Before prescribing any pharmaceutical medicine, the physician should consider certain factors that can modify the effect of the drug. The same dose of a drug can produce different degrees of response in different patients and even in the same patient under different situations. The Important factors modify the effect of a drug are subdivided into two groups: patient related factors and drug related factors. • Patient related factors: age, gender, body weight, presence of food, drug allergy, genetic variation, environmental state, pathological state, psychological state, etc. • Drug related factors: physical state of a drug, route of drug administration, time of drug administration, drug cumulation, drug combination, drug tolerance, drug dependence, etc.

1. Factors affecting drug action
Prof. Amol B. Deore
Department of Pharmacology
MVP’s Institute of
Pharmaceutical Sciences, Nashik

2. Introduction
• Before prescribing any pharmaceutical medicine, the physician should
consider certain factors which can modify the effect of the drug.
• The same dose of a drug can produce different degrees of response in
different patients and even in the same patient under different
situations.

3. Patient related factors
Age,
Gender,
Body weight,
Presence of food,
Drug allergy,
Genetic variation,
Environmental state,
Pathological state,
Psychological state

4. Drug related factors
Physical state of a drug,
Route of drug
administration,
Time of drug
administration,
Drug cumulation,
Drug combination,
Drug tolerance,
Drug dependence

5. Patient Related Factors

6. Age
The tissues of an infant and child are highly sensitive to drugs.
Infants require smaller amount of drug dose than children.
• Prolong gastric emptying time
• Inadequate gastric acid secretion
• Hepatic metabolizing capacity is also under developed
• Low glomerular filtration rate and tubular secretions
• Little plasma protein binding capacity of the drugs

7. Hence children and infants
may not respond to all the
drugs in the same manner as
young adults.
The child dose may be
calculated from the adult dose
until 8 years of age by
• Young’s formula,
• Dilling’s formula,
• Clark’s formula according to
body weight and body
surface area etc.

8. Geriatric age
• Reduced body weight
• Reduced body fat
• Reduced intestinal motility and blood flow
• Reduced renal function
• Reduced hepatic metabolizing capacity
• Altered metal functions
Certain physiological
changes occurring
with geriatric age
group (˃60 years)
and require
corresponding
pharmaceutical
alteration.

9. Gender
Drug response in male and female are not similar.
Physiological differences such as
• Body fat,
• Body-mass index,
• Surface area,
• Total body water,
• CYP isoenzymes
• Hormonal influences

10. Women have more fat cells than men do, so
drugs that deposit in fat may be slowly released
and cause effects for a prolonged period.
In male, testosterone increases the rate of
metabolism of drugs than female.
Special care should be taken if drugs are
administered during menstruation, pregnancy
and lactation.

11. Mensuration: Purgatives
Pregnancy: NSAIDs,
antibiotics such as
tetracycline, anticancer, CNS
depressants and teratogenic

12. Body weight
• Average dose of drug: milligram as a single dose
• adult weighing between 50 and 100 kg.
• The dose of the drug should be adjusted for
-abnormally slim (underweight persons)
-obese persons (overweight persons)
-edema, dehydration, malnutrition or skinniness.

13. Dose calculation
 Dose to be prescribed= Weight in kg x Adult dose
70
 Dose to be prescribed= Body surface area in m2 x Adult dose
1.7

14. Presence of food in stomach
Medicines are usually taken
after a meal
• to reduce the risk of
gastric irritation, nausea
and vomiting.
Food, however, can have
significant effect on the
pharmacokinetics of drugs.
• Generally, food reduces
the rate and the extent of
drug absorption.
Drugs may be given on
empty stomach:
• to prevent mixing with
the foodstuffs, e.g., the
anthelmintics,
• to get an immediate
action, e.g., drugs used
for motion sickness, and
• to prevent drug
inactivation in the
stomach, e.g., penicillin V.

15. For example
Tetracyclines make insoluble
chelates with aluminium,
calcium and magnesium salts,
which reduces their absorption.
Captopril, digoxin, thyroxine
sodium and rifampicin are
better absorbed on empty
stomach

16. Drug allergy
• The drug allergy is abnormal hypersensitive response to a medication
• One person may develop an allergic reactions when taking a certain
medication, while another person on the same drug may have no
adverse reaction at all.

