Pharmacokinetics 33(an aromatic compound) is excreted in the
urine as N-acetylcysteine derivatives called
as mercapturic acid.
Glycine Conjugation
Certain drugs having carboxylic acid
groups are often inactivated by conjugation
with glycine for example, salicylic acid.
FACTORS AFFECTING DRUG METABOLISMAGE
In general, infants and older (human or
animals) tend to be more sensitive to the
action of the drugs. The impairment of drug
metabolism in the new born infants usually
results from a diminished capacity to
deactivate drugs and consequently to more
prolonged pharmacological action and to
increased toxic reactions.
NUTRITION
Protein or calcium deficiency impairs
drug metabolism in animals, due to de-
creased activity of the microsomal enzymes
of the liver. The sleeping time by
hexobarbitone is increased as a result of pro-
longed protein malnutrition. Acetylsalicylic
acid has been shown to be more toxic to ani-
mals on a diet deficient in protein and mag-
nesium.
The rates of metabolism are also
impaired in vitamin deficiency states
(especially vitamin A, vitamin B 2 , C and E).
Starvation in mice leads to decrease in the
rates of metabolism of certain drugs like
pethidine, acetanilide, hexobarbitone etc.
Ethanol increases the hepatic content of
monooxygenase enzymes and cytochrome
P450 on chronic ingestion.
DISEASE CONDITIONS
Patients with liver disease may exhibit
an increased sensitivity of many drugs.
Patients with obstructive jaundice, hepatitis,
cirrhosis shows reduce ability to synthesize
glucuronide and sulfate conjugates.
Experimentally induced obstructive
jaundice in animals (by ligation of bile ducts)
decreases rate of metabolism of certain
drugs like hexobarbitone, chlorpromazine,
codeine etc.SEX
The sex difference in the metabolism of
drugs has not been observed in human
beings. However, in rats, the pharmacological
activity of a drug is more prolonged and the
toxicity more marked in females than males,
a difference which has been attributed to the
more rapid metabolism of the drugs by the
hepatic microsomal enzymes of the male rat.PREGNANCY
During late pregnancy in rats, the
conjugation of drugs with glucuronic acid
(a major pathway for the deactivation of
drugs) is reduced to about 50%. Certain
oxidative metabolic transformations of
drugs are also inhibited in pregnancy.HORMONAL EFFECTS
The hormones of adrenal glands, thyroid
and pancreas exert various effects on the
metabolism of drugs. Adrenalectomy of cer-
tain species e.g. rat impairs the metabolism
of certain drugs, which can be reversed by
administration of cortisone or prednisolone.
Administration of ACTH, adrenaline or thy-
roxine impairs the hepatic microsomal me-
tabolism of drugs. Thyroidectomy reduces the