Amlodipine, sold under the brand name Norvasc among others, is a calcium channel blocker medication used to treat hypertension, coronary artery disease (CAD)[ and variant angina (also called Prinzmetal angina or coronary artery vasospasm, among other names).][
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Common side effects include edema, feeling tired, abdominal pain, and nausea.[ Serious side effects may include hypotension or heart attack.][ Whether use is safe during pregnancy or breastfeeding is unclear.][ When used by people with liver problems, and in elderly individuals, doses should be reduced.][ Amlodipine works partly by vasodilation (relaxing the arteries and increasing their diameter).][ It is a long-acting calcium channel blocker of the dihydropyridine type.][
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Amlodipine was patented in 1982, and approved for medical use in 1990.
Medical uses
Amlodipine is used in the management of hypertension (high blood pressure)
Calcium channel blockers, including amlodipine, may provide greater protection against stroke than beta blockers.
Amlodipine along with other calcium channel blockers are considered the first choice in the pharmacological management of Raynaud's phenomenon.
Combination therapy
Amlodipine can be given as a combination therapy with a variety of medications:
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Amlodipine/atorvastatin, where amlodipine is given for hypertension or CAD and atorvastatin prevents cardiovascular events, or if the person also has high cholesterol.
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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.
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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.
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[[Amlodipine/celecoxib
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Amlodipine/lisinopril
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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.
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Amlodipine/perindopril if using amlodipine alone caused edema. Perindopril is a long-lasting ACE inhibitor.
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Amlodipine/telmisartan, where telmisartan is an angiotensin II receptor antagonist.
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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.
Those who have heart failure, or recently had a heart attack, should take amlodipine with caution.
Adverse effects
Some common dose-dependent adverse effects of amlodipine include vasodilatory effects, peripheral edema, dizziness, palpitations, and flushing.
Common but not dose-related adverse 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%).
Amlodipine-associated gingival overgrowth is a relatively common side effect with exposure to amlodipine.[ Poor dental health and buildup of dental plaque are risk factors.]
Amlodipine may increase the risk of worsening angina or acute myocardial infarction, especially in those with severe obstructive coronary artery disease, upon dosage initiation or increase. However, depending on the situation, amlodipine inhibits constriction and restores blood flow in coronary arteries as a result of its acting directly on vascular smooth muscle, causing a reduction in peripheral vascular resistance and a consequent reduction in blood pressure.[
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Amlodipine and other dihydropyridine calcium channel blockers are associated with primary open angle glaucoma.
Overdose
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
Amlodipine is a long-acting calcium channel antagonist that selectively inhibits calcium ion influx across cell membranes.
Amlodipine ends up significantly reducing total vascular resistance without decreasing cardiac output expressed by pressure-rate product and cardiac contractability in comparison with verapamil, a non-dihydropyridine.
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.[
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Negative inotrope effects can be detected in vitro, but such effects have not been seen in intact animals at therapeutic doses. Among the two Stereoisomerism R(+),, the (–) isomer has been reported to be more active than the (+) isomer.
The mechanisms by which amlodipine relieves angina are:
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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.
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Variant angina: amlodipine blocks vasospasm 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 has been studied in healthy volunteers following oral administration of 14C-labelled drug.
History
Pfizer's patent protection on Norvasc lasted until 2007; total patent expiration occurred later in 2007.[ on amlodipine and perindopril. Accessed 28 February 2020.]
The medical form comes as besilate, mesylate, or maleate.
Society and culture
Brand names
In the US, Norvasc is marketed by Viatris after Upjohn was spun off from Pfizer.
Veterinary use
Amlodipine is most often used to treat systemic hypertension in both cats and dogs.
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