This document summarizes a lecture on factors that can modify the effects of drugs. The lecturer discusses how physiological factors like body size, age, gender, and pregnancy can impact drug absorption, distribution, metabolism and excretion. Genetic factors like pharmacogenetics and environmental factors like concurrent illnesses can also influence drug effects. Multiple steps from prescription to a drug's effects can be modified, requiring dosage adjustments. The lecture aims to describe these modifying factors and their implications for personalized drug prescriptions.

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!