Pharmacodynamics covers how drugs act on the body. Drugs can act through receptor-mediated or non-receptor mediated pathways. Receptor-mediated drugs act by binding to receptors, which then trigger signal transduction pathways that result in a response. The main receptor families are ligand-gated ion channels, G-protein coupled receptors, enzymatic receptors, and nuclear receptors. Factors like dose, tolerance, and individual variability influence drug responses.

1. PHARMACODYNAMICS

2. • In Greek
Pharmacon = Drug
Dynamics = Action/Power
It covers all the aspects relating to
“What a drug does to the body”
Mechanism of action

3. • Action: How and Where the
effect is produced is called as
Action.
• Effect: The type of response
producing by drug.

4. Site of Drug Action
• Where:
1. Extra cellular
2. Cellular
3. Intracellular

5. Types of Drug Action
EFFECT (Type of responses):-
1.Stimulation
2.Inhibition/Depression
3.Replacement
4.Irritation
5.Cytotoxic

6. 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 (HOW)
Receptor mediated
Non receptor mediated

7. Receptor Mediated action
• Drug produce their effect through interacting
with some chemical compartment of living
organism c/s Receptor.
• Receptors are macromolecules
• Most are proteins
• Present either on the cell surface, cytoplasm or
in the nucleus

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

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

10. Drug classification
(on the basis of affinity & efficacy)

11. Response
No response

12. • 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

13. • 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
Benzodiazepines receptors.

14. Receptor families
Four types of receptors families
1. Ligand-gated ion channels (inotropic
receptors)
2.G-protien coupled receptor (Metabotropic
receptors)
3. Enzymatic receptors (tyrosinekinase)
4.Receptor regulating gene expression
(transcription factors/ Steroid )

15. 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

16. Signal transduction mechanism
• Ion gated receptors:- Localized on cell
membrane and coupled directly to an ion
Io
channel.
n
Blocker
Agonist
Receptor
Receptor
Na+2
Hyper polarization or
depolarization
Permeation of
ion is blocked
No cellular effect
Cellular effect

17. • Ex: Nicotinic cholinergic receptor

18. 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)

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

20. G-protein effector systems
• 1.Adenylase cyclase : cAMP system
• 2.Phospholipase –C: Inositol phosphate system
• 3. Ion channels

21. cAMP system

22. Phospholipase-C system

23. 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

24. Enzymatic receptors
• These receptor are directly linked tyrosine
kinase.
• Receptor binding domain present in extra
cellular site.
• Produce conformational changes in intra
cellular
Ex:- Insulin receptors

25. Enzymatic receptors
Extra cellular receptor
binding domain
Intra cellular
changes

26. Receptor regulating gene expression
(transcription factors)
Increase RNA
polymerase activity
Unfolds the receptor and
expose normally
masked DNA binding
site

27. 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.

28. • Receptor up regulation:
Prolonged use of antagonist
Receptor number and sensitivity
Drug effect
• Ex:- propranolol is stopped after prolong
use, produce withdrawal symptoms. Rise
BP, induce of angina.

29. Agonist: Both the high affinity as well as
intrinsic activity (IA=1)
These drug trigger the maximal biological response or
mimic effect of the endogenous substance.
Ex:- Methacholine is a cholinomimetic drug which
mimics the effect of Ach on cholinergic receptors.

30. Types of agonism
• Summation :- Two drugs eliciting same
response, but with different mechanism and their
combined effect is equal to their summation.
(1+1=2)
Aspirin
Codiene
PG
Opiods receptor
Analgesic+
Analgesic+
++

31. Types of agonism
• Additive: combined effect of two drugs acting by
same mechanism
Aspirin
PG
PG
Analgesic+
Analgesic+
++

32. • Synergism (Supra additive):-
(1+1=3)
The combined effect of two drug effect is
higher than either individual effect.
Ex:1.Sulfamethaxazole+ Trimethoprim
2. Levodopa + Carbidopa.

33. Types of antagonism
Antagonism: Effect of two drugs is less than sum
of the effects of the individual drugs.
1. Chemical antagonism
Ex: -heparin(-ve) protamine +ve, Chelating agents
1. Physiological /Functional antagonism
2. Pharmacokinetic antagonism
3. Pharmacological antagonism
I. Competitive ( Reversible)
II. Non competitive (Irreversible)

34. 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, it effect
is reduced.

35. Pharmacological antagonism
• Pharmacodynamic antagonism between two
drugs acting at same receptors.
• Two important mechanism according to which
these antagonists
»1.Reversible(Competitive)
»2.Irreversible(Non)

36. Reversible antagonism
(Competitive antagonism)
• These inhibition is commonly observed
with antagonists that bind reversibly to the
same receptor site as that of an agonist.
• These type inhibition can be overcome
increasing the concentration of agonist
• Ex:- Atropine is a competitive antagonist of
Ach.

37. Irreversible Antagonism
• It occurs when the antagonist dissociates
very slow or not at all from the receptors
result that no change when the agonist
applied.
• Antagonist effect cannot be overcome
even after increasing the concentration of
agonist

38. 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.

