2. Drug metabolism is the metabolic breakdown
of drugs by living organisms, usually through specialized
enzymatic systems.
DrugDrug
MetabolismMetabolism
3. Many factors affect the rate and pathway of
metabolism of drugs, and the major influences can be sub-
divided into internal (physiological and pathological) and
external (exogenous) factors as indicated below:
Internal: species, genetic sex, age, hormones,
pregnancy, disease.
External: diet, environment.
Factors that affect drug metabolismFactors that affect drug metabolism
5. Drug metabolism in Thyroid disease:
Non Hepatic
Thyroid hormone regulates the metabolism of
drugs by hepatic cytochrome p 450 enzyme.
ExampleExample: Anti seizures medication, digoxin, narcotics
drug decrease the metabolism in hypothyroidism.
6. Effects of Renal diseases on Drug Metabolism
1. Most drug Phase II metabolites are effectively
prevented by their water solubility
2.Effects on other variables such as protein binding,
hepatic blood flow and accumulation of metabolites
7. Abnormal drug metabolism in chronic pancreatitis
1. Functional and morphological changes in
hepatocytes, indicating induction of the drug
metabolizing enzymes and free radical-mediated
damage.
2.Pancreatic and liver damage in chronic pancreatitis
proceed independently but by the same mechanism-
heightened, but unmitigated, oxidative detoxification
of xenobiotics by cytochromes P450
8. Hepatic DiseasesHepatic Diseases
Effects of Liver Disease on Drug Metabolism:
A number of hepatic diseases have showed effects on
drug metabolism. These are:
1.Cirrhosis of the liver
2.Alcoholic liver disease
Acute Ethanol Exposure = Chronic Ethanol Exposure =
Alcoholic Cirrhosis
9. 3.Cholestatic jaundice
4.Viral hepatitis
Viral hepatitis causes the decrease of hepatic drug
metabolism.
ExampleExample:
most common types of viral hepatitis are Hepatitis
A, Hepatitis B, and Hepatitis C.
10. 5.Liver carcinoma
6.Hepatoma
It is actually cancerous growth of liver parenchymal
cells. The presence of different parenchymal cells can
decrease the hepatic drug metabolism by 20%.
7.Tumor growths in liver
11. The possible reasons for liver decrease capacity are listed
below:
1.Decrease enzyme activity in liver
2.Altered hepatic blood flow (intra/extra hepatic
shunting)
3.Hypoalbuminaemia (leading to lower plasma binding
of drugs).
12. The effect of Jaundice on drug metabolism
• Obstructive jaundice affects liver microsomal drug
metabolism in rough proportion to the degree of
histologically observable cell damage.
• Livers with mild cellular damage often retain essentially
normal hexobarbital metabolism while other pathways
are markedly reduced from normal levels.
• Severe cellular damage leads to nearly complete loss of
all the drug enzyme activities studied.
