cardiactoxicology-theuniversityofnorthcarolinaat心臟毒理學-北卡羅來那大學-文庫吧
2025-01-03 23:54 本頁面
【正文】 stream tissue/an effects CompoundInduced Toxicity ? Toxicants that alter aerobic metabolism ? Toxicants that alter myocardial conduction ? Toxicants that alter cell membrane function ? Toxicants that directly damage myocardium ? Toxicants that induce vascular changes Toxicants That Interfere With Aerobic Metabolism ? High energy demands of the heart make it susceptible to toxicants that interfere with: – oxygen availability (., nitrite, carbon monoxide) – carbohydrate metabolism (., fluoroacetate), or – oxidative phosphorylation (., dinitrophenols) ? rotenone ? antimycin A ? cyanide and carbon monoxide ? Toxicity may result in myocardial necrosis Direct Cardiotoxicity: Myocardial Degeneration amp。 Myocytolysis Toxicant Interference With Oxidative Phosphorylation Rotenone X Antimycin A X Cyanide and carbon monoxide X Toxicants That Alter Myocardial Conduction ? Alter impulse formation and cause arrhythmias – Toxicants that cause acidosis and hyperkalemia (., ethylene glycol) ? enhance slow current activity ? increase automaticity and promote arrhythmia – Cardiotoxic divalent ions (., barium, strontium) ? replace calcium in slowcurrent channels ? alter efflux of potassium from myocardial cells ? hypokalemia and arrhythmias Toxicants That Alter Myocardial Conduction ? Alter impulse formation and cause arrhythmias – Toxicants that cause prolongation of the QT interval (., seldane) – Blockage of multiple ionic channels that may lead to syncope and ventricular fibrillation (torsade de pointes) P Q S R T U QT Interval Toxicants That Cause Prolongation of the QT Interval ? Over 100 marketed pharmaceutical agents cause interference in ventricular repolarization ? QT prolongation is mentioned in the FDAapproved labeling as a known action of the drug ? . Terfenadine (Seldane174。) – antihistamine/removed in 1997 Chlorpromazine (Thorazine174。) – antipsychotic Arsenic trioxide (Trisenox174。) – anticancer/leukemia Erythromycin (Erythrocin174。) – antibiotic Fluoxetine (Prozac174。, Sarafem174。) – antidepressant Haloperidol (Haldol174。) – antipsychotic/schizophrenia Toxicants That Alter Myocardial Conduction ? Alter impulse formation and cause arrhythmias – Halogenated hydrocarbons (., chloroform) ? suppress SA node (AV node bees pacemaker) ? sensitizes myocardium to arrhythmogenic effects of sympathomimetic amines (catecholamines) – Cardiac glycosides (., digitalis) ? inhibit the sodiumpotassium exchange mechanism ? decreased intracellular potassium, increased intracellular sodium ? catecholamine sensitivity ? increase refractory period of the AV node Toxicants That Alter Cell Membrane Function ? Alter cell membrane control of ion movement and affect cardiac contraction – Cardiac glycosides and catecholamines – Chemical ionophores (., monensin) ? facilitates the passage of sodium, potassium, or calcium ? monensin: alters Ca2+ and Na+ transport ? increased intracellular calcium ? changes myocardial contractility ? excessive calcium accumulation impairs mitochondrial oxidative phosphorylation ?
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