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Additional information about the drug Amlodipine


Amlodipine, sold under the brand name Norvasc among others, is a medication used to treat high blood pressure and coronary artery disease.
Common side effects include swelling, feeling tired, abdominal pain, and nausea.
Amlodipine was first patented in 1986 with commercial sale beginning in 1990.
Contents
1 Medical uses
1.1 Combination therapy
2 Contraindications
3 Side effects
4 Overdose
5 Interactions
6 Pharmacology
6.1 Mechanism of action
6.2 Pharmacokinetics
7 History
8 Veterinary use
9 References
10 External links
Medical uses
Amlodipine is used in the management of hypertension
Combination therapy
Amlodipine can be given as a combination therapy with a variety of medications:
Amlodipine/atorvastatin, where amlodipine is given for hypertension or CAD and atorvastatin prevents cardiovascular events, or if the person also has high cholesterol.
Amlodipine/aliskiren or amlodipine/aliskiren/hydrochlorothiazide if amlodipine alone cannot reduce blood pressure. Aliskiren is a renin inhibitor, which works to reduce primary hypertension (that with no known cause) by binding to renin and preventing it from initiating the renin–angiotensin system (RAAS) pathway to increase blood pressure. Hydrochlorothiazide is a diuretic and decreases overall blood volume.
Amlodipine/benazepril if either drug has failed individually, or amlodipine alone caused edema. Benazepril is an ACE inhibitor and blocks the conversion of angiotensin I to angiotensin II in the RAAS pathway.
Amlodipine/olmesartan or amlodipine/olmesartan/hydrochlorothiazide if amlodipine is insufficient in reducing blood pressure. Olmesartan is an angiotensin II receptor antagonist and blocks part of the RAAS pathway.
Amlodipine/perindopril if using amlodipine alone caused edema. Perindopril is a long-lasting ACE inhibitor.
Amlodipine/telmisartan, where telmisartan is an angiotensin II receptor antagonist.
Amlodipine/valsartan or amlodipine/valsartan/hydrochlorothiazide, where valsartan is an angiotensin II receptor antagonist.
Contraindications
The only absolute contraindication to amlodipine is an allergy to amlodipine or any other dihydropyridines.
Other situations occur, however, where amlodipine generally should not be used. In patients with cardiogenic shock, where the heart’s ventricles are not able to pump enough blood, calcium channel blockers exacerbate the situation by preventing the flow of calcium ions into cardiac cells, which is required for the heart to pump.
Amlodipine’s safety in pregnancy has not been established, although reproductive toxicity at high doses is known. Whether amlodipine enters the milk of breastfeeding mothers is also unknown.
Side effects
Some common dose-dependent side effects of amolodipine include vasodilatory effects, peripheral edema, dizziness, palpitations, and flushing.
Common but not dose-related side effects are fatigue (4.5% vs. 2.8% with a placebo), nausea (2.9% vs. 1.9%), abdominal pain (1.6% vs. 0.3%), and somnolence (1.4% vs. 0.6%).
Overdose
See also: Calcium channel blocker toxicity
Although rare,
Interactions
Several drugs interact with amlodipine to increase its levels in the body. CYP3A inhibitors, by nature of inhibiting the enzyme that metabolizes amlodipine, CYP3A4, are one such class of drugs. Others include the calcium-channel blocker diltiazem, the antibiotic clarithromycin, and possibly some antifungals.
Pharmacology
Mechanism of action
Amlodipine is an angioselective calcium channel blocker and inhibits the movement of calcium ions into vascular smooth muscle cells and cardiac muscle cells which inhibits the contraction of cardiac muscle and vascular smooth muscle cells. Amlodipine inhibits calcium ion influx across cell membranes, with a greater effect on vascular smooth muscle cells. This causes vasodilation and a reduction in peripheral vascular resistance, thus lowering blood pressure. Its effects on cardiac muscle also prevent excessive constriction in the coronary arteries.
Negative inotropic effects can be detected in vitro, but such effects have not been seen in intact animals at therapeutic doses. Among the two stereoisomers
The mechanisms by which amlodipine relieves angina are:
Stable angina : amlodipine reduces the total peripheral resistance (afterload) against which the heart works and reduces the rate pressure product, thereby lowering myocardial oxygen demand, at any given level of exercise.
Variant angina : amlodipine blocks spasm of the coronary arteries and restores blood flow in coronary arteries and arterioles in response to calcium, potassium, epinephrine, serotonin, and thromboxane A2 analog in experimental animal models and in human coronary vessels in vitro.
Amlodipine has additionally been found to act as an antagonist of the mineralocorticoid receptor, or as an antimineralocorticoid.
Pharmacokinetics
Amlodipine and one of its major metabolites: The nitrogen-containing ring is oxidized, and two of the side chains are hydrolyzed.
Amlodipine has been studied in healthy volunteers following oral administration of 14 C-labelled drug.
History
Pfizer ‘s patent protection on Norvasc lasted until 2007; total patent expiration occurred later in 2007.
The medical form comes as besylate, mesylate or maleate.
Veterinary use
Amlodipine is most often used to treat systemic hypertension in cats and dogs.

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