This interesting ppt contains Pharmacodynamics illustrated with pictures and diagrams for II MBBS CBME students.

1. PH 1.5 PHARMACODYNAMICS
DR. V. SATHYANARAYANAN M.B.B.S., M.D., ACME
PROFESSOR OF PHARMACOLOGY
SRM MCH & RC

2. COMPETENCY ACHIEVEMENT
• PH 1.5 DESCRIBE GENERAL PRINCIPLES OF MECHANISM OF DRUG ACTION

3. SPECIFIC LEARNING OBJECTIVES
AT THE END OF THIS
SESSION ALL THE
PARTICIPANTS SHALL BE
ABLE TO
Define pharmacodynamics
Enumerate and explain
different types of drug
action
Enumerate and explain
different sites of drug action
Classify receptor families
Explain signal transduction
mechanisms
State the clinical
implications of upregulation
and downregulation with
examples
Define potency and efficacy
with examples
Discuss drug synergism and
antagonism with examples
Enumerate the factors that
modify drug effects

4. CONTENTS • DEFINITION
• HISTORY
• TYPES OF DRUG ACTION
• SITES OF DRUG ACTION
• MECHANISM OF ACTION OF DRUGS
• DRUG AFFINTY AND EFFICACY
• SOME DEFINITION OF TERMS
• RECEPTOR FAMILIES
• SIGNAL TRANSDUCTION MECHANISMS
• RECEPTOR REGULATION AND ITS IMPLICATIONS
• DOSE RESPONSE RELATIONSHIP
• DRUG SYNERGISM AND ANTAGONISM WITH EXAMPLES
• FACTORS THAT MODIFY THE EFFECTS OF DRUGS

5. DEFINITION
Pharmacon = Drug
Dynamics = Action/Power
It covers all the aspects relating to “What a drug does to the body”
(Mechanism of action)

6. Site of
Action
Dosage Effects
Plasma
Concen.
Pharmacokinetics Pharmacodynamics

7. HISTORY
• Molecular pharmacology is concerned with studies of basic
mechanisms of drug actions on biological systems.
• The idea that drugs act upon specific sites (receptive substance)
began with John New Port Langley (1852-1926) of Cambridge.
• However the word ‘receptor’ is given by Paul Ehrlich (1854- 19 15).
• The receptor concept which forms a key note in the development of
molecular pharmacology became firmly established by the
quantitative work of Alfred Joseph Clark (1885-1941), a professor
of pharmacology at Kings College London.

8. DRUG ACTION VS DRUG EFFECT
•Action: How and Where the effect is
produced is called as Action.
•Effect: The type of response produced by
drug.

9. TYPES OF DRUG ACTION
EFFECT (Type of responses):-
1.Stimulation
2.Inhibition/Depression
3.Replacement
4.Irritation
5.Cytotoxic
6. Modification of immune status

10. STIMULATION
• Some drugs act by increasing the activity of
specialized cells.
Ex: Catecholamines stimulate the heart and
Heart rate, Force of contraction

11. INHIBITION
• Some drug act by decreasing the activity of specialized cells.
Ex: Alcohol, Barbiturates, General anesthetic these drug depress the CNS system.
Atropine inhibits Ach action.

12. REPLACEMENT
• When there is a deficiency of endogenous substances, they can be replaced by
drugs.
Ex: Insulin in Diabetes mellitus
Throxine in cretinism and myxedema

13. IRRITATION
• Certain drugs on topical application cause irritation of the skin and adjacent
tissues.
• These drugs are used for counterirritant purpose.
Ex: Eucalyptus oil, methyl salicylates (Used in sprains, joint pain, myalgia.

14. CYTOTOXIC
• Treatment of infectious disease/cancer with drugs that are selectively toxic for
infecting organism/cancer cells
Ex: Anticancer drugs
All Antibiotics

15. MODIFICATION OF IMMUNE STATUS
• Vaccines and sera  improve our immunity
• Immunosuppressants  depress immunity

17. SITE OF DRUG ACTION
• Where:
1. Extra cellular
2. Cellular
3. Intracellular

18. EXTRA CELLULAR SITE OF ACTION
1.ANTACIDS NEUTRALIZING GASTRIC
ACIDITY.
2.CHELATING AGENTS FORMING
COMPLEXES WITH HEAVY METALS.
3.MGSO4 ACTING AS PURGATIVE BY
RETAINING THE FLUID INSIDE THE LUMEN
OF INTESTINE.

