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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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Amlodipine is a long-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, amlodipine 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. Some studies have shown that amlodipine also exerts inhibitory effects on voltage-gated N-type calcium channels. N-type calcium channels located in the central nervous system may be involved in nociceptive signaling and pain sensation. Amlodipine is used to treat hypertension and chronic stable angina. |
| Indication |
For the treatment of hypertension and chronic stable angina. |
| Pharmacology |
Amlodipine belongs to the dihydropyridine (DHP) class of calcium channel blockers (CCBs), the most widely used class of CCBs. There are at least five different types of calcium channels in Homo sapiens: L-, N-, P/Q-, R- and T-type. It was widely accepted that DHP CCBs target L-type calcium channels, the major channel in muscle cells that mediate contraction; however, some studies have indicated that amlodipine also binds to and inhibits N-type calcium channels (see references in Targets section). Similar to other DHP CCBs, amlodipine binds directly to inactive L-type 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 amlodipine additional arterial selectivity. At therapeutic sub-toxic concentrations, amlodipine has little effect on cardiac myocytes and conduction cells. |
| Toxicity |
Gross overdosage could result in excessive peripheral vasodilatation and possibly reflex tachycardia. Marked and probably prolonged systemic hypotension up to an including shock with fatal outcome have been reported. |
| Affected Organisms |
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Humans and other mammals |
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| Biotransformation |
Hepatic. Metabolized extensively (90%) to inactive metabolites via the cytochrome P450 3A4 isozyme. |
| Absorption |
Amlodipine is slowly and almost completely absorbed from the gastrointestinal tract. Peak plasma concentrations are reached 6-12 hour following oral administration. Its estimated bioavailability is 64-90%. Absorption is not affected by food. |
| Half Life |
30-50 hours |
| Protein Binding |
97.5% |
| Elimination |
Amlodipine is extensively (about 90%) converted to inactive metabolites via hepatic metabolism with 10% of the parent compound and 60% of the metabolites excreted in the urine. |
| References |
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Nayler WG, Gu XH: The unique binding properties of amlodipine: a long-acting calcium antagonist. J Hum Hypertens. 1991 Aug;5 Suppl 1:55-9.
[Pubmed]
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| • |
van Zwieten PA: Amlodipine: an overview of its pharmacodynamic and pharmacokinetic properties. Clin Cardiol. 1994 Sep;17(9 Suppl 3):III3-6.
[Pubmed]
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| External Links |
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