Calcium channel blocker

Calcium channel blocker

A calcium channel blocker (CCB) is a chemical that disrupts the movement of calcium (Ca2+) through calcium channels.[1]

CCB drugs devised to target neurons are used as antiepileptics. However, the most widespread clinical usage of calcium channel blockers is to decrease blood pressure in patients with hypertension. CCBs are particularly efficacious in treating elderly patients.[2] Calcium channel blockers are also frequently used to alter heart rate, to prevent cerebral vasospasm, and to reduce chest pain caused by angina pectoris. Despite their effectiveness, CCB's often have a high mortality rate over an extended dosage peroid, and have been known to have a high amount of side effects.

Contents

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.[2]

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 beta 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 beta 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 beta 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, bioavailable supplements of magnesium, possibly including magnesium chloride, magnesium lactate and magnesium aspartate, may increase or enhance the effects of calcium channel blockade.[3]

Cardiovascular action

The calcium channel blockers known as non-dihydropyridines decrease the force of contraction of the myocardium (muscle of the heart). This is known as the negative inotropic effect of calcium channel blockers. It is because of these negative inotropic effects that the nondihydropyridine calcium channel blockers, such as verapamil or diltiazem, may be avoided (or used with caution) in individuals with cardiomyopathy.[4]

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, or a lowering of heart rate. This can increase 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 generally a goal. Negative chronotropy can be beneficial when treating a variety of disease processes because lower heart rates represent lower cardiac oxygen requirements. Elevated heart rate can result in significantly higher 'cardiac work', which can result in symptoms of angina.

Classes

Dihydropyridine

Dihydropyridine calcium channel blockers are often used to reduce systemic vascular resistance and arterial pressure, but are not used to treat angina (with the exception of amlodipine, nicardipine, and nifedipine, which carry an indication to treat chronic stable angina as well as vasospastic angina) because the vasodilation and hypotension can lead to reflex tachycardia. Dihydropiridine calcium channel blockers can worsen proteinuria in patients with nephropathy.[5] This CCB class is easily identified by the suffix "-dipine".

Side effects of these drugs may include but are not limited to:

  • Dizziness, headache, redness in the face
  • Fluid buildup in the legs
  • Rapid heart rate.
  • Slow heart rate.
  • Constipation
  • Gingival overgrowth
  • Ankle edema

Non-dihydropyridine

Phenylalkylamine

Skeletal formula of verapamil

Phenylalkylamine calcium channel blockers are relatively selective for myocardium, reduce myocardial oxygen demand and reverse coronary vasospasm, and are often used to treat angina. They have minimal vasodilatory effects compared with dihydropyridines and therefore cause less reflex tachycardia, making it appealing for treatment of angina, where tachycardia can be the most significant contributor to the heart's need for oxygen. Therefore, as vasodilation is minimal with the phenylalkylamines, the major mechanism of action is causing negative inotropy. Phenylalkylamines are thought to access calcium channels from the intracellular side, although the evidence is somewhat mixed.[6]

Benzothiazepine

Structural formula of diltiazem

Benzothiazepine calcium channel blockers are an intermediate class between phenylalkylamine and dihydropyridines in their selectivity for vascular calcium channels. By having both cardiac depressant and vasodilator actions, benzothiazepines are able to reduce arterial pressure without producing the same degree of reflex cardiac stimulation caused by dihydropyridines.

Nonselective

While most of the agents listed above are relatively selective, there are additional agents that are considered nonselective. These include mibefradil, bepridil, fluspirilene[7], and fendiline.[8]

Toxicity

Mild CCB toxicity is treated with supportive care. Non-dihydropyridine CCB may produce profound toxicity and early decontamination, especially for slow release agents, is essential. Treatment involves intravenous calcium, atropine, fluids, insulin and inotropes. Insulin is required because at high doses CCB block the effect of insulin. If unsuccessful ventricular pacing should be used.[9]

