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Namespace Prefixes

PrefixIRI
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Statements

Subject Item
n2:DB01115
rdf:type
n3:Drug
n3:description
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.
n3:dosage
n11:271B4325-363D-11E5-9242-09173F13E4C5 n11:271B4326-363D-11E5-9242-09173F13E4C5 n11:271B4327-363D-11E5-9242-09173F13E4C5 n11:271B4328-363D-11E5-9242-09173F13E4C5 n11:271B4329-363D-11E5-9242-09173F13E4C5 n11:271B431B-363D-11E5-9242-09173F13E4C5 n11:271B431C-363D-11E5-9242-09173F13E4C5 n11:271B4321-363D-11E5-9242-09173F13E4C5 n11:271B4322-363D-11E5-9242-09173F13E4C5 n11:271B4323-363D-11E5-9242-09173F13E4C5 n11:271B4324-363D-11E5-9242-09173F13E4C5 n11:271B431A-363D-11E5-9242-09173F13E4C5 n11:271B431D-363D-11E5-9242-09173F13E4C5 n11:271B431E-363D-11E5-9242-09173F13E4C5 n11:271B431F-363D-11E5-9242-09173F13E4C5 n11:271B4320-363D-11E5-9242-09173F13E4C5
n3:generalReferences
# 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":http://www.ncbi.nlm.nih.gov/pubmed/10972368 # 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":http://www.ncbi.nlm.nih.gov/pubmed/16552473 # 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":http://www.ncbi.nlm.nih.gov/pubmed/15811168 # 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":http://www.ncbi.nlm.nih.gov/pubmed/8861992 # 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":http://www.ncbi.nlm.nih.gov/pubmed/18310913 # Varon J, Marik PE: Clinical review: the management of hypertensive crises. Crit Care. 2003 Oct;7(5):374-84. Epub 2003 Jul 16. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/12974970
n3:group
approved
n3:halfLife
2 hours
n3: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).
owl:sameAs
n29:DB01115 n31:DB01115
dcterms:title
Nifedipine
adms:identifier
n13:D00437 n14:0378-3475-01 n15:2514 n16:C07266 n17:2514 n18:4330 n19:DB01115 n20:46505103 n21:PA450631 n22:4485 n25:50000778 n26:7565 n30:Nifedipine
n3:mechanismOfAction
Nifedipine decreases arterial smooth muscle contractility and subsequent vasoconstriction by inhibiting the influx of calcium ions through L-type calcium channels. Calcium ions entering the cell through these channels bind to calmodulin. Calcium-bound calmodulin then binds to and activates myosin light chain kinase (MLCK). Activated MLCK catalyzes the phosphorylation of the regulatory light chain subunit of myosin, a key step in muscle contraction. Signal amplification is achieved by calcium-induced calcium release from the sarcoplasmic reticulum through ryanodine receptors. Inhibition of the initial influx of calcium inhibits the contractile processes of smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload. The vasodilatory effects of nifedipine result in an overall decrease in blood pressure.
n3:packager
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n3:patent
n10:5264446
n3:routeOfElimination
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.
n3:synonym
Nifecor Procardia Adalat Nifecard Nifedipino Coracten Nifedipine Nifedipinum Adapine Nifedipres 4-(2'-Nitrophenyl)-2,6-dimethyl-1,4-dihydropyridin-3,5-dicarbonsaeuredimethylester
n3:toxicity
Symptoms of overdose include dizziness, drowsiness, nausea, severe drop in blood pressure, slurred speech, and weakness. LD<sub>50</sub>=494 mg/kg (orally in mice); LD<sub>50</sub>=1022 mg/kg (orally in rats)
n6:hasAHFSCode
n7:24-28-08
n3:foodInteraction
Grapefruit down-regulates post-translational expression of CYP3A4, the major metabolizing enzyme of nifedipine. Grapefruit, in all forms (e.g. whole fruit, juice and rind), can significantly increase serum levels of nifedipine and may cause toxicity. Avoid grapefruit products while on this medication. Take with low fat meal. Avoid alcohol. Avoid natural licorice.
n3:proteinBinding
92-98%
n3:synthesisReference
Hiroitsu Kawata, Tadayoshi Ohmura, Katsuhiko Yano, Mikio Matsumura, Saburo Higuchi, Yoshiaki Soeishi, "Nifedipine-containing solid preparation composition." U.S. Patent US4412986, issued November, 1976.
