Transcript 02. Factors modifying drug actions

FACTORS MODIFYING DRUG
ACTONS
DR. SHABANA ALI
(Associate Professor)
FACTORS MODIFYING DRUG
ACTIONS
 Individuals vary in drug effect from time to time &
from other individuals
Nature of systemic effects of drugs depends on following
factors:
Physiological factors (age, sex, pregnancy, lactation, body
wt., food)
Pathological state (kidney or liver disease)
Environmental factors
cont.
Psychological /emotional state
Interaction with other drugs (drug-drug interactions)
I. Physiological factors
i) Age
Extreme of age show extreme drug sensitivity
 Newborn babies & elderly= greater & more prolonged
effect of drugs b/c of less efficient drug metabolism &
renal functions

Infants
Premature infants= poor renal & hepatic functions
sensitive to various drugs
more
E.g.,
 Chloramphenicol = Gray baby syndrome (inadequate
metabolism)
 Ampicillin & morphine =
GIT absorption (less acidity)
 Tetrycycline = staining of teeth
 Corticosteroids = retardation of growth in children
Elderly
 Renal & hepatic function decline slowly after
middle age
 Activity of hepatic microsomal enzymes decline
with age
 Vd of lipid soluble drugs increases
 Elderly require less due to degenerative changes
in kidney, liver, brain, heart
Cont.,
E.g., Diazepam & benzodiazepines =
Digoxin = Vd
t1/2
Benzodiazepines= more confusion & less sedation in
elderly
Hypotensive dugs= postural hypotension in elderly
ii) Sex/Gender
 Response & dose= d/f in men & women
 Metabolism of some drugs= less in women (more
adipose tissues)
E.g., alcohol, diazepam
 Women require lesser dose than male
iii) Pregnancy
 Avoid drugs during pregnancy due to teratogenic effects
Reasons
 Lipophilic drugs cross placental barrier
 CO
 GFR & renal elimination
 Vd
 Metabolism of some drugs
E.g., pregnant uterus becomes more sensitive to
oxytocin
iv) Lactation
 Avoid drugs during lactation due to harm to baby
 Drugs easily appear in milk but < therapeutic dose
E.g., tetracycline, sedatives, hypnotics, opoids
V) Body wt./surface area & size
 Conc. Of drug at site of action=ratio b/w body wt. &
amount of drug
 D/f quantity of drug for light & heavier persons
 D/f quantity of drug for smaller & larger persons
 Low amount of drug for smaller perosns
vi) food
 Some drugs have interaction with food and they alter the
response of drug
 E.g., toxic symptoms appear after eating of cheese, red wine
& chicken liver if patient is taking MAOI (more release of
NA=fatal cerebral hemorrhage)
II. Pathological state
 Pathological condition modify drug action
E.g., impaired renal function =
drug excretion = drug
accumulation
Liver disease= metabolism of drug=accumulation
Cont.
 Disease
can
cause
pharmacokinetic
pharmacodynamic variation
a) PK variation
Variation in absorption
Gastric statis –in migraine
Malbsorption ---ileal or pancreatic disease
Cont.
or
Variation in distribution
 Alterd PPB of phenytoin in chronic renal failure (binding
of phenytoin to PPB 
Variation in metabolism
Hepatic cirrhosis & portal HTN
Variation in excretion
Acute and /or chronic renal failure
Pharmacodynamic alterations
Variation in receptors
 In mysthania gravis, nephrogenic diabetes inspidus,
familial hypercholesterolemia
III. Genetic factors

It affects drug action due to genetic differences
among the races & certain persons in same
population
 Genetic variation is an important source of PK
variability
Examples:
a) Genetic polymorphism= fast/slow acetylators
(hydralazine, procainamide, isoniazid)
Cont.
 Plasma choline estrase variant (suxamethonium)
 Hydrooxylase polymorphism (extensive or poor
metabolism of debrisoquine)
 Ethnic
differences in drug metabolism =
propranolol, hemolytic anemia due to some
oxidizing agents (primaquine, sulphonamides)
IV. Environmental factors
Microsomal enzyme inducers
e.g., Hydrocarbons in tobacco smoke, charcoal
broiled meat induce CYP1A
Smokers metabolize drugs more rapidly than non
smokers
V) Psychological state
 General anesthetics required in dose for
nervous & anxious patients
 Higher doses of chlorpromazine needed in
schizophrenics
 Placebos
(inert dosage form) produce
therapeutic benefits in psychomotor angina
pectoris & bronchitis in asthma
VI) Interaction with other drugs
 Administration of one drug (A) can alter action
of another drug (B) by PK or PD mechanisms
 This is c/d drug-drug interaction
 May be desired or beneficial like multidrug
treatment of tuberculosis
 Or undesirable or harmful