17. Certain medications are more likely to produce
allergic reactions than others.
• Antibiotics, such as penicillin
• Aspirin and NSAIDs medications, such as ibuprofen
• Anticonvulsants
• Monoclonal antibody therapy
• Chemotherapy

18. Genetic variation
Pharmacogenetics deals with the
genetic differences that cause
variations in drug response among
individuals or population.
The variation in drug response is
most commonly due
defective/deficient enzyme systems
responsible for inactivating the drug.

19. Genetic variations in drug response are:
Patients with deficiency of hepatic parahydroxylase
enzyme show marked neurotoxicity, during phenytoin
therapy of epilepsy.
Patients with hereditary deficiency of erythrocyte NAD-
diaphorase are likely to develop methemoglobinemia,
during sulfonamides and nitrites therapy.
Patients with deficiency of G6PD cause hemolytic
anemia during primaquine, sulphonamides,
nitrofurantoin, phenacetin, probenecid etc.

20. Environmental state
In certain cases, climate also affects drug action.
Drug metabolism is low in hot and humid climate.
Purgatives act better in summer while diuretics act better in winters.
Alcohol is well tolerated in winter than in summer season.
High altitude with low barometric pressure reduces the capacity of the
body to oxidize drugs and this may precipitate drug toxicity.

21. Pathological state
The presence of any pathological abnormality in the body shows
variation in drug response.
Achlorhydria decreases absorption
of aspirin. Celiac disease decreases
the absorption of amoxicillin,
vitamin A, D, E and K.
Hepatic dysfunction increases risk
of hepatotoxicity with certain drugs
such as isoniazid, rifampicin,
paracetamol etc.

22. Renal dysfunction increases risk of
nephrotoxicity with certain drugs such as
cephalosporione, penicillamine,
aminoglycosides etc.
The patients with thyroid dysfunction are
more sensitive to the actions of certain drugs
such as sedative-hypnotics, morphine, and
digoxin.

23. Psychological state
The personality of the physician may
influence the drug effect considerably,
particularly if the drug is intended for
use in a psychosomatic disorder.
Inert dosage forms called placebos are
known to produce therapeutic benefit
in conditions like angina pectoris and
bronchial asthma.

24. Placebos
Placebos are inactive dosage forms usually tablets
containing sucrose or lactose.
It has been observed that the administration of a placebo
produces improvement in sleep, depression, angina,
hypertension, constipation, and general well-being.

25. DRUG RELATED FACTORS

26. Physical state of a drug
If a drug is administered in the
solution form, then it is rapidly
absorbed and produces rapid
effect.
Among the oral preparation,
solutions, and powder form of the
drugs are more rapidly absorbed
than tablets and capsules and so
produce rapid effects.

27. Route of drug administration
The route of administration can greatly affect the drug response,
Magnesium sulphate when given orally is purgative. On the
other hand, if injected intravenously to control the convulsions
in pregnancy.

28. For example
Drugs like insulin and adrenaline are
ineffective by oral route and so
administered subcutaneously.
N-acetyl cycteine given orally or IV as an
in paracetamol overdose and acts as
lifesaving antidote. On the other hand,
if N-acetyl cycteine inhaled by nebulizer
then acts as mucolytic.

29. Time of drug administration
The time of the day affects
drug action.
Daylight is stimulant and
enhances the effects of
CNS stimulant drugs, while
the action of hypnotics is
reduced.
The dose of a hypnotic
required to produce sleep
during daytime is higher
than that required to
produce sleep at night.

30. Drug cumulation
If a drug is excreted slowly (delayed), then its repeated
administration leads to accumulation of drug in the
body tissues to produce cumulative toxicity.
e.g., digoxin, emetine, chloroquine and heavy metals.
Substances like lead can remain deposited in bones
without producing toxic effects.

31. Drug combination
when one drug is given together with
second drug, the effects produced by
the first drug may either ne increased
or decreased by the concurrent
administration of second drug.

