Fatal Overdoses

Overdose fatalities are rare unless benzodiazepines are taken with other CNS depressants. 

The concurrent administration of methadone to heroin addicts known to be recidivists has been questioned because of the increased risk of overdose death secondary to respiratory arrest. Buprenorphine, a partial M-receptor agonist with long-acting properties, has been found to be effective in opioid detoxification and maintenance programs and is presumably associated with a lower risk of such overdose fatalities. 

Vinblastine G+, M++, N+, Ex++ Myelosuppiession, ileus, syndrome ot inappropriate antidiuretic hormone reported after overdose. Fatal it given intiathecally. 

Vincristine sultate G+, M , N++, Ex++ Delayed (up to 9 days) seizures, delirium, coma reported after overdoses. Fatal it given intrathecally. Glutamic acid 500 mg TID orally may reduce the incidence ot neurotoxicity. 

Whittington RM Barclay AD. The epidemiology of dextropropoxyphene (Distalgesic) overdose fatalities in Birmingham and tiie West Midlands. JC/mWospP/iarrw (1981) 6, 251-7. 

Unfortunately, antihistamine overdose is common. The list of symptoms include agitation, blurred vision, coma, confusion, convulsions, delirium, diarrhea, drowsiness, dry mouth, flushing, inability to urinate, incoherence, lack of sweat, fever, nausea, rapid heart rate, stomach pain, and unsteadiness. The patient may be treated with activated charcoal, oxygen, IV fluids, and gastric lavage. If the patient survives the first 24 hours after an antihistamine overdose, fatalities are rare (NIH, 2010). 

Drag overdose Fatal and non-fatal cases of clozapine overdose have been reported [SED-15, 833 SEDA-32, 98]. The minimal dose for severe poisoning and the factors that influence acute human clozapine intoxication have been studied in 73 cases of acute clozapine monointoxication reported to the Swiss Toxicological Information Center [94 ]. The most common symptoms were central nervous system depression (63%), tachycardia (40%), restlessness/agitation (16%), confusion/disorientation (15%), dysarthria (15%), arterial hypertension (11%), bradykinesia (9.6%), respiratory depression... 

Drag overdose Fatal intoxication involving topiramate has been described [299 ]. 

Darke S, Duflou J, Torok M. A reduction in blood morphine concentrations amongst heroin overdose fatalities associated with a sustained reduction in street heroin purity. Forensic Sci Int 2010 198 118-20. 

Drug overdose Fatal self-poisoning with metformin, a diuretic, and an ACE inhibitor has been reported [23 ]. 

Most opioid overdoses are witnessed [lO ] [ll ] [12 ]. The concept of a take-home opioid antagonist to be administered by a friend or family member in the event of an heroin overdose was first pioneered in 1995 in European countries [94 ]. Estimates are that two-thirds of all opioid overdose fatalities could be avoided by naloxone administered by bystanders [ll ]. A brief period of training enables lay persons to correctly identify a patient with opioid overdose and administer antidotal treatment [13 ]. Most importantly, up to 99% of drug abusers would be willing to administer naloxone to a friend or family member if needed [13 ]. Attitudes of family members of drug abusers towards take-home naloxone are generally positive [13 ]. Of all take-home naloxone dispensed, about 11 % serve to reverse and acute opioid overdose the remainder was reported as lost, stolen or confiscated by police/shelters... 

Strang J, Powis B, Best D, Vingoe L, Griffiths P, Taylor C, et al. Preventing opiate overdose fatalities with take-home naloxone pre-launch study of possible impact and acceptability. Addiction February 1999 94(2) 199-204. 

The lethal dose of mescaline varies because of the development of tolerance to the action of the drug. After a massive overdose, hypotension, bradycardia, CNS depression, and respiratory failure may be life threatening. Fatal intoxications from mescaline are rare, and fatalities associated with mescaline use are usually attributed to traumas resulting from altered perceptions. 

Fatal anaphylaxis occurs mostly due to bronchial obstruction or cardiac arrest, but also disseminated intervascular coagulation as well as adrenalin overdose [2, 7, 21, 31]. When anaphylactic reactions are survived, long-lasting sequels are rare. However,... 

In very extreme cases fatal overdoses have occurred. 

Osterloh, J.D, Loth, M., and Pond, S.M. (1983) Toxicologic studies in a fatal overdose of 2,4-D, MCPP, and chlorpyrifos, Journal of Applied Toxicology, 7 125-129. 

Staley J., Hearn W., Ruttenber A., Weth C., Mash D. High affinity cocaine recognition sites on the dopamine transporter are elevated in fatal cocaine overdose victims. Pharmacol. Exp. Ther. 271 1678, 1994. 

Staley J.K., Rothman R.B., Rice K.C., Partilla J., Mash D.C. Kappa2 opioid receptors in limbic areas of the human brain are upregulated by cocaine in fatal overdose victims. J. Neurosci. 17 8225, 1997. 

Acetaminophen is usually well tolerated, but potentially fatal hepatotoxicity with overdose is well documented. It should be used with caution in patients with liver disease and those who chronically abuse alcohol. Chronic alcohol users (three or more drinks daily) should be warned about an increased risk of liver damage or GI bleeding with acetaminophen. Other individuals do not appear to be at increased risk for GI bleeding. Renal toxicity occurs less frequently than with NSAIDs. 

An analysis of 19 deaths from PCP overdose that occurred in two California counties from 1970 to 1976 showed that 12 were accidental, five suicidal, and two homicidal. Eight of the 12 accidental deaths were from drowning. Blood concentrations ranged from 1,250 to 2,300 ng/ml. Virtually all patients with levels of 1,000 ng/ml or more had coma, with the possible evolution of death due to medical complications, seizures, or respiratory depression. Levels greater than 2,000 ng/ml were almost always fatal (12). 

Saincher A, Swirsky N, Tenenbein M. 1994. Cyanide overdose Survival with fatal blood concentration without antidotal therapy. JEmergMed 12(4) 555-557. 

Aspirin is generally low in toxicity and produces comparatively little tolerance and no addiction. However, its effects are not entirely benign, especially in certain medical conditions. Acute overdose of aspirin is fatal in doses of 10 to 30 mg, although some high doses have been reported... 

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). 

Of greater concern is the safety of the TCAs. Toxic levels of these medications can produce lethal cardiac arrhythmias, seizures, and suppression of breathing. An overdose of a 1-2 week supply of most TCAs is often fatal, a serious consideration when prescribing medication to depressed patients with suicidal thoughts. Children taking imipramine for treatment of ADHD have died from sudden cardiac death consequently, child psychiatrists seldom use TCAs. Likewise, patients with heart disease or seizure disorders are more likely to have dangerous complications from TCAs and should avoid them. 

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