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  Haloperidol   Brand name: Haldol Drug monograph Contents  Pharmacology   Indications   Contraindications   Warnings   Precautions   Adverse Effects   Overdose   Dosage   Supplied   Research  Pharmacology  Antipsychotic Haloperidol is a butyropherone derivative with antipsychotic properties that has been considered particularly effective in the management of hyperactivity, agitation, and mania. Haloperidol is an effective neuroleptic and also possesses antiemetic properties; it has a marked tendency to provoke extrapyramidal effects and has relatively weak alpha-adrenolytic properties. It may also exhibit hypothermic and anorexiant effects and  potentiate the action of barbiturates, general anesthetics, and other CNS depressant drugs.1  The mechanism of action of haloperidol has not been entirely elucidated, but has been attributed to the inhibition of the transport mechanism of cerebral monoamines,  particularly by blocking the impulse transmission in dopaminergic neurons. Peak plasma levels of haloperidol occur within 2 to 6 hours of oral dosing and about 20 minutes after i.m. administration. The mean plasma (terminal elimination) half-life has  been determined as 20.7+/-4.6 (SD) hours, and although excretion begins rapidly, only 24to 60% of ingested radioactive drug is excreted (mainly as metabolites in urine, some in feces) by the end of the first week, and very small but detectable levels of radioactivity  persist in the blood and are excreted for several weeks after dosing. About 1% of the ingested dose is recovered unchanged in the urine. to top Indications Haloperidol is indicated in the management of manifestations of acute and chronic  psychosis, including schizophrenia and manic states. It may also be of value in the management of aggressive and agitated behavior in patients with chronic brain syndrome and mental retardation and in the symptomatic control of Gilles de la Tourette's syndrome. to top Contraindications Comatose states and CNS depression due to alcohol or other depressant drugs; severe depressive states; previous spastic diseases; lesions of the basal ganglia; Parkinson's syndrome, except in the case of dyskinesias due to levodopa treatment; sensitivity to haloperidol; senile patients with pre-existing Parkinson-like symptoms. 2  Children: Safety and effectiveness in young children have not been established; therefore, haloperidol is contraindicated in this age group. Pregnancy and Lactation: Safety for use in pregnancy and lactation has not been established; do not administer to women of childbearing potential or nursing mothers unless, in the opinion of the  physician, the expected benefits of the drug outweigh the potential hazard to the fetus or child. Haloperidol is excreted in breast milk. to top Warnings Tardive Dyskinesia: Tardive dyskinesia is known to occur in patients treated with neuroleptics with antipsychotic properties and other drugs with substantial neuroleptic activity. Although the dyskinetic syndrome may remit partially or completely if the medication is withdrawn, it is irreversible in some patients. At the present time there is uncertainty as towhether neuroleptic drugs differ in their potential to cause tardive dyskinesia. Since there is a significant prevalence in this syndrome associated with the use of neuroleptic drugs, and since there is no known effective treatment, chronic use of these drugs should generally be restricted to patients for whom neuroleptics are known to be effective and for whom there is no alternative therapy available with better risk acceptability. If manifestations of tardive dyskinesia are detected during the use of a neuroleptic, the drug should be discontinued. The risk of a patient developing tardive dyskinesia and of the syndrome becoming irreversible appear to increase with the duration of treatment and the total amount of drugs administered, although, in some instances, tardive dyskinesia may develop after relatively short periods of treatment at low doses. The risk of developing tardive 3  dyskinesia may, therefore, be minimized by reducing the dose of the neuroleptic drug used and its duration of administration, consistent with the effective management of the  patient's condition. Continued use of neuroleptics should be periodically reassessed. Withdrawal Emergent Neurological Signs: Generally, patients receiving short-term therapy experience no problems with abrupt discontinuation of antipsychotic drugs. However, some patients on maintenance treatmentexperience transient dyskinetic signs after abrupt withdrawal. In certain of these cases thedyskinetic movements are indistinguishable from the syndrome described under Tardive Dyskinesia except for duration. It is not known whether gradual withdrawal of antipsychotic drugs will reduce the rate of occurrence of withdrawal emergent neurological signs but until further evidence becomes available it seems reasonable to gradually withdraw use of antipsychotic drugs. An encephalopathic syndrome (characterized by weakness, lethargy, fever, tremulousnessand confusion, extrapyramidal symptoms, leukocytosis, elevated serum enzymes, BUN and FBS, followed by irreversible brain damage) has occurred in a few patients treated with lithium plus haloperidol. A causal relationship between these events and the concomitant administration of lithium and haloperidol has not been established; however, patients receiving such combined therapy should be monitored closely for early evidence of neurological toxicity and treatment discontinued promptly if such signs appear. Elderly or debilitated patients receiving the drug should be carefully observed for lethargy and a decreased sensation of thirst due to central inhibition which might lead to dehydration and reduced pulmonary ventilation and could result in complications, such asterminal bronchopneumonia. Occupational Hazards: Although haloperidol is a relatively nonsedating neuroleptic, sedation may occur in some  patients. Therefore, physicians should be aware of this possibility and caution patients about the danger of participating in activities requiring complete mental alertness, 4
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