Propranolol Cimetidine

In patients with heart failure, lidocaine s volume of distribution and total body clearance may both be decreased. Thus, both loading and maintenance doses should be decreased. Since these effects counterbalance each other, the half-life may not be increased as much as predicted from clearance changes alone. In patients with liver disease, plasma clearance is markedly reduced and the volume of distribution is often increased the elimination half-life in such cases may be increased threefold or more. In liver disease, the maintenance dose should be decreased, but usual loading doses can be given. Elimination half-life determines the time to steady state. Thus, although steady-state concentrations may be achieved in 8-10 hours in normal patients and patients with heart failure, 24-36 hours may be required in those with liver disease. Drugs that decrease liver blood flow (eg, propranolol, cimetidine) reduce lidocaine clearance and so increase the risk of toxicity unless infusion rates are decreased. With infusions lasting more than 24 hours, clearance falls and plasma concentrations rise. Renal disease has no major effect on lidocaine disposition. 

Aluminum salts, cholestyramine, and colestipol may decrease absorption of /3 blockers. Pheny-toin, rifampin, and phenobarbital, as well as smoking, induce hepatic biotransformation enzymes and may decrease plasma concentrations of /3 receptor antagonists that are metabolized extensively (e.g., propranolol). Cimetidine and hydralazine may increase bioavailability of propranolol and metoprolol by affecting hepatic blood flow, fi Receptor antagonists can impair the clearance o/lidocaine. 

The answer is b. (Hardmanr p 906.) Cimetidine reversibly inhibits cytochrome P450. This is important in phase I bio transformation reactions and inhibits the metabolism of such drugs as warfarin, phenytoin, propranolol, metoprolol, quinidine, and theophylline. None of the other enzymes are significantly affected. 

The H2RAs are generally well tolerated. The most common adverse effects are headache, somnolence, fatigue, dizziness, and either constipation or diarrhea. Cimetidine may inhibit the metabolism of theophylline, warfarin, phenytoin, nifedipine, and propranolol, among other drugs. 

P4 ONl OlONE PROPRANOLOL ASPIfllN CEPHALEXIN CEfaTR12In - 250 mg CEFATPIZINE - 500 mg CIMETIDINE PENICILLIN V cefatrizi.ne METHYLdopa cefusoxime theoretical line... 

Fig. 4.3 CSF concentration/free (unbound) plasma concentration ratios for neutral and basic drugs 1, ritropirronium 2, atenolol 3, sulpiride 4, morphine 5, cimetidine 6, meto-prolol 7, atropine 8, tacrine 9, digoxin 10, propranolol 11, carbamazepine 12, ondansetron 13, diazepam 14, imipramine 15, digitonin 16, chlorpromazine and acidic drugs, a, salicylic acid b, ketoprofen c, oxyphenbutazone and d, indomethacin compared to log D.

Drugs that may affect flecainide include amiodarone, cimetidine, cisapride, disopyramide, propranolol, ritonavir, urinary acidifiers/alkalinizers, and verapamil. Smoking may also have an effect. Drugs that may be affected by flecainide include cisapride, propranolol, and digoxin. 

Drugs that may affect HMG-CoA reductase inhibitors include alcohol, amiodarone, antacids, azole antifungals, bile acid sequestrants, cimetidine, cyclosporine, diltiazem, erythromycin, gemfibrozil, isradipine, nefazodone, niacin, nicotinic acid, omeprazole, phenytoin, propranolol, protease inhibitors, ranitidine, rifampin, St. John s wort, and verapamil. 

Drugs that may affect benzodiazepines include alcohol, antacids, barbiturates, cimetidine, disulfiram, fluoxetine, isoniazid, ketoconazole, metoprolol, oral contraceptives, narcotics, probenecid, propoxyphene, propranolol, ranitidine, rifampin, scopolamine, theophylline, and valproic acid. 

Flurazepam (Dalmane) [C-IV] [Sedative/Hypnotic/ Benzodiazepine] Uses Insomnia Action Benzodiazepine Dose Adults Beds >15 y. 15-30 mg PO qhs PRN X in elderly Caution [X, /-] Elderly, low albumin, hepatic impair Contra NAG PRG Disp Caps SE Hangover d/t accumulation of metabolites, apnea, anaphylaxis, angioedema, amnesia Interactions T CNS depression W/ antidepressants, antihistamines, opioids, EtOH T effects OF digoxin, phenytoin T effects W/ cimetidine, disulfiram, fluoxetine, iso-niazid, ketoconazole, metoprolol, OCPs, propranolol, SSRIs, valproic acid. 

Substrates Inhibitors Inducers CYP1A2 Acetaminophen, caffeine, clozapine, imipramine, theophylline, propranolol Most fluoroquinolone antibiotics, fluvoxamine, cimetidine Tobacco smoking, charcoal-broiled foods, cruciferous vegetables, omeprazole... 

Concurrent administration of propafenone with digoxin, warfarin, propranolol, or metoprolol increases the serum concentrations of the latter four drugs. Cimetidine slightly increases the propafenone serum concentrations. Additive pharmacological effects can occur when lidocaine, procainamide, and quinidine are combined with propafenone. 

Cimetidine with propranolol. Altered metabolism Decreased drug clearance. 

Cimetidine Lidocaine, propranolol, verapamil, imipramine Increased absorption... 

Lignocaine Cimetidine, propranolol Increased risk of lignocaine toxicity. 

Antacids reduce the absorption and enzyme-inducing drugs may decrease serum levels. Cimetidine and propranolol both increase serum levels. There can be competition for metabolic pathways by some tricyclic antidepressants (TCAs) and SSRIs (especially fluoxetine) which may increase serum levels. 

Omeprazole can inhibit the metabolism of drugs metabolised mainly by the cytochrome P-450 enzyme subfamily 2C (diazepam, phenytoin), but not of those metabolished by subfamilies lA (caffeine, theophylline), 2D (metoprolol, propranolol), and 3A (ciclosporin, lidocaine (lignocaine), quinidine). Since relatively few drugs are metabolised mainly by 2C compared with 2D and 3A, the potential for omeprazole to interfere with the metabolism of other drugs appears to be limited, but the half lives of diazepam and phenytoin are prolonged as much as by cimetidine. 

Cimetidine [P] Decreased metabolism of 13 blockers that are cleared primarily by the liver, eg, propranolol. Less effect (if any) on those cleared by the kidneys, eg, atenolol, nadolol. 

Drug Interactions Gemfibrozil Niacin Erythromycin Cholestyramine Digoxin Cimetidine/ranitidine/ omeprazole Rifampicin Warfarin Itraconazole Gemfibrozil Niacin Erythromycin Propranolol Digoxin Warfarin Antacids Colestipol Digoxin Erythromycin Oral contraceptives Fibrates Niacin Azole antifungals... 

Certain drugs can reduce the ability of the liver to clear benzodiazepines from the body. These include ulcer drugs, such as cimetidine (Tagamet), birth control pills, propranolol (used to treat hypertension, heart disorders, and migraines), and disulfuram (Antabuse), which is used for the treatment of alcoholism. 

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