19. CELLULAR SITE
OF ACTION
1.Ach on Nicotinic receptors of motor end
plate, leading to contraction of skeletal
muscle.
2.Effect of sympathomimetics on heart
muscle and blood vessels.

20. INTRACELLULAR SITE OF ACTION - EXAMPLES
-Folic acid synthesis inhibitors.
Folic acid which is intracellular component essential for synthesis of proteins.
Trimethoprim and sulfa drug interfere with synthesis.

22. MECHANISM OF ACTION OF DRUGS
Drug act either by
receptor or by non
receptor or by targeting
specific genetic changes.
Majority of drugs acts by
receptor mechanism
Receptor mediated
Non receptor mediated

23. FUNDAMENTAL MECHANISMS OF DRUG ACTION
THROUGH
1. Receptors
2. Enzymes and pumps
3. Ion channels
4. Transporters and symporters
5. By Physical action
6. By chemical action
7. By altering metabolic processes

24. RECEPTOR
MEDIATED
ACTION
Drugs produce their effect through interacting with some
chemical component of living organism eg Receptor.
Receptors are macromolecules
Most are proteins
Present either on the cell surface, cytoplasm or in the
nucleus

25. Receptor Functions : Two essential functions
• 1. Recognition of specific ligand molecule (Ligand
binding domain) and binding
• 2. Transduction of signal into response (Effector
domain)
Ligand binding
domain
Transduction of
signal into response

26. Drug(D) +Receptor® Drug receptor complex Response
1. Selectivity:- Degree of complimentary correlation between drug and
receptor.
Ex:- Adrenaline Selectivity for α, ß Receptor
2. Affinity:- Ability of drug to bind to a receptor.
3. Intrinsic activity (IA) or Efficacy:- Ability of a drug to produce a
pharmacological response after making the drug receptor complex.
Drug receptor interaction

27. DRUGS ARE
DESCRIBED
BASED ON
THE
MAGNITUDE
OF TWO
PROPERTIES:
1. Affinity for the receptor. Affinity is related to
potency.
2. Efficacy once bound to the receptor. Efficacy
refers to the maximal effect the drug can elicit.

28. DRUG CLASSIFICATION
(ON THE BASIS OF AFFINITY & EFFICACY)

29. AGONISTS AND ANTAGONISTS
AGONIST - Has affinity
for receptor and intrinsic
activity/efficacy.
ANTAGONIST - Has
affinity but no efficacy.
Competitive Antagonist
Noncompetitive
Antagonist
Partial Agonist or
Agonist- Antagonist
Has affinity but lower
efficacy than full agonist.

30. Response No response

31. • Partial agonist :These drug have full affinity to
receptor but with low intrinsic activity (IA=0 to 1).
• These are only partly as effective as agonist
(Affinity is lesser when comparison to agonist)
Ex: Pindolol, Pentazocine

32. INVERSE
AGONIST
These have full affinity towards the receptor
but intrinsic activity is zero to -1 i.e.,
produces effect is just opposite to that of
agonist.
Ex:- ß-Carboline is inverse agonist for
Benzodiazepine receptors.

33. RECEPTOR LIGAND TYPES

35. RECEPTOR FAMILIES
Four types of receptors
families
2. ion channel receptors
(ionotropic receptor)
1.G-protein-coupled
receptors (Metabotropic
receptor)
3. Enzymatic receptors
(kinase-linked receptor)
4.Receptor regulating
gene expression
(transcription factors/
Steroid )

36. CHARACTERISTICS OF RECEPTOR
FAMILIES
Ligand
gated
G-protein
coupled
Enzymatic Nuclear
Location Membrane Membrane Membrane Intracellular
Effector Ion channel Ion Channel
or enzyme
Enzyme Gene
coupling Direct G-protein Direct Via DNA
Example Nicotinic Muscarinic Insulin Steroid
Hormone