foaf:page
n24:nifedipine.html n27:nifedip.htm
n3:IUPAC-Name
n5:271B432E-363D-11E5-9242-09173F13E4C5
n3:InChI
n5:271B4334-363D-11E5-9242-09173F13E4C5
n3:Molecular-Formula
n5:271B4333-363D-11E5-9242-09173F13E4C5
n3:Molecular-Weight
n5:271B4330-363D-11E5-9242-09173F13E4C5
n3:Monoisotopic-Weight
n5:271B4331-363D-11E5-9242-09173F13E4C5
n3:SMILES
n5:271B4332-363D-11E5-9242-09173F13E4C5
n3:Water-Solubility
n5:271B4343-363D-11E5-9242-09173F13E4C5 n5:271B432C-363D-11E5-9242-09173F13E4C5
n3:logP
n5:271B4345-363D-11E5-9242-09173F13E4C5 n5:271B432A-363D-11E5-9242-09173F13E4C5 n5:271B432D-363D-11E5-9242-09173F13E4C5
n3:logS
n5:271B432B-363D-11E5-9242-09173F13E4C5
n6:hasATCCode
n8:C08CA05
n3:H-Bond-Acceptor-Count
n5:271B433A-363D-11E5-9242-09173F13E4C5
n3:H-Bond-Donor-Count
n5:271B433B-363D-11E5-9242-09173F13E4C5
n3:InChIKey
n5:271B4335-363D-11E5-9242-09173F13E4C5
n3:Polar-Surface-Area--PSA-
n5:271B4336-363D-11E5-9242-09173F13E4C5
n3:Polarizability
n5:271B4338-363D-11E5-9242-09173F13E4C5
n3:Refractivity
n5:271B4337-363D-11E5-9242-09173F13E4C5
n3:Rotatable-Bond-Count
n5:271B4339-363D-11E5-9242-09173F13E4C5
n3:absorption
Rapidly and fully absorbed following oral administration.
n3:affectedOrganism
Humans and other mammals
n3:casRegistryNumber
21829-25-4
n3:category
n3:containedIn
n4:271B430E-363D-11E5-9242-09173F13E4C5 n4:271B430B-363D-11E5-9242-09173F13E4C5 n4:271B430C-363D-11E5-9242-09173F13E4C5 n4:271B4311-363D-11E5-9242-09173F13E4C5 n4:271B4312-363D-11E5-9242-09173F13E4C5 n4:271B430F-363D-11E5-9242-09173F13E4C5 n4:271B4310-363D-11E5-9242-09173F13E4C5 n4:271B4305-363D-11E5-9242-09173F13E4C5 n4:271B4306-363D-11E5-9242-09173F13E4C5 n4:271B4303-363D-11E5-9242-09173F13E4C5 n4:271B4304-363D-11E5-9242-09173F13E4C5 n4:271B4309-363D-11E5-9242-09173F13E4C5 n4:271B430A-363D-11E5-9242-09173F13E4C5 n4:271B4307-363D-11E5-9242-09173F13E4C5 n4:271B4308-363D-11E5-9242-09173F13E4C5 n4:271B42FD-363D-11E5-9242-09173F13E4C5 n4:271B42FE-363D-11E5-9242-09173F13E4C5 n4:271B42FB-363D-11E5-9242-09173F13E4C5 n4:271B42FC-363D-11E5-9242-09173F13E4C5 n4:271B4301-363D-11E5-9242-09173F13E4C5 n4:271B4302-363D-11E5-9242-09173F13E4C5 n4:271B42FF-363D-11E5-9242-09173F13E4C5 n4:271B4300-363D-11E5-9242-09173F13E4C5 n4:271B42F9-363D-11E5-9242-09173F13E4C5 n4:271B42FA-363D-11E5-9242-09173F13E4C5 n4:271B42F7-363D-11E5-9242-09173F13E4C5 n4:271B42F8-363D-11E5-9242-09173F13E4C5 n4:271B4315-363D-11E5-9242-09173F13E4C5 n4:271B4316-363D-11E5-9242-09173F13E4C5 n4:271B4313-363D-11E5-9242-09173F13E4C5 n4:271B4314-363D-11E5-9242-09173F13E4C5 n4:271B4319-363D-11E5-9242-09173F13E4C5 n4:271B4317-363D-11E5-9242-09173F13E4C5 n4:271B4318-363D-11E5-9242-09173F13E4C5 n4:271B430D-363D-11E5-9242-09173F13E4C5
n3:Bioavailability
n5:271B433F-363D-11E5-9242-09173F13E4C5
n3:Ghose-Filter
n5:271B4341-363D-11E5-9242-09173F13E4C5
n3:MDDR-Like-Rule
n5:271B4342-363D-11E5-9242-09173F13E4C5
n3:Melting-Point
n5:271B4344-363D-11E5-9242-09173F13E4C5
n3:Number-of-Rings
n5:271B433E-363D-11E5-9242-09173F13E4C5
n3:Physiological-Charge
n5:271B433D-363D-11E5-9242-09173F13E4C5
n3:Rule-of-Five
n5:271B4340-363D-11E5-9242-09173F13E4C5
n3:Traditional-IUPAC-Name
n5:271B432F-363D-11E5-9242-09173F13E4C5
n3:pKa--strongest-basic-
n5:271B433C-363D-11E5-9242-09173F13E4C5