Amlodipine

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Contents

[edit] BRAND NAMES

[edit] STRUCTURE

Amlodipine.jpg

[edit] MECHANISM OF ACTION

Amlodipine is a dihydropyridine calcium-channel blocker that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle.

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 than on cardiac muscle cells.

The decrease in intracellular calcium inhibits the contractile processes of the coronary arteries smooth muscle cells and systemic arteries, and thus increases oxygen delivery to the myocardial tissue and, decreases total peripheral resistance and systemic blood pressure.

In patients with hypertension, once daily dosing provides clinically significant reductions of blood pressure in both the supine and standing positions throughout the 24-hour interval. Due to the slow onset of action, acute hypotension is not a feature of Amlodipine administration.

In patients with angina, once daily administration of Amlodipine increases total exercise time, time to angina onset and time to 1 mm ST segment depression, and decreases both angina attack frequency and nitroglycerine tablet consumption.

[edit] INDICATIONS

  • Hypertension
  • Chronic stable angina (chest pain or discomfort that usually occurs with activity or stress, due to poor blood flow through coronary vessels to the heart muscle)
  • Prinzmetal's variant angina (A vasospastic angina consisting of cardiac chest pain at rest, caused by contraction of the coronary vessels )

[edit] DOSAGE

Adults:

Hypertension: the recommended starting dose is 5 mg once daily with maximum dose 10 mg once daily. Small, fragile, or elderly patients, or patients with hepatic insufficiency may be started on 2.5 mg once daily.

Dosage should be adjusted according to each patient's need. In general, Titration should proceed over 7 to 14 days so that the physician can fully assess the patient's response to each dose level. Titration may proceed more rapidly, however, if clinically warranted, provided the patient is assessed frequently.


Chronic stable or vasospastic angina: The recommended dose for chronic stable or vasospastic angina is 5-10 mg, with the lower dose suggested in the elderly and in patients with hepatic insufficiency. Most patients will require 10 mg for adequate effect.


Co-administration with Other Antihypertensive and/or Antianginal Drugs: Amlodipine has been safely administered with thiazides, ACE inhibitors, beta-blockers, long-acting nitrates, and/or sublingual nitroglycerin.

[edit] CONTRAINDICATIONS

  • Known sensitivity to amlodipine
  • Patients with advanced aortic stenosis

[edit] WARNINGS AND PRECAUTIONS

  • Symptomatic hypotension is possible, particularly in patients with severe aortic stenosis. However, acute hypotension is unlikely.
  • Increased Angina and/or Myocardial Infarction: Rarely, patients, particularly those with severe obstructive coronary artery disease, have developed documented increased frequency, duration, and/or severity of angina or acute myocardial infarction on starting calcium channel blocker therapy or at the time of dosage increase. The mechanism of this effect has not been elucidated.
  • Amlodipine is extensively metabolized by the liver and the plasma elimination half-life (t 1/2) is 56 hours in patients with impaired hepatic function. Titrate slowly in patients with severe hepatic impairment

[edit] INTERACTIONS

Simvastatin: Do not exceed doses greater than 20 mg daily of simvastatin

Sildenafil (Erectile Dysfunction): When Amlodipine and sildenafil are used in combination, each agent independently exerted its own blood pressure lowering effect.

[edit] PHARMACOKINETICS

Amlodipine is well absorbed orally with peak blood levels occurring 6-12 hours post-dose. Oral administration of a single therapeutic dose gave a mean absolute bioavailability of 64% (range 52-88%). The volume of distribution is approximately 20 L/kg. The absorption of Amlodipine is unaffected by consumption of food. The terminal plasma elimination half-life is about 35-50 hours and is consistent with once daily dosing. Steady state plasma levels reached after 7-8 days of consecutive dosing. Amlodipine is extensively metabolised by the liver to inactive metabolites with 10% of the parent compound and 60% of metabolites excreted in the urine. Approximately 97.5% of circulating Amlodipine is bound to plasma proteins. Amlodipine is not dialyzable.

[edit] PREGNANCY AND LACTATION

  • Pregnancy Category C (US). There are no adequate and well-controlled studies in pregnant women. Amlodipine should be used during pregnancy only if the potential benefit justifies the risk to the fetus.
  • Nursing: Discontinue when administering Amlodipine.

[edit] SIDE EFFECTS

Most common adverse reactions to amlodipine is peripheral edema, headache, fatigue, nausea, abdominal pain, and somnolence.

[edit] OVERDOSAGE

Available data suggest that gross overdosage could result in excessive peripheral vasodilatation and possibly reflex tachycardia. Marked and probably prolonged systemic hypotension including shock with fatal outcome has been reported.

Administration of activated charcoal to healthy volunteers immediately or up to two hours after ingestion of Amlodipine 10 mg has been shown to significantly decrease Amlodipine absorption. Gastric lavage may be worthwhile in some cases. Clinically significant hypotension due to Amlodipine overdosage calls for active cardiovascular support including frequent monitoring of cardiac and respiratory function, elevation of extremities, and attention to circulating fluid volume and urine output. A vasoconstrictor may be helpful in restoring vascular tone and blood pressure, if there is no contraindication to its use. Intravenous calcium gluconate may be beneficial in reversing the effects of calcium channel blockade. Dialysis is not likely to be of benefit since Amlodipine is highly protein-bound.

[edit] RELATED LINKS

Calcium Channel Blockers Pharmacology

[edit] REFERENCES

Antihypertensives
ACE inhibitors Benazepril (Lotensin)   Captopril (Capoten)   Cilazapril   Delapril   Enalapril (Renitec, Vasotec)   Fosinopril (Monopril)  Lisinopril (Prinivil, Zestril)   Moexipril (Univasc)  Perindopril (Aceon)  Quinapril (Accupril)  Ramipril (Altace, Triatec)   Trandolapril (Mavik)  Zofenopril (Bifril, Zopranol)
Angiotensin II receptor antagonist Azilsartan (Edarbi)   Candesartan (Atacand)   Eprosartan (Teveten)   Irbesartan (Aprovel, Avapro, Karvea)   Losartan (Cozaar)   Olmesartan (Benicar, Olmetec)   Telmisartan (Micadis)   Valsartan (Diovan, Tareg)
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Alpha-2 agonists (centrally acting) Clonidine (Oral route)   Clonidine (Transdermal) (Catapresan)   Guanfacine (Tenex)   Methyldopa (Aldomet)
Calcium channel blockers Dihydropyridines‎ Amlodipine (Norvasc)   Barnidipine (Vasexten)   Felodipine (Plendil)   Isradipine (Dynacirc)   Lacidipine (Lacipil, Motens)   Lercanidipine (Zanidip)   Manidipine   Nicardipine   Nifedipine (Adalat)   Nisoldipine   Nitrendipine
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Nonselective (Beta1, Beta2 and Alpha1 blockers) Carvedilol (Dilatrend)   Labetalol (Trandate)
Beta blocker with intrinsic sympathomimetic activity (ISA) Acebutolol (Sectral)   Celiprolol (Cordiax)
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