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 interactions) other drugs (drug-drug

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 more sensitive to various drugs

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

or

a) PK variation
Variation in absorption Gastric statis in migraine Malbsorption ---ileal or pancreatic disease
Cont.

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