Calcium channel blockers of all subclasses reduce pancreatic insulin secretion and induce end-organ insulin resistance, causing hyperglycemia. Nifedipine triggers hypotension and reflex sinus tachycardia. Thus, both verapamil and diltiazem causes significant bradycardia, hypotension, conduction disturbances, and escape rhythms. With significant overdoses, the serum and tissue concentration of these drugs are so excessive that the pharmacological difference in affinity and action between subclasses is overwhelmed. Dihydropyridines are very effective vasodilators but exert less influence on cardiac pacemakers and myocardial contractility. Diltiazem has a similar range of effects as verapamil with less vasodilation its effect is more potent on chronotropic action. It suppresses cardiac contractility, SA nodal automaticity, AV nodal conduction and causes potent vasodilation. Verapamil has a strong affinity for both myocardium and vascular smooth muscle. Elimination by hemodialysis or hemofiltration is ineffective.Īt higher doses clearance slows, because hepatic clearance changes from first-order to zero-order kinetics.Ĭonventionally used CCBs belong to three main chemical classes, with each subclass having differing affinities for cardiac tissue and vascular smooth muscle:ĭihydropyridines (nifedipine, amlodipine, felodipine, isradipine, nicardipine, nimodipine) All CCBs are very well absorbed orally across the subtypes, undergo extensive hepatic first-pass metabolism, are lipophilic, bind readily to plasma proteins, and have a large volume of distribution ( > 2 liters/kg). The influx of calcium is also responsible for insulin secretion. Cytosolic calcium concentration mediated by membrane gated influx of calcium is responsible for maintaining vascular smooth muscle tone. Contraction strength is directly proportional to intracellular calcium concentration, allowing actin and myosin to interact.
Calcium entry during the plateau phase of the action potential in myocardial cells releases calcium from the sarcoplasmic reticulum to the cytosol, triggering myocardial contraction. L type voltage-gated calcium channels are predominant in the following sites and roles:ĭepolarization of the sinoatrial node (SA) and impulse propagation through the atrioventricular node (AV).
Calcium channel blockers in all their subtypes target the L-type voltage-gated calcium channels.
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