What is the major effect of a calcium channel blocker such as verapamil on cardiac contractions
What are calcium channel antagonists? Show What are the effects of calcium channel antagonists? All of the calcium channel antagonists have their predominant effects on arteriolar smooth muscle, the myocardium and cardiac conducting tissue. The profile of effects is characteristic for each class. Other tissues which are 'calcium-dependent', e.g. skeletal muscle, secretory cells, nervous tissue, are not affected by the available calcium channel antagonists, either because they are dependent on intracellular calcium stores (skeletal muscle) or they have different types of calcium channels. All calcium channel antagonists have an intrinsic natriuretic effect. Verapamil Diltiazem Dihydropyridines Despite having an intrinsic diuretic effect, the dihydropyridines cause peripheral oedema. The oedema represents a redistribution of extra cellular fluid rather than a net retention of salt and water and hence does not respond to diuretics. What are the clinically relevant pharmacokinetic properties of the calcium channel antagonists? The calcium channel antagonists have a range of elimination half-lives which have a considerable impact on their clinical use. Verapamil and diltiazem have short half-lives which require them to be given 3-4 times daily. However, slow-release formulations now allow once-daily dosing. The original fluid-filled nifedipine capsule releases the drug rapidly in the gut. This causes both a rapid onset and offset of response. Nifedipine capsules are thus prone to produce a rapid drop in blood pressure with adverse reflex cardiac effects. These responses probably account for the adverse outcome with enhanced risk of myocardial infarction which has been associated with the rapidly-acting nifedipine preparation. As a result, the availability of nifedipine capsules in Australia is currently under review. These haemodynamic effects are attenuated when nifedipine is given in hard compressed tablets and not seen with the slow-release osmotically-driven preparation. As absorption occurs from the stomach and small intestine and not from the buccal mucosa, there is no rational basis for the use of nifedipine by the buccal route.
The longer half-life of felodipine was sufficient for the original compressed tablets to be given twice daily, but a once-daily, slow-release formulation of felodipine was also developed and this has become the standard preparation. The intrinsically much longer half-life of amlodipine makes it suitable for once-daily dosing as a conventional tablet preparation. This long half-life also means that it takes longer for steady-state plasma concentrations to be achieved, causing the clinical response to be delayed for several days until sufficient drug has accumulated. Adverse effects may also take days to resolve. What are the current clinical uses of calcium channel antagonists? Verapamil Verapamil is also used in the treatment of hypertension. It is effective in reducing blood pressure either as monotherapy or in combination with either diuretics or ACE inhibitors. Combination with a beta blocker is not recommended because of additive deleterious myocardial depression. Compared with the other calcium channel antagonists, the limiting factors for the use of verapamil in hypertension are its cardio depression and the almost universal occurrence of constipation. Verapamil has a unique role among the calcium channel antagonists in the management of supraventricular arrhythmias. Normal conduction through the AV node is dependent on calcium entry into the conducting tissue cells for depolarisation. Verapamil reduces calcium entry and thus slows AV conduction. This action can be beneficial in terminating or preventing paroxysmal supraventricular tachycardia by interfering with AV nodal re-entry and also in controlling ventricular rate in the presence of atrial fibrillation. Verapamil and diltiazem are sometimes also used to enhance myocardial relaxation either when there is significant diastolic dysfunction or with hypertrophic obstructive cardiomyopathy. Diltiazem Although it has been somewhat slow to be accepted, diltiazem has a role in the management of hypertension as a moderately effective arterial vasodilator. It is well tolerated both as monotherapy and in combination with all of the other major classes of antihypertensive drugs. Dihydropyridines Recently, the long-term safety of treatment has been questioned (see 'Calcium antagonists: the current controversy' Aust Prescr 1996;19:35). It is possible that the adverse outcomes are only related to the shorter-acting preparations. Several major outcome studies using longer-acting calcium channel antagonists are currently in progress and should answer these questions. Calcium channel antagonists as first-line antihypertensive therapy cannot be generally recommended. However, their role is well established in situations where other drugs cannot be used or have been ineffective as monotherapy. The practice of using rapid-release nifedipine to produce acute blood pressure reduction can rarely be justified. The original role of rapid-release nifedipine was in the management of angina. Although it still has marketing approval for this indication, its only real role is in the treatment of proven coronary artery spasm. The tablet and slow-release preparations of nifedipine also have marketing approval for the management of angina. Although the major use of amlodipine is as an antihypertensive, it is approved for the management of angina as it is the least likely of all the dihydropyridines to cause reflex-mediated cardiac stimulation. However, diltiazem would generally be preferred to amlodipine for angina because of its pharmacological profile. Felodipine does not have marketing approval for this indication. Dihydropyridines can be used to treat peripheral vasospasm. This is useful in patients treated with beta blockers who develop Raynaud's phenomenon. Are there any particular advantages of calcium channel antagonists? Calcium channel antagonists have no adverse metabolic effects on potassium or glucose homeostasis, renal function or lipids. They do produce a small uricosuric effect. There are potential benefits from calcium channel antagonists which have been claimed on the basis of animal studies, but definitive evidence in humans is lacking. These benefits include reduction of cardiovascular hypertrophy in hypertension, reduction of atherosclerotic lesions, relative reduction of the size of any incident cerebral infarction and myocardial protection from ischaemic damage. What are the problems with calcium channel antagonists? Pregnancy
F U R T H E R - R E A D I N G Robertson RM, Robertson D. Drugs used for the treatment of myocardial ischaemia. In: Hardman JG, Limbird LE, editors. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York: McGraw-Hill, 1996:759-79. Victorian Drug Usage Advisory Committee. Cardiovascular drug guidelines. 2nd ed. Melbourne: Victorian Medical Postgraduate Foundation, 1995. What is the major effect of a calcium channel blocker in cardiac contractions?Because muscle contraction is largely dependent upon influx of calcium, its inhibition causes relaxation, particularly in arterial beds. Thus, the major effects of the calcium channel blockers are relaxation of vascular and arterial smooth muscle cells resulting in arterial vasodilation.
What does verapamil do to the heart?Verapamil is a calcium channel blocker. It works by affecting the movement of calcium into the cells of the heart and blood vessels. As a result, verapamil relaxes blood vessels and increases the supply of blood and oxygen to the heart while reducing its workload .
What are the direct effects of calcium channel blockers?Calcium antagonists have been shown to have a direct negative inotropic effect, a direct negative chronotropic effect and a direct effect to produce relaxation of vascular smooth muscle and vasodilation.
Do calcium channel blockers affect cardiac muscle?Calcium channel blockers prevent calcium from entering the cell, which prevents calcium release from the sarcoplasmic reticulum. Although all the calcium channel blockers exert this effect on cardiac muscle, one compound may be more effective for a specific heart condition than another.
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