37. RECEPTOR FAMILIES
• 5. Transmembrane non-enzymes ( cytokine and TLR )

38. SIGNAL TRANSDUCTION MECHANISMS

39. SIGNAL TRANSDUCTION MECHANISMS
• Ion channel receptors:- proteins localized on cell membrane and coupled directly to an ion channel.
Receptor
Agonist
Hyperpolarization or
depolarization
Receptor
Blocker
Permeation of
ion is blocked
Cellular effect
No cellular effect
Ion
Na+2

40. • Ex: Nicotinic cholinergic receptor

41. ION CHANNELS
• SODIUM CHANNEL
• CALCIUM CHANNEL
• POTASSIUM CHANNEL
• CHLORIDE CHANNEL

43. G-PROTEIN COUPLED RECEPTORS
• Membrane bound, which are coupled to effector system through GTP
binding proteins called as G-proteins
Bound to inner
face of plasma
membrane (2nd
messenger)

44. R
+
E
G G
- + -
Ions
Second messengers
Change in
excitability
Ca2+ release Protein
phosphorylation
other
Cell effects
G protein coupled receptors

45. VARIETIES OF G-PROTEIN
G-protein Receptor for Signaling pathway/
Effector
Gs ß adrenegic,
H,5HT,Glucagon
AC— cAMP
Gi1,2,3 α2 adrenergic, Ach, AC— cAMP,
Open K+
Gq Ach Phospholipase-C,
IP3’cytoplasmic Ca+2
Go Neurotransmitters
in brain
Not yet clear

46. G-PROTEIN
EFFECTOR
SYSTEMS
1.Adenylase cyclase : cAMP
system
2.Phospholipase –C: Inositol
phosphate system
3. Ion channels

47. CAMP
SYSTEM

48. • Phospholipase-C /
IP3-DAG Pathway
system

49. E Cam E*
Gq PLC PIP2
DAG
S
Agonist
Hydrolysis
Activation
IP3
PKC
ATP ADP
Product
Ca+2
Cam
Water soluble
release
Response
Phospholipase-C system
Hydrolysis
PLC= Phospholipase-C PIP2 =Phosphotiydl inositol 4,5 di phosphate
IP3 =Inositol tri phosphate DAG = Diacylglycerol
E= Ezyme PKC = Phosphokinase -C

50. GS/GI
or
FC of heart muscle
Lipolysis Glycogen Glycogen breakdown
synthesis to glucose
G protein
+ -
Effector
AC
cAMP ATP
Protein kinase Active
Ca+2 release
Phosphorylation

51. ION CHANNEL
REGULATION
• G-protein coupled receptors can control the
functioning of ion channel by don't
involving any second messenger
• Ex:- In cardiac muscle

53. ENZYMATIC
RECEPTORS
• These receptor are directly linked tyrosine
kinase.
• Receptor binding domain present in extra
cellular site.
• Intracellular domain produce conformational
changes
• Ex:- Insulin receptors

54. ENZYMATIC RECEPTORS
Extra cellular receptor
binding domain
Intra cellular
changes

55. R/E
Protein
phosphorylation
Gene transcription
Protein synthesis
Cellular effects
Kinase linked receptors

57. RECEPTOR REGULATING GENE EXPRESSION
(TRANSCRIPTION FACTORS)
Unfolds the receptor
and expose normally
masked DNA binding
site
Increase RNA
polymerase activity

58. R
Nucleus
Gene
transcription
Protein synthesis
Cellular effects
Nuclear receptors

60. JAK-STAT BINDING RECEPTOR

63. RECEPTOR REGULATION THEORY
Receptors are in dynamic state.
The affinity of the response to drugs is not fixed. It alters according to situation.
Receptor down regulation:
Prolonged use of agonist
Receptor number and sensitivity
Drug effect
Ex: Chronic use of salbutamol down regulates ß2 adrenergic receptors.

64. RECEPTOR UPREGULATION
Prolonged use of antagonist
Receptor number and sensitivity
Drug effect
• Ex:- propranolol is stopped after prolonged use, produce withdrawal symptoms. Rise BP,
induce of angina.

