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Information |
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Drug Groups
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approved |
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Description
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Nifedipine has been formulated as both a long- and short-acting 1,4-dihydropyridine calcium channel blocker. It acts primarily on vascular smooth muscle cells by stabilizing voltage-gated L-type calcium channels in their inactive conformation. By inhibiting the influx of calcium in smooth muscle cells, nifedipine prevents calcium-dependent myocyte contraction and vasoconstriction. A second proposed mechanism for the drug’s vasodilatory effects involves pH-dependent inhibition of calcium influx via inhibition of smooth muscle carbonic anhydrase. Nifedipine is used to treat hypertension and chronic stable angina. |
| Indication |
For the management of vasospastic angina, chronic stable angina, hypertension, and Raynaud's phenomenon. May be used as a first line agent for left ventricular hypertrophy and isolated systolic hypertension (long-acting agents). |
| Pharmacology |
Nifedipine, the prototype of the dihydropyridine class of calcium channel blockers (CCBs), is similar to other dihydropyridines including amlodipine, felodipine, isradipine, and nicardipine. There are at least five different types of calcium channels in Homo sapiens: L-, N-, P/Q-, R- and T-type. CCBs target L-type calcium channels, the major channel in muscle cells that mediates contraction. Similar to other DHP CCBs, nifedipine binds directly to inactive calcium channels stabilizing their inactive conformation. Since arterial smooth muscle depolarizations are longer in duration than cardiac muscle depolarizations, inactive channels are more prevalent in smooth muscle cells. Alternative splicing of the alpha-1 subunit of the channel gives nifedipine additional arterial selectivity. At therapeutic sub-toxic concentrations, nifedipine has little effect on cardiac myocytes and conduction cells. By blocking the calcium channels, Nifedipine inhibits the spasm of the coronary artery and dilates the systemic arteries, results in a increase of myocardial oxygen supply and a decrease in systemic blood pressure. |
| Toxicity |
Symptoms of overdose include dizziness, drowsiness, nausea, severe drop in blood pressure, slurred speech, and weakness. LD50=494 mg/kg (orally in mice); LD50=1022 mg/kg (orally in rats) |
| Affected Organisms |
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Humans and other mammals |
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| Biotransformation |
Hepatic metabolism via cytochrome P450 system. Predominantly metabolized by CYP3A4, but also by CYP1A2 and CYP2A6 isozymes. |
| Absorption |
Rapidly and fully absorbed following oral administration. |
| Half Life |
2 hours |
| Protein Binding |
92-98% |
| Elimination |
Nifedipine is extensively metabolized to highly water-soluble, inactive metabolites accounting for 60 to 80% of the dose excreted in the urine. The remainder is excreted in the feces in metabolized form, most likely as a result of biliary excretion. |
| References |
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Brown MJ, Palmer CR, Castaigne A, de Leeuw PW, Mancia G, Rosenthal T, Ruilope LM: Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT). Lancet. 2000 Jul 29;356(9227):366-72.
[Pubmed]
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Poole-Wilson PA, Kirwan BA, Voko Z, de Brouwer S, van Dalen FJ, Lubsen J: Safety of nifedipine GITS in stable angina: the ACTION trial. Cardiovasc Drugs Ther. 2006 Feb;20(1):45-54.
[Pubmed]
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Odou P, Ferrari N, Barthelemy C, Brique S, Lhermitte M, Vincent A, Libersa C, Robert H: Grapefruit juice-nifedipine interaction: possible involvement of several mechanisms. J Clin Pharm Ther. 2005 Apr;30(2):153-8.
[Pubmed]
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Grossman E, Messerli FH, Grodzicki T, Kowey P: Should a moratorium be placed on sublingual nifedipine capsules given for hypertensive emergencies and pseudoemergencies? JAMA. 1996 Oct 23-30;276(16):1328-31.
[Pubmed]
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Takahashi D, Oyunzul L, Onoue S, Ito Y, Uchida S, Simsek R, Gunduz MG, Safak C, Yamada S: Structure-activity relationships of receptor binding of 1,4-dihydropyridine derivatives. Biol Pharm Bull. 2008 Mar;31(3):473-9.
[Pubmed]
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Varon J, Marik PE: Clinical review: the management of hypertensive crises. Crit Care. 2003 Oct;7(5):374-84. Epub 2003 Jul 16.
[Pubmed]
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