Document Type

Thesis - Open Access

Award Date

1970

Degree Name

Master of Science (MS)

Department

Pharmacy

Abstract

Gout is one of the earliest disease entities to be described in medical writings. Hippocrates noted familial distribution patterns and described its classic symptomatology in the 5th century B.C. Empirical treatment employing colchicine was advocated by Alexander of Tralles in the 5th century A.D. A better understanding of the complex association between clinical manifestations of gout and uric acid, carbohydrate and lipid metabolism has made rational treatment possible only very recently. Ample experimental and clinical data now available show a definite association between disorders of purine metabolism resulting in hyperuricemia and frequent concomitant hyperlipidemia. A high incidence of both hypercholesterolemia and hypertriglyceridemia has been documented. Elevated serum lipids may explain, in part, clinical manifestations of atherosclerosis, occlusive peripheral and coronary arterial disease and vascular nephrosclerosis so common in approximately 800,000 individuals suffering from gout in the United States. Renal failure, ischemic and degenerative cardiovascular disease are the most common cause of: death in these patients. Therefore, the need for safe and reliable drugs that may be employed in the rational treatment of both gout, and associated cardiovascular alterations is abundantly clear. Allopurinol (hydroxypyrazolo(3,4-d)pyrimidine) (HPP) is by far the most promising drug now available for treatment of gout and related hyperuricemic disorders. It represents a new and rational approach to therapy by inhibiting an enzyme essential to uric acid biosynthesis. The correlation between gout and clinical manifestations of atherosclerosis associated with hypercholesterolemia and hypertriglyceridemia dictates that drugs used in treating hyperuricemic conditions should not elevate serum lipids. A further elevation of these parameters could increase the incidence of cardiovascular disease in highly susceptible gouty subjects. A possible causal relationship between therapeutic use of allopurinol and elevations· in blood lipid values (human subject) was reported for the first time by this station in April, 1969. A subsequent preliminary animal study indicated an apparent experimentally provoked hypercholesterolemic hyperlipemia in rabbits administered allopurinol. This study was initiated to examine the problem in greater detail.

Library of Congress Subject Headings

Gout
Uric acid

Number of Pages

72

Publisher

South Dakota State University

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