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	C08 CA05
PubChem	4485
DrugBank	APRD00590
Chemical data
Formula	C₁₇H₁₈N₂O₆
Mol. weight	346.335 g/mol
Physical data
Melt. point	6 °C (43 °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 and Procardia) is a dihydropyridine calcium channel blocker. Its main uses are in angina pectoris (especially Prinzmetal's angina) and hypertension, 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 patients. It is also commonly used for the small subset of pulmonary hypertension patients whose symptoms respond to calcium channel blockers.

Nifedipine rapidly lowers the 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).

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 it lowers CYP3A4 activity (the enzyme that digests nifedipine) and may lead to increased levels of nifedipine or other medications that are metabolised by CYP3A4 in the blood.

[edit] Incorrect use of Nifedipine

While Nifedipine is safe for use in sustained-release form, some doctors continue to use it for hypertensive crises (emergency situations where bringing down the blood pressure is of critical importance to avoid organ damage). When used in this way, the doctor asks for the patient to bite open the capsule, and keep it under their tongue as the contents is absorbed sublingually. This sublingual use of Nifedipine has not been approved by the FDA, and there are documented cases indicating that the incorrect use of this drug has caused:

death
stroke
acute myocardial infarction (tissue death of the heart muscle mass)
cerebrovascular ischemia (Lack of blood flow to the brain, causing lack of oxygen and vital nutrients)
severe hypotension (very low blood pressure)
conduction disturbances
fetal distress

For a detailed review of management of hypertensive crises, with reference to Nifedipine, see "Clinical review: The management of hypertensive crises" by Joseph Varon (Associate Professor of Medicine, Pulmonary and Critical Care Section, Baylor College of Medicine, Clinical Associate Professor, The University of Texas Health Science Center, Houston, Texas, USA) and Paul E Marik (Professor of Critical Care and Medicine, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA). From the above document at http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=270718

Sudden uncontrolled and severe reductions in blood pressure accompanying the administration
of nifedipine may precipitate cerebral, renal, and myocardial ischemic events, which have
been associated with fatal outcomes . Elderly hypertensive patients with underlying organ
impairment and structural vascular disease are more vulnerable to the rapid and uncontrolled
reduction in arterial pressure. Given the seriousness of the reported adverse events and
the lack of any clinical documentation attesting to a benefit, the use of nifedipine
capsules for hypertensive emergencies and 'pseudo-emergencies' should be abandoned.
The Cardiorenal Advisory Committee of the US Food and Drug Adminsitration has concluded
that the practice of administering sublingual/oral nifedipine should be abandoned
because this agent is neither safe nor efficacious.

[edit] References

Calcium channel blockers (C08) edit
Dihydropyridines:	Amlodipine, Felodipine, Isradipine, Lacidipine, Lercanidipine, Nicardipine, Nifedipine, Nimodipine, Nisoldipine
Phenylalkylamines:	Verapamil
Benzothiazepines:	Diltiazem