This document discusses factors that can modify drug actions in different individuals. It notes that individuals can vary in how they metabolize and respond to drugs due to differences in physiology, pathology, environmental exposures, and psychological state. Some key modifying factors mentioned are body size, age, pregnancy, liver and kidney function, smoking, and interactions with other medications. Understanding these sources of variability helps explain why the same prescription may have different effects between people.

1. FACTORS MODIFYING
DRUG ACTONS
DR. VANI. J
Assistant Professor

2. DIFFERENT PEOPLE - SAME PRESCRIPTION
Individuals vary in drug effect from time to time & from other individuals

3. REASON:
• Individual Variation in Pharmacokinetic handling
• Variation in number / state of receptors
• Variations in neurogenic / hormonal tone

4. DIFFERENT PEOPLE - SAME PRESCRIPTION
QUANTITATIVE

5. QUALITATIVE -IDIOSYNCRASY

7. Variables:

8. I. Physiological factors
i) BODY SIZE
 Drug Concentration
 Individual dose= BW/70* Average adult dose
 Body Surface Area
 Individual dose = BSA /1.7 * Average adult dose
 BSA – BW & Height

9. I. Physiological factors
i) BODY SIZE
 Drug Concentration
 Individual dose= BW/70* Average adult dose
 Body Surface Area
 Individual dose = BSA /1.7 * Average adult dose
 BSA – BW & Height

10. I. Physiological factors
i) Age
 Extreme of age show extreme drug sensitivity
 Newborn babies & elderly

12. CHILDREN

14. 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

15. iv) Lactation
Drugs easily appear in milk but < therapeutic dose
E.g., tetracycline, sedatives, hypnotics, opoids

19. Plasma choline estrase variant (suxamethonium)
 Hydrooxylase polymorphism (extensive or poor
metabolism of debrisoquine)

20. ROUTES OF DRUG DELIVERY

21. IV. Psychological Factors

23. 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

24. II. Pathological state
• Pathological condition modify drug action
E.g., impaired renal function = drug excretion = drug accumulation
Liver disease= metabolism of drug=accumulation

25. Gastrointestinal (g.i.) diseases
• NSAIDs- aggravate peptic ulcer disease
• Achlorhydria – aspirin absorption by favouring its ionization

26. Liver disease
Cirrhosis - * Bioavailability of drugs with high first pass metabolism
*Serum albumin  more drug in free form
*Metabolism and elimination of Morphine ,Lidocaine ,
Propranolol  dose to be reduced
*Prodrug – Bacampicillin less effective
Brisk diuresis  Hepatic encephalopathy ( NH4  NH3)

27. Renal diseases
• Cl cr  Clearance of Aminglycosides, Digoxin
Phenobarbitone  maintainance dose to be
reduced

28. Renal disease
• BBB permeability in renal failure  CNS depression( Opiates
,barbiturates)
• . Nephrotoxic drugs – Aminoglycosides, Tetracyclines ,Vancomycin to
be avoided in renal failure
• . Potassium sparing diuretics contraindicated

30. 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

31. VI) Interaction with other drugs
 Ampicillin /Amoxicillin + OCP = Contraceptive
failure
Probenecid + Penicillin = Prolongation of
Penicillin activity (Inhibits tubular secretion )