Abstract
The most commonly occurring cardiotoxic reactions in humans are due to over-exposure to chemicals that affect physiological function of the heart. These effects, which are usually receptor-mediated, are dose related and can generally be predicted from safety studies in animals. Direct chemical toxicity is initiated by an interaction of a reactive metabolite of the xenobiotic with cellular macromolecules. The incidence of such cardiotoxicity is low because few of these chemicals are metabolized in the heart. The concentration of cellular protective substances influences the development of such toxicity, and therefore species variation should be considered in safety studies. Chemically induced immune system-mediated reactions can develop in the heart, and may occur in anaphylaxis. Antibody mediated cytotoxic or immune complex reactions are rare events, and the predictability is poor. In some instances sensitivity is immunogenetically controlled. Cardiotoxic effects can also develop after prenatal exposure to chemicals, and thus consideration should be given to examining the offspring for those effects in teratology studies.
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References
Balazs T, Bloom S (1982) Cardiotoxicity of adrenergic brochodilator and vasodilating antihypertensive drugs. In: Van Stee EW (ed) Cardiovascular toxicology. Raven Press, New York, pp 199–220
Balazs T, Johnson G, Joseph X, Ehrreich S, Bloom S (1983) Sensitivity and resistance of the myocardium to the toxicity of isoproterenol in rats in myocardial injury. Adv Exp Med Biol 161: 563–577
Boor PJ, Nelson Ti (1982) Biotransformation of the cardiovascular toxin allylamine, by rat and human cardiovascular tissue. J Mol Cell Cardiol 14: 679–682
Chouinard G, Annable L (1977) Phenothiazine induced ECG abnormalities. Arch Gen Psychiatry 34: 951–955
Dertinger DL, Beaver DC, Lands AH (1948) Toxicity of 1-(3,4-dihydroxyphenyl)-2-isopropylamino ethanol. Proc Soc Exp Biol Med 68: 501–507
Ehrreich SJ, Kandil A (1981) Cardiotoxicity of ß-adrenergic blocking agents. In: Balazs T (ed) Cardiac toxicology, vol 2. CRC Press, Boca Raton, FL, pp 113–125
Ferrans VJ (1983) Anthracycline cardiotoxicity in myocardial injury. Adv Exp Med Biol 161: 519–532
Fowler NO, McCall D, Chou T-C, Holmes JC, Hanenson IB (1976) Electrocardiographic changes and cardiac arrhythmias in patients receiving psychotropic drugs. Amer J Cardiol 37: 223–230
Harned HS (1983) Cardiovascular problems of the newborn and their etiologies. In: Grabowsky CT, Kavlock RJ (eds) Abnormal development of the heart, lungs and kidneys. Approaches to functional teratology. Alan R Liss, New York, pp 169–183
Heath A, Swensson C, Martensson E (1985) Thioridazine toxicity — An experimental cardiovascular study of thioridazine and its major metabolites in overdose. Vet Human Toxicol 27: 100–106
Heggtveit HA, Grice HC, Wiberg GS (1970) Cobalt cardiomyopathy. Experimental basis for the human lesion. Pathol Microbiol 35: 110–113
Magos L (1981) The effects of industrial chemicals on the heart. In: Balazs T (ed) Cardiac toxicology, vol 2. CRC Press, Boca Raton, FL, pp 203–213
Moir DC, Crooks J, Cornwell WB, O’Malley K, Dingwall-Fordyce I, Turnbull MJ, Weir RD (1972) Cardiotoxicity of amitriptyline. Lancet 2: 561–564
Mullick FY, McAllister HA (1977) Myocarditis associated with methyldopa therapy. J Am Med Assoc 237: 1699–1701
Müller V, Burckhardt D (1974) Die Wirkung tri-and tetrazyklischer Antidepressiva auf Herz and Kreislauf. Schweiz Med Wochenschr 104: 1911–1913
Prichard BNC, Walden RJ (1982) The syndrome associated with the withdrawal of ß-adrenergic receptor blocking drugs. Br J clin Pharmac 13: 337S - 344S
Rangno RE, Langlois S (1982) Comparison of withdrawal phenomena after propranolol, metoprolol and pindolol. Br J clin Pharmac 13: 345S - 3525
Slotkin TA (1983) The cardiac-sympathetic axis as a teratological model. In: Grabowsky CT, Kavlock RJ (eds) Abnormal functional development of the heart, lungs, and kidneys. Approaches to functional teratology. Alan R Liss, New York, pp 237–248
Thompson GE (1981) The heart as a target organ in immune hypersensitivity reactions. In: Balazs T (ed) Cardiac toxicology, vol 1. CRC Press Inc., Boca Raton, FL, pp 201–213
Vohra JK (1974) Cardiovascular abnormalities following tricyclic antidepressant drug overdose. Drugs 7: 323–325
Williams BJ, Abreu ME (1983) Cardiotoxicity of perinatal lead exposure. In: Grabowsky CT, Kavlock RJ (eds) Abnormal functional development of the heart, lungs, and kidneys. Approaches to functional teratology. Alan R Liss, New York, pp 223–235
Zbinden G (1973) Progress in toxicology, vol 1. Springer-Verlag, New York, p 53
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Balazs, T. (1986). Cardiotoxicity Mechanisms from the Point of View of Preclinical or Premarketing Safety Evaluation. In: Chambers, C.M., Chambers, P.L., Tuomisto, J. (eds) Toxic Interfaces of Neurones, Smoke and Genes. Archives of Toxicology, vol 9. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-71248-7_22
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DOI: https://doi.org/10.1007/978-3-642-71248-7_22
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