الفهرس 
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Abstract
[Since the orignal description by Fleckenstein in 1967 of an agent that manifested effects on conduction tissue appearently compatible with calcium antogonist actions, a veritable explosion of investigations has taken place. The calcium antagenists-or, as more currently referred to, the calcium-channel blocking agents-have been used as molecular probes to determine both the basic physiologic and pathophysiologic workings of tissues and organs, and as clinical agents to treat a wide variety of diseases. (Epstein et al.
1985)].
Calcium—channel blockers represent a new class of drugs that have found wide acceptance in the treatment of cardiovascular diseases. The therapeutic actions of these agesnts arise from their ability to inhibit directly the influx of calcium-ion-CaT-across the plasma membranes of excitable cells. In the cardiovascular system, inhibitory effects are found in arterial smooth muscle-both coronary and peripheral- as well as in the heart. Because they affect tissue other than the heart and vasculature, calcium—channel blockers have considerable potential for use in other diseases (Langer, 1980).
The basis for these effects lies in the ability of thes drugs to block Ca entry into ce.lls, and thus to prevent this
critical messenger from reaching sites with-in the cell that
initiate, or regulate, key cellular processes, Because Ca is prevented from serving its essential role as an intracellular messenger, the term calcium antagonist is often used to describe thes drugs, However, the calcium-channel blockers do not themselves antagonize the effects of Ca4,instead, they prevent this ion from gaining access to its intracellular sites of action. In cardiac mucle, the role of calcium as an activator of contraction arises from its ability to initiate and modulate the interactions of the contractile proteins. These important functions of calcium are made possible by the very low Ca4 concentrations found within the resting myocar— dial cells, coupled with the presence in the cytosol of a family of high-affinity Ca” -binding proteins. Calcium also plays a central role in the initiation of smooth muscle contraction. Calcium activated processes are also found in nonvascular smooth muscle and in a variety of nonmotile cells. The ability of the calcium-channel blockers to inhibit many of these Ca -dependent activation processes has been
the basis for a growing number of clinical studies in which
these drugs have been tested for their potential use to
prevent or treat disorders arising from theseCa14-activited processes. (Katz, 1985).
As regard, cardiovascular field, calcium-blockers are included in conditions such as angina pectoris, coronary • -- - .•_jj-• -. -- - .LL” -- - -
___ ..--- vasospastic disorders, cardiac arrhythmias, systemic hypertension, atherosclerosis, hypertrophic cardiomyopathy, abnormal cardiac diastolic function, migraine, subarachnoid hemorrhage and raynaud1s syndrome. Also, in the treatment of myocardial infarction,stroke,preservation of myocardium during cardiopulmonary hypass, and in the treatment of pulmonary hypertension. Extracardiovascular uses include asthma and gastrointestinal disorders. (Epstein et al. 1985).
[Thus, this essay aims to review the results of the thought, effort and studies of many investigators with the hope that it will provide a stimulus for further studies that will permit a more fundamental understanding of the processes controlling cellular function, and provide inforrnations leading to the more effective clinical use of calcium-channel blocking drugs.]