RESUMO
Adriamycin (ADM) is an effective antineoplastic drug. However, the amount of ADM that can be administered must be limited because of the risk of developing a severe dose-dependent myocardiopathy. Prenylamine (PNL), a calcium antagonistic drug, provided partial protection against ADM-induced cardiotoxicity in mice and in the rabbit. Thus, it was considered important to evaluate the cardioprotective potential of PNL in patients given ordinary doses of ADM. Twenty-six patients were selected and randomized in two groups, and a double-blind trial was begun. Group A (n = 13): patients received ADM, i.v. at standard oncological doses up to 550 mg/m2, plus placebo, orally. Group B (n = 13): ADM was administered as in Group A, but PNL 200 mg/day was given instead of placebo. Standard ECG and chest radiographs were performed at the beginning of treatment and every two months. Mode-M echocardiograms and 24-hour ambulatory ECGs were obtained previously to the beginning of the ADM treatment and two months after the administration of the last dose of the drug. In Group A, three patients died from oncological causes, total ADM dose was 359 +/- 100 mg/m2, and the mean age was 59.7 years. One patient in this group developed a congestive myocardiopathy while another patient developed a severe supraventricular arrhythmia. In Group B, four patients died from oncological causes, total ADM dose was 367 +/- 132 mg/m2, and the mean age was 63.8 years. No myocardiopathy was found in this group. These findings suggest that simultaneous administration of PNL may mitigate ADM cardiotoxicity, but larger trials are needed to draw definite conclusions.
Assuntos
Cardiomiopatias/prevenção & controle , Doxorrubicina/efeitos adversos , Prenilamina/farmacologia , Idoso , Cardiomiopatias/induzido quimicamente , Doxorrubicina/uso terapêutico , Estudos de Avaliação como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Estudos Prospectivos , Distribuição AleatóriaAssuntos
Cálcio/antagonistas & inibidores , Cardiomiopatias/induzido quimicamente , Eletrocardiografia , Isoproterenol , Prenilamina/farmacologia , Animais , Cálcio/metabolismo , Cálcio/fisiologia , Citoesqueleto/efeitos dos fármacos , Feminino , Haplorrinos , Frequência Cardíaca/efeitos dos fármacos , Masculino , Contração Miocárdica/efeitos dos fármacos , Miocárdio/patologia , Miofibrilas/ultraestruturaAssuntos
Doença das Coronárias/fisiopatologia , Coração/fisiopatologia , Hipóxia/fisiopatologia , Prenilamina/farmacologia , Animais , Doença das Coronárias/prevenção & controle , Eletrocardiografia , Estudos de Avaliação como Assunto , Coração/efeitos dos fármacos , Isquemia/fisiopatologia , CoelhosRESUMO
1. Dopamine was found in the tortoise brain; the highest concentration (3.7 mug/g) occurred in a region of the telencephalon containing the nucleus basalis and cortex olfactoria. This region may be considered similar to the mammalian and avian corpus striatum with respect to dopamine.2. The administration of reserpine or prenylamine substantially decreased the concentration of dopamine in the tortoise brain. This effect appeared later and lasted longer than in birds or mammals. When these drugs were given in doses which nearly depleted brain dopamine the characteristic signs observed in birds or mammals were not present.