Lidocaine Erythromycin

Codeine, dextromethorphan, haloperidol, thioridazine, perphenazine, nortriptyline, desipramine, fluoxetine, norfluoxetine, TCAs (hydroxylation), beta-blockers such as timolol and metoprolol, type 1C antiarrhythmics encainide, flecainide TCAs (desmethylation), triazolam, alprazolam, midazolam, carbamazepine, terfenadine, quinidine, lidocaine, erythromycin, cyclosporin... 

The enzyme is the principal participant in N-demethylation reactions where the substrate is a tertiary amine. The list of substrates includes erythromycin, ethylmor-phine, lidocaine, diltiazem, tamoxifen, toremifene, verapamil, cocaine, amiodarone, alfentanil and terfenadine. Carbon atoms in the allylic and benzylic positions, such as those present in quinidine, steroids and cyclosporin A, are also particularly prone to oxidation by CYP3A4, a range of substrates is illustrated in Figure 7.10. 

Lopinavir/Ritonavir (Kaletra) [Anrirelroviral/Protease Inhibitor] Uses HIV Infxn Action Protease inhibitor Dose Adults. Tx naive 2 tab PO daily or 1 tab PO bid Tx experiencedpt 1 tab PO bid (T dose if w/ amprenavir, efavirenz, fosamprenavir, nelfinavir, nevirapine) Peds. 7-15 kg 12/3 mg/kg PO bid 15-40 kg 10/2.5 mg/kg PO bid >40 kg Adult dose w/ food Caution [C, /-] Numerous interactions Contra w/drugs dependent on CYP3A/CYP2D6 (Table VI-8) Disp Tab, soln SE Avoid disulfiram (soln has EtOH), metronidazole GI upset, asthenia, T cholesterol/triglycerides, pancreatitis protease metabolic synd Interactions T Effects Wl clarithromycin, erythromycin T effects OF amiodarone, amprenavir, azole andfungals, bepridil, cisapride, cyclosporine, CCBs, ergot alkaloids, flecainide, flurazepam, HMG-CoA reductase inhibitors, indinavir, lidocaine, meperidine, midazolam, pimozide, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, tacrolimus, terfenadine, triazolam, zolpidem 1 effects Wl barbiturates, carbamazepine, dexamethasone, didanosine, efavirenz, nevirapine, phenytoin, rifabutin, rifampin, St. John s wort 1 effects OF OCPs, warfarin EMS Use andarrhythmics and benzodiazepines... 

A4 Acetaminophen, alfentanil, amiodarone, astemizole, cocaine, cortisol, cyclosporine, dapsone, diazepam, dihydroergotamine, dihydropyridines, diltiazem, ethinyl estradiol, gestodene, indinavir, lidocaine, lovastatin, macrolides, methadone, miconazole, midazolam, mifepristone (RU 486), paclitaxel, progesterone, quinidine, rapamycin, ritonavir, saquinavir, spironolactone, sulfamethoxazole, sufentanil, tacrolimus, tamoxifen, terfenadine, testosterone, tetrahydro-cannabinol, triazolam, troleandomycin, verapamil Barbiturates, carbamazepine, macrolides, glucocorticoids, pioglitazone, phenytoin, rifampin Erythromycin, 613-hydroxy cortisol... 

Cyt 3A3/4 metabolizes clozapine, sertindole, quetiapine common substrates -tricyclic antidepressants, nefazodone, sertraline, carbamazepine, ethosuximide, terfenadine, benzodiazepines, diltiazem, nifedipine, verapamil, erythromycin, cyclosporine, lidocaine, quinidine, cisapride, paracetamol. Common inhibitors -nefazodone, fluvoxamine, fluoxetine, ketoconazole. 

The most used and validated probe drugs for C YP3 A phenotyping are midazolam and 14C-erythromycin (Watkins 1994). Alfentanyl, alprazolam, dapsone, dextromethorphan, lidocaine. nifedipine, omeprazole, quinine, verapamil have also been used but less frequently, and CYP3A specificity for some of them has been questioned. The endogenous 6(->-hydroxycortisol test (measurement of 6 3-hydroxycortisol cortisol ratio in urine) is only useful for detecting CYP3A induction, and may be influenced by renal CYP3 A activity. 

Erythromycin can increase the plasma concentration and toxicity of oral lidocaine, as shown in a crossover study in nine volunteers who took erythromycin orally (500 mg tds) for 4 days and 1 mg/kg of oral lidocaine on day 4 (77). 

The effects of erythromycin, an inhibitor of CYP3A4, on the pharmacokinetics of lidocaine have been studied in nine healthy volunteers. Steady-state oral erythromycin had no effect on the plasma concentration versus time curve of lidocaine after intravenous administration, but erythromycin increased the plasma concentrations of the major metabolite of lidocaine, MEGX (78). It is not clear what the interpretation of these results is, particularly since the authors did not study enough subjects to detect what might have been small but significant changes in various disposition parameters of lidocaine and did not report unbound concentrations of Udocaine or its metabolites. However, whatever the pharmacokinetic explanation, the clinical relevance is that one would expect that erythromycin would potentiate the toxic effects of lidocaine that are mediated by MEGX. 

