This document discusses factors that can cause variability in individual responses to drugs. It identifies two types of factors - quantitative factors that increase or decrease drug levels, and qualitative factors that alter the type of response. Some key factors discussed include body weight, age, sex, genetics, disease states, and environmental influences. Tolerance, drug interactions, and cumulative effects can also impact drug responses. Adjusting drug dosages based on these factors can help optimize treatment for each individual.

2. On administration of a drug ,a predicted
response is obtained but some times
Individuals may vary considerably in their
responsiveness such as. . . . . .
respond differently to drugs both from time to
time and from other individuals.
Some would show less than the usual
response , and some may show more than
usual response.
INTRODUCTION

3. QUANITATIVELY: The plasma concentration
and/or action of drug is increased or
decreased.
Most of the factors introduce this type of change
and can be dealt with by adjustment of drug
dosage.
QUALITATIVELY: The type response is
altered.
e.g. drug allergy or idiosyncrasy.
This is less common but often precludes
further use of that drug in the
affected patient.
TWO TYPES OF FACTORS

4. Body weight.
Age.
Sex.
Species and race.
Genetics.
Route of administration.
Time of administration.
Environmental factors.
Pathological state.
Psychotic factors.
Cumulation.
Tolerance.
Drug resistance.
The various factors are . . .

5. • It influences the concentration of the drug attained at
the site of action.
• The average adult dose refers to individuals of medium
built.
• For exceptionally obese or lean individuals and for
children dose may be calculated on body weight(BW)
basis:
Individual dose=BW(kg)/70Xaverage adult dose

6. It has been argued that body surface area(BSA) provides a more
accurate basis for dose calculation, because total body water,
extracellular fluid volume and metabolic activity are better
paralleled by BSA
Individual dose=BSA(m2)/1.7xaverage adult dose.
The BSA of an individual can be calculated from
DUBOIS FORMULA
BSA(m2)=BW(kg)0.425xHeight(cm)0.725x0.007184
BODY SURFACE AREA . . .

7. IN CHILDREN;
• The dose of a drug for children is often calculated from the
adult dose
YOUNG`S FORMULA:
•Child dose = age/age+12xadult dose
DILLINGS FORMULA:
•Child dose =age/20xadults dose
•It can also be calculated (more accurately)
on the basis of BW and BSA.
AGE. . .

8. Children are growing and are susceptible to
special adverse effects of drugs.
e.g. Tetracycline cause permanent staining of
teeth.
•corticosteroids cause suppression of growth and
development of retardation.
•Androgens may promote early fusion of epiphysis resulting
in stunting of stature.
EFFECTS OF DRUGS IN CHILDREN

9. Hepatic drug metabolising system is inadequate in newborns
Chloramphenicol can produce gray baby syndrome
Blood brain barrier is more permiable – drugs attain higher
concentrations in the CNS
accumulation of unconjugated bilirubin causes kernicterus.
GIT absorption of ampicillin and amoxicillin is greater in
neonates due to decreased gastric acidity

10. Drug absorption may also be altered in infants
because of lower gastric acidity and slower
intestinal transit.
Transdermal absorption is faster because their
skin is thin and more permeable.
Therefore infant doses must be learned as such
and are not derived from any formula.
IN INFANTS . . . .

11. Decreased liver function
(diazepam, theophylline)
Decreased kidney function
(digoxin , lithium)
Decreased plasma protein binding
Increased sensitivity to CNS depressants
(diazepam, morphine)
IN OLD AGE PEOPLE . . . .

12. Evidences show that men and women may respond differently
to same drugs.
This may be due to body size, and amount of body fats.
But there are also some less easily explained differences in
gender –specific drug response.
Aspirin shows greater benefit in men than women in
cardiovascular diseases
benzodiazepines decrease metabolism of some drugs in
females.
Testosterone increases the rate of metabolism in males.
 females are more susceptible to
autonomic drugs
( estrogen inhibits choline estrase)

13.  There are many examples of differences in responsiveness to drugs
among different species;
Rabbits are resistant to atropine,
 rats and mice are resistant to digitalis and rat is more sensitive
to curare than cat.
These differences are important while extrapolating results
from experimental animals to man.
Among human beings some racial differences have been observed
e.g. blacks require higher and mongols requires lower
concentration of atropine and Ephedrine to dilate their pupil.
Indians tolerate thiacetazone better than whites

14. GENETICS
Pharmacogenetics; it is the study of relationship
between the genetic factors and drug response.
Pharmacogenomics; it is the use of genetic
information to guide the choice of drug and dose on an
individual basis.
It intends to identify individuals who are either more
likely or less likely to respond to a drug, as well as
those who require altered dose
of certain drugs.

