Τόμος 4 (1986) – Τεύχος 3 – Άρθρο 4 – Επιθεώρηση Κλινικής Φαρμακολογίας και Φαρμακοκινητικής-Ελληνική Έκδοση – Volume 4 (1986) – Issue 3 – Article 4 – Epitheorese Klinikes Farmakologias και Farmakokinetikes-Greek Edition

Calcium Antagonists: Pharmacodynamic Effects and Mechanism of Action

S. T. PLESSAS AND CH. T. PLESSAS

4: 109-127 (1986)

PHARMAKON-Press: Epitheorese Klin. Farmakol. Farmakokinet.

4: 109-127 (1986)

The calcium antagonistic drugs (also called calcium channel blockers or slaw channel blockers or calcium entry block­ers) represent a major development in cardio­vascular pharmacology. Τheir main mechanism of action is related to the inhibition of the movement of calcium ions into the cells, or to its mobilization from intracellular stores, with resultant inhibition of excitation-contraction coupling. The list of these drugs, with the more recently developed ones, includes: (1) chemical relatives of verapamil (phenylalkylamine group) such as gallopamil (D-600), tiapamil, prenyla­mine and perhexiline, (2) dihydroxy pyridine de­rivatives, such as nifedipine, nimodipine, nitrendipine, felodipine and PV108-068, (3) the ben­zothiazine derivative diltiazem, (4) piperazines, such as cinnarizine, flunarizine and lidoflazine. Verapamil, nifedipine and diltiazem are the most important representatives. These drugs have quite different chemical structures, but their pharmacological characteristics are simi­lar. Their action is primarily confined to the cardiovascular system: in the heart, they all depress the mechanical activity and the rate of the heart and protect the ischaemic myocar­dium from calcium injury. Verapamil and dil­tiazem (but not nifedipine) prolong A-V condu­ction and refractoriness, which is important for their use as antiarrhythmic agents. All 3 drugs reduce vascular tone; for this effect they are powerful dilators of the coronary and periphe­ral arteries. These in vitro effects can be sub­stantially altered by activation of baroreceptor reflexes in vivo, as is expected with vasodilators that cause little or no inhibition of norad­renalίπe release from sympathetic nerve endings. The combination of coronary dilatation with decreased oxygen demand of the myocar­dium, and its decreased preload explain their value in the treatment of vasospastic and ef­fort angina. Given the involvement of calcium ions in excitation-response coupling in practi­cally all types of cells, the effects of calcium antagonists would be on other physiological functions, e.g. neurotransmission and secretion from exocrine and endocrine glands. Therefore, their clinical indications have already moved beyond the presently accepted boundaries of angina, cardiac arrhythmias and hypertension into the areas of concern of respiratory physi­cians (asthma), gastroenterologists (esophageal motor disorders) and gynaecologists (dys­menorrhoea). The development and study of such drugs will also reveal still further thera­peutic potentials, probably involving neurolo­gists and endocrinologists.

1. Fleckenstein, A., Tritthart, M., Fleckenstein, B. et al.: Α new group of competitive Ca antagonists (iprove­ratril, D600, prenylamine) with highly potent inhibitory effects on excitation-contraction coupling in mamma­lian myocardium. Pflugers Archif fur die gesamte Phy­siol. Mensch. Tier. 307: R25 (1969)
2. Fleckenstein, A.: Specific pharmacology of calcium in myocardium, cardiac pacemakers and vascular smooth muscle. Rev. Pharmacol. Toxic. 17: 149 (1977)
3. Fleckenstein, Α., Von Grun, G., Tritthart, H. et al.: Ute­rus-Relaxation durch hochaktive Ca plus, plus-antago­nistische Hemmstoffe der elektro-mechanischen Koppe­lung wie Isoptin (Verapamil, Iproveratril), Substanz D 600 uncl Segontin (Prenylamin). Versuche am isolierten Uterus virgineller Ranee. Klin. Woch., 49: 32 (1971)
4. Nayler, W.G.: Calcium antagonists. Εur. Heart. J. 1: 225 (1960)
5. Nayler, W.G. and Poole-Wilson, P.: Calcium antago­nists: Definition and mode of action. Bas. Res. Card. 76: 1 (1981)