Additionally, sodium bicarbonate is used in solutions as a buffering agent for erythromycin, lidocaine, local anesthetic solutions, and total parenteral nutrition (TPN) solutions. In some parenteral formulations, e.g., niacin, sodium bicarbonate is used to produce a sodium salt of the active ingredient that has enhanced solubility. Sodium bicarbonate has also been used as a freeze-drying stabilizer and in toothpastes. 

Rimback G, Cassuto J, Tollesson P O 1990 Treatment of postoperative paralytic ileus by intravenous lidocaine infusion. Anesthesia and Analgesia 70 414-419 Ringger N C, Lester G D, Neuwirth L et al 1996 Effect of bethanechol or erythromycin on gastric emptying in horses. American Journal of Veterinary Research 57 1771-1775... 

Benzodiazepines alprazolam, clonazepam, diazepam, midazolam, triazolam, zolpidem Calcium channel blockers diltiazem, nifedipine, nimodipine, verapamil Steroids androgens, estrogens, cortisol Others erythromycin, terfenadine, cyclosporine, dapsone, ketoconazole, lovastatin, lidocaine, alfentanil, amiodarone, astemizole, codeine, sildenafil... 

CYP3A4 Alfentanil Alprazolam Astern izole Carbamazepine Cisapride Cyclosporine Diltiazem Erythromycin Felodipine Fluconazole Itraconazole Ketoconazole Lidocaine Lova statin Midazolam Nifedipine Quinidine Simvastatin Tacrolimus Terfenadine Verapamil... 

Alprazolam (C4-hydroxylation), lidocaine (JV-deethylation), erythromycin (N-demethylation), midazolam (Cl -hydroxylation), testosterone (C6j3-hydroxylation)... 

EMLA - local anaesthetic combination of lidocaine and prilocaine Entacapone - catechol-o-methyl transferase inhibitor Parkinson s disease Enoxaparin - low molecular weight heparin thrombosis prophylaxis prior to surgery Epoetin - erythropoietin replacement anaemia Erythromycin - antibiotic... 

Noninterfering acebutolol, acetaminophen, acetazolamide, alprenolol, apraclonidine, atenolol, atropine, betamethasone, betaxolol, bupivacaine, caffeine, Q clopentolate, dexa-methasone, diphenhydramine, erythromycin, haloperidol, lidocaine, phenylephrine, polymyxin B, procaine, scopolamine, timolol, tropicamide... 

Simultaneous amitriptyline, clomipramine, disopyramide, erythromycin estolate, erythromycin ethylsuccinate, erythromycin stearate, imipramine, josamycin, lidocaine, spiramycin... 

Noninterfering amitriptyline, amphetamine, atropine, benzoylecgonine, benztropine, caffeine, carbamazepine, carisoprodol, chlorpheniramine, chlorpromazine, chlorprothixene, cimetidine, cocaine, codeine, dextromethorphan, diazepam, diphenhydramine, diphenox-ilate, disopyramide, doxepin, dojylamine, emetine, erythromycin, flurazepam, gluteth-imide, hydrocortisone, hydromorphone, hydroxyzine, imipramine, lidocaine, loxapine, meperidine, meprobamate, methadone, methamphetamine, methapyrilene, methaqualone, methocarbamol, methylphenidate, nicotine, nordiazepam, nortriptyline, orphenadrine, papaverine, pentazocine, phenacetin, phencyclidine, phenmetrazine, phenolphthalein, phentermine, phenylpropanolamine, phenytoin, prazepam, procaineimide, procaine, propoxyphene, propranolol, protriptyline, pseudoephediine, pyrilamine, quinine, salicylam-ide, spironolactone, strychnine, terpin hydrate, thioridazine, thiothixene, triamterene, trifluoperazine, triflupromeizine, trihexyphenidyl, trimeprazine, trimethobenzamide, trimethoprim, tripeleimamine... 

CYP3A4 alprazolam, calcium channel blockers, cisapride, clarithromycin, cyclosporin A, erythromycin, HIV protease inhibitors, lidocaine, midazolam, simvastatin, terfenadine carbamazepine, dexamethsone, phenobarbital, phenytoin, rifampicin, St John s wort cimetidine, erythromycin, grapefruit juice, HIV protease inhibitors, itraconazole, ketoconazole... 

The performed experiments indicate that ascorbic acid, procainamide, digoxine, streptomycin, tetracyclin, erythromycin, lidocain, valium, quinidin and lactate do not influence the determination of potassium, sodium, calcium and chloride in serum in the conditions existing in the KONE Microlyte analyzer. A positive error in chloride determination is observed when the dose of aspirine strongly exceeds the therapeutical dose. 

Svirbely, J.E. Pesce, A.J. Himethoprim analysis by LC. J.Lig.Chromatogr., 1988,11,1075—1085 [LOD 50 ng/mL serum plasma dialysate urine CSF SPE interfering atenolol, procainamide, oxazepam non-interfering acetaminophen, amitriptyline, ampicillin, caffeine, cefitoxin, chlordiazepoxide, chlorpheniramine, chlorpromazine, cimetidine, clonidine, desipramine, diazepam, digoxin, diphenhydramine, doxepin, doi lamine, erythromycin, flurazepam, imipramine, lidocaine, minoxidil, nadolol, nortriptyline, prazosin, propranolol, quinidine, theophylline, thioridazine]... 

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