Cardiovascular diseases are a leading cause of morbidity and mortality in most developed countries of the world. Pharmaceuticals, illicit drugs, and toxins can significantly contribute to the overall cardiovascular burden and thus deserve attention. The present article is a systematic overview of drugs that may induce distinct cardiovascular toxicity. The compounds are classified into agents that have significant effects on the heart, blood vessels, or both. The mechanism(s) of toxic action are discussed and treatment modalities are briefly mentioned in relevant cases. Due to the large number of clinically relevant compounds discussed, this article could be of interest to a broad audience including pharmacologists and toxicologists, pharmacists, physicians, and medicinal chemists. Particular emphasis is given to clinically relevant topics including the cardiovascular toxicity of illicit sympathomimetic drugs (e.g., cocaine, amphetamines, cathinones), drugs that prolong the QT interval, antidysrhythmic drugs, digoxin and other cardioactive steroids, beta-blockers, calcium channel blockers, female hormones, nonsteroidal anti-inflammatory, and anticancer compounds encompassing anthracyclines and novel targeted therapy interfering with the HER2 or the vascular endothelial growth factor pathway.

• Klíčová slova
• dysrhythmia, heart failure, hypertension, myocardial infarction, stroke,
• MeSH
• alkaloidy škodlivé účinky   MeSH
• amfetaminy škodlivé účinky   MeSH
• antiarytmika škodlivé účinky   MeSH
• antiflogistika nesteroidní škodlivé účinky   MeSH
• beta blokátory škodlivé účinky   MeSH
• blokátory kalciových kanálů škodlivé účinky   MeSH
• cévní mozková příhoda farmakoterapie   MeSH
• digoxin škodlivé účinky   MeSH
• hormony škodlivé účinky   MeSH
• kardiovaskulární nemoci chemicky indukované   farmakoterapie   MeSH
• kardiovaskulární systém účinky léků   MeSH
• kokain škodlivé účinky   MeSH
• lidé MeSH
• protinádorové látky škodlivé účinky   MeSH
• srdeční frekvence účinky léků   MeSH
• steroidy škodlivé účinky   MeSH
• vaskulární endoteliální růstový faktor A MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• alkaloidy MeSH
• amfetaminy MeSH
• antiarytmika MeSH
• antiflogistika nesteroidní MeSH
• beta blokátory MeSH
• blokátory kalciových kanálů MeSH
• cathinone MeSH Prohlížeč
• digoxin MeSH
• hormony MeSH
• kokain MeSH
• protinádorové látky MeSH
• steroidy MeSH
• vaskulární endoteliální růstový faktor A MeSH

OBJECTIVES: Rutin, quercetin-3-O-rutinoside, a natural flavonol glycoside, has shown various in vitro benefits with potential use treating human diseases, especially cardiovascular system disorders. Antioxidant properties are assumed to underlie the majority of these benefits. Yet rutin pro-oxidant properties have been reported as well. Our research group has recently shown aggravating effects on isoprenaline (ISO)-induced cardiotoxicity in Wistar:Han rats after 24 hours. METHODS: This study was designed to examine in more detail the reasons for the negative effects of rutin (11.5 and 46 mg/kg, i.v.) after administration of ISO (100 mg/kg, s.c.) in rats within 2 hours of continuous experiment and in the H9c2 cardiomyoblast-derived cell line. RESULTS: Like our previous findings, rutin did not (11.5 or 46 mg/kg, i.v.) reduce the ISO-induced mortality within 2 hours although the lower dose significantly reduced cardiac troponin T (cTnT) and partly improved the histological findings. In contrast, the higher dose increased the mortality in comparison with solvent (1.26% w/v sodium bicarbonate). This was not caused by any specific haemodynamic disturbances. It appears to be associated with oxidative stress as rutin enhanced intracellular reactive oxygen species formation in vitro and had the tendency to increase it in vivo. CONCLUSIONS: Rutin, likely due to its pro-oxidative effects, can exacerbate catecholamine cardiotoxicity depending on the dose used.

• Klíčová slova
• Catecholamine, Flavonoid, H9c2 cell line, Isoprenaline, Reactive oxygen species, Rutin, Wistar rat,
• MeSH
• buněčné linie MeSH
• dinoprost analogy a deriváty   krev   MeSH
• elektrokardiografie MeSH
• glutathion krev   MeSH
• injekce intravenózní MeSH
• isoprenalin škodlivé účinky   MeSH
• Kaplanův-Meierův odhad MeSH
• kardiotoxicita etiologie   mortalita   MeSH
• myokard patologie   MeSH
• potkani Wistar MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• rutin aplikace a dávkování   škodlivé účinky   farmakokinetika   MeSH
• srdce účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 8-epi-prostaglandin F2alpha MeSH Prohlížeč
• dinoprost MeSH
• glutathion MeSH
• isoprenalin MeSH
• reaktivní formy kyslíku MeSH
• rutin MeSH

Catecholamines are endogenous amines that participate in the maintenance of cardiovascular system homeostasis. However, excessive release or exogenous administration of catecholamines is cardiotoxic. The synthetic catecholamine, isoprenaline (isoproterenol, ISO), with non-selective β-agonistic activity has been used as a viable model of acute myocardial toxicity for many years. Since the pathophysiology of ISO-cardiotoxicity is complex, the aim of this study was to elucidate the effect of oral quercetin pretreatment on myocardial ISO toxicity. Wistar-Han rats were randomly divided into four groups: solvent or quercetin administered orally by gavage in a dose of 10 mg kg(-1) daily for 7 days were followed by s.c. water for injection or ISO in a dose of 100 mg kg(-1). Haemodynamic, ECG and biochemical parameters were measured; effects on blood vessels and myocardial histology were assessed, and accompanying pharmacokinetic analysis was performed. Quercetin was unable to protect the cardiovascular system against acute ISO cardiotoxicity (stroke volume decrease, cardiac troponin T release, QRS-T junction elevation and histological impairment). The sole positive effect of quercetin on catecholamine-induced cardiotoxicity was the normalization of increased left ventricular end-diastolic pressure caused by ISO. Quercetin did not reverse the increased responsiveness of rat aorta to vasoconstriction in ISO-treated animals, but it decreased the same parameter in the control animals. Accompanying pharmacokinetic analysis showed absorption of quercetin and its metabolite 3-hydroxyphenylacetic acid formed by bacterial microflora. In conclusion, a daily oral dose of 10 mg kg(-1) of quercetin for 7 days did not ameliorate acute ISO-cardiovascular toxicity in rats despite minor positive cardiovascular effects.

• MeSH
• aorta thoracica účinky léků   fyziologie   MeSH
• aplikace orální MeSH
• hemodynamika MeSH
• isoprenalin MeSH
• kardiotoxicita krev   farmakoterapie   patologie   patofyziologie   MeSH
• krysa rodu Rattus MeSH
• myokard patologie   MeSH
• quercetin krev   farmakokinetika   terapeutické užití   MeSH
• troponin T krev   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• isoprenalin MeSH
• quercetin MeSH
• troponin T MeSH