This document discusses factors that can modify a drug's effects in the body. It summarizes that individual responses to drugs can vary due to differences in pharmacokinetics and pharmacodynamics. Genetic and non-genetic factors like age, disease states, diet, and concurrent medications can impact drug absorption, distribution, metabolism, and excretion. Drug interactions, tolerance, and cumulative effects are also reviewed. The document emphasizes considering a patient's individual factors when determining appropriate drug dosing to achieve the desired therapeutic effects while avoiding unnecessary adverse reactions.
3. Variation in response to the same dose of a drug
between different patients & even in the same patient
on different occasions
(1) Individuals differ in pharmacokinetic handling of
drugs
(2) Variations in number or state of receptors, coupling
proteins or other components
(3) Variations in neurogenic/hormonal tone or
concentrations of specific constituents
5. Quantitatively - plasma concentration and/or the
action of the drug is increased or decreased
Qualitatively-The type of response is altered
e.g. drug allergy or idiosyncrasy.
6. Factors modifying dose &
drug action
Biological Factors
Modified drug effect after repeated
administration of single drug
Modified drug effect after concurrent
administration of two different drugs
8. Infants & Neonates
Low gastric acidity- bioavailability of penicillins
Prolonged gastric emptying time
immature intestinal mucosa
Reduced splanchnic & enteric blood flow
Reduced PPB – higer plasma conc of free drug eg;
phenytoin, phenobarbitone
Delayed absorption of valproic acid, carbamazepine
Reduced absorption of Phenytoin , Phenobarbitone
9. Immature BBB & relatively high cerebral
blood flow higher amounts of lipophilic drugs
enter brain
Deficient Conjugation – Chloramphenicol
induced grey baby syndrome
Deficient renal tubular secretion – prolongs
half life of penicillins
10.
11. Young’s Formula
Child’s Dose =
Age in yrs
Age + 12
× Adult dose
Dilling’s Formula
Child’s Dose =
Age in yrs
20
× Adult dose
12. Cowlings formula
Dose of child = Age(years) + 1/24 x Adult dose
Fried’s formula
Dose of child= Age(months)/150 x Adult dose
13. Bastedo’s formula:
Dose of child = Age (years) + 3/30 x Adult dose
Clarks formula:
Dose of child = weight (pounds)/150 x Adult dose
14.
15. Cardio Vascular response to sympathomimetic
agents is reduced
Age related decrease in renal function
renal elimination of Digoxin
K
3/4th of the adult dose
to pt above 60 yrs
16. The recommended dose is calculated for
medium built persons
For obese and underweight person dose is
calculated individually
Dose =
Body weight(kg) × average adult dose
70
17. Doses calculated may not be accurate
In odema there is increase in BW due to fluid &
hence dose will be higher
In severe dehydration BW is decresed & dose
will be less
18. More precise index than body weight
Dose =
BSA (M2)
1.8
× Adult dose
For anticancer drugs eg methotrexate dose is
calculated depending on Body surface area
19. Drug responses in men & women are not always
same
Eg: 1. Ephedrine may produce more excitation
and tremors in women than men
2. α-methyldopa, β blockers, diuretics,
ketoconazole cause loss of libido in men
20. In females
During menstruation : purgatives -increase
pelvic congestion -increase menstrual blood loss
During pregnancy : Physiological changes that
alter drug disposition—
1. GI motility reduced—delayed absorption of
orally administered drug.
21. 2. Plasma and ECF volume expands—volume of drug
distribution may increase
3. Plasma albumin fall, alpha glycoprotein increases—
unbound fraction of acidic drugs increases but
basic drug decreases.
4. Hepatic microsomal enzymes undergo induction
drugs are metabolized faster.
