Calcium channel blocker
alcium channel blockers (CCBs) are a class of drugs and natural substances that disrupt the calcium (Ca2+) through calcium channels.
It has effects on many excitable cells of the body, such as cardiac muscle, i.e. heart, smooth muscles of blood vessels, or neurons. Drugs used to target neurons are used as antiepileptics and are not covered in this article.
The most widespread clinical usage of calcium channel blockers is to decrease blood pressure in patients with hypertension, with particular efficacy in treating elderly patients. Also, calcium channel blockers frequently are used to control heart rate, prevent cerebral vasospasm, and reduce chest pain due to angina pectoris.
Explanation
Most calcium channel blockers decrease the force of contraction of the myocardium (muscle of the heart). This is known as the negativeinotropic effect of calcium channel blockers. It is because of the negative inotropic effects of most calcium channel blockers that they are avoided (or used with caution) in individuals with cardiomyopathy.
Many calcium channel blockers also slow down the conduction of electrical activity within the heart, by blocking the calcium channel during the plateau phase of the action potential of the heart (see: cardiac action potential). This results in a negative chronotropic effect resulting in a lowering of the heart rate and the potential for heart block. The negative chronotropic effects of calcium channel blockers make them a commonly used class of agents in individuals with atrial fibrillation or flutter in whom control of the heart rate is an issue. Negative chronotropy can be beneficial in that elevated heart rate can result in significantly higher 'cardiac work', which can result in anginal symptoms: lower heart rates represent lower cardiac oxygen requirements.
Pharmacologic Beta blockade is superior to Calcium channel blockade regarding chronotropic properties of the myocardium. Titration of aBeta Blocker to a desired heart rate is decidedly easier than titration of a non-dihydropyridine CCB.
Mechanism of action
Calcium channel blockers work by blocking voltage-gated calcium channels (VGCCs) in cardiac muscle and blood vessels. This decreases intracellular calcium leading to a reduction in muscle contraction. In the heart, a decrease in calcium available for each beat results in a decrease in cardiac contractility. In blood vessels, a decrease in calcium results in less contraction of the vascular smooth muscle and therefore an increase in arterial diameter (CCBs do not work on venous smooth muscle), a phenomenon called vasodilation. Vasodilation decreases total peripheral resistance, while a decrease in cardiac contractility decreases cardiac output. Since blood pressure is determined by cardiac output and peripheral resistance, blood pressure drops. Calcium channel blockers are especially effective against large vessel stiffness, one of the common causes of elevated systolic blood pressure in elderly patients.
With a relatively low blood pressure, the afterload on the heart decreases; this decreases how hard the heart must work to eject blood into the aorta, and so the amount of oxygen required by the heart decreases accordingly. This can help ameliorate symptoms of ischemic heart disease such as angina pectoris.
Unlike β-blockers, calcium channel blockers do not decrease the responsiveness of the heart to input from the sympathetic nervous system. Since moment-to-moment blood pressure regulation is carried out by the sympathetic nervous system (via the baroreceptor reflex), calcium channel blockers allow blood pressure to be maintained more effectively than do β-blockers.
However, because calcium channel blockers result in a decrease in blood pressure, the baroreceptor reflex often initiates a reflexive increase in sympathetic activity leading to increased heart rate and contractility. A β-blocker may be combined with a dihydropyridine calcium channel blocker to minimize these effects.
Ionic calcium is antagonized by magnesium ions in the nervous system. Because of this, dietary supplements of magnesium oxide and other magnesium preparations may increase or enhance the effects of calcium channel blockade.
pharmacokinetics
All the selective calcium channel blockers are well absorbed after oral administration, although there are marked differences in oral bioavailability that relate to differences in first-pass metabolism. Verapamil and isradipine undergo fairly extensive first-pass metabolism, whereas diltiazem, nifedipine, and nicardipine do not. Protein binding percentages are higher with the dihydropyridines than with either diltiazem or verapamil. With nifedipine and possibly other dihydropyridines, protein binding is concentration dependent, allowing for the possibility of protein-binding interactions, although none of clinical significance has been reported. With verapamil and diltiazem, protein binding is independent of drug concentrations, making displacement interactions unlikely.
Because the older calcium channel blockers have relatively short half-lives, extended-release formulations have been developed to permit once- or twice-daily administration. Isradipine, felodipine, and amlodipine have substantially longer elimination half-lives, although only amlodipine's half-life allows once-daily administration.
What are the side effects of calcium channel blockers?
· The most common side effects of CCBs are constipation, nausea, headache,rash, edema (swelling of the legs with fluid), low blood pressure, drowsiness, and dizziness.
· Liver dysfunction and over growth of gums may also occur. When diltiazem (Cardizem) or verapamil (Calan, Isoptin) are given to individuals with heart failure, symptoms of heart failure may worsen because these drugs reduce the ability of the heart to pump blood.
· Like other blood pressure medications, CCBs are associated with sexual dysfunction.
uses
Calcium channel blockers belong to a class of medications that are used to treat a variety of illnesses and conditions. These drugs, also known as calcium antagonists, prevent calcium from infiltrating the cells of the heart and blood vessel walls, according to MayoClinic.com. Their impact on muscle cells in arterial walls allows blood vessels to relax and dilate, easing stress on the circulatory system and relieving conditions in which elevated blood pressure is a factor.
Hypertension and Heart Disease
The ability of calcium channel blockers to relax and dilate blood vessels makes them a valuable tool in the treatment of high blood pressure, according to Lawrence D. Chilnick, author of "Heart Disease: An Essential Guide for the Newly Diagnosed." Because these drugs also block the uptake of calcium by the heart muscle, thus slowing its contractions and making them less intense, CCBs often are prescribed for the treatment of coronary heart disease as well, according to Chilnick, a former editorial director for the Cleveland Clinic Press. CCBs commonly prescribed for hypertension and heart disease include amlodipine, diltiazem, felodipine, isradipine, nicardipine, nifedipine, nisoldipine and verapamil.
Angina and Arrhythmias
Calcium channel blockers often are effective in preventing angina pectoris, which is a chest pain that occurs when the heart muscle fails to get enough oxygen-rich blood. CCBs' ability to dilate blood vessels and improve circulation helps to ensure that blood flow to the heart is unimpeded. Registered pharmacist W. Renée Acosta, author of "LWW's Foundations in Pharmacology for Pharmacy Technicians," points out that although CCBs can prevent angina, they are of little value in relieving the pain of short-term angina attacks. Acosta also reports that the same CCBs used to prevent angina often are prescribed for the treatment of arrhythmias, which are irregular heart rhythm patterns.
Migraine Headaches
Joan Raymond, author of "Migraine," reports that calcium channel blockers often are effective in relieving the pain and aura symptoms of migraine headaches. However, she points out, the drugs must be taken for quite some time before their benefits are seen. The CCB most widely prescribed for the treatment of migraines is verapamil, according to Raymond. Possible side effects from CCBs include constipation and hypotension.
Raynaud's Disease
Raynaud's disease is a rare circulatory disorder in which blood flow to the fingers and toes may be temporarily impeded, causing tingling and discoloration. Seen most often in women, the disorder appears to be caused by spasm of the small arteries, known as arterioles, which is triggered by exposure to cold temperatures. Isadore Rosenfeld, M.D., author of "Doctor, What Should I Eat?" reports that calcium channel blockers, most notably diltiazem and nifedipine, often are effective in preventing the arterial spasms that are the root cause of Raynaud's.
No comments:
Post a Comment