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Calcium channel blocker

Calcium channel blockers are a class of drugs and natural substances that disrupt the calcium (Ca2+) conduction of calcium channels.[1]

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 main clinical usage of calcium channel blockers is to decrease blood pressure. It is for this action that they are used in individuals with hypertension.

Explanation

Most calcium channel blockers 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 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.

Pharmacologic Beta blockade is superior to Calcium channel blockade regarding chronotropic properties of the myocardium. Titration of a Beta 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 (CCB's 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.

With a relatively low blood pressure, the afterload on the heart decreases; this decreases the amount of oxygen required by the heart. 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 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.[]

Classes of calcium channel blockers

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 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. This CCB class is easily identified by the suffix "-dipine".

Side effects of these synthetic 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

Phenylalkylamine

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. Action is intracellular.

Benzothiazepine

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 and fluspirilene.[2]

Another example is fendiline.[3]

Other drugs with similar uses

Other classes of pharmaceutical agents that have overlapping effects as calcium channel blockers include ACE inhibitors, beta-blockers, and nitrates.

Toxicity

CCB overdose is often treated with glucagon.

See also

References

  1. ^ calcium channel blocker at Dorland's Medical Dictionary
  2. ^ 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. 
  3. ^ Scultéty S, Tamáskovits E (1991). "Effect of Ca2+ antagonists on isolated rabbit detrusor muscle". Acta Physiol Hung 77 (3-4): 269–78. PMID 1755331. 

External links

 

The content of this section is licensed under the GNU Free Documentation License (local copy). It uses material from the Wikipedia article "Calcium channel blocker" modified November 23, 2009 with previous authors listed in its history.