Pharmacotherapeutic group: Beta Blocker.
Pharmacology: Beta blockers (beta-adrenoceptor blocking drugs or antagonists) are competitive antagonist of catecholamines at beta-adrenergic receptors in a wide range of tissues. Although they have broadly similar properties they differ in their affinity for beta₁, or beta₂ receptor subtypes, intrinsic sympathomimetic properties including differences in lipid solubility. These differences may affect the choice of drug in specific situations.
Bioavailability and Pharmacokinetics: Carvedilol is well absorbed from the gastrointestinal tract but is subject to considerable first-pass metabolism in the liver, the absolute bioavailability is about 25%. Peak plasma concentrations occur 1 to 2 hours after an oral dose, it has high lipid solubility, Carvedilol is more than 98% bound to plasma proteins. It is extensively metabolized in the liver, primarily by the cytochrome P450 isoenzymes CYP2D9, and the metabolites are excreted mainly in the bile. The elimination half-life is about 6 to 10 hours. Carvedilol has been shown to accumulate in breast milk in animals.
For the management of hypertension and angina pectoris, and as an adjunct to standard therapy in symptomatic heart failure.
For Hypotension: An initial dose of 6.25 mg is given twice daily, increase one to two weeks to 12.5 mg twice daily. The dose may be increased further if necessary at intervals of at least two weeks to 50 mg once daily or in divided doses. A dose of 12.5 mg once daily may be adequate for elderly patients or as prescribed by the physician.
For Angina Pectoris: Initial dose of 12.5 mg is given twice daily by mouth. Increase after two days to 25 mg twice daily or as prescribed by the physician.
For Heart Failure: Initial dose of 3.125 mg twice daily by mouth. It should be taken with food to reduce the risk of hypotension. If tolerated, the dose should be doubled after two weeks to 6.25 mg twice daily and then increase gradually at intervals of not less than two weeks, to the maximum dose tolerated by the patients, this should not exceed 25 mg twice daily in weighing less than 65 kg or 50 mg twice daily in patients weighing more than 85 kg. Patient should be monitored for 2 to 3 hours after initiation and after each dose increase or as prescribed by the physician.
Should not be given to patients with bronchospasm or asthma to those with a history of obstructive airways disease, hepatic impairment or those hypersensitive to carvedilol.
Should not be given to patients with bronchospasm or asthma to those with a history of obstructive airways disease. This contraindication applies even to those beta blockers considered to be cardioselective. However, some authorities consider that a cardioselective beta blocker might be used with extreme caution when there is no alternative treatment. Other contraindications include metabolic acidosis, severe peripheral arterial disease, sinus bradycardia, and second or third-degree atrioventricular block; caution should be observed in first-degree block. Although beta blockers are used in the management of heart failure, they should be given to patient with uncontrolled heart failure and treatment should be initiated with great care. Patients with phaeochromocytoma should not receive beta blocker without concomitant alpha-adrenoceptor blocking renal insufficiency.
The most frequent and serious adverse effects of these drugs are related to their beta-adrenergic blocking activity. Among the most serious adverse effects are heart failure, heart block, and bronchospasm. Troublesome subjective side-effects include fatigue and coldness of the extremities. Reactions may be more severe following intravenous than oral administration; ocular use has also been associated with systemic adverse effects. When beta blockers are used for long term treatment of asymptomatic diseases such as hypertension, subjective side-effects may be an important determinant of patient compliance.
Pharmacodynamic interactions may occur with drug whose actions enhance or antagonize the various effects of beta₁ and beta₂ receptors, including their hypertensive effect, on carbohydrate metabolism or effect on bronchial beta₂ receptors. Drugs that enhance the antihypertensive effects of beta blockers, such as ACE inhibitors, calcium-channel blockers, and clonidine may be useful in controlling hypertension. Drugs that cause hypotension such as aldesleukin and general anesthetics also enhance the antihypertensive effects of beta blockers while other drugs, for example NSAIDS, antagonize the antihypertensive effects. Use of beta blockers with other cardiac depressants such as antiarrhythmics and rate limiting calcium channel blockers can precipitate bradycardia and heart block.
The interaction between beta blockers and sympathomimetics is complex and depends on the selectivity of both drugs. Patients taking beta blockers may have an exaggerated hypertensive response to adrenaline, caused by unopposed alpha-mediated vasoconstriction, while the bronchodilator effects are inhibited; the response to adrenaline given for anaphylaxis may also be reduced in patients on long-term treatment with beta blockers. In diabetic patients beta blockers can reduced the response to insulin and oral hypoglycaemic through their effects on pancreatic beta receptors. Blockade of peripheral receptors interferes with the effects of sympathomimetics; patients on beta blocker especially non-selective beta blockers, may develop elevated blood pressure if they are given adrenaline (ephedrine) and the bronchodilator effects of adrenaline (ephedrine are also inhibited).
Pharmacokinetic interactions occurs with drugs that alter the absorption or metabolism of beta blockers. Although these interactions may alter the beta blocker plasma concentration, they are not usually clinically significant since there is little association between plasma concentration and therapeutic effect or toxicity and there are wide interindividual differences in steady-state plasma concentrations of beta blockers. Drugs that reduce absorption include aluminum salts and bile-acid resins such as cholestyramine.
Metabolism of some beta blockers can be increased by drugs such as barbiturates and rifampicin and decreased with drugs such as cimetidine, erythromycin, fluvoxamine and hydralazine. Drugs that alter hepatic blood flow also affect metabolism of some beta blockers. For example, cimetidine and hydralazine decrease hepatic blood flow and this contributes to the decreased hepatic clearance seen with these drugs. Drugs that influence hepatic metabolism affect beta blockers that are extensively metabolized, such as labetalol, propranolol, and timolol, while beta blockers that are excreted largely unchanged, for example atenolol and nadolol, are unaffected.
Since systematic absorption can occur after ocular use of beta blockers the possibility of similar interactions should be considered.
C07AG02 - carvedilol ; Belongs to the class of alpha and beta blocking agents. Used in the treatment of cardiovascular diseases.
Tab 6.25 mg x 100's. 25 mg x 100's.