Antipsychotics overdose

Catalano G, Catalano MC, Nunez CY, Walker SC. Atypical antipsychotic overdose in the pediatric population. J Child Adolesc Psychopharmacol 2001 ll(4) 425-34. 

The short-acting clomethia2ole [533-45-9] (1), sometimes used as therapy for sleep disorders ia older patients, shares with barbiturates a risk of overdose and dependence. Antihistamines, such as hydroxy2iae [68-88-2] (2), are also sometimes used as mild sedatives (see HiSTAMlNES AND HISTAMINE antagonists). Antidepressants and antipsychotics which have sedative effects are used to treat insomnia when the sleep disorder is a symptom of some underlyiag psychiatric disorder. 

The answer is c. (Hardman, pp 574—575.) Phencyclidine is a hallucinogenic compound with no opioid activity Its mechanism of action is amphetamine-like. A withdrawal syndrome has not been described for this drug in human subjects. In overdose, the treatment of choice for the psychotic activity is the antipsychotic drug haloperidol. 

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). 

Contraindications for antipsychotic therapy are few they may include Parkinson s disease, hepatic failure, hypotension, bone marrow depression, or use of CNS depressants. Overdoses of antipsychotics are rarely fatal, except for thioridazine, which is associated with major ventricular arrhythmias, cardiac conduction block, and sudden death. For other agents gastric lavage should be attempted even if several hours have elapsed since the drug was taken, because gastrointestinal motility is decreased and the tablets may still be in the stomach. Moreover, activated charcoal effectively binds most of these drugs and can be followed by a saline cathartic. The hypotension often responds to fluid replacement or pressor agents such as norepinephrine. 

Trenton A, Currier G, Zwemer F. Fatalities associated with therapeutic use and overdose of atypical antipsychotics. CNS Drugs. 2003 17 307-324. 

Widening of the QRS complex duration to greater than 100 milliseconds is typical of tricyclic antidepressant and quinidine overdoses (Figure 59-1). The QTC interval may be prolonged to more than 440 milliseconds in many poisonings, including quinidine, tricyclic antidepressants, several newer antidepressants and antipsychotics, lithium, and arsenic (see also http //www.torsades.org/). Variable atrioventricular (AV) block and a variety of atrial and ventricular arrhythmias are common... 

Although sedative antihistamines do not potentiate the effect of alcohol, they should be avoided in excess quantity. Overdose of astemizole can be treated with gastric lavage and supportive measures.86 Coadministration of astemizole and ter-fenadine with antiarrhythmics, antipsychotics, cisapride, and diuretics should be avoided. Chlorpheniramine maleate has been found to be incompatible with phe-nobarbitone sodium, kanamycin sulfate, and calcium chloride. Cyclizines have been used alone or with opioids in tablets or in injectable form for euphoric effects. Cyproheptadine has shown dependence in long-term use. Diphenhydramine is reported to be incompatible with amphotericin, cephalothin sodium, and hydrocortisone sodium succinate. Diphenhydramine and pheniramine maleate are sometimes used as drugs of abuse. Studies have shown that promethazine is adsorbed onto glass, plastic containers, and infusion systems.87... 

Mianserin Hydrochloride An acute overdose of mianserin is most hazardous in patients due to multiple drug overdose. The main feature of overdose is mild coma without chance of deep coma or convulsions. Mianserin may potentiate the effects of CNS depressants such as alcohol, antipsychotics, and anxiolytics. 

Barbiturate overdose may be treated with gastric lavage and oral administration of activated charcoal. Supportive therapy of cardiovascular, respiratory, and renal function also should be provided. Coadministration of alcohol and barbiturates may increase the sedative effect of chloral hydrate. Long-term use of barbiturates leads to dependence. Sudden discontinuation of an antipsychotic drug may cause withdrawal symptoms such as nausea, vomiting, anorexia, diarrhea, rhinorrhea, sweating, insomnia, restlessness, and vertigo.151... 

Capel MM, Colbridge MG, Henry JA. Overdose profiles of new antipsychotic agents. Int J Neuropsychopharmacol 2000 3(l) 51-4. 

Fatal overdoses in which novel antipsychotic drugs were the sole ingestant have been reported with olanzapine (249). In two cases blood olanzapine concentrations were 237 ng/ml in one and 675 ng/ml in the other (250). The usual target range for plasma olanzapine concentrations is 9-23 ng/ml. 

Atypical antipsychotics may be useful in freafing stimulanf or psychotic consequences of overdose... 

As the degree of presystemic elimination differs much between drugs and between individuals, the phenomenon of first-pass elimtnation adds to variation in systemic plasma concentrations, and thus particularly in initial response to the drugs that are subject to this process. When a drug is taken in overdose, presystemic elimination may be reduced, and bioavailability increased this may explain rapid onset of toxicity with antipsychotic drugs, many of which undergo first-pass elimination. 

Because this group as a whole engages in frequent suicidal acting out, it is advisable to treat borderline patients with medications that have been found to have a low degree of toxicity when taken in overdose. These include antipsychotics and the following antidepressants fluoxetine, paroxetine, bupropion (note above caution), trazodone, and sertraline. Most other antidepressants are quite toxic when taken in overdose. 

Sometimes patients will report a reexpeiiendng or "flashback" of halludnations they had during a previous ingestion of halludnogen. These leadions likewise usually do not require treatment with medication but, when severe, may benefit from antianxiety or antipsychotic medication. Severe overdoses of PCP can lead to convulsions and may require emergency medical treatment. 

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