15. Some genetic defects which lead to discontinuous variation in
drug responses
e.g.G-6-PD is responsible for haemolysis with primaquine, and
some oxidizing drugs like sulfonamides,dapsone,quinine,nalidixic
acid.
The low activity of CYP2C9 variants metabolize warfarin at a
slow rate and are at higher risk of bleeding.
Acute intermittent porphyria precipitated by barbiturates is due to
genetic defect in repression of porphyrine synthesis.
Malignant hyperthermia after halothane is due to
abnormal ca2+ release channel
(ryanodine receptor) in the
sarcoplasmic reticulum of skeletal muscle.

16. Route of administration governs the speed and intensity
of drug response
Parenteral administration is often restored to for more
rapid, more pronounced and predictable drug action.
A drug may have entirely different uses through different
routes.
e.g. magnesium sulfate given orally cause purgation,
applied on sprained joints decreases swelling
while intravenously it produces
CNS depression and
hypotension.

17. Subjective effects of drugs may be markedly influenced by
the setup in which it is taken.
Hypnotics taken at night and in quiet familiar
surroundings may work more easily.
.It has been shown that corticosteroids taken as a single
morning dose cause less
pituitary-adrenal supression.

18. Not only drugs modify disease processes
several diseases can influence drug disposition and drug action.
GASTROINTESTINAL DISEASES:
These can alter the absorption of orally administered drugs.
 The changes are Complex and drug absorption can increase or
decrease,
e.g. in coeliac disease absorption amoxicillin is decreased but
that of cephalexin and cotrimoxazole is increased.
 Thus malabsorption syndrome not necessarily reduce
absorption of all drugs.
Gastric stasis occurring during migraine attack
retards the absorption of ingested drugs.
NSAIDs can aggravate
peptic ulcer disease.

19. Bioavailability of drugs having high first pass metabolism is
increased due to loss of hepatocellular function and portocaval
shunting.
 Serum albumin is reduced –
 protien binding of acidic drugs(diclofenac, warfarin) is
reduced and more drug is present in the free form.
Metabolism and elimination of some drugs
 (morphine, lidocaine, propronolol)
is decreased-their dose should
be reduced.

20. Clearance of drugs that are primarily excreted
unchanged (aminoglycosides, digoxin, phenobarbitone)
is reduced parallel to decrease in creatinine clearence.
Binding of acidic drugs is reduced, but that of basic
drugs is not much affected.
The permiability of blood brain barrier is increased in
renal failure
( opiates, barbiturates,phenothiazines,
benzodiazepines etc).

21. Several environmental factors affect drug responses.
Exposure to insecticides, carcinogens, tobacco smoke and
consumption of charcoal broiled meat are well known to induce
drug metabolism.
Type of diet and temporal relation between ingestion and meals
can alter drug absorption.
e.g. food interferes with absorption of ampicillin, but fatty meal
enhances absorption of griseofulvin.

22. Efficacy of a drug can be affected by patient`s beliefs,
altitudes and expectations
.
This is particularly applicable to centrally acting drugs
e.g.nervous and anxious patient requires more
general anasthetic.
Alcohol generally impairs performance but if punishment
(which induces anxiety) is introduced, it may actually
improve perfomance.

23. Any drug will cumulate in the body if rate of
administration is more than the rate of elimination.
However, slowly eliminated drugs are particularly
liable to cause cumulative toxicity.
e.g. prolonged use of chloroquine causes retinal
damage.
Full loading dose of digoxin should not be given if
patient has received it within the past week.
A course of emetine should not be repeated
within 6 weeks.

24. Requirement of higher dose of a drug to produce a given
response.
It’s an adaptive biological phenomenon
Drug tolerance may be two types
1)Natural
2)Acquired
Natural tolerance– the individual is inherently less sensitive
to the drug.
 E.g. black races are tolerant to mydriatics

25. Acquired tolerance:
This occurs by repeated use of a drug in an individual who was
initially responsive.
Body is not capable of developing tolerance to most drugs but
the phenomenon is very easily recognized in the case of CNS
depressants.
An uninterrupted presence of the drug in the body favours
development of tolerance.
However, significant tolerance does not develop to atropine,
digitalis,cocaine,sodium nitroprusside, etc.
Cross tolerance:
It is the development of tolerance to pharmacologically related
drugs
e.g. alcoholics are relatively tolerant
to barbiturates and general anasthetics.

26. Tolerance develops to sedative action of chlorpromazine but not
to its antipsychotic action.
Tolerance occurs to the sedative action of phenobarbitone but not
as much to its antiepileptic action.
Tolerance occurs to anaphylatic and euphoric action of morphine,
but not to its constipating and miotic actions.
DRUG RESISTANCE:
It refers to tolerance of microorganisms to inhibitory action
of antimicrobials,
e.g. staphylococci to pencillin.