Discrimination Between Drug Abuse and Medical Therapy: Case report of a tranylcypromine overdose-related fatality.

Tranylcypromine is an effective antidepressant from the class of monoamine oxidase inhibitors and is structurally related to amphetamine. However, reports differ regarding the potential metabolism of tranylcypromine to amphetamine and methamphetamine within the human body. We report a 25-year-old woman with severe depression who died due to a fatal tranylcypromine overdose in 2016. She had been prescribed tranylcypromine one day previously and had no history of previous suicide attempts or substance abuse. The body was transferred to a forensic medicine department in Tehran, Iran for the autopsy. A urine sample was positive for tranylcypromine, amphetamine and methamphetamine using gas chromatography/mass spectrometry after derivatisation with heptafluorobutyric acid. As amphetamines were present in the urine sample, it was assumed that the tranylcypromine had been converted to amphetamines metabolically. As such, it is possible that the legitimate use of certain prescription drugs may complicate the interpretation of test results for illegal drugs.

Ping-pong gaze in combined intoxication with tranylcypromine, thioridazine, and clomipramine.

OBJECTIVE: This paper reports the occurrence of ping-pong gaze, a neuro-ophthalmological syndrome usually related to severe structural brain damage, in a patient intoxicated with tranylcypromine, thioridazine, and clomipramine. BACKGROUND: Although there have been some reports about the occurence of Ping-pong gaze after intoxications, it is usually related to severe bilateral hemispheric brain damage following stroke or traumatic injuries. METHOD: We report the case of a 56-year old woman who developed a neurotoxic syndrome with coma, hyperthermia, muscular rigidity, myoclonic jerks and tachycardia following an intoxication. Additionally rhythmic and pendular conjugate horizontal eye movements could be observed for three days, so that the diagnosis of ping-pong gaze was made. RESULTS: A treatment with dantrolene lead to complete remission of the neurotoxic syndrome with no signs of neurological or physical deficits. At the stage of regaining consciousness the eye movements became normal. CONCLUSION: In our case the combined intoxication with an monoamine oxidase inhibitor, a neuroleptic and a tricyclic agent lead to a neurotoxic syndrome and the occurrence of a rare neuro-ophthalmological syndrome usually related to bilateral hemispheric brain dysfunction.

The GCMS analysis of tranylcypromine (Parnate) in a suspected overdose.

A fatal overdose involving tranylcypromine (Parnate) where blood, urine and tissues were quantitated using a pentafluoroproprionic anhydride (PFPA) derivative and gas-chromatography/mass spectroscopy (GCMS). The samples were re-quantified over several weeks demonstrating a significant loss of drug in tissues but not blood or urine specimens. The urine was positive for methamphetamine which has been a suspected metabolite.

One fatal and one nonfatal intoxication with tranylcypromine. Absence of amphetamines as metabolites.

Two very different cases of overdose with tranylcypromine are presented. One clinical case involving the ingestion of 400 mg tranylcypromine with suicidal intention and one fatality with a suspicion of possible tranylcypromine overdose were examined. Both cases showed similar blood concentrations (0.5 and 0.7 mg/L, respectively), but the clinical case exhibited only mild symptoms of intoxication. The fatality showed no other drugs that could provide an explanation for the death of a 40-year-old male except tranylcypromine. Consideration of the drug concentrations in the fatality in relation to the case findings and other reported data indicates the tranylcypromine overdose as the probable cause of death, despite the low blood concentration. In addition, we looked for evidence of amphetamine as a putative metabolite in both cases. No amphetamines were detected in the overdose cases reported here.

Postmortem changes in blood tranylcypromine concentration: competing redistribution and degradation effects.

