Haloperidol drug additives

There is an increased central nervous system (CNS) depressant effect when the skeletal muscle relaxants are administered with other CNS depressants, such as alcohol, antihistamines, opiates, and sedatives. There is an additive anticholinergic effect when cyclobenzaprine is administered with other drugs with anticholinergic effects (eg, antihistamines, antidepressants, atropine, haloperidol). See Chapter 30 for information on diazepam. 

There is, however, a unique risk in the bipolar form that antidepressant treatment may trigger a switch into mania. This may occur either as the natural outcome of recovery from depression or as a pharmacological effect of the drug. Particular antidepressants (the selective serotonin reuptake inhibitors) seem less liable to induce the switch into mania than other antidepressants or electroconvulsive therapy. Treatment for mania consists initially of antipsychotic medication, for instance the widely used haloperidol, often combined with other less specific sedative medication such as the benzodiazepines (lorazepam intramuscularly or diazepam orally). The manic state will usually begin to subside within hours and this improvement develops further over the next 2 weeks. If the patient remains disturbed with manic symptoms, additional treatment with a mood stabilizer may help. 

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). 

Extrapyramidal symptoms (EPS) Dystonic reactions develop primarily with the use of traditional antipsychotics. EPS has occurred during the administration of haloperidol and pimozide frequently, often during the first few days of treatment. Neuroleptic malignant syndrome (NMS) A potentially fatal symptom complex sometimes referred to as NMS has been reported in association with administration of antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, rhabdomyolysis, and acute renal failure. 

The work that has been done with chlorpromazine, haloperidol, and pimozide suggests that these drugs are metabolized more rapidly in children than in adults (Morselli et ah, 1982 Sallee et ah, 1987 Furlanut et ah, 1990). In addition, it appears that larger doses of chlorpromazine and haloperidol per body weight are needed in young people to achieve the same plasma concentrations as those in adults (Morselli et ah, 1979 Rivera-Calimlim et ah, 1979). 

A variety of relatively uncommon dermatological side effects have been noted to be associated with antipsychotic agents. These include maculopapular rashes, urticaria, and erythema multiforme (Arana, 2000). Photosensitivity and skin pigmentation can also occur during treatment with these drugs. Although skin pigmentation has been most frequently reported with chlorpromazine, this can occur with thioridazine and trifluoperazine (Harth and Rapoport, 1996). In addition, treatment-induced alopecia has been reported for haloperidol, olanzapine, and risperidone (Mercke et ah, 2000). 

The use of two or more agents concurrently has the potential for possibly deleterious drug interactions. Thus, as noted in subsequent chapters, the addition or elimination of an agent may significantly alter the activity of the concurrent drug treatment (e.g., carbamazepine lowering haloperidol plasma levels nefazodone increasing the levels of triazolam). 

Dopamine is a major neurotransmitter which acts on multiple receptors. It can activate both a and 3 adrenoceptors in addition to acting on specific dopamine receptors. These are widely distributed throughout the CNS and are also present in the renal tubules and renal and mesentric blood vessels, and many dopaminergic drugs are used in the treatment of Parkinson s disease, psychiatric disorders, as antiemetics, and for renal protection. Neuroleptic drugs, such as haloperidol and droperidol, are dopamine receptor antagonists. 

Some patients who take clozapine take another neuroleptic drug, and the consequences of this practice in terms of prolactin have been studied in five patients (758). After the addition of haloperidol (4 mg/day) to clozapine the mean prolactin concentration increased from 9.7 ng/ml to 16 ng/ml at week 4 and 19 ng/ml at week 6. Each subject had an increase in the percentage of D2 receptor occupancy, and the group mean increased from 55% at baseline to 79% at week 4 the increased prolactin concentrations correlated with receptor occupancy. 

In recent years traditional neuroleptics, as exemplified by chlorpromazine, have been structurally modified to produce drugs with greater affinity for dopamine receptors while retaining some of their activity on other receptor systems (e.g. on alpha] adrenoceptors, 5-HT2 receptors and histamine] receptors). In the non-phenothiazine series, a high degree of specificity for the D2 receptors has been achieved with sulpiride and pimozide, with haloperidol showing antagonistic effects on the 5-HT2 and alpha] adrenoceptors in addition to its selectivity for D2 receptors. The czs-(Z) isomers of the thioxanthines are potent neuroleptics that, in addition to... 

Carbamazepine is a hepatic microsomal enzyme inducer and therefore will lower the serum concentration of a wide variety of drugs given concurrently. These include the antiepileptic drugs phenytoin, primidone, valproate, ethosuximide and clonazepam. In addition, carbamazepine can compromise the therapeutic effects of oral contraceptives, oral anticoagulants, beta-blockers, haloperidol and theophylline. 

The global efficacy of olanzapine was not substantially different from that of haloperidol in two of three comparative trials involving 2500 patients, according to a comprehensive review of the safety and efficacy of olanzapine in addition, the only relevant comparative trial failed to demonstrate superiority of olanzapine over risperidone (52). Olanzapine has fewer adverse neurological effects than haloperidol, but there is no evidence that it differs from other atypical neuroleptic drugs in this respect. 

There have been reports of neuroleptic malignant syndrome precipitated by promethazine 100 mg/day to treat neuroleptic drug-induced extrapyramidal symptoms and lorazepam 6 mg/day to treat agitation (349), after the addition of intramuscular haloperidol 23 mg to atypical neuroleptic drugs (350), and in other instances in children and adolescents (351). 

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