Metoprolol Cimetidine

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. 

Drugs that affect all phosphodiesterase type 5 inhibitors include the following alcohol, amlodipine, angiotensin II receptor blockers, antacids, bendroflumethiazide, beta blockers, cimetidine, diuretics, enalaphl, metoprolol, nifedipine, rifampin, tacrolimus. 

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. 

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. 

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. 

Figure 6.3 Plot of the fraction of dose absorbed (in %) of various drugs as a function of the permeability estimates in the Caco-2 system. Key 1 D-glucose 2 verapamil 3 piroxicam 4 phenylalanine 5 cyclosporin 6 enalapril 7 cephalexim 8 losartan 9 lisinopril 10 amoxicillin 11 methyldopa 12 naproxen 13 an-tipyrine 14 desipramine 15 propanolol 16 amiloride 17 metoprolol 18 terbu-taline 19 mannitol 20 cimetidine 21 ranitidine 22 enalaprilate 23 atenolol 24 hydrochlorothiazide.

Figure 6.17 The classification of 42 drugs in the (solubility-dose ratio, apparent permeability) plane of the QBCS. The intersection of the dashed lines drawn at the cutoff points form the region of the borderline drugs. Key 1 acetyl salicylic acid 2 atenolol 3 caffeine 4 carbamazepine 5 chlorpheniramine 6 chlorothiazide 7 cimetidine 8 clonidine 9 corticosterone 10 desipramine 11 dexamethasone 12 diazepam 13 digoxin 14 diltiazem 15 disopyramide 16 furosemide 17 gancidovir 18 glycine 19 grizeofulvin 20 hydrochlorothiazide 21 hydrocortisone 22 ibuprofen 23 indomethacine 24 ketoprofen 25 mannitol 26 metoprolol 27 naproxen 28 panadiplon 29 phenytoin 30 piroxicam 31 propanolol 32 quinidine 33 ranitidine 34 salicylic acid 35 saquinavir 36 scopolamine 37 sulfasalazine 38 sulpiride 39 testosterone 40 theophylline 41 verapamil HC1 42 zidovudine.

BETA-BLOCKERS CIMETIDINE, RANITIDINE t plasma concentrations and effects of labetalol, metoprolol and propranolol t systemic effects of timolol eye drops Cimetidine inhibits CYP2D6, which metabolizes these beta-blockers, and inhibits CYP1A2- and CYP2E1 -mediated metabolism of propanolol. Ranitidine is a weaker inhibitor of CYP2D6 Monitor BP at least weekly until stable... 

Enzyme inhibition. Ciprofloxacin and cimetidine inhibit hepatic metabolism of lipid-soluble J-adrenoceptor blockers, e.g. metoprolol, labetalol, propranolol, increasing their effect. Methyldopa plus an MAO inhibitor may cause excitement and hallucinations. 

Kirch W, Kohler H, Spahn H, Mutschler E. Interaction of cimetidine with metoprolol, propranolol, or atenolol. Lancet 1981 2(8245) 531-2. 

Houtzagers JJ, Streurman O, Regardh CG. The effect of pretreatment with cimetidine on the bioavailability and disposition of atenolol and metoprolol. Br J Clin Pharmacol 1982 14(l) 67-72. 

Chellingsworth MC, Laugher S, Akhlaghi S, Jack DB, Kendall MJ. The effects of ranitidine and cimetidine on the pharmacokinetics and pharmacodynamics of metoprolol. Aliment Pharmacol Ther 1988 2(6) 521-7. 

Cimetidine (but not ranitidine) or rifampin reduces the plasmic level of tocainide, whereas metoprolol has added effects with tocainide on wedge pressure and cardiac index. 

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... 

Also analj ed acebutolol, alprenolol, antazoline, betaxolol, bisoprolol, bopindolol, bupran-olol, carteolol, celiprolol, chloropyramine, chlorpheniramine, cicloprolol, cimetidine, cin-narizine, cirazoline, clonidine, dilevalol, dimethindene, diphenhydramine, doxazosin, es-molol, famotidine, isothipendyl, ketotifen, metiamide, metoprolol, moxonidine, nadolol, naphazoline, nifenalol, nizatidine, oxprenolol, pheniramine, phentolamine, pindolol, pi-zotyline (pizotifen), practolol, prazosin, promethazine, propranolol, pyrilamine (mepyra-mine), ranitidine, roxatidine, sotalol, tiamenidine, timolol, tramazoline, tripelennamine, triprolidine, tymazoline, UK-14,304... 

Noninterfering acetaminophen, amiloride, aspirin, atenolol, chlorothiazide, cimetidine, cyclopenthiazide, diazepam, furosemide, indapamide, labetalol, lorazepam, metoprolol, phenytoin, propranolol, ranitidine, salicylic acid, theophylline... 

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