Site and temporal changes in tranylcypromine (TCP) and lithium concentrations in blood were studied in a human poisoning case. Blood samples from peripheral vessels and six central vessels were obtained at 0, 6, 24, 48 and 72 h after starting the autopsy. Nine tissue samples were obtained on completion. TCP showed preferential concentration in liver (2.21 micrograms/g) and brainstem (2.46 micrograms/g). There was a moderate post mortem redistribution phenomenon with TCP concentrations lowest in peripheral blood (0.17 micrograms/ml) at 0 h and highest in central vessels at 24 h (0.52 micrograms/ml). At 72 h blood TCP concentrations fell below those at 0 time but the samples showed marked putrefactive changes. Control blood samples spiked with TCP and incubated for 48 h at 37 degrees C showed a 58% fall in drug concentration. By contrast with TCP, lithium, which has a small Vd (0.8 l/kg) and is chemically stable, did not show this pattern of change in blood concentration. The site and temporal differences in TCP concentration in blood can be explained by the competing effects of post mortem redistribution and drug degradation. Redistribution is an early post mortem phenomenon characterised by diffusion, along a concentration gradient, from drug reservoirs in solid organs into adjacent blood vessels. Drug degradation is a later phenomenon associated with putrefactive change.

Dependence on monoamine oxidase inhibitors in high dose.

A 37-year-old woman with a personality disorder and chronic dysthymia developed a dependence on MAOIs. She ingested 440 mg tranylcypromine daily without any side-effects while taking no dietary precautions. The features of MAOI dependence and their resemblance to amphetamine dependence are discussed.

Two cases of fatal intoxication due to tranylcypromine overdose.

Two cases of death following the ingestion of tranylcypromine are presented. High concentrations of tranylcypromine were determined in blood, urine, and liver by gas-liquid chromatography. Tranylcypromine was extracted from buffered blood with n-butyl chloride. The evaporated extract was derivatized with trifluoroacetic anhydride and analyzed by gas chromatography with nitrogen-phosphorus selective detection. The method was linear in blood over the range 0.5-20 mg/L with a limit of quantitation of about 0.2 mg/L.

Fatal malignant hyperthermia as a result of ingestion of tranylcypromine (Parnate) combined with white wine and cheese.

Fatal malignant hyperthermia occurred in a patient who was taking tranylcypromine (Parnate) and ingested wine and cheese. The case findings are presented along with a review of the literature concerning adverse interactions between monoamine oxidase (MAO) inhibitors and certain foods and beverages. Hyperthermia and its possible causative mechanisms and treatments are discussed. The facts suggest that the complicated dietary restrictions attending the use of MAO inhibitors and the possibility of severe and even catastrophic reactions resulting from violations of these restrictions make the use of these drugs fraught with danger and therefore not a first choice for the treatment of depression.

Peaked "T" waves with tranylcypromine (parnate) overdose.

A case of tranylcypromine (Parnate) overdose is presented in which the main toxic effects were headache, obtundation, hypertension, and diffusely peaked T-waves on ECG. The latter effect, which occurred in the absence of hyperkalemia, has not been previously associated with monoamine oxidase inhibitors (MAOI). Recent case reports of tranylcypromine toxicity are briefly reviewed, confirming the potential for hypertension, hypotension, shock, hyperpyrexia, intracranial hemorrhage, agitation, hyperkinesis, coma and death in association with overdosage, or concomitant ingestion of sympathomimetic substances or other drugs. These ECG changes add to the worrisome list of potential toxicities in an era in which MAOI are finding increased clinical use.

Drug-induced hyperpyrexia. A case report.

A patient who developed hyperpyrexia and heat stroke after taking overdoses of a monoamine oxidase inhibitor, benzodiazepines and a beta-adrenergic receptor blocking agent is described. The possible mechanisms involved in drug-induced hyperpyrexia are briefly discussed.

Tranylcypromine ('Parnate') overdose: measurement of tranylcypromine concentrations and MAO inhibitory activity and identification of amphetamines in plasma.

A case of tranylcypromine overdose is reported. Tranylcypromine, amphetamine methamphetamine and phenylethylamine were detected in the plasma by gas chromatography and their identity confirmed by mass spectrometry. The data suggested that the amphetamines were metabolic products of tranylcypromine. Platelet monoamine oxidase activity was more than 95% inhibited during the 72 h after the overdose despite complete clinical recovery by that time. The possible role of amphetamines and phenylethylamine in causing the clinical manifestations of tranylcypromine overdose is discussed.