reduce blood pressure and in the treatment of angina pectoris. ... 

Unlike skeletal muscles, which contain endogenons stores of calcium ions, both cardiac muscle and vascnlar smooth muscle require extracellular calcium for contractile function. Therefore, cardiac muscle and vascnlar smooth muscle are subject to regulation by calcium antagonists or calcium entry blockers (Figure 103 and Table 21), which are used in the treatment of hypertension, Raynand s disease, Prinzmetal s angina, and migraine syndromes. 

Calcium antagonists (Figure 4.3) are agents which block the flow of calcium ions into cardiac and vascular smooth muscle when they are stimulated to contract. They have value as vasodilators for use in hypertension and also reduce blood flow resistance and cardiac workload in the treatment of angina. Verapamil (Knoll Pfizer, 1967) is also used as an antiarrhythmic because of its effects on ion channels in the heart s electrical conduction system. Nifedipine (Bayer, 1977) is among the world s top 25 drugs and is the forerunner of several agents of the dihydropyridine class. 

The calcium ion antagonists nifedipine 21829-25A] (62), verapamil [52-55-9] (63), and flunarizine [52468-60-7] (64) exhibit antitussive effects in a dose-dependent manner in guinea pigs (91). Pretreatment with a subthreshold dose of nifedipine also markedly increased the antitussive effects of morphine, dihydrocodeine, and dextromethorphan. However, none of the calcium ion antagonists are used clinically as antitussive agents. They are used in the treatment of angina and hypertension (see Cardiovascularagents). 

Verapamil, a slow calcium channel antagonist used in treatment of angina, hypertension and superventricular tachycardia56,57, labelled with 13C in the 1-position of the phenethyl side chain, 61, and with 13C-labels in all four O-methyl groups, 62, and also containing 50% of 13C in the TV-methyl group, 62, has been prepared58 in multistep syntheses which involved, in the case of the synthesis of 61, the displacement of mesylate 63 with N-methyl-2-(3,4-dimethoxyphenyl)-l-[13C]-ethyl amine, 64 (equation 25). 

Kumar S, Hall RJ. Drug treatment of stable angina pectoris in the elderly defining the place of calcium channel antagonists. Drugs Aging. 2003 20 805-815. 

There are approximately a dozen calcium channel antagonists marketed in the United States for the treatment of hypertension, certain dysrhythmias, and some forms of angina (see Chaps. 13,15, and 17). The calcium channel blockers are classified by their chemical structure as phenylalkylamines (e.g., verapamil), benzothiapines (e.g., diltiazem), and dihydropyridines (e.g., amlodipine, felodipine, nicardipine, and nifedipine). Several of these agents, namely, diltiazem, nicardipine, nifedipine, and verapamil, are formulated as sustained-release oral dosage forms or have a slow onset of action and longer half-life (e.g., amlodipine " ), allowing once-daily administration. 

Amlodipine is a calcium-channel-blocking agent, which is indicated in the treatment of hypertension, chronic stable angina, and vasospastic (Prinzmetal or variant) angina. The ten Ca2+ channel antagonists that are in chnical use in the... 

A number of the 1,4-dihydropyridine calcium channel antagonists are chiral and are used as the racemate for the treatment of hypertension and angina. 

Dihydropyrimidinones (DHPMs) are found to exhibit a wide spectrum of biological activities (Singh et al., 1999 Fu et al., 2002 Atwal et al., 1991 Janis and Triggle, 1983 Godfraid et al., 1986). They also show remarkable pharmacological properties such as calcium channel antagonists and are used extensively as therapeutics in the clinical treatment of cardiovascular diseases such as hypertension, cardiac arrhythmias, and angina pectoris (Jauk et al., 1999 Rovynak et al., 1995 Atwal et al, 1990). Furthermore, they have been found to exhibit a wide spectrum of antiviral, antitumor, antibacterial, and anti-inflammatory activities (Patil et al., 1995 Snider et al., 1996). 

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