32. Additive effect (Summation)
When the total pharmacological action of two or more drugs
administered together is equivalent to the alembic sum of
their individual pharmacological actions (1+1=2), the
phenomenon is termed as an additive effect.
• Paracetamol + Ibuprofen (analgesic and antipyretic action)
• Paracetamol + Tramadol (analgesic action)
• Ephedrine + Theophylline (antiasthmatic action)
• Furosemide + Aminophylline (diuretic action)

33. Synergism
When the total pharmacological action of two or more
drugs administered together is greater than the alembic
sum of their individual pharmacological actions (2+2=5),
the phenomenon is termed as synergism.
• Ofloxacin + Ethambutol (antiTB action),
• Losartan + Hydrochlorothiazide (antihypertensive action),
• Levodopa + Carbidopa (antiparkinsonian action),
• Adrenaline + Procaine (local anesthetic action),

34. Antagonism
The phenomenon of opposing
actions of two drugs on the
same physiological system is
termed as drug antagonism.
It can be chemical,
competitive, non-
competitive and
physiological antagonism,
Atropine antagonizes the
action of acetylcholine,
Cetirizine antagonizes the
action of histamine.

36. Drug tolerance
It is a state of decreased in responsiveness
of tissue due to repeated administration
of same dose of drug for prolong period.
Therefore, increasingly larger doses are
needed to achieve a therapeutic effect.

37. Natural tolerance
Natural tolerance is seen in various animal species
and also among the various human races.

39. Species tolerance
• Rabbits can tolerate large quantities of
belladonna.
• Because they have higher levels of enzyme
atropine esterase in their liver and plasma,
which show rapid metabolism of belladonna.
• Rats and mice are more resistant to digoxin
than dogs and cats.
Certain animal
species can tolerate
large dose of
particular drug
which may be lethal
to the humans,

40. Racial tolerance
Some human races are tolerant
to certain drugs due to racial
variation,
Negroes required high dose of
ephedrine, atropine and other
mydriatics to produce pupil
dilatation than Mongolians.

41. Indians tolerate high dose of thiacetazone
(antitubercular) more than Europeans.
Japanese people suffer from optic
neuropathy by taking di-iodohydroxyquin,
but not Indian people.

42. Acquired tolerance
Acquired tolerance results only on repeated
administration of a drug and may take
weeks or months to develop
e.g., opiates, barbiturates, nitrates and
xanthines.

43. Tissue tolerance
In this type, the development of tolerance is
limited to certain tissues or to certain organs
of the body,
e.g., morphine produces tolerance for its
euphoriant effect, but the pupils and the GI
tract do not become tolerant.
Thus, the same dose of morphine invariably
produces pinpoint pupils and constipation
but may fail to produce euphoria.

44. Cross tolerance:
It is the development of tolerance to pharmacologically related drugs.
If an individual initially develops tolerance to one drug belonging to a
particular group, he also shows tolerance to another drugs from the same
group. Those drugs resemblance in chemical structures show cross tolerance.

45. e.g., if the patient shows tolerance to
nitroglycerin in treatment of angina
pectoris then he also shows tolerance
to other drugs of same nitro group
containing class of drugs.

46. Pseudotolerance
It is a state of resistance to
drug response on oral
administration only, if a
drug is taken for a long
time in small amounts.
In this type, the drug
resistance is developed due
to poor drug absorption on
oral administration due to
its prolonged use.
Drug molecules undergo
excretion before interacting
with their site of action.

47. For example-
• the ancient kings were much worried about the poison threat.
• So they consumed small doses of arsenic poison orally from their
childhood to develop resistance to poison threat.

48. Acute tolerance
Acute tolerance develops due to repeated or continuous administration
of a drug over a relatively short period of time (within few minutes).
It means acute tolerance that develops rapidly, when certain indirectly
acting sympathomimetic drugs like amphetamine, ephedrine and
tyramine, etc.

49. Drug dependence
Drug dependence is a psychic or physical state resulting from repeated
administration of mood altering drugs.
Drug dependence is resulting from the interaction between a living
organism and a drug, and characterized by compulsion to take the drug
on continuous basis in order to experience its psychic effects.
withdrawal symptoms characterized by psychic/physical disturbances like
headache, restlessness and emotional upset and/or convulsions and
vasomotor collapse.

50. For example-
• morphine, codeine, methadone, ethyl alcohol, barbiturates,
paraldehyde, chloral hydrate, meprobamate, benzodiazepines,
methaqualone, amphetamine, methamphetamine etc.

51. Question Bank
List the factors affecting drugs action and explain any two.
Define drug cumulation with example.
Define with example: Synergism, Additive effect.
Define with example: Drug tolerance, Tachyphylaxis, Drug dependence.
Describe the types of drug tolerance in short.
Define with example: antagonism

52. Thanking you