Haloperidol liver

The antipsychotics are contraindicated in patients with known hypersensitivity to the drug s, in comatose patients, and in those who are severely depressed, have bone marrow depression, blood dysera ias, Parkinson s disease (haloperidol), liver impairment, coronary artery disease, or severe hypotension or hypertension. 

Many antipsychotics show great interindividual variation in plasma levels and so analysis of therapeutic levels can be important clinically as well as in the research laboratory. In addition, nonresponse to the drugs may actually be due to excessive levels of neuroleptics, a paradoxical situation that requires analysis to identify (Rockland, 1986). Several methods using FID were cited in the previous edition of the Handbook of Neurochemistry but ECD and NPD have both shown utility for the typically low therapeutic levels (Cooper, 1988). GC-FID has been used to analyze levels of clozapine in blood, gastric, and urine samples in fatal cases of overdose with this drug (Ferslew et al., 1998), and olanzapine has been measured in blood and urine samples by GC-NPD in overdoses (Stephens et al., 1998). 4-(4-Chlorophenyl)-4-hydroxypiperidine, a metabolite of haloperidol, was analyzed in urine, plasma, brain, and liver from haloperidol-treated rats by GC-ECD, after derivatization with PFBC under aqueous conditions (Fang et al., 1996). 

Antiadrenergic] Uses HTN Action Centrally acting antihypCTtensive Dose Adults. 250-500 mg PO bid-tid (max 2-3 g/d) or 250 mg-1 g IV q6-8h Peds. 10 mg/kg/24 h PO in 2-3 doses (max 40 mg/kg/24 h q6-12h) or 5-10 mg/kg/dose IV q6-8h to total dose of 20 0 mg/kg/24 h X in renal insuff/elderly Caution [B (PO), C (IV), +] Contra Liver Dz MAOIs Disp Tabs, inj SE Discolors urine initial transient sedation/drowsiness frequent, edema, hemolytic anemia, hepatic disorders Interactions T Effects W/ anesthetics, diuretics, levodopa, Li, methotrimeprazine, thioxanthenes, vasodilators, verapamil T effects OF haloperidol, Li, tolbutamide effects W/amphetamines, Fe, phenothiazine, TCAs ... 

The majority of cases reported in the literature have occurred with CPZ and rarely with other agents such as promazine, thioridazine, mepazine, prochlorperazine, fluphenazine, and triflupromazine. There is no convincing evidence that haloperidol or other nonphenothiazine agents produce this type of jaundice. It is occasionally useful to obtain baseline liver function tests on patients with increased susceptibility (e.g., prior history of hepatitis) in the unlikely event that jaundice may develop. Routine serial liver function tests have never proven useful or necessary. The offending drug should be discontinued if a patient develops jaundice, but the value of this practice is also unproven, because many patients have been maintained on CPZ throughout an episode of jaundice without adverse consequences ( 509). 

The neuroleptics show variable absorption after oral administration. These agents readily pass into the brain, have a large volume of distribution, bind well to plasma proteins, and are metabolized to many different substances by the P-450 system in the liver. Fluphenazine decanoate and haloperidol decanoate are slow release (up to 3 weeks) formulations of neuroleptics, administered by intramuscular injection. These drugs are increasingly used in treating outpatients and individuals who are noncompliant. However, about 30% of these patients develop extrapyramidal symptoms. The neuroleptic drugs produce some tolerance but little physical dependence. 

Inaba T, Kovacs J (1989) Haloperidol reductase in human and guinea pig livers. Drug Metab Dispos 17 330-333 Lewis AJ, Otake Y, Wafie UK, Walle T (2000) Sulphona-tion of N-hydroxy-2-acetylaminofluorene by human dehydroepiandrosterone sulphotransferase. Xenobiotica 30 253-261... 

A 41-year-old woman, with liver lacerations, rib fractures, and pneumothorax after a motor vehicle accident, was given haloperidol for agitation on day 7. During the first 24 hours she received a cumulative intravenous dose of 15 mg, 70 mg on day 2, 190 mg on day 3,160 mg on days 4 and 5, and 320 mg on day 6. An hour after the first dose of 80 mg on day 7, she had ventricular extra beats followed by 5-beat and 22-beat runs of ventricular tachycardia. The rhythm strips were consistent with polymorphous ventricular tachycardia or torsade de pointes and the QTC interval was 610 ms (normally under 450 in women). She received intravenous magnesium sulfate 2 g. Concurrent medications included enoxaparin, famotidine, magnesium hydroxide, ampicillin/sulbactam, nystatin suspension, midazolam, and 0.45% saline with 20 mmol/1 of potassium chloride. She had no further dysrhythmias after haloperidol was withdrawn. Eight days after the episode of torsade de pointes she had a QTC interval of 426 ms. 

Dincsoy HP, Saelinger DA. Haloperidol-induced chronic cholestatic liver disease. Gastroenterology 1982 83(3) 694-700. 

When treating alcoholic liver diseases, it should be taken into account that one is generally dealing with chronic alcoholics. Therefore, one should be aware of the fact that a withrawal syndrome might occur, possibly requiring the application of clomethiazole, haloperidol or clonidine. In this complicated phase, the administration of zinc is likewise recommended. (138)... 

Flaloperidol is well absorbed orally with a bioavailability of 60-65% due to first-pass hepatic metabolism. It has a reversible oxidation/reduction metabolic pathway it is metabolized via reduction to reduced haloperidol, which is biologically inactive. Both agents are rapidly absorbed after intramuscular injection, peaking within 10 min. Butyrophenones are metabolized in the liver to inactive metabolites. Concentrations of butyrophenones are found in the liver, central nervous system, and throughout the body. Flaloperidol is 92% protein bound. Haloperidol is 15% eliminated through the bile. The elimination half-life is 14-41 h. The half-life of droperidol is 2 h 10% is recovered unchanged in the urine. 

Usuki, E. Pearce, R. Parkinson, A. and Castagnoli, N., Jr. "Studies on the Conversion of Haloperidol and its Tetrahydrophyridine Dehydration Product to Potentially Neurotoxic Pyridinium Metabolites by Human Liver Microsomes." Manuscript submitted for publication. 

K41.1 (ergl) KCNH2 7q35-36 minK, MiRPl Brain, heart, kidney, liver, lung, ovary, pancreas, testis, prostate, uterus, small intestine Astemizole, BeKM-1, ergtoxin, sertindole, dofetilide, cisapride, pimozide, terfenadine, halofantrine, BRL32872, E-4031, CT haloperidol, imipramine, cocaine, ketoconazole None... 

Haloperidol is absorbed well orally and intramuscularly (haloperidol decanoate), distributed widely in the body while accumulating in adipose tissue, binds to protein heavily (90 to 99%), and is metabolized in the liver. Haloperidol is eliminated unchanged in the feces and urine to the extent of 15 and 40%, respectively. 

Fluvoxamine inhibits liver drug-metabolizing enzymes. Dosages of alprazolam, theophylline, and warfarin must be reduced if any of these drugs are given concomitantly with fluvoxamine. Nefazodone may also decrease the metabolism of benzodiazepines, and venlafaxine may inhibit haloperidol metabolism. The answer is (B). 

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