Severe Rhabdomyolysis Associated with Acute Amphetamine Toxicosis in a Dog

A 3-year-old female spayed rat terrier presented for hyperactivity and repetitive circling to the right of less than one-hour duration. On examination, the patient was dehydrated, hyperactive, and dysphoric. Laboratory tests initially revealed elevations in creatine kinase (CK) and aspartate aminotransferase (AST). Serial chemistries indicated significant progression of CK elevation to a maximum of 181,900 U/L on day 3 along with the development of profuse myoglobinuria. A urine drug screening test was positive for amphetamine metabolites. This patient was treated with sedatives, aggressive fluid diuresis, and antioxidants. The dog recovered uneventfully with no indicators of renal dysfunction based on serial blood chemistries and was discharged five days after presentation. Follow-up blood chemistries taken four days after discharge revealed near normalization of CK and resolution of myoglobinuria. This case report describes a particularly severe case of rhabdomyolysis associated with amphetamine toxicity and its successful treatment.

A fatal case of amphetamine induced ischaemic colitis

Amphetamine induced ischaemic colitis is an exceedingly rare presentation of amphetamine toxicity. The cases reported in the literature have described mild or transient disease. We present a fatal case of ischaemic colitis induced by amphetamine use in a 44-year-old woman who presented in extremis after a cardiac arrest en route to the emergency department. A short history of headache, abdominal pain, vomiting and agitation preceded her admission. Imaging revealed changes consistent with ischaemic colitis. Emergency laparotomy revealed widespread colonic necrosis necessitating a subtotal colectomy. Despite aggressive resuscitation and inotropic support from arrival, the patient deteriorated intraoperatively and died in the immediate postoperative period. Histology showed arterial type ischaemia/reperfusion injury of the area supplied by the superior mesenteric artery. The patient’s serum amphetamine level was 0.52mg/l (peak therapeutic levels <0.2mg/l). The postmortem examination concluded that amphetamines were the likely cause of the vasospasm, leading to profound colonic ischaemia.

The ugly side of amphetamines: short- and long-term toxicity of 3,4-methylenedioxymethamphetamine (MDMA, ‘Ecstasy’), methamphetamine and d-amphetamine

Amphetamine (‘Speed’), methamphetamine (‘Ice’) and its congener 3,4-methylenedioxymethamphetamine (MDMA; ‘Ecstasy’) are illicit drugs abused worldwide for their euphoric and stimulant effects. Despite compelling evidence for chronic MDMA neurotoxicity in animal models, the physiological consequences of such toxicity in humans remain unclear. In addition, distinct differences in the metabolism and pharmacokinetics of MDMA between species and different strains of animals prevent the rationalisation of realistic human dose paradigms in animal studies. Here, we attempt to review amphetamine toxicity and in particular MDMA toxicity in the pathogenesis of exemplary human pathologies, independently of confounding environmental factors such as poly-drug use and drug purity.

D-Amphetamine Toxicity in Freshly Isolated Rat Hepatocytes: A Possible Role of CYP3A

D-Amphetamine Toxicity in Freshly Isolated Rat Hepatocytes: A Possible Role of CYP3AThe aim of this study was to trace D-amphetamine toxicity in isolated rat hepatocytes and to elucidate a possible involvement of CYP3A in the mechanisms of its toxicity. To this end, male Wistar rats were treated with nifedipine (5 mg kg-1i.p., 5 days), a substrate and inducer of CYP3A. Hepatocytes isolated from nifedipine-treated and control rats were incubated with D-amphetamine at a concentration of 100 μmol L-1, which was determined to be an average toxic concentration (TC50) for the compound. To evaluate the possible toxic effects of D-amphetamine on freshly isolated rat hepatocytes, we assessed the following parameters: cell viability, lactate dehydrogenase (LDH) activity, and glutathione (GSH).The results showed that nifedipine potentiated amphetamine cytotoxicity in vitro, as follows: cell viability dropped by 65% (p>0.001), GSH by 80% (p>0.001), and LDH activity increased by 190% (p>0.001). To clarify the role of nifedipine in amphetamine cytotoxicity, we used amiodarone, a substrate and an inhibitor of CYP3A. Pre-incubation of nifedipine-treated hepatocytes with amiodarone (14 μmol L-1) significantly lowered amphetamine cytotoxicity.Our results confirmed the toxicity of D-amphetamine in isolated rat hepatocytes and the involvement of CYP3A in its metabolism and hepatotoxicity.