1. FACTORS AFFECTING
BIOTRANSFORMATION OF
DRUGS
PRESENTED BY:
HADIA ARSHAD

2. TYPES OF FACTORS
• Chemical
• Biological
• Altered Physiological
• Temporal
• Route of Drug Administration
• Enviornmental

3. Chemical Factors
1. Enzyme Induction
2. Enzyme Inhibition

4. Enzyme Induction
It is a process in which a drug induces or enhances
the expression of an enzyme.
Rifampicin If taken by female patients taking
contraceptives, causes decreased therapeutic effect, leading to
pregnancy.
Phenobarbitone If administered to patients taking warfarin, may
cause therapeutic failure, leading to increased bleeding
tendency.
Auto induction: The phenomenon in which a
drug induces metabolism of other drugs as well
as its own E.g. carbamazepine-antiepileptic.

5. Enzyme Inhibition
Decrease in the drug metabolizing ability of
enzymes. Competition for the active sites
takes place between the inhibitor and the
drugs. When enzyme inhibitor attaches,
less metabolism occurs. E.g.
 Sulfonamides decrease the metabolism of phenytoin so that its
blood levels become toxic.
 Cimetidine decreases the metabolism of propanolol leading to
enhanced bradycardia.
 Oral contraceptives inhibit metabolism of antipyrine.

6. Biological Factors
Age
Gender
Genetics
Race
Diet

7. AGE
In infants microsomal enzyme system is not fully
developed. The rate of metabolism is very low.
Care should be taken in administering drugs in
younger patients.
 Chloramphenicol does not have great efficacy in
infants. Toxic effects in the form of grey baby
syndrome might occur. The baby may be
cyanosed, hypothermic, flaccid and grey in color.
Shock and even death might occur if toxic levels
get accumulated.
 Diazepam may result in floppy baby syndrome in
which flaccidity of the baby is seen.

8. AGE
In elderly, most processes slow down
which leads to decreased metabolism.
Shrinkage of organs occurs as well
along with decreased liver functions
and decreased blood flow through the
liver. All these factors decrease the
metabolism.
The drug doses should be decreased in
the elderly

9. GENDER
Gender related differences in the rate of
metabolism are attributed to sex hormones and
are generally observed following puberty.
 Male have a higher BMR as compared to the
females, thus can metabolize drugs more
efficiently, e.g. salicylates and others might
include ethanol, propanolol, benzodiazepines.
 Women on oral contraceptives metabolize drugs
at a slower rate

10. GENETICS
Drugs behave differently in different individuals due to
genetic variations
Succinyl choline, which is a skeletal muscle relaxant, is metabolized
by pseudocholine esterase. Some people lack this enzyme, due to
which lack of metabolism of succinyl choline might occur. When
administered in those individuals, prolonged Apnea might result.
Different groups of populations might be classified as fast
metabolizers and poor metabolizers of drugs.
For drugs, like Isoniazid, fast acetylators as well as slow acetylators
are present. Fast acetylators cause rapid acetylation, while poor
metabolizers metabolize less. Hepatic acetyl transferrase catalyzes
acetylation. Slow acetylation might occur due to genetic
malformation leading to decreased production.

11. RACE/SPECIES
 Asians, Orientals, Blacks and Whites
might have different drug metabolizing
capacity. Examples include difference in
drug metabolizing capacity of certain
anti malarial.
 Eskimos metabolize drugs faster than
Asians.
 Laboratory animals can metabolize
drugs faster than man e.g. barbiturates.

12. DIET
The enzyme content and activity is altered
by a number of dietary components.
 Low protein diet decreases and high
protein content in diet increases the drug
metabolizing ability.
 Dietary deficiency of vitamins and
minerals retard the metabolic activity of
enzymes.

13. ALTERED PHYSIOLOGICAL
FACTORS
Pregnancy
Hormonal
Imbalance
Disease states

14. PREGNANCY
During pregnancy, metabolism of some
drugs is increased while that of others
is decreased due to the presence of
steroid hormones e.g.
 Phenytoin
 Phenobarbitone
 Pethidine

15. HORMONAL IMBALANCE
Higher levels of one hormone may inhibit the
activity of few enzymes while inducing that of
others. E.g.
 Hypothyroidism increases drug metabolizing
capacity (increased half life of
antipyrine, digoxin, methimazole, practolol)
while hyperthyroidism decreases it.

16. DISEASE STATES
Liver disease such as hepatic
carcinoma, cirrhosis, hepatitis, obstructive jaundice etc
reduce the hepatic drug metabolizing ability and thus
increase the half lives of almost all drugs.
In renal diseases conjugation of salycylates, oxidation of
vitamin D and hydrolysis of Procaine are impaired.
Cardiovascular diseases, although have no direct
effect, decrease the blood flow, which may slow
down biotransformation of drugs like
isoniazid, morphine and propanolol.
Pulmonary conditions may decrease biotransformation.
Procaine and procainamide hydrolysis is impaired.

17. TEMPORAL FACTOR
Diurnal variations and variations in enzyme activity
with light cycle is circadian rhythm.
Enzyme action is maximum during early morning
and minimum in late afternoon which is probably
due to high levels of coticosterone.

18. ROUTE OF ADMINISTRATION
Oral route can result in extensive hepatic metabolism of some
drugs (first pass effect).
Lignocaine is almost completely metabolized if taken by oral
route therefore the preferable route is Topical.

19. ENVIRONMENTAL FACTORS
 Aromatic hydrocarbon contained in Cigarette
smokers act as enzyme inducers.
 Chronic alcoholism might lead to enzyme induction
as well.
 Pesticides or Organophosphate insecticides may act
as enzyme inducers.
 In hot and humid climate biotransformation is
decreased and vice versa.
 At high altitude decreased biotransformation occurs
due to decreased oxygen leading to decreased
oxidation of drugs.

21. EAT A BIG BREAKFAST
AVERAGE LUNCH AND
A TINY DINNER