RESUMO
Amiodarone is the drug of choice in the treatment of atrial fibrillation and other forms of tachyarrhythmia. It is usually combined with anticoagulants and antiplatelets. Drug interactions are a common event in medical practice and occur more frequently than is clinically recognized. This study aimed to explore the possible interactions between amiodarone and both aspirin and warfarin. Sixty adult male albino rats were used and divided into 6 groups [n=l0]; control group was given distilled water, aspirin group was given aspirin [7.5 mg/kg/day], warfarin group was given warfarin [0.9 mg/kg/day], amiodarone group was given amiodarone [18 mg/kg/day], amiodarone plus aspirin group was given amiodarone and aspirin in the same previous doses and amiodarone plus warfarin group was given amiodarone and warfarin as previously. All drugs were given orally daily for two weeks. At the end of the experiment, thyroid function represented by serum triiodothyronine [T3] and thyroxine [T4] were measured by radioimmunoassay. In addition serum thyroid stimulating hormone [TSH] by chemiluminescnce [immunoassay]. Serum aspirin, warfarin and amiodarone levels by HPLC method, prothrombin time [PT] and international nornialized ratio [INR] were also determined. Histopathological examination of thyroid glands by light microscope was also performed. The results of the study revealed that amiodarone either alone or combined with aspirin or warfarin increased serum T4 levels and decreased serum T3 and TSH levels. Amiodarone/aspirin combination represented the highest increase in T4.While, amiodarone /warfarin combination represented the marked decrease in serum T3 and TSH levels. Moreover, serum amiodarone level was non significantly increased in amiodarone /aspirin group and highly increased in amiodarone /warfarin group. Serum warfarin level was also increased in amiodarone /warfarin group. Histopathological examination of thyroid glands showed signs of thyrotoxicosis in amiodarone either alone or combined with aspirin or warfarin groups that revealed lymphocyte infiltration, lymphoid follicles, vacuolated colloid and papillary folds of the acinar epithelium. The pathological changes were more severe in amiodarone/warfarin group that showed destructed acini, degenerative changes and fibrosis. Moreover, prothrombin time [PT] and INR were highly increased in amiodarone/ warfarin combination group and slightly increased in aspirin, warfarin, amiodarone and amiodarone/aspirin groups. Amiodarone/warfarin combination led to increase in serum amiodarone level and its thyrotoxic effect. Also this combination led to increase in serum warfarin and augmented its anticoagulant effect to great extent represented by elevated PT and INR. While amiodarone /aspirin combination represented less effect on thyroid gland and PT and INR. It is recommended to asses thyroid function regularly and should be performed at short intervals when amiodarone combined with anticoagulant or antiplatelet therapy, in order to detect AM induced hypo- or hyperthyroidism. Also, frequent monitoring of PT and INR with modification of the dose especially of warfarin as controlled by measuring PT and INR