Lorazepam

Toxicity

Plasma concentrations of 0.3 to 0.6 mg/L were reported in 3 subjects suffering toxic effects after
the ingestion of overdoses of lorazepam; the estimated amounts ingested were 100 and 120 mg in
2 of the cases. The subjects recovered within 24 to 30 h [M. D. Allen et al.,Am. J.
Psychiatry,1980, 137, 14141415].

Methadone

The estimated minimum lethal dose is 50 mg but addicts on maintenance treatment may tolerate
doses of 200 mg or more. In nonaddicted subjects, toxic reactions are associated with plasma
concentrations in the region of 1 to 2 mg/L and concentrations above 2 mg/L may be lethal. With
serious overdose, respiratory depression, extreme somnolence including stupor or coma, skeletal
muscle flaccidity, cold and clammy skin, bradycardia and hypotension may occur and with
severe overdose, circulatory collapse, cardiac arrest and death.

In 3 cases in which death was attributed to methadone overdose, liver concentrations of 1.9, 1.3,
and 0.7 g/g and urine concentrations of 13, 25, and 4 g/L, respectively, were reported [P. E.
Nelson and R. C. Selkirk,Forensic Sci.,1975, 6, 175186].

Morfin

Toxicity.

The estimated minimum oral lethal dose for adults is 200 mg but addicts may be able to tolerate
up to 10 times as much. Morphine is initially eliminated from the blood fairly quickly and blood
concentrations are difficult to interpret, especially as toxic effects depend on the degree of
tolerance that has been acquired.

An 8yearold girl accidentally ingested morphine before going to bed and was found dead the
next morning. Following a tonsillectomy, she was prescribed pethidine syrup at a dose of 100 mg
every 4 h but the pharmacist accidentally dispensed Roxanol containing 20 mg/mL morphine
sulfate. The girl took 1 to 2 teaspoons as prescribed. The blood morphine concentration was
0.128 mg/L, bile, 135 mg/L, and morphine was found in the stomach contents at a concentration
of 16 mg/L (a total amount of 2.3 mg). The cause of death was determined as morphine
poisoning which resulted in respiratory depression. [A. Poklis et al.,Forens. Sci. Int.,1995, 761,
5559.]

Aspirin

Toxicity.

The estimated minimum lethal dose is 15 g. Plasma concentrations of salicylic acid greater than
300 mg/L are likely to produce toxic reactions and concentrations greater than 500 mg/L are
associated with moderate to severe intoxication. The maximum permissible atmospheric
concentration is 5 mg/m3.

A 43yearold female attempted suicide by selfadministration, in the form of an enema, of

approximately 700 aspirin tablets dissolved in water. The initial salicylate concentration in the
serum was 590 mg/L and rose to 900 mg/L 12 h later; after haemodialysis, serum salicylate
concentration fell to 160 mg/L but the patient remained in a coma for more than a year. The
patients poor outcome was attributed to retention of aspirin products in the rectal vault plus poor
recognition of the delayed absorption properties of rectally administered aspirin. [J. E. Watson
and E. T. Tagupa,Ann. Pharmacother.,1994, 28, 467469.]