66. NON RECEPTOR MEDIATED ACTION
• All drugs action are not mediated by receptors. Some of drugs may act through chemical
action or physical action or other modes.
• Chemical action
• Physical action (Astringents, sucralfate)
• False incorporation (PABA)
• Being protoplasmic action (antiseptics)
• Formation of antibody (Vaccines)
• Targeting specific genetic changes.

67. CHEMICAL
ACTION
1.Ion Exchanges:-Anticoagulant effect of heparin(-ve
charge) antagonized by protamine (+ve charged)
protein.
2.Neutralization:- Excessive gastric acid is neutralized by
antacids.
3. Chelation:-These bind heavy metals. Ex:-EDTA, BAL.

68. PHYSICAL
ACTION
Adsorption: Kaolin adsorbs bacterial toxin
and thus acts as antidiarrhoeal agent.
Protectives:- Various dusting powders.

69. PHYSICAL ACTION
• Osmosis:- MgSo4 acts as a purgative by exerting osmotic effect within lumen of the
intestine.
• Astringents:- They precipitate the surface proteins and protect the mucosa Ex:
tannic acid in gum patients
• Demulcent:- These drugs coat the inflamed mucus membrane and provide soothing
effect. Ex: Menthol
• Radioactivity – I131
• Radio-opacity – Barium sulphate

70. FALSE
INCORPORATION
Bacteria synthesis folic acid from PABA (Para
Amino Benzoic Acid), for growth sand
development.
Sulfa drugs resemble PABA, therefore falsely
enter into the synthesis process of PABA, cause
nonfunctional production and no utility for
bacterial growth.

71. PROTOPLASMIC POISON
• Germicides and antiseptics like phenol and formaldehyde act as non specifically
as protoplasmic poison causing the death of bacteria

72. THROUGH
FORMATION OF
ANTIBODIES
Vaccines produce their effect by inducing
the formation of antibodies and thus
stimulate the defense mechanism of the
body
Ex:- Vaccines against small pox and cholera

73. TARGETING
SPECIFIC GENETIC
CHANGES.
Anti cancer drugs that specifically
target genetic changes.
Inhibitors of specific tyrosine
kinase that that block the activity
of oncogenic kinases.

74. THROUGH ENZYMES AND PUMPS
• Large number of drugs act by inhibition of various enzymes – eg ASPIRIN,
ENALAPRIL
• Some drugs act by inhibiting membrane pumps – eg OMEPRAZOLE, DIGOXIN

75. THROUGH TRANSPORTERS AND SYMPORTERS

78. PHARMACODYNAMICS
• Drug-receptor affinity
• Governed by stereochemical fit
• Effects on brain determined by location of
receptor types
• The dose-response relationship
• Dose
• Potency
• Efficacy or maximum effect
• Slope

79. 0
20
40
60
80
100
120
Dose
Response
% • The dose-response curve
relates the amount
administered to the
response.
• Response may be measured
as % responding or as
intensity of response

80. DRUG
EFFECTIVENESS
• Dose-response (DR) curve
• Depicts the relation between drug
dose and magnitude of drug effect
• Drugs can have more than one effect
• Drugs vary in effectiveness
• Different sites of action
• Different affinities for receptors
• The effectiveness of a drug is considered
relative to its safety (therapeutic index)

81. Potency
• Relative strength of response for a given dose
– Effective concentration (EC50) is the concentration of an agonist needed to
elicit half of the maximum biological response of the agonist
– The potency of an agonist is inversely related to its EC50 value
• D-R curve shifts left with greater potency

82. Efficacy
• Maximum possible effect relative
to other agents
• Indicated by peak of D-R curve
• Full agonist = 100% efficacy
• Partial agonist = 50% efficacy
• Antagonist = 0% efficacy
• Inverse agonist = -100% efficacy

83. THE DOSE-RESPONSE CURVE: EFFECTIVENESS AND
SAFETY
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Dose
Intensity
of
response,
% Efficacy
Slope
Potency

