Lidocaine Cimetidine

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

Drugs that may affect lidocaine include beta-blockers, cimetidine, procainamide, tocainide, and succinylcholine. 

Drugs that may affect amiodarone include hydantoins, cholestyramine, fluoroquinolones, rifamycins, ritonavir, and cimetidine. Drugs that may be affected by amiodarone include anticoagulants, beta-blockers, calcium channel blockers, cyclosporine, dextromethorphan, digoxin, disopyramide, fentanyl, flecainide, hydantoins, lidocaine, methotrexate, procainamide, quinidine, and theophylline. Drug/Lab test interactions Amiodarone alters the results of thyroid function tests, causing an increase in serum T4 and serum reverse T3 levels and a decline in... 

The concurrent administration of lidocaine with cimeti-dine but not ranitidine may cause an increase (15%) in the plasma concentration of lidocaine. This effect is a manifestation of cimetidine reducing the clearance and volume of distribution of lidocaine. The myocardial depressant effect of lidocaine is enhanced by phenytoin administration. 

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. 

Beta-blockers interact with a large number of other medications. The combination of beta-blockers with calcium antagonists should be avoided, given the risk for hypotension and cardiac arrhythmias. Cimetidine, hydralazine, and alcohol all increase blood levels of beta-blockers, whereas rifampicin decreases their concentrations. Beta-blockers may increase blood levels of phenothiazines and other neuroleptics, clonidine, phen-ytoin, anesthetics, lidocaine, epinephrine, monoamine oxidase inhibitors and other antidepressants, benzodiazepines, and thyroxine. Beta-blockers decrease the effects of insulin and oral hypoglycemic agents. Smoking, oral contraceptives, carbamazepine, and nonsteroidal anti-inflammatory analgesics decrease the effects of beta-blockers (Coffey, 1990). 

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. 

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. 

Drugs metabolized by CYP that interact with cimetidine include, but are not limited to, the following lidocaine, quinidine, midazolam, triazolam, nifedipine, verapamil, and fentanyl (4). In each instance, inhibition of CYP by cimetidine results in reduced metabolic clearance and increases in serum concentrations of the other drug, which can lead to the expected toxicity and adverse experiences characteristic of the other drug. 

LIDOCAINE H2 RECEPTOR BLOCKERS -CIMETIDINE, RANITIDINE t efficacy and adverse effects of local anaesthetic, e.g. lightheadedness, paraesthesia Unknown for most local anaesthetics. Lidocaine t bioavailability Uncertain. Monitor more closely. No toxicity reported to date with bupiva-caine. If using intravenous lidocaine, monitor closely for symptoms of toxicity 1 dose may be required... 

Pharmacokinetic. Agents metabolised in the liver provide higher plasma concentrations when another drug that inhibits hepatic metabolism, e.g. cimetidine, is added. Enzyme inducers enhance the metabolism of this class of P-blockers. P-adrenoceptor blockers themselves reduce hepatic blood flow (fall in cardiac output) and reduce the metabolism of p-blockers and other drugs whose metabolic elimination is dependent on the rate of delivery to the liver, e.g. lignocaine (lidocaine), chlorpromazine. 

The many drug interactions described with cimetidine are largely attributable to inhibition of CYP isozymes or renal clearance of other drugs. Cimetidine also reduces hepatic blood flow and so can, for example, reduce the clearance of lidocaine. In the kidneys cimetidine interferes with the tubular excretion of procainamide and quinidine. Both effects are small, and the long list of drugs for which interference is demonstrable (Table 1) is out of all proportion to the number for which interference is of chnical significance. 

Berk SI, Gal P, Bauman JL, Douglas JB, McCue JD, Powell JR. The effect of oral cimetidine on total and unbound serum lidocaine concentrations in patients with suspected myocardial infarction. Int J Cardiol 1987 14 (l) 91-4. 

Cimetidine inhibits the metabolism of lidocaine (76,77) and reduces protein binding, increasing toxicity. 

Kowalsky SF. Lidocaine interaction with cimetidine and ranitidine a critical analysis of the literature. Adv Ther I988 5 229-44. 

Clinically important, potentially hazardous interactions with alcohol, amiodarone, beta-blockers, cimetidine, donidine, digoxin, diltiazem, disopyramide, ephedrine, epinephrine, ergot alkaloids, guanethidine, halothane, isoprenaline, lidocaine, noradrenaline, NSAIDs, phenylephrine, quinidine, reserpine, verapamil... 

Also analyzed acebutolol, acepromazine, acetaminophen, acetazolamide, acetophenazine, albuterol, amitriptyline, amobarbital, amoxapine, antipsrrine, atenolol, atropine, azata-dine, baclofen, benzocaine, bromocriptine, brompheniramine, brotizolam, bupivacaine, buspirone, butabarbital, butalbital, caffeine, carbamazepine, cetirizine, chlorqyclizine, chlordiazepoxide, chlormezanone, chloroquine, chlorpheniramine, chlorpromazine, chlorpropamide, chlorprothixene, chlorthalidone, chlorzoxazone, cimetidine, cisapride, clomipramine, clonazepam, clonidine, clozapine, cocaine, codeine, colchicine, qyclizine, (yclo-benzaprine, dantrolene, desipramine, diazepam, diclofenac, diflunisal, diltiazem, diphenhydramine, diphenidol, dipheno late, dipyridamole, disopyramide, dobutamine, doxapram, doxepin, droperidol, encainide, ethidium bromide, ethopropazine, fenoprofen, fentanyl, flavoxate, fluoxetine, fluphenazine, flurazepam, flurbiprofen, fluvoxamine, fii-rosemide, glutethimide, glyburide, guaifenesin, haloperidol, homatropine, hydralazine, hydrochlorothiazide, hydrocodone, hydromorphone, hydro g chloroquine, hydroxyzine, ibuprofen, imipramine, indomethacin, ketoconazole, ketoprofen, ketorolac, labetalol, le-vorphanol, lidocaine, loratadine, lorazepam, lovastatin, loxapine, mazindol, mefenamic acid, meperidine, mephenytoin, mepivacaine, mesoridazine, metaproterenol, methadone, methdilazine, methocarbamol, methotrexate, methotrimeprazine, methoxamine, methyl-dopa, methylphenidate, metoclopramide, metolazone, metoprolol, metronidazole, midazolam, moclobemide, morphine, nadolol, nalbuphine, naloxone, naphazoline, naproxen, nifedipine, nizatidine, norepinephrine, nortriptyline, oxazepam, oxycodone, oxymetazo-line, paroxetine, pemoline, pentazocine, pentobarbital, pentoxifylline, perphenazine, pheniramine, phenobarbital, phenol, phenolphthalein, phentolamine, phenylbutazone, phenyltoloxamine, phenytoin, pimozide, pindolol, piroxicam, pramoxine, prazepam, prazosin, probenecid, procainamide, procaine, prochlorperazine, procyclidine, promazine, promethazine, propafenone, propantheline, propiomazine, propofol, propranolol, protriptyline, quazepam, quinidine, quinine, racemethorphan, ranitidine, remoxipride, risperidone, salicylic acid, scopolamine, secobarbital, sertraline, sotalol, spironolactone, sulfinpyrazone, sulindac, temazepam, terbutaline, terfenadine, tetracaine, theophylline, thiethyl-perazine, thiopental, thioridazine, thiothixene, timolol, tocainide, tolbutamide, tolmetin, trazodone, triamterene, triazolam, trifluoperazine, triflupromazine, trimeprazine, trimethoprim, trimipramine, verapamil, warfarin, xylometazoline, yohimbine, zopiclone... 

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