Beta blocker used safely in hepatic disease is
Ans) a (Esmolol) Ref: Gondmun & Gilman 11thedition KDT 6th ed p.139, Katzung edEsmolol has a half-life of about 8 minutes and it contains an ester linkage, and it is hydrolyzed rapidly by esterases in erythrocytes. The half-life of the carboxylic acid metabolite of esmolol is far longer and is about 4 hours which accumulates during prolonged infusion of esmolol which is excreted in the urine. Soit can be safely given in liver diseasesBisoprolol is well absorbed following oral administration with bioavailability of -90%. It is eliminated by renal excretion (50%) and liver metabolism to pharmacologically inactive metabolites (50%).CarvedilolCarvedilol is a third-generation b receptor antagonist that has a unique pharmacological profile. It blocks bl, b2, and al receptors similarly to labetalol, but also has antioxidant and antiproliferative effects. It has membrane-stabilizing activity but it lacks intrinsic sympathomimetic activity. Carvedilol produces vasodilation.It is thought that the additional properties (e.g., antioxidant and antiproliferative effects) contribute to the beneficial effects seen in treating congestive heart failure. Carvedilol does not increase b receptor density and is not associated with high levels of inverse agonist activity. Carvedilol is rapidly absorbed following oral administration, with peak plasma concentrations occurring in 1 to 2 hours. It is highly lipophilic and thus is extensively distributed into extravascular tissues. It is >95% protein bound and is extensively metabolized in the liver, predominantly by CYP2D6 and CYP2C9. No significant changes in the pharmacokinetics of carvedilol were seen in elderly patients with hypertension, and no change in dosage is needed in patients with moderate-to- severe rend insufficiencyBETA BLOCKERSCardioselective (betal) beta blockersMetoprolol, Acebutalol, Atenolol. Bisoprolol ,Esmolol, Betaxolol, Celiprolol, and NebivololNon selective beta blockersPropranolol ,SotalolTimolol, Pindolol, Labetalol, Carvedilol, Medroxolol, Bucindolol and Levubunonol.Beta blocker with intrinsic sympathomimetic activityDilevalolPindololAcebutalolLabetalolCarteololOxyprenololAlprenololPenbutalol Non selective blocker betal + beta2 + alphaK - Crazy Buss Die in Medicine Lab)CarvedilolBucindololLabetolol,DilevalolMedroxalol, IMPORTANT POINTS REGARDING BETA BLOCKERSPropranalol has highest degree of membrane stabilizing action. Nadolol is longest acting beta blocker (t 1/2 -14-24 hrs) and Esmolol is the shortest acting.(t 1/2 2-10 minutes)Propranolol has poor oral bioavailability. Pindolol and Penbutolol have approx 100% bioavailabilityHepatic elimination - propranolol, metoprolol and labetalol. Renal elimination - atenololbeta blockers not crossing CNS -Atenolol, Nadolol and Sotalol (mnemonic: ANS will not cross CNS)Pindolol has intrinsic sympathomimetic activity. Butoxamine is a beta 2 selective blocker.Carvedilol is a non-selective beta blocker showing anti-oxidant property and alpha 1 receptor antagonism.Labetolol, Medroxalol, and Bucindolol also shows alpha 1 receptor blocking activity.Propranalol has highest degree of membrane stabilizing actionNadolol is longest acting beta blocker (t Y=2-14-24 hrs) and Esmolol is the shortest acting.(t Y=2 -10 minutes)Propranolol has poor oral bioavailability. Pindolol and Penbutolol have approx 100% bioavailability Propranolol and Metoprolol are extensively metabolized in the liver, with little unchanged drug appearing in the urine.USES1) Hypertension -They are one of the first choice drugs used in treat ment of hypertension.2) Angina pectoris- Beta-blockers reduces the frequency of anginal episodes and improves exercise tolerance in many patients with angina3) Cardiac arrhythmias- Beta antagonists are often effective in the treatment of both supraventricular and ventricular arrhythmias.4) Myocardial infarction- beta antagonists are strongly indicated in the acute phase of a myocardial infarction. In this setting, relative contraindications include bradycardia, hypotension, moderate or severe left ventricular failure, shock, heart block, and active airways disease5) Congestive heart failure - drugs used are bisoprolol, metoprolol & carvedilol (BMC)6) Dissecting aortic aneurysm7) Pheochromocytoma8) Thyrotoxicosis - controls the sympathetic symptoms without affecting thyroid status.9) Migraine - Propranolol is the most effective drag for prophylaxis of migraine10) Anxiety,11) Essential tremor12) Glaucoma13) HOCM- drags used are beta blockers and calcium channel blockers14) Portal hypertensionAdverse effectsCentral nervous system effects include sedation, sleep disturbances, and depressionWorsens pre existing asthma and COPD Worsening of peripheral vascular diseaseBeta-receptor blockade depresses myocardial contractility and excitability, caution must be exercised in starting a beta receptor antagonist in patients with compensated heart failureBeta blockers may interact with the calcium antagonist verapamil causing severe hypotension, bradycardia, heart failure, and cardiac conduction abnormalities.Exacerbates variant (prinzmetal's) angina.The incidence of hypoglycemic episodes in diabetics that are exacerbated. They also can cause impaired carbohydrate tolerance Plasma lipid profile is altered. Total triglycerides and LDL cholesterol tend to increase while HDL cholesterol decreases.
Esmolol
Betaxolol
Bisoprolol
Carvedilol
A.N.S.