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Amlodipine - Wikipedia, the free encyclopedia

Amlodipine
From Wikipedia, the free encyclopedia

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]

Amlodipine

Contents
1 Medical uses
2 Contraindications
3 Adverse effects
4 Mechanism
5 Metabolism
6 Comparison of Candesartan and Amlodipine
for Safety, Tolerability and Efficacy (CASTLE)
Study
7 History
8 See also
9 References
10 External links

Systematic (IUPAC) name

(RS)-3-ethyl 5-methyl 2-[(2-aminoethoxy)methyl]-4-(2chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5dicarboxylate

Clinical data
Trade names

Norvasc

AHFS/Drugs.com

monograph

MedlinePlus

a692044

Licence data

US FDA:link

Medical uses

Pregnancy
category

AU:

Amlodipine is used in the management of hypertension[4]

and coronary artery disease.

Legal status

UK:

Contraindications
Breastfeeding
Cardiogenic shock
Unstable angina
Systolic and diastolic blood pressure below 90/60
mmHg
https://en.wikipedia.org/wiki/Amlodipine

C
US: C (Risk not ruled
out)
Prescription-only
(POM)
US: -only

Routes of
administration

Oral (tablets)

Pharmacokinetic data
Bioavailability

64 to 90%

Metabolism

Hepatic

Biological half-life 30 to 50 hours

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Aortic stenosis

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

Mechanism

Excretion

Renal
Identifiers

CAS Registry
Number
ATC code

88150-42-9

PubChem

CID: 2162

IUPHAR/BPS

6981

DrugBank

DB00381

ChemSpider

2077

UNII

1J444QC288

KEGG

D07450

ChEBI

CHEBI:2668

ChEMBL

CHEMBL1491

C08CA01

Amlodipine inhibits calcium ions into vascular smooth

Chemical data
muscle cells and cardiac muscle cells. The contractile
Formula
C20H25ClN2O5
processes of cardiac muscle and vascular smooth muscle
are dependent upon the movement of extracellular
Molecular mass
408.879 g/mol
calcium ions into these cells through specific ion
SMILES
channels. Amlodipine inhibits calcium ion influx across
cell membranes selectively, with a greater effect on
InChI
vascular smooth muscle cells. Negative inotropic effects
(what is this?) (verify)
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]
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.[9]

Metabolism

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Amlodipine has been studied in healthy volunteers following oral administration of 14 C-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 3050
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
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]

History
Pfizer's patent protection on Norvasc lasted until 2007; total patent expiration occurred later in 2007.[13]
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.[14]

See also
Aliskiren/amlodipine
Amlodipine/valsartan

References
1. "Amlodipine: MedlinePlus Drug Information"
(http://www.nlm.nih.gov/medlineplus/druginfo/meds/a692044.html). www.nlm.nih.gov. Retrieved 2015-05-21.
2. Cash, Jill C.; Glass, Cheryl Anne (2014-02-10). Family Practice Guidelines, Third Edition
(https://books.google.com/books?
id=SLPWAgAAQBAJ&pg=PA206&dq=amlodipine+calcium+channel+blocker&hl=en&sa=X&ei=r3FeVcazAcW
-ggSLrYHQBw&ved=0CFYQ6AEwCQ#v=onepage&q=amlodipine%20calcium%20channel%20blocker&f=false)
(in English). Springer Publishing Company. ISBN 9780826197825.
3. "WHO Model List of EssentialMedicines" (http://apps.who.int/iris/bitstream/10665/93142/1/EML_18_eng.pdf?
ua=1) (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
https://en.wikipedia.org/wiki/Amlodipine

