||This article needs more medical references for verification or relies too heavily on primary sources. (May 2015)|
|Systematic (IUPAC) name|
(RS)-3-ethyl 5-methyl 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate
|Licence data||US FDA:|
|Bioavailability||64 to 90%|
|Biological half-life||30 to 50 hours|
|CAS Registry Number|
|Molecular mass||408.879 g/mol|
|(what is this?)|
Amlodipine (as besylate, mesylate or maleate) is a medication used to lower blood pressure and prevent chest pain. It belongs to a group of medications known as dihydropyridine-type calcium channel blockers. By widening of blood vessels it lowers blood pressure. In angina, amlodipine increases blood flow to the heart muscle to relieve pain due to angina. It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.
- Cardiogenic shock
- Unstable angina
- Systolic and diastolic blood pressure below 90/60 mmHg
- Aortic stenosis
Adverse side effects of the use of amlodipine may include:
- Common: peripheral edema and fatigue
- Uncommon: blood disorders, development of breasts in men (gynecomastia), impotence, depression, insomnia, tachycardia, or gingival enlargement
- Rarely: erratic behavior, hepatitis, jaundice
Amlodipine inhibits calcium ions into vascular smooth muscle cells and cardiac muscle cells. The contractile processes of cardiac muscle and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells. Negative inotropic effects can be detected in vitro, but such effects have not been seen in intact animals at therapeutic doses. Serum calcium concentration is not affected by amlodipine. Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure. As a calcium channel blocker, amlodipine is expected to inhibit the currents of L-type Cav1.3 channels in the zona glomerulosa. 
The mechanisms by which amlodipine relieves angina include:
- 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.
- Prinzmetal's 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 been studied in healthy volunteers following oral administration of 14C-labelled drug. amlodipine is well absorbed by the oral route with a mean oral bioavailability around 60%. It is metabolized in the liver to inactive metabolites via CYP3A4. The half-life of amlodipine is about 30–50 hours, and steady-state plasma concentrations are achieved after 7 to 8 days of daily dosing. Renal elimination is the major route of excretion with about 60% of an administered dose recovered in urine, largely as inactive pyridine metabolites. However, renal impairment does not significantly influence amlodipine elimination.
Comparison of Candesartan and Amlodipine for Safety, Tolerability and Efficacy (CASTLE) Study
The "Comparison of Candesartan and Amlodipine for Safety, Tolerability and Efficacy" (CASTLE) Study gave the result that both the cheap generic Amlodipine and the more expensive Candesartan cilexetil were both effective in the treatment of mild hypertension stage-1 (maximum 160/100 mm Hg) with no significant difference. Amlodipine decreased systolic and diastolic BP by -15.4/-11.3 mm Hg, while Candesartan cilexetil did so by -15.2/-10.2 mm Hg. But the most common side effect was Peripheral edema, which happened with greater frequency using Amlodipine (22.1%; mild 8.7%, moderate 11.8%, and severe 1.6%), while the increase using Candesartan cilexetil was 8.9%; (mild 8.1%, and moderate 0.8%).
If monotherapy with Amlodipine or Candesartan is not sufficient to reach the reducing blood pressure target, a combination of Amlodipine 5mg and Candesartan 8mg can be effective, lowering blood pressure after 12 weeks in patients not adequately controlled by monotherapy.
Pfizer's patent protection on Norvasc lasted until 2007; total patent expiration occurred later in 2007. A number of generic versions are available. In the United Kingdom, tablets of amlodipine from different suppliers may contain different salts. The strength of the tablets is expressed in terms of amlodipine base, i.e., without the salts. Tablets containing different salts are therefore considered interchangeable.The efficacy and tolerability of a fixed-dose combination of amlodipine 5 mg and perindopril 4 mg, an angiotensin converting enzyme inhibitor, have recently been confirmed in a prospective, observational, multicentre trial of 1250 hypertensive patients.
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