Calcium Channel Blockers: Amlodipine
Indication
Amlodipine is used in adults for the treatment of angina pectoris and also for hypertension. In pediatric patients, it is used to treat systemic hypertension.
Mechanism of Action
Amtopidine prevents calcium ions from entering both vascular smooth muscle cells and myocardial cells via specific slow calcium channels during depolarization. Thus, it decreases the intracellular concentration of calcium such that less calcium is available to contractile proteins in these cells. As a result, vasodilation occurs. Relaxation of the coronary vascular smooth muscle specifically treats anginal pain by increasing myocardial oxygen delivery.
Dosing
Neonates and infants:
Specific dosing information has not been obtained for neonates and infants
Oral, hypertension: for children ages 6 to 17 years, the manufacturer’s recommended dose is 2.5 to 5 mg P.O./N.G. once daily. Initial doses reported in the literature have varied from 0.05 to 0.13mg/kg/day. Doses are typically titrated by 25 to 50% every 5 to 7 days. Required doses reported in the literature have varied from 0.12 to 0.5mg/kg/ day, and younger patients tend to need higher doses for effect. Insufficient data exist on doses greater than 5 mg/day in pediatrics
Adults:
Oral:
Hypertension: initial, 2.5 to 5 mg RO./N.G. once daily, with a 2.5 mg/ dose recommended for smaller, less stable patients. Titrate dose to a maximum of 10 mg/dose once daily over 7 to 24 days. Usual dose is 5mg/dose once daily Angina: 5 to 10 mg/dose P.O./N.G. once daily. Lower doses are appropriate for patients with hepatic impairment; no adjustment for renal impairment is required
Pharmacokinetics
Onset of action: 30 to 50 minutes
Absorption: well absorbed orally
Distribution: mean volume of distribution:
Children older than 6 years: similar to adults on a per-kilogram basis
Adults: 21 L/kg
Maximum effect: peak serum concentration at 6 to 12 hours
Half-life: terminal half-life 30 to 50 hours
Duration: > 24 hours with routine dosing
Protein binding: 93%
Metabolism: in the liver, with 90% metabolized to inactive metabolites
Clearance: in children older than 6 years of age, weight-adjusted clearance is similar to adults
Elimination: 10% of unchanged drug and 60% of metabolites are excreted in the urine. Amlodipine is not removed by dialysis
Monitoring Parameters
Blood pressure and liver enzymes.
Contraindications
Hypersensitivity to amlodipine or any of its components.
Adverse Effects
Cardiovascular:
More common: flushing, palpitations, peripheral edema
Rare: hypotension, dysrhythmia, chest pain, syncope, peripheral ischemia, vasculitis, myocardial infarction
Respiratory: dyspnea, pulmonary edema, epistaxis
Central nervous system:
More common: headache, dizziness, somnolence, fatigue
Less common: insomnia, vertigo, depression, anxiety
Gastrointestinal: nausea, abdominal pain, dyspepsia, anorexia, constipation, diarrhea, dysphagia, pancreatitis, vomiting, xerostomia, gingival hyperplasia
Hepatic: jaundice, elevated liver enzymes
Genitourinary: sexual dysfunction
Neuromuscular and skeletal: muscle cramps, asthenia, arthralgia, myalgia, paresthesia, peripheral neuropathy, hypoesthesia, tremor
Endocrine/metabolic: weight gain or loss, gynecomastia, hyperglycemia
Hematological: thrombocytopenia,leukopenia,purpura
Ophthalmological: diplopia, abnormal vision, eye pain, and conjunctivitis
Cutaneous/peripheral: rash, pruritus, erythema multiforme, angioedema
Other: tinnitus, diaphoresis, increased thirst
Precautions
In adult patients with severe coronary artery disease, both initiation of amlodipine therapy and increased dosing have been associated with increased severity and frequency of angina as well as acute myocardial infarction. Acute hypotension is more common in patients with congestive heart failure and left ventricular outflow tract obstruction (e.g., aortic stenosis).
Increased caution should be used in patients with impaired hepatic function because of amlodipine’s hepatic metabolism. Do not discontinue amlodipine abruptly in patients with angina or significant coronary artery disease.
Drug-Drug Interactions
Concomitant administration of rifampin may decrease serum amlodipine concentration. Azole antifungal agents (e.g., ketoconazole) may inhibit metabolism in the liver and increase serum amlodipine concentration. Amlodipine may increase serum cyclosporine level (uncertain). As for all calcium channel-blocking agents, administration of calcium may mitigate the drug’s effect.
Compatible Diluents/Administration
Amlodipine tablets maybe administered without regard to food, because food does not affect its bioavailability. Concomitant ingestion of grapefruit juice increased amlodipine peak serum concentration in some reports but not others.
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