Nifedipine, sold under the brand names Adalat among others, is a medication used to manage angina, high blood pressure, Raynaud's phenomenon, and premature labor. It is one of the treatments of choice for Prinzmetal angina. It may be used to treat severe high blood pressure in pregnancy. Its use in preterm labor may allow more time for steroids to improve the baby's lungs and time to transfer the mother to a well qualified medical facility before delivery. Nifedipine is taken by mouth and comes in fast and slow release formulations.
|Trade names||Adalat, Procardia, others|
|by mouth, topical|
|Biological half-life||2 hours|
|Excretion||Kidneys: >50%, Biliary: 5-15%|
|Chemical and physical data|
|Molar mass||346.335 g/mol|
|3D model (JSmol)|
|Melting point||173 °C (343 °F)|
Common side effects include lightheadedness, headache, feeling tired, leg swelling, cough, and shortness of breath. Serious side effects may include low blood pressure and heart failure. There is tentative evidence that its use in pregnancy is safe; however, it is not recommended during breastfeeding. It is a calcium channel blocker of the dihydropyridine type.
Nifedipine was discovered in 1969 and approved for use in the United States in 1981. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. It is available as a generic medication. The wholesale price in the developing world for the slow release form is about 1.90 to 3.80 USD per month. In the United States it is about 40 to 60 USD a month depending on the dose.
High blood pressureEdit
The approved uses are for 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.
Sublingual nifedipine has previously been used in hypertensive emergencies. It was once frequently prescribed as needed to people taking MAOIs for real or perceived hypertensive crises. 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. 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.
Nifedipine has been used frequently as a tocolytic (agent that delays premature labor). A Cochrane review has concluded that it has benefits over placebo or no treatment for prolongation of pregnancy. It has also benefits over beta-agonists and may also have some benefits over atosiban and magnesium sulphate, although atosiban results in fewer maternal adverse effects. No difference was found in the rate of deaths among babies around the time of birth, and data on longer-term outcomes were limited.
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.
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.
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.
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.
Mechanism of actionEdit
Nifedipine is a calcium channel blocker. Although nifedipine and other dihydropyridines are commonly regarded as specific to the L-type calcium channel, they also possess nonspecific activity towards other voltage-dependent calcium channels.
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. 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.
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