See also

References

  1. ^ "calcium channel blocker" at Dorland's Medical Dictionary
  2. ^ a b Nelson, Mark. "Drug treatment of elevated blood pressure". Australian Prescriber (33): 108–112. http://www.australianprescriber.com/magazine/33/4/108/12. Retrieved August 11, 2010. 
  3. ^ 1. Iseri LT & French JH. “Magnesium: nature’s physiologic calcium blocker.” Am Heart J, 108, 188-193, 1984.
  4. ^ Lehne, Richard (2010). Pharmacology for Nursing Care, Seventh Edition. St. Louis, Missouri: Saunders Elsevier. pp. 505. ISBN 978-1-4160-6249-3. 
  5. ^ Remuzzi G, Scheppati A, Ruggenenti P: Nephropathy in patients with type 2 diabetes. N Engl J Med 2002;346:1145.
  6. ^ Hockerman et al, Annu Rev Pharmacol Toxicol. 1997;37:361-96
  7. ^ Bezprozvanny I, Tsien RW (September 1995). "Voltage-dependent blockade of diverse types of voltage-gated Ca2+ channels expressed in Xenopus oocytes by the Ca2+ channel antagonist mibefradil (Ro 40-5967)". Mol. Pharmacol. 48 (3): 540–9. PMID 7565636. http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=7565636. 
  8. ^ Scultéty S, Tamáskovits E (1991). "Effect of Ca2+ antagonists on isolated rabbit detrusor muscle". Acta Physiol Hung 77 (3–4): 269–78. PMID 1755331. 
  9. ^ Calcium Channel Blockers. Medicine 2007;35:599-602

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Look at other dictionaries:

  • calcium channel blocker — n any of a class of drugs (as verapamil) that prevent or slow the influx of calcium ions into smooth muscle cells esp. of the heart and that are used esp. to treat some forms of angina pectoris and some cardiac arrhythmias called also calcium… …   Medical dictionary

  • calcium channel blocker — n. any of a class of drugs, including nifedipine, diltiazem, and verapamil, that relax vascular and other smooth muscle tissue by preventing calcium ions from entering their cells, used to treat headaches, high blood pressure, angina pectoris,… …   Universalium

  • calcium channel blocker — n. any of a class of drugs, including nifedipine, diltiazem, and verapamil, that relax vascular and other smooth muscle tissue by preventing calcium ions from entering their cells, used to treat headaches, high blood pressure, angina pectoris,… …   English World dictionary

  • calcium-channel blocker — calcium antagonist a drug that inhibits the influx of calcium ions into cardiac and smooth muscle cells; it therefore reduces the strength of heart muscle contraction, reduces conduction of impulses in the heart, and causes vasodilatation.… …   The new mediacal dictionary

  • calcium-channel blocker — noun any of a class of drugs that block the flow of the electrolyte calcium (either in nerve cell conduction or smooth muscle contraction of the heart); has been used in the treatment of angina or arrhythmia or hypertension or migraine • Syn:… …   Useful english dictionary

  • calcium channel blocker — noun or calcium blocker : any of a class of drugs (as verapamil) that prevent or slow the influx of calcium ions into smooth muscle cells especially of the heart and that are used especially to treat some forms of angina pectoris and some cardiac …   Useful english dictionary

  • calcium channel blocker — noun Date: 1980 any of a class of drugs (as verapamil) that prevent or slow the influx of calcium ions into smooth muscle cells and are used especially to treat some forms of angina pectoris and some cardiac arrhythmias …   New Collegiate Dictionary

  • calcium channel blocker — noun A class of drug used to treat hypertension and also angina and arrhythmia …   Wiktionary

  • Channel blocker — A channel blocker (CB) or ion channel blocker (ICB) is a type of drug which binds inside the pore of a specific type of ion channel and blocks the flow of ions through it, resulting in an alteration of the electrochemical gradient of the cell… …   Wikipedia

  • Calcium channel — A Calcium channel is an ion channel which displays selective permeabiltiy to calcium ions. It is sometimes synonymous as voltage dependent calcium channel, [DorlandsDict|two/000019812|calcium channel] although there are also ligand gated calcium… …   Wikipedia

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