84. Drug Concentration
SEMILOG DOSE-RESPONSE CURVE
Effect
or

85. Drug Concentration
SEMILOG DOSE-RESPONSE CURVE
ED50
50% Effect
Maximal Effect
Effect
or

86. SEMILOG DOSE-RESPONSE CURVE
POTENCY
EFFICACY
ED50
Maximal Effect
Log [Dose]

87. SEMILOG DOSE-RESPONSE CURVE
RANK ORDER OF POTENCY: A > B > C > D
A B C D
Log [Dose]

88. SEMILOG DOSE-RESPONSE CURVE
RANK ORDER OF POTENCY: A > B > C > D
RANK ORDER OF EFFICACY: A = C > B > D
A
B
C
D
ED50

89. THERAPEUTIC INDEX
• Margin of safety
• Depend upon factor of dose producing desirable effect  dose eliciting toxic
effect.
• TI should be more than one
50
50
ED
LD
index
c
Therapeuti 

90. THERAPEUTIC WINDOW
• Optimal therapeutic range of plasma concentrations at which most o the patients
experience the desired effect.
• Therapeutic range Therapeutic window
Sub
optimal
optimal

91. THERAPEUTIC WINDOW
OF SOME DRUGS
Cyclosporine – 100-400ng/ml
Carbamazapine- 4-10µg/ml
Digoxin- 0.8-2ng/ml
Lithium- 0.8-1.4 mEq/L
Phenytoin – 10-20µg/ml
Quinidine- 2-6µg/ml

93. COMBINED EFFECT OF DRUGS

94. • Additive: combined effect of two drugs acting by same
mechanism ( 1+1 =2 )
Ibuprofen and Paracetamol

95. SYNERGISM
(SUPRA- ADDITIVE
EFFECT)
(1+1=3 OR 5)
The combined effects of two drugs are greater
than the sum of their independent effects.
1.Sulfamethaxazole+ Trimethoprim
2. Levodopa + Carbidopa.

96. TYPES OF
ANTAGONISM
Antagonism: Effect of two
drugs is less than sum of
the effects of the individual
drugs.
Chemical antagonism
•Ex: -heparin(-ve) protamine +ve,
Chelating agents
Physiological /Functional
antagonism
Ex histamine and adrenaline
Pharmacokinetic
antagonism
Pharmacodynamic
antagonism
•Competitive ( Reversible)
•Non competitive (Irreversible)

97. PHYSIOLOGICAL
ANTAGONISM
• Two antagonists, acting at different sites,
counter balance each other by producing
opposite effect on same physiological
system.
• Histamine – bronchospasm
• Adrenaline/epinephrine – bronchodilatation

98. PHARMACOKINETIC
ANTAGONISM
One drug affects the absorption,
metabolism or excretion of other drug
and reduce their effect.
Ex:-Warfarin in presence of
phenobarbitone, warfarin metabolism
is increased, its effect is reduced.

99. PHARMACODYNAMIC ANTAGONISM
• Pharmacodynamic antagonism between two drugs acting at
same receptors.
•1.Reversible(Competitive)
•2.Irreversible
•3. Non-Competitive

100. REVERSIBLE
ANTAGONISM
(COMPETITIVE
ANTAGONISM)
Ex:- Atropine is a competitive antagonist of Ach.
These type inhibition can be overcome by increasing the
concentration of agonist
These inhibition is commonly observed with antagonists that
bind reversibly to the same receptor site as that of an agonist.

101. IRREVERSIBLE
ANTAGONISM
It occurs when the antagonist dissociates
very slow or not at all from the receptors
resulting that no change when the agonist
is administered .
Antagonist effect cannot be overcome even
after increasing the concentration of
agonist

102. FACTORS THAT MODIFY
THE EFFECTS OF DRUGS

103. • Individuals differ both in the degree and the
characteristic of the response that a drug
may elicit
• Variation in response to the same dose of a
drug between different patients and even in
the same patient on different occasions.

