Diazepam Cimetidine

Noninterfering acetaminophen, cimetidine, diazepam, digoxin, ibuprofen, phen3dx>in, propranolol, salicyhc acid, warfarin... 

Noninterfering acetaminophen, caffeine, cimetidine, diazepam, diltiazem, doxepin, flur-azepam, nifedipine, procainamide, quinidine, theophylline, verapamil... 

Noninterfering brompheniramine, chlorpheniramine, cimetidine, diazepam, diclofenac, glyhuride, ihuprofen, ketoprofen, metoclopramide, naproxen, phenylbutazone, verapamil... 

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 valproic acid include carbamazepine, charcoal, chlorpromazine, cholestyramine, cimetidine, erythromycin, ethosuximide, felbamate, lamotrigine, phenytoin, rifampin, and salicylates. Drugs that may be affected by valproic acid include carbamazepine, clonazepam, diazepam, ethosuximide, lamotrigine, phenobarbital, phenytoin, tolbutamide, tricyclic antidepressants, warfarin, and zidovudine. 

Diazepam (Valium, Diastat) [C-IVj [Anxiolytic, Skeletal Muscle Relaxant, Anticonvulsant, Sedative/Hypnotic/ Benzodiazepine] Uses Anxiety, EtOH withdrawal, muscle spasm, status epilepticus, panic disorders, amnesia, preprocedure sedation Action Benzodiazepine Dose Adults. Status epilepticus 5-10 mg IV/IM Anxiety 2-5 mg IM/IV Preprocedure 5-10 mg IV just prior to procedure Peds. Status epilepticus 0.5-2 mg IV/IM Sedation 0.2-0.5 mg/kg IV (onset w/in 5IV and 30 min IM duration about 1 h IV and IM) Caution [D, / -] Contra Coma, CNS depression, resp d es-sion, NAG, severe uncontrolled pain, PRG Disp Tabs 2, 5, 10 mg soln 1, 5 mg/mL inj 5 mg/mL rectal gel 2.5, 5, 10, 20 mg/mL SE Sedation, amnesia, bradycardia, i BP, rash, X resp rate Interactions T Effects W/ antihistamines, azole antifungals, BBs, CNS depressants, cimetidine, ciprofloxin, disulfiram, INH, OCP, omeprazole, phenytoin, valproic acid, verapamil, EtOH, kava kava, valman T effects OF digoxin, diuretics X effects w/ barbiturates, carbamazepine. 

Cimetidine slows the metabolism of BZs. This slowing causes clinically significant increases in cognitive impairment when coadministerd with midazolam (Chouinard et ah, 1999). Cimetidine increases the levels of diazepam and its metabolite, but no pharmacodynamic effects have been demonstrated (Greenblatt et ah, 1984). 

With the important exception of additive effects when combined with other CNS depressants, including alcohol, BZDs interact with very few drugs. Disulfiram (see the section The Alcoholic Patient in Chapter 14) and cimetidine may increase BZD blood levels, and diazepam may increase blood levels of digoxin and phenytoin. Antacids may reduce the clinical effects of clorazepate by hindering its biotransformation to desmethyidiazepam. Coadministration of a BZD and another drug known to induce seizures may possibly increase seizure risk, especially if the BZD is abruptly withdrawn. Furthermore, as noted earlier, important interactions have been reported among nefazodone, erythromycin, troleandomycin, and other macrolide antibiotics, as well as itraconazole. In each case, metabolism is inhibited, and triazolam levels can increase significantly. 

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. 

Other medications that can slow down the metabolism of the liver, thereby causing a person to get a higher dose of methadone than they normally would, include Cimetidine, commonly used for upset stomachs, diazepam, a commonly used anti-anxiety medication, and fluvoxamine, a recently introduced antidepressant medication. Interestingly, alcohol, when used only occasionally, increases methadone levels as compared to decreasing methadone levels when it is used and abused on a chronic basis. 

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.

In a fatality due to the ingestion of cimetidine and diazepam, postmortem blood concentrations of llOpg/ml of cimetidine and 5.8iig/ml of diazepam were reported (J. Hiss et al. Lancet, 1982,2,982). 

Cimetidine may reduce the clearance and raise the levels of diazepam... 

Adverse effects include nausea, headache, diarrhoea, constipation and rash but are uncommon. Omeprazole inhibits the 2C family of the cytochrome P450 system, decreasing the metabolism of warfarin, diazepam, carbamazepine and phenytoin, and enhancing the action of these drugs (but inhibition is less than with cimetidine). 

Cimetidine. Since cimetidine may inhibit certain metabolic pathways, an increased action of concurrently administered drugs that are metabolized via these pathways should be anticipated. For example, cimetidine may inhibit the metabolism of diazepam and certain other benzodiazepines, and the sedative effect of these agents may be enhanced as a result of the interaction. Particular caution is necessary in older patients who may exhibit an increased sensitivity to the depressant... 

Cimetidine Carbamazepine Clobazam Clonazepam Diazepam Phenytoin Valproate Risk of toxicity, particularly with phenytoin Inhibition of metabolism of the object drugs... 

Divoll M, Greenblatt DJ, Abernethy DR, Shader RI. Cimetidine impairs clearance of antipyrine and desmethyl-diazepam in the elderly J Am Geriatr Soc 1982 30(11) 684-9. 

Greenblatt DJ, Abernethy DR, Morse DS, Harmatz JS, Shader RI. Clinical importance of the interaction of diazepam and cimetidine. N Engl J Med 1984 310(25) 1639-43. 

---