5. Renal blood flow increased
Uterine stimulants -risk of abortion eg ; castor oil,
ergot alkaloids
23. There is difference in response to drugs
among different species
e.g 1) Rabbits are resistant to atropine
2) Rats & mice are resistant to digitalis
3) Rat is more sensitive to curare than
cat
These differences are important while
extrapolating results from experimental
animals to man
24. Blacks require higher & mongols
require lower concentration of
atropine & ephedrine to dilate to
dilate their pupil
ẞ blockers are less effective as
antihypertensive in blacks
Indians tolerate thiacetazone
better than whites
Race
25. At high altitudes, due to reduced rate of
biotransformation even usual doses may
produce toxicity
Glucocorticoid taken as OD dose in morning
minimise the risk of pituitary adrenal
supression
Diurnal variation should be considered while
determining the dose of antihypertensive drug
26. Food interferes with absorption of
many drugs
Eg; tetracyclines form complexes
with calcium in food & are poorly
absorbed
Polycyclic hydrocarbons in cigarette
smoke may cause microsomal enzyme
induction
Absorption increased by
food-
Spironolactone
Lithium
Riboflavin
Absorption Reduced by
food-
Ampicillin
Rifampicin
INH
27. Drug’s Efficacy can be affected by patient ’s
expectations and attitudes
Some patients respond to Placebo
PLACEBO = “I SHALL PLEASE”
Placebo is inert dosage form with no specefic
biological activity but only resembles the actual
prepaation in appearance(dummy medication)
Uses
1. Clinical trials
2. Benefit a pt
psychoogically
28. Eg : lactose, vitamins, minerals, distilled water
injection
Injections have more pronounced effect
Placebo can release endorphins in brain -
analgesia
30. Production of drug metabolizing enzyme is
genetically controlled & variations are
common
Eg:
Oxidation of Drugs : genetic polymorphism in
cyt P450 leads to variation in metabolism
eg: SSRI, Phenytoin, Warfarin
31. Acetylation of drugs:
slow acetylators – lupus erythematous
(hydralazine)
Fast acetylators- hepatotoxicity
Atypical Pseudocholinesterase: prolonged
apnea due to persistent action of
succinylcholine
32. Variations in receptor, enzymes, susceptibility
to ADRs & disease
G6PD deficiency : hemolysis (primaquine,
sulphones)
Malignant hyperthermia: inherited abnormality
in Ca 2+release from sarcoplamic reticulum
(halothane, sevoflurane, succinylcholine)
33. 1) Gastrointestinal diseases
• Can alter absorption of orally administered drugs
• Drug absorption can be increased or decreased
e.g
In coeliac disease absorption of amoxicillin is
decreased but that of cephalexin & cotrimoxazole is
increased
34. 2) Liver disease
Bioavailability of drugs having high first pass
metabolism is increased
Protein binding of acidic drugs
(phenylbutazone,etc) is reduced & more drug is
present in free form
35. Metabolism & elimination of some drugs
(morphine, lidocaine, propranolol, etc) is
decreased & dose should be reduced
Prodrugs needing hepatic metabolism for
activation (e.g prednisone, bacampicillin) are
less effective & should be avoided
36. 3) Kidney disease
Albumin level is altered – binding of
acidic drugs is reduced
Permeability of blood brain barrier
is increased – opiates, barbiturates
produce more CNS depression
Target organ sensitivity may also be
increased – antihypertensive drugs
produce more postural hypotension
37. NSAIDs cause more fluid retention
Thiazide diuretics which tend to reduce GFR
are ineffective in renal failure – can worsen
uremia
Potassium sparing diuretics C/I, can cause
hyperkalemia – cardiac depression
38. 4) Congestive heart failure
Mucosal edema & splanchnic vasoconstriction
→ decrease in drug absorption from GIT
e.g Procainamide & hydrochlorothiazide
Expansion of extracellular fluid volume → Vd
of some drugs can increase
Loading doses of drugs like
lidocaine & procainamide should be
lowered
39. Decreased perfusion & congestion of liver,
reduced GFR & increased tubular reabsorption
↓
decreases drug elimination
Dosing rate of drugs like lignocaine,
theophylline should be reduced
40. 5) Thyroid disease
Hypothyroid patient → more sensitive to
digoxin, morphine & other CNS depressants
Hyperthyroid patient → more prone to
arrhythmic action of digoxin
41. governs speed & intensity of drug responses
A drug may have entirely different uses through
different routes
e.g Magnesium sulphate
• Orally → purgation
• Applied on inflamed areas → decreases swelling
• Intravenously → produces CNS depression
& hypotension
42. Modified drug effect after repeated
administration of single drug
Drug tolerance
Drug resistance
Cumulation
43. Need to increase the dose to produce response