104. FACTORS MODIFYING THE EFFECTS OF DRUGS
• One or more of the following categories of differences among individuals are
responsible for the variations in drug response:
• Individuals differ in pharmacokinetic handling of drugs
• Variation in number or state of receptors, coupling proteins or other components of
response
• Variation in neurogenic/ hormonal tone or concentrations of specific constituents

105. FACTORS MODIFYING THE EFFECTS OF DRUGS
a) Quantitatively
• The plasma concentration and / or the drug action is increased or decreased
b) Qualitatively
• The type of response is altered, eg: drug allergy and idiosyncrasy

106. THE VARIOUS FACTORS ARE:
1. Body weight/size:
 It influences the concentration of drug attained at the site of action
 The average adult dose refers to individuals of medium built

107. FACTORS MODIFYING THE EFFECTS OF DRUGS –
BODY WEIGHT
• For exceptionally obese or lean individuals and for children dose may be calculated on body weight basis
 BSA=BW(Kg)0.425 x Height(cm)0.725 x 0.007184
dose
adult
Average
x
70
(kg)
BW
dose
Individual 
dose
adult
Average
x
1.7
(m2)
BSA
dose
Individual 

108. FACTORS MODIFYING THE EFFECTS OF DRUGS
 However, infants and children have important physiological differences
 Higher proportion of water
 Lower plasma protein levels
 More available drug
 Immature liver/kidneys
 Liver often metabolizes more slowly
 Kidneys may excrete more slowly

109. 2. AGE
Infants and Children:
• The dose of drug for children often calculated from the adult dose
formula)
s
Young'
.........(
dose
adult
x
12
Age
Age
dose
Child


formula)
s
g'
...(Dillin
dose......
adult
x
20
Age
dose
Child 

110. FACTORS MODIFYING THE EFFECTS OF DRUGS
Elders:
•In elderly, renal function progressively
declines (intact nephron loss) and drug
doses have to be reduced
Chronic disease states
Decreased plasma protein
binding
Slower metabolism
Slower excretion Dietary deficiencies Use of multiple medications Lack of compliance

111. FACTORS MODIFYING THE EFFECTS OF DRUGS
3. Sex:
• Females have smaller body size, and so require doses of drugs on the lower
side of the dose range
• They should not be given uterine stimulants during menstruation, quinine
during pregnancy and sedatives during lactation

112. FACTORS MODIFYING THE EFFECTS OF DRUGS
4. Pregnancy:
• Profound physiological changes which may affect drug responses:
• GI motility reduced –delayed absorption of orally administered drugs
• Plasma and ECF volume expands
• Albumin level falls
• Renal blood flow increases markedly
• Hepatic microsomal enzyme induction

113. FACTORS MODIFYING THE EFFECTS OF DRUGS
5. Food:
 Delays gastric emptying, delays absorption (ampicillin)
 Calcium in milk –interferes with absorption of tetracyclines and iron by chelation
 Protein malnutrition
 Loss of BW
 Reduced hepatic metabolizing capacity
 Hypoproteinemia

114. FACTORS MODIFYING THE EFFECTS OF DRUGS
6. Species and race:
• Rabbits resistant to atropine
• Rat & mice are resistant to digitalis
• In humans: blacks require higher, Mongols require lower concentrations of
atropine and ephedrine to dilate their pupil

115. FACTORS MODIFYING THE EFFECTS OF DRUGS
7. Route of drug administration:
 I.V route dose smaller than oral route
 Magnesium sulfate:
 Orally –purgative
 Parenterally –sedative
 Locally –reduces inflammation

116. FACTORS MODIFYING THE EFFECTS OF DRUGS
8. Biorhythm: (Chronopharmacolgy)
• Hypnotics –taken at night
• Corticosteroid –taken at a single morning dose
9. Psychological state:
• Efficacy of drugs can be effected by patients beliefs, attitudes and expectations
• Particularly applicable to centrally acting drugs
• In some patients inert drugs (placebo) may produce beneficial effects equivalent to the drug, and
may induce sleep in insomnia

117. FACTORS MODIFYING THE EFFECTS OF DRUGS
10. Presence of diseases/pathological states:
 Drug may aggravate underlying pathology
 Hepatic disease may slow drug metabolism
 Renal disease may slow drug elimination
 Acid/base abnormalities may change drug absorption or elimination
 Severe shock with vasoconstriction delays absorption of drugs from s.c. or i.m
 Drug metabolism in:
 Hyperthyroidism –enhanced
 Hypothyroidism -diminished

118. FACTORS MODIFYING THE EFFECTS OF DRUGS
11. Cumulation:
• Any drug will cumulate in the body if rate of administration is more than the
rate of elimination
• Eg: digitalis, heavy metals etc.

