Amlodipine

Source: Wikipedia, the free encyclopedia.

Amlodipine
Clinical data
Pronunciation/æmˈldɪˌpn/[1]
Trade namesNorvasc, Istin, Norliqva, others
AHFS/Drugs.comMonograph
MedlinePlusa692044
License data
Pregnancy
category
Routes of
administration
Oral
Drug classCalcium channel blocker
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability64–90%
Protein binding93%[7]
MetabolismLiver
MetabolitesVarious inactive pyrimidine metabolites
Onset of actionHighest availability 6–12 hours after oral dose[10]
Elimination half-life30–50 hours
Duration of actionAt least 24 hours[10]
ExcretionUrine[10]
Identifiers
  • (RS)-3-ethyl 5-methyl 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate
JSmol)
ChiralityRacemic mixture
  • Clc1ccccc1C2/C(C(=O)OC)=C(/C)N/C(COCCN)=C2/C(=O)OCC
  • InChI=1S/C20H25ClN2O5/c1-4-28-20(25)18-15(11-27-10-9-22)23-12(2)16(19(24)26-3)17(18)13-7-5-6-8-14(13)21/h5-8,17,23H,4,9-11,22H2,1-3H3 checkY
  • Key:HTIQEAQVCYTUBX-UHFFFAOYSA-N checkY
  (verify)

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

dihydropyridine type.[10]

Amlodipine was patented in 1982, and approved for medical use in 1990.

generic medication.[10][14] In 2021, it was the fifth most commonly prescribed medication in the United States, with more than 73 million prescriptions.[15][16]

Medical uses

Amlodipine is used in the management of hypertension (high blood pressure)

beta blockers.[19] [20] Evidence from two meta-analyses has reported no significant difference between calcium channel blockers, ACE inhibitors, diuretics [21] [19] and angiotensin receptor blockers[21] in stroke protection while one 2015 meta-analysis has suggested that calcium channel blockers offer greater protection against stroke than other classes of antihypertensive.[20]

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]

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

liver function are unable to metabolize amlodipine to its full extent, giving it a longer half-life than typical.[7][6]

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,

interstitial space.[29] Amlodipine-association edema can be avoided by adding ACE inhibitors or angiotensin II receptor antagonist.[10] Of the other dose-dependent side effects, palpitations (4.5% at 10 mg vs. 0.6% in placebos) and flushing (2.6% vs. 0%) occurred more often in women; dizziness (3.4% vs. 1.5%) had no sex bias.[7]

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

primary open angle glaucoma.[33]

Overdose

Although rare,

Vasopressors are also administered when low blood pressure is not alleviated by fluid resuscitation.[7][35]

Interactions

Several drugs interact with amlodipine to increase its levels in the body. CYP3A inhibitors, by nature of inhibiting the enzyme that metabolizes amlodipine,

Viagra increases the risk of hypotension.[7][10]

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

peripheral vascular resistance, thus lowering blood pressure. Its effects on cardiac muscle also prevent excessive constriction in the coronary arteries.[10]

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 and one of its major metabolites: The nitrogen-containing ring is oxidized, and two of the side chains are hydrolyzed.[50]

Amlodipine has been studied in healthy volunteers following oral administration of 14C-labelled drug.

hydrolyzed, resulting in an inactive pyridine metabolite.[52] 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.[53] 20-25% of the drug is excreted in the faeces.[54]

History

angiotensin converting enzyme inhibitor are also available.[56]

The medical form comes as

Veterinary use

Amlodipine is most often used to treat systemic

References

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  2. ^ a b "Amlodipine Use During Pregnancy". Drugs.com. 28 October 2019. Archived from the original on 28 December 2019. Retrieved 29 December 2019.
  3. ^ "Poisons Standard June 2017". legislation.gov.au. 29 May 2017. Archived from the original on 13 December 2020. Retrieved 7 January 2018.
  4. ^ "Norvasc Product and Consumer Medicine Information Licence". TGA eBS. Archived from the original on 20 June 2022. Retrieved 19 June 2022.
  5. ^ "Norvasc product information". Health Canada. 25 April 2012. Archived from the original on 20 June 2022. Retrieved 19 June 2022.
  6. ^ a b c "Istin 5 mg Tablets - Summary of Product Characteristics (SmPC)". (emc). 28 September 2020. Archived from the original on 20 June 2022. Retrieved 19 June 2022.
  7. ^ a b c d e f g h i j k l m n o "Norvasc- amlodipine besylate tablet". DailyMed. 14 March 2019. Archived from the original on 10 June 2020. Retrieved 29 December 2019.
  8. ^ "Norliqva- amlodipine solution". DailyMed. 28 February 2022. Archived from the original on 20 June 2022. Retrieved 19 June 2022.
  9. ^ "Amlodipine" (PDF). List of nationally authorised medicinal products. European Medicines Agency. Archived (PDF) from the original on 3 March 2022. Retrieved 20 June 2022.
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  12. from the original on 27 August 2021. Retrieved 1 June 2020.
  13. . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
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External links