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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 =
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.,
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
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
dose
vi) food
Some drugs have interaction with food and they
cheese, red wine & chicken liver if patient is taking MAOI (more release of NA=fatal cerebral hemorrhage)
E.g., impaired renal function = drug excretion = drug accumulation Liver disease= metabolism of drug=accumulation Cont.
Disease
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
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
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.
metabolism of debrisoquine)
Ethnic
differences in drug metabolism = propranolol, hemolytic anemia due to some oxidizing agents (primaquine, sulphonamides)
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
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