Diltiazem chemical structure

Four categories of calcium channel blockers can be defined based on their chemical structures and actions diphenylalkylamines, benzothiazepines, dihydropyridines, and bepridil. Both diphenylalkylamines (verapamil) and benzothiazepines (diltiazem) exhibit effects on both cardiac and vascular tissue. With specificity for the heart tissue, these two types of calcium channel blockers can slow conduction through the AV node and are useful in treating arrhythmias. The dihydropyridines (nifedipine is the prototypical agent) are more potent peripheral and coronary artery vasodilators. They do not affect cardiac conduction, but can dilate coronary arteries. They are particularly useful as antianginal agents. Bepridil is unique in that it blocks both fast sodium channels and calcium channels in the heart. All calcium channel blockers, except nimodipine and bepridil, are effective in treating HTN. 

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. 

Figure 16.11 Chemical structure of the three most important representatives of the Cayl (L-type) channel organic antagonists DHPs (nifedipine), phenylalkylamines (verapamil), and benzothiazepines (diltiazem). The DHP derivative. Bay K8644, can be either agonist or antagonist depending on the optical enantiomer.

United States have diverse chemical structures. Five classes of compounds have been examined phenylalkylamines, dihy-dropyridines, benzothiazepines, diphenylpiperazines, and a diarylaminopropylamine. At present, verapamil (a phenyl-alkylamine) diltiazem (abenzothiazepine) nifedipine, amlo-dipine, felodipine, isradipine, nicardipine, nisoldipine, and nimodipine (dihydropyridines) and bepridil (a diarylaminopropylamine ether used only for refractory angina) are approved for clinical use in the United States. 

Calcium-channel blockers in current clinical usage affect the slow L-type channel. They are usually classified by their chemical structure, which determines their selectivity for vascular smooth muscle over myocardium, and hence their potential to slow the heart rate (negative inotropic activity) see Table 23. T, (below). Interactions due to additive inotropic effects will therefore apply only to the benzothiazepine (diltiazem) and phenyla-Ikylamine-type (verapamil) calcium-channel blockers, and usually not to the dihydropyridine-type (e.g. nifedipine) calcium-channel blockers. All three types of calcium-channel blocker will have additive hypotensive effects with other drugs with blood-pressure lowering activity. 

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