Nifedipine

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Nifedipine
Systematic (IUPAC) name
dimethyl2,6-dimethyl-4-(2-nitrophenyl)- 1,4-dihydropyridine-3,5-dicarboxylate
Identifiers
CAS number 21829-25-4
ATC code C08CA05
PubChem 4485
DrugBank APRD00590
Chemical data
Formula C17H18N2O6 
Mol. mass 346.335 g/mol
Physical data
Melt. point 173 °C (343 °F)
Pharmacokinetic data
Bioavailability 45-56%
Protein binding 92-98%
Metabolism Gastrointestinal, Hepatic
Half life 2 hours
Excretion Renal: >50%, Biliary: 5-15%
Therapeutic considerations
Pregnancy cat.

C: (USA)
Legal status
Routes Oral

Nifedipine (brand name Adalat, Nifedical, and Procardia) is a dihydropyridine calcium channel blocker. Its main uses are as an antianginal (especially in Prinzmetal's angina) and antihypertensive, although a large number of other uses have recently been found for this agent, such as Raynaud's phenomenon, premature labor, and painful spasms of the esophagus in cancer and tetanus patients. It is also commonly used for the small subset of pulmonary hypertension patients whose symptoms respond to calcium channel blockers.

Contents

[edit] Dosing

Nifedipine rapidly lowers blood pressure, and patients are commonly warned they may feel dizzy or faint after taking the first few doses. Tachycardia (fast heart rate) may occur as a reaction. These problems are much less frequent in the sustained-release preparations of nifedipine (such as Adalat OROS). A more novel release system is GITS (Gastro-Intestinal Therapeutic System), which - according to Bayer - provides 24-hour continuous release through an osmotic push system. Recent trials with GITS include INSIGHT (for blood pressure)[1] and ACTION (for angina).[2]

Extended release formulations of nifedipine should be taken on an empty stomach, and patients are warned not to consume anything containing grapefruit or grapefruit juice, as they raise blood nifedipine levels. There are several possible mechanisms, including the lowering of CYP3A4 activity.[3]

It is also used to block pre-term contractions in pregnant women.

[edit] Uses

[edit] Approved uses

The approved uses for nifedipine are the long-term treatment of hypertension (high blood pressure) and angina pectoris. In hypertension, recent clinical guidelines generally favour diuretics and ACE inhibitors, although calcium channel antagonists are still favoured as primary treatment for older black patients.[4]

Sublingual nifedipine has previously been used in hypertensive emergencies. This was found to be dangerous, and has been abandoned.[5][6]

[edit] Off-label uses

Nifedipine has been used frequently as a tocolytic (agent that delays premature labor). A Cochrane review has concluded that it is comparable with magnesium sulfate and beta-agonists (such as ritodrine) with fewer side-effects.[7] Its role vis à vis atosiban is not established.

Raynaud's phenomenon is often treated with nifedipine. A 2005 meta-analysis showed modest benefits (33% decrease in attack severity, 2.8-5 reduction in absolute number of attacks per week); it does conclude that most included studies used low doses of nifedipine.[8]

Topical nifedipine has been shown to be as effective as topical nitrates for anal fissures.[9]

Nifedipine is also used in high-altitude medicine to treat high altitude pulmonary edema.[10]

[edit] History

Nifedipine (initially BAY a1040) was developed by the German pharmaceutical company Bayer, with most initial studies being performed in the early 1970s.[11]

The use of nifedipine and related calcium channel antagonists was reduced much in response to 1995 trials that mortality was increased in patients with coronary artery disease who took nifedipine.[12] This study was a meta-analysis, and demonstrated harm mainly in short-acting forms of nifedipine (that could cause large fluctations in blood pressure) and at high doses of 80 mg a day and more.[13]

[edit] References

  1. ^ Brown MJ, Palmer CR, Castaigne A, et al (2000). "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 356 (9227): 366-72. doi:10.1016/S0140-6736(00)02527-7. PMID 10972368. 
  2. ^ Poole-Wilson PA, Kirwan BA, Vokó Z, de Brouwer S, van Dalen FJ, Lubsen J (2006). "Safety of nifedipine GITS in stable angina: the ACTION trial". Cardiovas Drugs Ther 20 (1): 45-54. doi:10.1007/s10557-006-6312-4. PMID 16552473. 
  3. ^ Odou P, Ferrari N, Barthélémy C, et al (2005). "Grapefruit juice-nifedipine interaction: possible involvement of several mechanisms". Journal Clinical Pharm Ther 30 (2): 153-8. doi:10.1111/j.1365-2710.2004.00618.x. PMID 15811168. 
  4. ^ Hypertension: management of hypertension in adults in primary care. Clinical guideline CG34. National Institute for Health and Clinical Excellence (NICE), June 2006. Fulltext index. ISBN 1-86016-285-1.
  5. ^ Grossman E, Messerli FH, Grodzicki T, Kowey P (1996). "Should a moratorium be placed on sublingual nifedipine capsules given for hypertensive emergencies and pseudoemergencies?". JAMA 276 (16): 1328-31. doi:10.1001/jama.276.16.1328. PMID 8861992. 
  6. ^ Varon J, Marik PE (2003). "Clinical review: the management of hypertensive crises". Critical care (London, England) 7 (5): 374-84. doi:10.1186/cc2351. PMID 12974970. 
  7. ^ King JF, Flenady VJ, Papatsonis DN, Dekker GA, Carbonne B (2003). "Calcium channel blockers for inhibiting preterm labour". Cochrane database of systematic reviews (Online) (1): CD002255. doi:10.1002/14651858.CD002255. PMID 12535434. 
  8. ^ Thompson AE, Pope JE (2005). "Calcium channel blockers for primary Raynaud's phenomenon: a meta-analysis". Rheumatology (Oxford, England) 44 (2): 145-50. doi:10.1093/rheumatology/keh390. PMID 15546967. 
  9. ^ Ezri T, Susmallian S (2003). "Topical nifedipine vs. topical glyceryl trinitrate for treatment of chronic anal fissure". Dis. Colon Rectum 46 (6): 805-8. doi:10.1097/01.DCR.0000070044.62336.1D. PMID 12794583. 
  10. ^ Ali, Mir Omar and Qazi, Samia (2007-09-19). Pulmonary Edema, High-Altitude. eMedicine. Retrieved on 2007-11-25.
  11. ^ Vater W, Kroneberg G, Hoffmeister F, et al (1972). "[Pharmacology of 4-(2'-nitrophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid dimethyl ester (Nifedipine, BAY a 1040)]" (in German). Arzneimittel-Forschung 22 (1): 1-14. PMID 4622472. 
  12. ^ Furberg CD, Psaty BM, Meyer JV (1995). "Nifedipine. Dose-related increase in mortality in patients with coronary heart disease". Circulation 92 (5): 1326-31. PMID 7648682. 
  13. ^ Opie LH, Messerli FH (1995). "Nifedipine and mortality. Grave defects in the dossier". Circulation 92 (5): 1068-73. PMID 7648646. 

[edit] External links

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Calcium channel blockers (C08)
Dihydropyridines
Phenylalkylamines
Benzothiazepines