Amlodipine

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Amlodipine
Amlodipine.svg
Amlodipine 3D ball.png
Systematic (IUPAC) name
(RS)-3-ethyl 5-methyl 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate
Clinical data
Trade names Norvasc
AHFS/Drugs.com monograph
MedlinePlus a692044
Licence data US FDA:link
Pregnancy
category
  • AU: C
  • US: C (Risk not ruled out)
Legal status
Routes of
administration
Oral (tablets)
Pharmacokinetic data
Bioavailability 64 to 90%
Metabolism Hepatic
Biological half-life 30 to 50 hours
Excretion Renal
Identifiers
CAS Registry Number 88150-42-9 YesY
ATC code C08CA01
PubChem CID: 2162
IUPHAR/BPS 6981
DrugBank DB00381 YesY
ChemSpider 2077 YesY
UNII 1J444QC288 YesY
KEGG D07450 YesY
ChEBI CHEBI:2668 YesY
ChEMBL CHEMBL1491 YesY
Chemical data
Formula C20H25ClN2O5
Molecular mass 408.879 g/mol
 YesY (what is this?)  (verify)

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.[1][2] 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.[3]

Medical uses[edit]

Amlodipine is used in the management of hypertension[4] and coronary artery disease.

Contraindications[edit]

Adverse effects[edit]

Adverse side effects of the use of amlodipine may include:[5]

Mechanism[edit]

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.[6] [7]

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.[8]

Metabolism[edit]

Amlodipine has been studied in healthy volunteers following oral administration of 14C-labelled drug.[10] 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.[11]

Comparison of Candesartan and Amlodipine for Safety, Tolerability and Efficacy (CASTLE) Study[edit]

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%).[12]

Combination therapy[edit]

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.[13]

History[edit]

Pfizer's patent protection on Norvasc lasted until 2007; total patent expiration occurred later in 2007.[14] 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.[15]

See also[edit]

References[edit]

  1. ^ "Amlodipine: MedlinePlus Drug Information". www.nlm.nih.gov. Retrieved 2015-05-21. 
  2. ^ Cash, Jill C.; Glass, Cheryl Anne (2014-02-10). Family Practice Guidelines, Third Edition. Springer Publishing Company. ISBN 9780826197825. 
  3. ^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014. 
  4. ^ Wang, JG (2009). "A combined role of calcium channel blockers and angiotensin receptor blockers in stroke prevention". Vascular health and risk management 5: 593–605. doi:10.2147/vhrm.s6203. PMID 19688100. 
  5. ^ Munoz, Ricardo; Vetterly, Carol G.; Roth, Stephen J.; Cruz, Eduardo da (2007-10-18). Handbook of Pediatric Cardiovascular Drugs. Springer Science & Business Media. ISBN 9781846289538. 
  6. ^ Arcangelo, Virginia Poole; Peterson, Andrew M. (2006). Pharmacotherapeutics for Advanced Practice: A Practical Approach. Lippincott Williams & Wilkins. ISBN 9780781757843. 
  7. ^ Ritter, James; Lewis, Lionel; Mant, Timothy; Ferro, Albert (2012-12-11). A Textbook of Clinical Pharmacology and Therapeutics, 5Ed. CRC Press. ISBN 9781444113006. 
  8. ^ Li, Y. Robert (2015-04-06). Cardiovascular Diseases: From Molecular Pharmacology to Evidence-Based Therapeutics. John Wiley & Sons. ISBN 9780470915370. 
  9. ^ LEARNING, JONES & BARTLETT; Bartlett, Jones and (2012-07-15). 2013 Nurse's Drug Handbook. Jones & Bartlett Publishers. ISBN 9781449642846. 
  10. ^ Beresford AP, McGibney D, Humphrey MJ, Macrae PV, Stopher DA (February 1988). "Metabolism and kinetics of amlodipine in man". Xenobiotica 18 (2): 245–54. doi:10.3109/00498258809041660. PMID 2967593. 
  11. ^ Brittain, Harry G. (2012-05-09). Profiles of Drug Substances, Excipients and Related Methodology. Academic Press. ISBN 9780123977564. 
  12. ^ AM J Cardiol. "Comparative effects of candesartan cilexetil and amlodipine in patients with mild systemic hypertension. Comparison of Candesartan and Amlodipine for Safety, Tolerability and Efficacy (CASTLE) Study Investigators". Retrieved June 22, 2015. 
  13. ^ Kazuaki Nishio, Takeshi Kondo, Youichi Kobayashi. "Efficacy and Tolerability of Candesartan Cilexetil and Amlodipine in Patients with Poorly Controlled Essential Hypertension". Retrieved July 21, 2015. 
  14. ^ Kennedy VB (22 March 2007). "Pfizer loses court ruling on Norvasc patent". MarketWatch. 
  15. ^ Bahl VK, Jadhav UM, Thacker HP (2009). "Management of hypertension with the fixed combination of perindopril and amlodipine in daily clinical practice: results from the STRONG prospective, observational, multicenter study". Am J Cardiovasc Drugs 9 (3): 135–42. doi:10.2165/00129784-200909030-00001. PMID 19463019. 

External links[edit]