119. FACTORS MODIFYING THE EFFECTS OF DRUGS
12. Genetic factors:
• Lack of specific enzymes
• Lower metabolic rate
• Acetylation
• Plasma cholinesterase (Atypical pseudo cholinesterase)
• G-6PD
• Glucuronide conjugation

120. FACTORS MODIFYING THE EFFECTS OF DRUGS
13. Tolerance:
 It means requirement of a higher dose of the drug to produce an effect, which is ordinarily
produced by normal therapeutic dose of the drug
 Drug tolerance may be:
 Natural
 Acquired
 Cross tolerance
 Tachyphylaxis (ephedrine, tyramine, nicotine)
 Drug resistance

121. TOLERANCE
• Tolerance: Increased amount of drug required to produce initial pharmacological
response.
• Usually seen with alcohol, morphine, barbiturates, CNS active drugs
• Reverse tolerance:- Same amount drug produces increased pharmacological
response.
• Cocaine, amphetamine  rats- increase motor activity

122. TYPES OF TOLERANCES
• Innate tolerance: Genetically lack of sensitivity to a drug.
Ex:
• Rabbits tolerate to atropine large doses
• Chinese Castor oil
• Negros  Mydriatic action of sympathomimetics
• Eskimos high fatty diets

123. ACQUIRED
TOLERANCES
Occurs due to repeated use of drug
• Pharmacokinetic tolerances
• Pharmacodynamic tolerance
• Acute tolerance
Pharmacokinetic tolerances:- Repetitive administration causes
decrease in their absorption or increase in its own metabolism
Ex: Alcohol  dec. absorption
Barbiturates Inc. own metabolism

124. PHARMACODYNAMIC
TOLERANCE
Down regulation of receptors
Impairment in signal transduction
Ex: Morphine, caffeine, nicotine.
Acute tolerance: Tachyphylaxis Acute development of tolerance after a
rapid and repeated administration of a drug in shorter intervals
Ex; Ephedrine, tyramine

125. FACTORS MODIFYING THE EFFECTS OF DRUGS
14. Other drugs:
 By interactions in many ways

126. SUMMARY

127. SUMMARY
What the drug does to the body is Pharmacodynamics
Drugs act on extracellular or intracellular sites
There are several types of drug action
Most drugs act produce their effects by binding to specific target proteins
Many drugs act by interacting with specific receptors
There are 5 types of receptor families and they have specific signal transduction mechanisms
Receptors are either upregulated or downregulated depending upon their number and sensitivity
Clinical response to the increasing dose of the drug is defined by the shape of the dose response curve
When two or more drugs are given concurrently, the effect may be additive, synergistic or antagonistic
There are various factors modify the response to a drug

128. POST-TEST MCQS
1. What the drug does to the body is called as
a) Pharmacokinetics b) Pharmacodynamics
c) Pharmacotherapeutics d) Chronopharmacology
2. The upper limit of dose response curve is the index of
a) Drug potency b) Drug efficacy c) Drug safety d) Drug toxicity

129. POST-TEST MCQS
• 3. The transducer mechanism which is the FASTEST in its time course of action is
a) G-protein coupled receptors (GPCR)
b) Receptors with intrinsic ion channel
c) Enzyme - linked receptors
d) Receptors regulating gene expression

130. POST-TEST MCQS
4. All are second messengers EXCEPT
a)Cyclic AMP b) G-Protein c) IP3 d) DAG
5. The therapeutic index of a drug is a measure of its
a) Safety b) Potency c) Efficacy d) Dose variability

131. • The young physician starts life with 20
drugs for each disease, and the old
physician ends life with one drug for 20
diseases
Sir. William Osler
1849 - 1919

132. THANK YOU