Calcium channel blocker
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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. 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 extended periods of use, and have been known to have multiple side effects. Potential major risks however were mainly found to be associated with short-acting CCB's.
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 ischaemic 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.
Cardiac 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.
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.
Only the non-dihydropyridine CCBs are considered to have negative inotropic and chronotropic effects. The dihydropyridine CCBs increase contractility and heart rate, therefore decreasing vascular resistance.
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. This CCB class is easily identified by the suffix "-dipine".
- Amlodipine (Norvasc)
- Aranidipine (Sapresta)
- Azelnidipine (Calblock)
- Barnidipine (HypoCa)
- Benidipine (Coniel)
- Cilnidipine (Atelec, Cinalong, Siscard)
- Clevidipine (Cleviprex)
- Isradipine (DynaCirc, Prescal)
- Efonidipine (Landel)
- Felodipine (Plendil)
- Lacidipine (Motens, Lacipil)
- Lercanidipine (Zanidip)
- Manidipine (Calslot, Madipine)
- Nicardipine (Cardene, Carden SR)
- Nifedipine (Procardia, Adalat)
- Nilvadipine (Nivadil)
- Nimodipine (Nimotop)
- Nisoldipine (Baymycard, Sular, Syscor)
- Nitrendipine (Cardif, Nitrepin, Baylotensin)
- Pranidipine (Acalas)
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.
- Gingival overgrowth
- Ankle edema
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.
- Verapamil (Calan, Isoptin)
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.
- Diltiazem (Cardizem)
Ziconotide, a peptide compound derived from the omega-conotoxin, is a selective N-type calcium channel blocker that has potent analgesic properties that are equivalent to approximate 1,000 times that of morphine. It must be delivered via the intrathecal (directly into the cerebrospinal fluid) route via an intrathecal infusion pump.
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. For severe overdoses, treatment usually includes close monitoring of vital signs and the addition of vasopressive agents and intravenous fluids for blood pressure support. IV calcium gluconate (or calcium chloride if a central line is available) and atropine are first-line therapies. If the time of the overdose is known and presentation is within two hours of ingestion, activated charcoal, gastric lavage, and polyethylene glycol may be used to decontaminate the gut. Efforts for gut decontamination may be extended to within 8 hours of ingestion with extended release preparations.
Hyperinsulinemia-euglycemia (HIE) therapy has emerged as a viable form of treatment. Although the mechanism is unclear, it has been hypothesized that increased insulin mobilizes glucose from peripheral tissues to serve as an alternative fuel source for the heart (the heart mainly relies on oxidation of fatty acids). Theoretical treatment with lipid emulsion therapy has been considered in severe cases, but is not yet standard of care.
Caution should be taken when using verapamil with a Beta blocker due to the risk of severe bradycardia. If unsuccessful, ventricular pacing should be used.
See also 
- "calcium channel blocker" at Dorland's Medical Dictionary
- Nelson M (2010). "Drug treatment of elevated blood pressure" (pdf). Australian Prescriber 33 (4): 108–112.
- "Calcium Channel Blockers". MedicineNet. p. 2.
- Norman M Kaplan, MD; Burton D Rose, MD (Apr 3, 2000). "Major side effects and safety of calcium channel blockers". Chinese Medical & Biological Information.
- Iseri LT, French JH (1984). "Magnesium: Nature’s Physiologic Calcium Blocker". American Heart Journal 108 (1): 188–193. doi:10.1016/0002-8703(84)90572-6. PMID 6375330.
- Lehne R (2010). Pharmacology for Nursing Care (7th ed.). St. Louis, Missouri: Saunders Elsevier. p. 505. ISBN 978-1-4160-6249-3.
- Remuzzi G, Scheppati A, Ruggenenti P (2002). "Clinical Practice. Nephropathy in Patients with Type 2 Diabetes". New England Journal of Medicine 346 (15): 1145–1151. PMID 11948275.
- Hockerman GH, Peterson BZ, Johnson BD, Catterall WA (1997). "Molecular Determinants of Drug Binding and Action on L-Type Calcium Channels". Annual Review of Pharmacology and Toxicology 37: 361–396. doi:10.1146/annurev.pharmtox.37.1.361. PMID 9131258.
- Bezprozvanny I, Tsien RW (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)". Molecular Pharmacology 48 (3): 540–549. PMID 7565636.
- Scultéty S, Tamáskovits E (1991). "Effect of Ca2+ Antagonists on Isolated Rabbit Detrusor Muscle". Acta Physiologica Hungarica 77 (3–4): 269–278. PMID 1755331.
- Buckley N, Dawson A, Whyte I (2007). "Calcium Channel Blockers". Medicine 35 (11): 599–602. doi:10.1016/j.mpmed.2007.08.025.
- Calcium Channel Blockers at the US National Library of Medicine Medical Subject Headings (MeSH)
- Official Adalat (Nifedipine) site, Bayer
- Video - Calcium Channel Blockers