Nifedipine

Nifedipine

Nifedipine
Systematic (IUPAC) name
3,5-dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
Clinical data
Trade names Adalat, Procardia
AHFS/Drugs.com
MedlinePlus
Pregnancy
category
  • C: (USA)
Routes of
administration
Oral, Topical
Pharmacokinetic data
Bioavailability 45-56%
Protein binding 92-98%
Metabolism Gastrointestinal, Hepatic
Biological half-life 2 hours
Excretion Renal: >50%, Biliary: 5-15%
Identifiers
CAS Registry Number  Y
ATC code C08
PubChem CID:
IUPHAR/BPS
DrugBank  Y
ChemSpider  Y
UNII  Y
KEGG  Y
ChEBI  Y
ChEMBL  Y
Chemical data
Formula C17H18N2O6
Molecular mass 346.335 g/mol
Physical data
Melting point 173 °C (343 °F)
 Y   

Nifedipine (brand names Adalat CC and Procardia, according to health system.[2]

Contents

  • Medical uses 1
    • Other uses 1.1
  • Side effects 2
  • Overdose 3
  • History 4
  • See also 5
  • References 6
  • External links 7

Medical uses

The approved uses for 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, along with thiazide diuretics, are still favoured as primary treatment for patients over 55 and African American patients.[3]

Sublingual nifedipine has previously been used in hypertensive emergencies. It was once frequently prescribed pro re nata to patients taking MAOIs for real or perceived hypertensive crises.[4] This was found to be dangerous, and has been abandoned. Sublingual nifedipine causes blood-pressure lowering through peripheral vasodilation. It can cause an uncontrollable decrease in blood pressure, reflex tachycardia, and a steal phenomenon in certain vascular beds. There have been multiple reports in the medical literature of serious adverse effects with sublingual nifedipine, including cerebral ischemia/infarction, myocardial infarction, complete heart block, and death. As a result of this, the FDA reviewed all data regarding the safety and efficacy of sublingual nifedipine for hypertensive emergencies in 1995, and concluded that the practice should be abandoned because it was neither safe nor efficacious.[5][6] An exception to the avoidance of this practice is in the use of nifedipine in the treatment of hypertension associated with autonomic dysreflexia in spinal cord injury.[7]

Other 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.[8] 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.[9]

Topical nifedipine has been shown to be as effective as topical nitrates for anal fissures.[10]

Nifedipine is also used in high-altitude medicine to treat high altitude pulmonary edema.[11]

Oral nifedipine has also been found to cause iron loss in the urine of small animals.[12] A NIH NIDDK study[13] is currently seeing if the drug can increase the removal of iron into the urine in humans as well, thus becoming a possible treatment for iron overload.

A meta-analysis in 2006 showed that Nifedipine increased frequency of kidney stone passage by 90%. However Nifedipine is rarely used for this indication.

Side effects

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)[14] and ACTION (for angina).[15]

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.[16]

Overdose

A number of persons have developed toxicity due to acute overdosage with nifedipine, either accidentally or intentionally, and via either oral or parenteral administration. The adverse effects include lethargy, bradycardia, marked hypotension and loss of consciousness. The drug may be quantitated in blood or plasma to confirm a diagnosis of poisoning in hospitalized patients or to assist in a medicolegal death investigation. Analytical methods usually involve gas or liquid chromatography and specimen concentrations are usually in the 100-1000 μg/L range.[17][18]

History

Nifedipine (initially BAY a1040) was developed by the German pharmaceutical company Bayer, with most initial studies being performed in the early 1970s.[19]

The use of nifedipine and related calcium channel antagonists was much reduced in response to 1995 trials that mortality was increased in patients with coronary artery disease who took nifedipine.[20] 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.[21]

See also

References

  1. ^ Hayashi K, Homma K, Wakino S, Tokuyama H, Sugano N, Saruta T, Itoh H (2010). "T-type Ca channel blockade as a determinant of kidney protection". Keio J Med 59 (3): 84–95.  
  2. ^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014. 
  3. ^ 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.
  4. ^ "Nifedipine for MAOI Hypertension? Reversing a Previous Recommendation". Biological Therapies in Psychiatry. March 1997. Retrieved 22 Jan 2015. 
  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.  
  6. ^ Varon J, Marik PE (2003). "Clinical review: The management of hypertensive crises". Critical care (London, England) 7 (5): 374–84.  
  7. ^ Campagnolo, DI. "Autonomic Dysreflexia in Spinal Cord Injury". eMedicine. Retrieved 2011-07-14. 
  8. ^ King JF, Flenady VJ, Papatsonis DN, Dekker GA, Carbonne B (2003). Flenady, Vicki, ed. "Calcium channel blockers for inhibiting preterm labour". Cochrane database of systematic reviews (Online) (1): CD002255.  
  9. ^ Thompson AE, Pope JE (2005). "Calcium channel blockers for primary Raynaud's phenomenon: a meta-analysis". Rheumatology (Oxford, England) 44 (2): 145–50.  
  10. ^ Ezri T, Susmallian S (2003). "Topical nifedipine vs. topical glyceryl trinitrate for treatment of chronic anal fissure". Dis. Colon Rectum 46 (6): 805–8.  
  11. ^ Ali, Mir Omar and Qazi, Samia (2007-09-19). "Pulmonary Edema, High-Altitude". eMedicine. Retrieved 2007-11-25. 
  12. ^ Ludwiczek, S; Theurl, I; Muckenthaler, MU; Jakab, M; Mair, SM; Theurl, M; Kiss, J; Paulmichl, M; Hentze, MW; Ritter, M; Weiss, G (Apr 2007). "Ca2+ channel blockers reverse iron overload by a new mechanism via divalent metal transporter-1". Nat Med 13 (4): 448–54.  
  13. ^ http://clinicaltrials.gov/ct2/show/NCT00712738?term=iron+overload&rank=1
  14. ^ 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.  
  15. ^ 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.  
  16. ^ 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.  
  17. ^ Nifediac package insert, TEVA Pharmaceuticals, Sellersville, Pennsylvania, August, 2009.
  18. ^ Baselt, Randall C. (2008). Disposition of Toxic Drugs and Chemicals in Man. Foster City, CA: Biomedical Publications. pp. 1108–1110.  
  19. ^ 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)]". Arzneimittel-Forschung (in German) 22 (1): 1–14.  
  20. ^ Furberg CD, Psaty BM, Meyer JV (1995). "Nifedipine. Dose-related increase in mortality in patients with coronary heart disease". Circulation 92 (5): 1326–31.  
  21. ^ Opie LH, Messerli FH (1995). "Nifedipine and mortality. Grave defects in the dossier". Circulation 92 (5): 1068–73.  

External links