Amlodipine
Clinical data | |
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Pronunciation | /æmˈloʊdɪˌpiːn/[1] |
Trade names | Norvasc, Istin, Norliqva, others |
AHFS/Drugs.com | Monograph |
MedlinePlus | a692044 |
License data |
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Pregnancy category |
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Routes of administration | Oral |
Drug class | Calcium channel blocker |
ATC code | |
Legal status | |
Legal status | |
Pharmacokinetic data | |
Bioavailability | 64–90% |
Protein binding | 93%[7] |
Metabolism | Liver |
Metabolites | Various inactive pyrimidine metabolites |
Onset of action | Highest availability 6–12 hours after oral dose[10] |
Elimination half-life | 30–50 hours |
Duration of action | At least 24 hours[10] |
Excretion | Urine[10] |
Identifiers | |
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JSmol) | |
Chirality | Racemic mixture |
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Amlodipine, sold under the brand name Norvasc among others, is a calcium channel blocker medication used to treat high blood pressure, coronary artery disease (CAD)[10] and variant angina (also called Prinzmetal angina or coronary artery vasospasm, among other names).[11] It is taken orally (swallowed by mouth).[10]
Common side effects include
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)
Amlodipine along with other calcium channel blockers are considered the first choice in the pharmacological management of
Combination therapy
Amlodipine can be given as a combination therapy with a variety of medications:[10][23]
- Amlodipine/atorvastatin, where amlodipine is given for hypertension or CAD and atorvastatin prevents cardiovascular events, or if the person also has high cholesterol.
- 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. Hydrochlorothiazideis a diuretic and decreases overall blood volume.
- angiotensin IIin the RAAS pathway.
- Amlodipine/celecoxib
- Amlodipine/lisinopril
- angiotensin II receptor antagonistand blocks part of the RAAS pathway.
- Amlodipine/perindopril if using amlodipine alone caused edema. Perindoprilis 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.[7]
Other situations occur, however, where amlodipine generally should not be used. In patients with
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.[7][6]
Those who have heart failure, or recently had a heart attack, should take amlodipine with caution.[27]
Adverse effects
Some common dose-dependent adverse effects of amlodipine include vasodilatory effects,
Common but not dose-related adverse effects are
Amlodipine-associated gingival overgrowth is a relatively common side effect with exposure to amlodipine.[32] Poor dental health and buildup of dental plaque are risk factors.[32]
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.[10]
Amlodipine and other dihydropyridine calcium channel blockers are associated with
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,
Pharmacology
Amlodipine is a long-acting calcium channel antagonist that selectively inhibits calcium ion influx across cell membranes.[40] It targets L-type calcium channels in muscle cells and N-type calcium channels in the central nervous system which are involved in nociceptive signalling and pain perception.[41][42] Amlodipine has an inhibitory effect on calcium influx in smooth muscle cells to inhibit contraction.[citation needed]
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.[43] In turn, following treatment lasting a month, with amlodipine, cardiac output is significantly enhanced.[43] Unlike verapamil which has efficacy in moderation of emotional arousal and reduces cardiac load without lowering cardiac output demands, amlodipine increases the cardiac output response concomitantly with increased functional cardiac load.[43]
Mechanism of action
Amlodipine is an angioselective
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 [R(+), S(–)], the (–) isomer has been reported to be more active than the (+) isomer.[44] Serum calcium concentration is not affected by amlodipine. And it specifically inhibits the currents of L-type Cav1.3 channels in the zona glomerulosa of the adrenal gland.[45][46]
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.[47]
- epinephrine, serotonin, and thromboxane A2 analog in experimental animal models and in human coronary vessels in vitro.[48]
Amlodipine has additionally been found to act as an
Pharmacokinetics
Amlodipine has been studied in healthy volunteers following oral administration of 14C-labelled drug.
History
The medical form comes as
Veterinary use
Amlodipine is most often used to treat systemic
References
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