of equal magnitude & duration
44. Common with morphine, alcohol, barbiturates,
LSD
Not uniform to all pharmacoological effects
eg: 1.tolerance developes to all pharmacological
effects of morphine except miosis &
constipation
2. to sedative action of chlorpromazine & not to
its antipsychotic effect
46. Refers to genetically determined lack of
sensitivity to a drug
e.g. Rabbits - Tolerant to atropine
Black races - Tolerant to mydriatics
47. Occurs due to repeated use of drug
Two types
i) Pharmacokinetic (dispositional ) tolerance
e.g. alcohol , barbiturates, amphetamine
ii) Pharmacodynamic (cellular adaptive ) tolerance
e.g. Morphine , barbiturates(barbital)
48. Development of tolerance to pharmacologically
related drugs
e.g. 1)Tolerance between morphine (opioid) and
heroin (opioid)
2) Chronic alcoholics show tolerance to
barbiturates and general anaesthetics
49. Acute development of tolerance after rapid and
repeated administration of drug over a short
interval
Original effect can not be achieved even after
increasing dose
e.g. Amphetamine, tyramine, ephedrine
50. It is reduced effect or no effect of
antimicrobial agents against microorganism
Natural
• Penicillin G
is not active
against gram
positive
bacteria
Acquired
• Develops over a
period of time
• Eg:
staphylococci,
coliform
Cross
• Micro-
organisms
resistant to
one sulfa drug
exhibit
resistance to
all sulfonamides
51. Any drug will cumulate in the body if rate of
administration is more than the rate of
elimination
Slowly eliminated drugs can cause cumulative
toxicity
e.g. chloroquine, digoxin
52. To avoid cumulation-
A. One must know drug elimination- slowly or
rapidly.
B. Stop drug administration at appearance of
first warning symptom.
C. Select carefully form in which drug is to be
administered.
D. Check liver and kidney function before drug
administration.
53. Modified drug effects after concurrent
administration of two different drugs
1.Summation
2.Synergism
3.Drug
antagonism
54. When two drugs elicit the same response, but
with different mechanisms, their combined
effect is equal to the sum of their individual
effects (1+1=2)
55. Combined effect of two drugs is greater than
algebric sum of their individual effect
When two drugs act at different site
57. • Chemical antagonism
• Physiological antagonism
• At receptor level
One drug opposing or inhibiting the action of
another drug is antagonism
58. Two substances interact chemically to result in
inactivation of effect
eg: chelating agents form inactive soluble complexes
with heavy metals like lead
2. Physiological antagonism
Two drugs act at different site to produce opposing
effects
eg: histamine acts on H1 receptors to produce
bronchospasm & hypotension while adrenaline
reverses the action by acting on adrenergic receptors
60. When antagonist
combines with the
same receptor on
which agonist combines
& opposes the effect
of agonist, such
antagonism is called
competitive antagonism
61. Effect of agonist can again be obtained on
increasing the dose / concentration
Eg:1. atropine is competitive antagonist of ach at
muscarinic receptors
2. Naloxone competitive antagonist of morphine
at opioid receptor
62. Antagonist binds tightly with same receptor
(on which agonist combines) and does not
dissociates or dissociates very slowly from
the receptor, so that the agonist cannot bind
with receptor
Higher doses of agonist cannot overcome
effect of antagonist i.e. It is insurmountable
or irreversible
63. The log-dose response
curve show reduced
efficacy in the presence
of irreversible
antagonist
e.g. Irreversible
blockade of acetyl
choline esterase enzyme
by organophosphate
compounds
64. Response of agonist is
blocked by antagonist by
acting at different site
and not on the receptor
of agonist
e.g. verapamil
antagonises cardiac
contraction by
norepinephrine
65. Treatment of certain conditions and poisoning
e.g. Antacids for peptic ulcer (chemical
antagonism)
Naloxone for opioid poisoning
To overcome or reduce the adverse effect of a
drug
e.g. Use of benzhexol with trifluoperazine
reduces extrapyramidal side effects of
trifluoperazine
66. Drug response may vary in different individuals
even when same dose is used due to altered
pharmacokinetics & pharmacodynamics
It is very important to consider these factors
before prescribing drugs for any patient so
that desired response is achieved &
unnecessary adverse effects are avoided
67. Basic and clinical pharmacology, Katzung :13th
edition
H . L. Sharma, K. K. Sharma ;chapter 7
Pharmacodynamics; Principles of Pharmacology ;
2nd edition
Padmaja Udaykumar; chapter 3
Pharmacodynamics; Medical Pharmacology; 5th
edition