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4. Wang, JG (2009). "A combined role of calcium channel blockers and angiotensin receptor blockers in stroke
prevention". Vascular health and risk management 5: 593605. doi:10.2147/vhrm.s6203
(https://dx.doi.org/10.2147%2Fvhrm.s6203). PMID 19688100 (https://www.ncbi.nlm.nih.gov/pubmed/19688100).
5. Munoz, Ricardo; Vetterly, Carol G.; Roth, Stephen J.; Cruz, Eduardo da (2007-10-18). Handbook of Pediatric
Cardiovascular Drugs (https://books.google.com/books?
id=NiTR3Uzp_jMC&pg=PA96&dq=Amlodipine+contraindications&hl=en&sa=X&ei=AVFeVfWXFMyggSw6ICoBg&ved=0CEQQ6AEwBQ#v=onepage&q=Amlodipine%20contraindications&f=false) (in English).
Springer Science & Business Media. ISBN 9781846289538.
6. Arcangelo, Virginia Poole; Peterson, Andrew M. (2006). Pharmacotherapeutics for Advanced Practice: A
Practical Approach (https://books.google.com/books?
id=EaP1yJz4fkEC&pg=PA252&dq=Amlodipine++mechanism+of+action&hl=en&sa=X&ei=oGNeVfiDJ8vYggS
L7IK4Aw&ved=0CEwQ6AEwBg#v=onepage&q=Amlodipine%20%20mechanism%20of%20action&f=false) (in
English). 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 (https://books.google.com/books?
id=TD59BgAAQBAJ&pg=PA191&dq=Amlodipine++mechanism+of+action&hl=en&sa=X&ei=nGdeVae8LsK8g
gSipoCIAQ&ved=0CEMQ6AEwBQ#v=onepage&q=Amlodipine%20%20mechanism%20of%20action&f=false)
(in English). CRC Press. ISBN 9781444113006.
8. Li, Y. Robert (2015-04-06). Cardiovascular Diseases: From Molecular Pharmacology to Evidence-Based
Therapeutics (https://books.google.com/books?
id=rXy0BgAAQBAJ&pg=PA189&dq=Amlodipine+stable+angina&hl=en&sa=X&ei=FVleVa20AYmWNpSJgeAC
&ved=0CDoQ6AEwAw#v=onepage&q=Amlodipine%20stable%20angina&f=false) (in English). John Wiley &
Sons. ISBN 9780470915370.
9. LEARNING, JONES & BARTLETT; Bartlett, Jones and (2012-07-15). 2013 Nurse's Drug Handbook
(https://books.google.com/books?
id=ckdTGZe7aRAC&pg=PA73&dq=Amlodipine+Prinzmetal%27s+angina:&hl=en&sa=X&ei=B1peVYeGGsKeg
wS3iIGoBw&ved=0CDYQ6AEwAw#v=onepage&q=Amlodipine%20Prinzmetal's%20angina%3A&f=false) (in
English). 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): 24554. doi:10.3109/00498258809041660
(https://dx.doi.org/10.3109%2F00498258809041660). PMID 2967593
(https://www.ncbi.nlm.nih.gov/pubmed/2967593).
11. Brittain, Harry G. (2012-05-09). Profiles of Drug Substances, Excipients and Related Methodology
(https://books.google.com/books?
id=ew_MiZ_xBdcC&pg=PA68&dq=Amlodipine++metabolism&hl=en&sa=X&ei=PWNeVY25Koq8ggS9l4GQBg
&ved=0CDIQ6AEwAQ#v=onepage&q=Amlodipine%20%20metabolism&f=false) (in English). 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" (http://www.ncbi.nlm.nih.gov/pubmed/11249891). Retrieved June 22, 2015.
13. Kennedy VB (22 March 2007). "Pfizer loses court ruling on Norvasc patent"
(http://www.marketwatch.com/news/story/pfizer-loses-court-ruling-norvasc/story.aspx?guid=%7B9819D67E-B76B431D-835C-FB8D6D8327B7%7D). MarketWatch.
14. 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): 13542. doi:10.2165/00129784-200909030-00001
(https://dx.doi.org/10.2165%2F00129784-200909030-00001). PMID 19463019
(https://www.ncbi.nlm.nih.gov/pubmed/19463019).

External links
U.S. National Library of Medicine: Drug Information Portal - Amlodipine
https://en.wikipedia.org/wiki/Amlodipine

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(http://druginfo.nlm.nih.gov/drugportal/dpdirect.jsp?name=Amlodipine)
Retrieved from "https://en.wikipedia.org/w/index.php?title=Amlodipine&oldid=670981240"
Categories: Amines Calcium channel blockers Carboxylate esters Dihydropyridines Ethers
Chloroarenes World Health Organization essential medicines Ethyl esters Methyl esters
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