Intramuscular injection haloperidol

Intramuscular injection Haloperidol, ziprasidone, olanzapine Maximum blood levels achieved in a short period of time... 

The medication of choice was for many years haloperidol (Haldol), a high potency antipsychotic, that can be given orally or by injection. When used, haloperidol should be administered in low doses (0.5-1.0mg) and only on an as-needed basis. Due to concerns regarding the tolerability of haloperidol in patients with dementia, its role in the management of agitation associated with delirium has largely been supplanted by atypical antipsychotics. A number of atypical antipsy-chotics are available by either an oral or intramuscular (injection) route of administiation. 

Intramuscular haloperidol is a suitable drug for tranquillizing violent patients, but it can be difficult to determine the correct dosage, and there is the risk of an acute dystonic reaction, particularly in younger patients. The British National Formulary recommends intramuscular injections of from 2 to 10 mg, subsequent doses being given after 4-8 hours but in exceptional cases, initial doses of up to 30 mg may be necessary. 

Patients in whom haloperidol is contraindicated can be treated by intramuscular injection of benzodiazepines, but these can cause respiratory depression or respiratory arrest if given in too high a dose, are contra-indicated in patients with preexisting respiratory depression, and have no specific anti-psychotic effect. 

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. 

In a double-blind, placebo-controlled, dose-response trial, 270 acutely agitated patients were randomized to receive 1-3 intramuscular injections of olanzapine (2.5, 5, 7.5, or 10 mg), haloperidol (7.5 mg), or placebo within 24 hours (60). Olanzapine had a dose-related effect in reducing agitation olanzapine was better than placebo but not better than haloperidol the most frequently reported adverse event was hypotension, which occurred with olanzapine (n = 7) but not haloperidol or placebo. Acute dystonias did not occur in patients given olanzapine or placebo but occurred in two patients given haloperidol. 

Examples of plasma half-lives for antipsychotics include quetiapine 7 h, clozapine 12 h, haloperidol 18 h and olazapine 33 h. Depot intramuscular injections are available from which drug is released over 2-4 weeks. 

Haloperidol, zuclopenthixol, fluphenazine, flupentixol and pipothiazine are available as depot intramuscular injections for maintenance treatment of patients with schizophrenia and other chronic psychotic disorders. Provided the patient is willing to agree to have depot injections, usually by a community psychiatric nurse at intervals of 2-4 weeks, the need to take tablets two or three times a day is removed. Poor compliance with oral medication is the most common cause of admission to hospital with a relapse of schizophrenia. A reduced initial dose of the depot medication should be given, with a review for unwanted effects after 5-10 days. 

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. 

Figure 1—4. Variability of haloperidol concentrations in psychiatrically healthy volunteers after intramuscular injection of 0.5 mg haloperidol. The graph shows substantial interindividual variability within each ethnic group, dramatic differences in the pharmacokinetics of haloperidol between the two groups, and overlap of the pharmacokinetics between the two groups.

The depot FGAs fluphenazine decanoate (also available in an enanthate salt) and haloperidol decanoate are esterified drugs formulated in sesame seed oil for deep intramuscular injection. Their absorption from the muscle and metabolism to the free base is sufficiently slow to cause absorption to be the rate-limiting step in determining their respective apparent half-lives. ... 

In rats provided with drinking water containing 1% valerian tincture (estimated dose 200-250 mg/kg daily) for 12 weeks with intramuscular injection of haloperidol (equivalent to 1 mg/kg daily), an increase in lipid peroxidation levels and dichlorofluorescein-reactive species production was observed in the hepatic tissue. In the liver and kidneys, 8-aminolevulinate dehydratase activity was inhibited. Serum alanine aminotransferase (ALT) was elevated, as compared to controls, while aspartate aminotransferase (AST) levels were unchanged (Dalla Corte et al. 2008). 

Hamann GL, Egan TM, Wells BG, et al. Injection site reactions after intramuscular administration of haloperidol decanoate 100 mg/mL. J Clin Psychiatry 1990 51 502-504. 

Obstruction of airways. A patient with catatonic schizophrenia was given intravenous diazepam 20 mg followed by intramuscular haloperidol 10 mg and levomepromazine 50 mg. Because of combative behaviour about 50 minutes later, he was given intravenous flunitrazepam 2 mg, and about 2 hours later another dose of both intravenous haloperidol 12 mg and flunitrazepam 5 mg. An hour after the last injection he became mildly cyanotic due to collapse of glossopharyngeal structures and excessive oral and nasal secretions, causing airways obstruction. Four other cases of airways obstruction associated with the combination of intramuscular levomepromazine in doses of 0.52 mg/kg or more and intravenous flunitrazepam or diazepam are also described. A subsequent review of all cases found that there were no cases of airways obstruction in patients who received haloperidol with either levomepromazine or a benzodiazepine. The interaction occurred immediately after the last intravenous injection in one patient and about 25 minutes after intramuscular levomepromazine but onset may be delayed up to 2 hours or more. ... 

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