Mixed antihypertensive drug intoxication poses a significant risk for patient mortality. In tandem to antihypertensives, hypolipidemic medicines (especially statins) are often prescribed. Among their well-known adverse effects belongs rhabdomyolysis. We report a case of fatal multi-drug overdose in a 65-year-old female alcoholic. The patient was unconscious at admission. Empty blister packs indicated the abuse of 250 tablets of urapidil, 42 tablets of verapamil/trandolapril, 50 tablets of moxonidin, 80 tablets of atorvastatin and 80 tablets of diacerein. Standard measures (gastric lavage, activated charcoal, mechanical ventilation, massive doses of vasopressors, volume expansion, diuretics and alkalinization) failed to provide sufficient drug elimination and hemodynamic support and the sufferer deceased on the fourth day. Dramatic elevations of serum myoglobin (34,020 μg/L) and creatine kinase (219 μkat/L) were accompanied by rise in cardiac troponin I and creatinine. Gas chromatography revealed ethanol 1.17 g/kg (blood) and 2.81 g/kg (urine). Thin layer chromatography and gas chromatography of gastric content and urine verified verapamil, moxonidin and urapidil fragment (diacerein method was unavailable). Atorvastatin and trandolapril concentrations (LC-MS(n)) equaled 277.7 μg/L and 57.5 μg/L, resp. (serum) and 8.15 μg/L and 602.3 μg/L, resp. (urine). Histology confirmed precipitates of myoglobin with acute necrosis of proximal renal tubules in association with striated muscle rhabdomyolysis and myocardial dystrophy. Cardiogenic-distributive shock in conjunction with acute renal failure due to the combined self-poisoning with vasoactive agents and atorvastatin were determined to be this decedent's immediate cause of death. The manner of death was assigned to be suicidal.
- MeSH
- Acute Kidney Injury chemically induced MeSH
- Alcoholics MeSH
- Anthraquinones analysis poisoning MeSH
- Anti-Inflammatory Agents analysis poisoning MeSH
- Antihypertensive Agents analysis poisoning MeSH
- Atorvastatin analysis poisoning MeSH
- Gastrointestinal Contents chemistry MeSH
- Imidazoles analysis poisoning MeSH
- Indoles analysis poisoning MeSH
- Humans MeSH
- Piperazines analysis poisoning MeSH
- Drug Overdose MeSH
- Rhabdomyolysis chemically induced pathology MeSH
- Suicide * MeSH
- Aged MeSH
- Forensic Toxicology MeSH
- Hydroxymethylglutaryl-CoA Reductase Inhibitors analysis poisoning MeSH
- Vasodilator Agents analysis poisoning MeSH
- Verapamil analysis poisoning MeSH
- Check Tag
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
Tři různé přípravky obsahující 240 mg verapamil hydrochloridu v potahované tabletě se zpomale-ným uvolňováním byly porovnány zaslepeným disolučním testem. Množství uvolněné účinné látkyz tablety i její dynamika se po třetí hodině disoluce u všech tří přípravků významně lišily. U pří-pravku C (originální přípravek Isoptin SR, výrobce Knoll) se po sedmi hodinách uvolnilo 92,2 %účinné látky. U generického přípravku A bylo toto množství ve srovnání s originálním přípravkemvyšší, a u generického přípravku B nižší. Pouze u originálního přípravku byla dynamika uvolňováníúčinné látky lineární. Nepravidelné a nelineární uvolňování účinné látky z tablety může mít zanásledek klinicky suboptimální účinnost a bezpečnost generických přípravků.
Three different products containing 240 mg of verapamil hydrochloride in a coated tablet withsustained release were compared using the blinded dissolution test. The amount of the activesubstance released from the tablet and its dynamics differed significantly with all three productsafter 3 hours of dissolution. With product C (Isoptin SR, a proprietary product manufactured byKnoll), 92,2 % of the active substance was released after seven hours. With generic products A andB, the amounts were higher and lower, respectively. The dynamics of release of the active substancewas linear only with the proprietary product. Irregular and non-linear rates of active substancerelease from the tablet may result in clinically suboptimal efficacy and safety of generic products.
