Pharmacology & Therapeutics. Part C: Clinical Pharmacology and Therapeutics最新文献

Adriamycin is an effective antineoplastic agent with dose-limiting acute toxicity and a cumulative dose-dependent cardiotoxicity. It undergoes extensive biotransformation to both active and inactive compounds; changes in metabolism may affect its therapeutic index.

Hepatic metabolism and bile secretion are the major routes of drug elimination. Factors which affect liver function, whether disease-related or due to concomitant drug administration, may affect both adriamycin efficacy and toxicity.

Cardiomyopathy due to adriamycin has a biochemical basis, but presently the mechanisms are unknown. Methods to avoid this complication are under study.

Consideration of the cytokinetics of normal and tumor cells may be as important in planning adriamycin combinations as is consideration of drug-drug interactions.

Because of its broad spectrum of action and high antitumor activity, adriamycin is used in many cancer patients both as a single agent and in combination with other drugs. An understanding of the pharmacology of this drug by the physicians who administer it will lead to better selection of appropriate patients, drug combinations and dosage schedules. This increased awareness of adriamycin pharmacology should be translated into safer, more efficacious therapy for cancer patients.

The topic of thyroid cancer has been highly controversial in all its aspects, but most of all in its histologic classification and its management. The present section is an attempt to crystallize the vast literature in this area. The histology and the ultrastructure of thyroid tumors is discussed. The etiologic factors involved in the development of thyroid cancer are largely unknown; the high incidence of thyroid cancer in Hawaii points to important environmental factors causing malignancies in the thyroid. The importance of radiation to the neck area in childhood is another recognized etiologic factor in the development of thyroid tumors. Isotope scanning techniques are discussed. Ultrasonography is useful for the diagnosis of cystic lesions of the thyroid. Finally the variable surgical procedures used by various authors in the management of differentiated thyroid cancer is reviewed; the rationale for performing a total thyroidectomy in these cases, as advocated by the authors, is discussed. The use of radioiodine therapy following surgery', treatment with suppressive doses of thyroid hormone and the use of adriamycin as a treatment for thyroid cancer uncontrollable by other means are discussed.

Stimulation of erythropoiesis has been induced in patients by the administration of massive doses of androgenic hormones. There is an increase in hemoglobin and hematocrit, reticulocytosis, increase in red blood cell mass, development of a normoblastic hyperplasia of the bone marrow, and polycythemia may occur. The extensive studies of the influence of the endocrine glands on the formed elements of the blood in animals and man demonstrate the relationship of erythropoiesis and the androgenic hormone.

Because of the effect of androgenic hormones on hematopoiesis, these hormones have been employed in the treatment of a variety of hematopoietic diseases. Improvements have been noted in myelofibrosis, chronic lymphatic leukemia, aplastic anemia, and specific refractory anemias. The androgens have been employed as adjuvant therapy to stimulate bone marrow during the chemotherapy of a variety of neoplastic diseases. The androgenic hormones provide a specific treatment as well as an adjuvant therapy in the management of hematological abnormalities.

The actions of thyroid hormone in the obese patient appear to be qualitatively similar to the effects in normal weight individuals, although there may be some small quantitative differences in the magnitude of the response. These effects include an increase in metabolic requirements, an increase in turnover of protein, fatty acids and calcium, and modification of enzymatic and hormonal systems.

The decision as to whether thyroid is useful in the treatment of an obese patient depends on the particular question. If the patient is clinically or chemically hypothyroid, there is little question that its use is necessary. For the euthyroid obese patient, however, there may also be a place for the judicious use of thyroid hormones. Such a situation might arise during profound caloric restriction when metabolic rate is known to decline. In this situation, the appropriate doses of thyroid hormone may obviate this physiologic adaption of caloric deprivation.