General Principles Of Pharmacology:Drug transformation in diseases and drug metabolism

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1 Liver Disease
2 Cardiac Disease
3 Pulmonary Disease
4 Endocrine Dysfunction

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Liver Disease

Acute or chronic diseases that affect liver architecture or function markedly affect hepatic metabolism of some drugs. Such conditions include fat accumulation, alcoholic hepatitis, active or inactive alcoholic cirrhosis, hemochromatosis, chronic active hepatitis, biliary cirrhosis, and acute viral or drug hepatitis. These conditions may impair hepatic drug-metabolizing enzymes, particularly microsomal oxidases, and thereby markedly affect drug elimination. For example, the half-lives of chlordiazepoxide and diazepam in patients with liver cirrhosis or acute viral hepatitis are greatly increased, with a corresponding prolongation of their effects. Consequently, these drugs may cause coma in patients with liver disease when given in ordinary doses.

Liver cancer has been reported to impair hepatic drug metabolism. For example, aminopyrine metabolism is slower in patients with malignant hepatic tumors than in normal controls. Impairment of enzyme activity or defective formation of enzymes associated with heavy metal poisoning or porphyria also results in reduction of hepatic drug metabolism.

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Cardiac Disease

Cardiac disease, by limiting blood flow to the liver, may impair disposition of those drugs whose metabolism is flow-limited. These drugs are so readily metabolized by the liver that hepatic clearance is essentially equal to liver blood flow.

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Pulmonary Disease

Pulmonary disease may affect drug metabolism, as indicated by the impaired hydrolysis of procainamide and procaine in patients with chronic respiratory insufficiency and the increased half-life of antipyrine in patients with lung cancer.

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Endocrine Dysfunction

The effects of endocrine dysfunction on drug metabolism have been well explored in experimental animal models; corresponding clinical data for animals with endocrine disorders are scanty. Thyroid dysfunction has been associated with altered metabolism of some drugs and of some endogenous compounds as well. Hypothyroidism increases the half-life of antipyrine, digoxin, methimazole, and practolol, whereas hyperthyroidism has the opposite effect.

Malfunctions of the pituitary, adrenal cortex, and gonads markedly impair hepatic drug metabolism in rats. On the basis of these findings, it may be supposed that such disorders could significantly affect drug metabolism. However, until sufficient evidence is obtained from clinical studies, such extrapolations must be considered tentative.

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General Principles Of Pharmacology:Drug transformation in diseases and drug metabolism

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Liver Disease

Cardiac Disease

Pulmonary Disease

Endocrine Dysfunction

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