This presentation includes: Factors modifying drug effect- physiological factors

1. Pharmacodynamics-III
Dr. Pravin Prasad
M.B.B.S., MD Clinical Pharmacology
Lecturer, Lumbini Medical College & TH
13 December, 2018 (27 Mangsir, 2075),
Thursday

2. Pre-test
What factors do you think
can modify the affect of a
drug?
Can you categorize them?
What will be the clinical
implication of this topic?

3. By the end of the class, MBBS
Ist year students will be able
to:
List the factors that can modify the action of a
drug
Describe the basis of modification of drug
action by various factors
Apply the information to modify the drug
prescription in clinical setting

4. Introduction
Multiple steps between the drug being prescribed
and the effect of drug in an individual
Potential to affect each step exists
Modification of drug can be:
Qualitative: different effect than expected
Quantitative: increase or decrease in expected
effect
Modification can also be intra-individual as well as
inter-individual

5. From prescription to effect of
drug
Prescribed
Dose
Concentration at site(s) of
action
Drug effects
Administered
Dose

6. From prescription to effect of
drug
Prescribed
Dose
• Medication error
• Patient compliance
Administered
Dose

7. From prescription to effect of
drug
Concentration at site(s) of
Administered
Dose
• Rate and extent of absorption
• Body size and composition
• Distribution in body fluids
• Binding in plasma and tissues
• Rate of metabolism and excretion

8. From prescription to effect of
drug
Concentration at site(s) of
action
Drug effects
• Drug receptor interaction
• Functional state of targeted
system
• Selectivity of drug, propensity to
produce side effects
• Placebo effects
• Resistance

9. Factors affecting drug action
Physiological variables:
Body size/weight, age, gender, race,
pregnancy/ lactation,
Genetic factors:
Pharmacogenetics
Psychological factors:
Placebo, Nocebo

10. Factors affecting drug action
Environmental factors:
Environmental exposure, timing of drug
administration
Pharmacological variables:
Route of administration, tolerance and
desensitization, drug interaction, cumulation
Pathological variables:
Gastrointestinal, renal, cardiac, thyroid disease
conditions

11. Drug effect and body size
Influences the concentration of the drug attained
at the site of action
Obese/lean
Children
Dose can be modified using:
Body weight (BW)
• Individual dose = (BW x average adult
dose)/70
Body Surface area (BSA)

12. Drug effect and Age
Infant/Children vs Adult
Low g.f.r and tubular transport – Gentamicin
and Penicillin
Low hepatic drug metabolizing systems in
newborns – gray baby syndrome
Blood brain barrier (BBB) is more permeable
– Kernicterus

13. Drug effect and Age
Infant/Children vs Adult
lower gastric acidity ad slow intestinal
transit- altered absorption of drugs
Faster transdermal absorption and faster
rectal absorption – Diazepam
After one year age, faster metabolism than
adults – phenytoin, carbamazepine

14. Drug effect and Age
Calculation of child dose
Young’s formula
• Child dose = {Age/(Age+12)} x adult dose
Dilling’s formula
• Child dose = Age/20 x adult dose

15. Drug effect and Age
Elderly
Decreased gut motility and blood flow to
intestines  slower absorption
Decreased hepatic microsomal enzyme activity
• Decreased first pass metabolism
• Overall effect on drug metabolism: not
uniform
Lower plasma protein  lesser plasma protein
binding

16. Drug effect and Age
Elderly
Altered volume of distribution
Decreased renal function
• 50 years  75%, 75 years  50%
Prone to develop cumulative toxicity on
prolonged medication
Enlarged prostate

17. Drug effect and Age
Elderly
Intolerant to digitalis
Decreased responsiveness to β adrenergic
drugs
Likely to be on multiple drugs  Drug
interaction
More Likely to develop adverse drug
reactions
• Postural hypotension, giddiness, mental

18. Drug effects and Gender
Male gender and effects of drug:
Interfere with the sexual
function
• Antihypertensive (clonidine,
diuretics, methyldopa)
Gynaecomastia
• Ketoconazole,
metoclopramide,
chlorpromazine, digitalis

19. Drug effects and Gender
Female gender and effects of drugs:
Smaller body size  lower dose
Subjective effects may differ
Digoxin for heart failure in women  higher
mortality
Androgen in women  not acceptable
Physiological states: menstruation,
pregnancy, lactation

20. Conclusion
Modification of drug action can occur due to
multitude of reasons affecting each step from
the drug being prescribed to the effects of
drugs on the patient
Factors can be physiological, psychological,
genetic, pathological, environmental,
pharmacological
Choice of drug and the dose of drug needs to
be modified if any of these factors are present
in an individual

21. Next class…
Tuesday, 18 December (10-11 am)
Topics:
Factors modifying drug action- remaining
portion
Combined effects of drugs
Any queries?
Thank you!