39. Dose
• It is the required amount of drug in
weight, volumes, moles or IU to provide a
desired effect.
• In clinical it is called as Therapeutic dose
• In experimental purpose it is called as effective
dose.
• The therapeutic dose varies from person to
person

40. Single dose:
1.Piperazine (4-5g) is sufficient to eradicate round
worm.
2.Single IM dose of 250mg of ceftriaxone to treat
gonorrhoea.
Daily dose:
It is the quantity of a drug to be administered in
24hr, all at once or equally divided dose.
1.10mg of cetrizine (all at once) is sufficient to
relive allergic reactions.
2.Erythromycin is 1g per day to be given in 4
equally divided dose (i.e., 250mg every 6 hr)

41. • Total dose: It is the maximum quantity of the
drug that is needed the complete course of the
therapy.
Ex:- procaine penicillin early syphilis is 6 million unit 
given as 0.6 million units per day for 10days.
Loading dose:- It is the large dose of drug to be
given initially to provide the effective plasma
concentration rapidly. The drugs having high Vd
of distribution.
Chloroquine in Malaria – 600 mg Stat
300mg after 8 hours
300 mg after 2 days.

42. Maintenance dose:- Loading dose normally
followed by maintenance dose.
• Needed to maintain the steady state
plasma concentration attained after giving
the loading dose.

43. Therapeutic index:
• Margin of safety
• Depend upon factor of dose producing
desirable effect  dose eliciting toxic
effect.
Therapeutic index
LD 50
ED 50
• TI should be more than one

44. 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
Toxic

45. •
•
•
•
•
•
Cyclosporine – 100-400ng/ml
Carbamazapine- 4-10µg/ml
Digoxin- 0.8-2ng/ml
Lithium- 0.8-1.4 mEq/L
Phenotoin – 10-20µg/ml
Qunindine- 2-6µg/ml

46. • 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 inc pharmacological response.
• Cocaine, amphetamine  rats- inc. motor
activity

47. 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

48. • Acquired tolerances:
• Occurs due to repeated use of drug
– Pharmacokinetic tolerances
– Pharmacodynamic tolerance
– Acute tolerance
Pharmacokinetic tolerances:- Repetitive
administration causes decrease their
absorption or inc. its own metabolism
Ex: Alcohol  dec. absorption
Barbiturates Inc. own metabolism

49. • 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

50. • Ex: Monday disease.
• Nitroglycerine – Monday , Tuesday
workers get headache, after they get
tolerances.
• After holiday (Sunday) they get again
headache .
• Cross tolerances: Cross tolerance among
drugs belonging to same category.
• MORPHINHEROIN NARCOTIC

51. FACTORS MODIFYING THE
EFFECTS OF DRUGS

52. 
Individuals differ both in the degree and the
character 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.

53. 
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

54. 
These factors modify drug action either:
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

55. 
1.
The various factors are:
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

56. •
For exceptionally obese or lean individuals and for children
dose may be calculated on body weight basis
Individual dose
Individual dose

BW (kg)
x Average adult dose
70
BSA (m2)
x Average adult dose
1.7
BSA=BW(Kg)0.425 x Height(cm)0.725 x 0.007184

57. 2.
Age:
Infants and Children:

The dose of drug for children often calculated from the adult
dose
Age
Child dose
x adult dose .........( Young' s formula)
Age 12
Child dose
Age
x adult dose......
...(Dilling' s formula)
20

58. 
However, infants and children are 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

59. 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

60. 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

61. 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

62. 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

63. 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

64. 7.
Route of drug administration:

I.V route dose smaller than oral route

Magnesium sulfate:

Orally –purgative

Parenterally –sedative

Locally –reduces inflammation

65. 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

66. 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

67. 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.

68. 12.
Genetic factors:

Lack of specific enzymes

Lower metabolic rate

Acetylation

Plasma cholinesterase (Atypical pseudo cholinesterase)

G-6PD

Glucuronide conjugation

69. 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

70. 14.

Other drugs:
By interactions in many ways

72. Drug classification
(on the basis of affinity & efficacy)
Agonist: Both the high affinity as well as
intrinsic activity (IA=1)
These drug trigger the maximal biological response or
mimic effect of the endogenous substance.
Ex:- Methacholine is a cholinomimetic drug which
mimics the effect of Ach on cholinergic receptors.

73. • Antagonist:- Which have only the affinity
no intrinsic activity (IA=0). IA=0 so no
pharmacological activity.
• Rather these drug bind to the receptor
and produce receptor blockade.
• Atropine blocks the effects of Ach on the
cholinergic muscarinic receptors.

74. cAMP system
Some drugs, hormones or neurotransmitters
produce their effect by increasing or
decreasing the activity of adenylate cyclase
and thus raising or lower cAMP with in the
cell.

75. Stimulation
• Some of drug act by increasing the activity
of specialized cells.
Ex: Catecholamines stimulate the heart and
Heart rate, Force of contraction

76. 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.

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

78. Irritation
• Certain drugs on topical application cause
irritation of the skin and adjacent tissues.
• These drugs are using for counter irritant.
Ex: Eucalyptus oil, methyl salicylates (Used
in sprains, joint pain, myalgia.

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

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

81. 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.

82. Cellular Site of Action
1.Ach on Nicotinic receptors of motor end
plate, leading to contraction of skeletal
muscle.
2.Effect of sympathomimetics on
muscle and blood vessels.
heart

83. Intracellular site of action
-Folic acid synthesis inhibitors.
Folic acid which is intracellular component
essential for synthesis of proteins.
Trimethoprim and sulfa drug interfere with
synthesis.

84. Gs/Gi
G protein
Effector
or
AC
+
cAMP
ATP
Phosphorylation
Ca+2 release
Protein kinase Active
FC of heart muscle
Lipolysis
Glycogen
synthesis
Glycogen breakdown
to glucose

85. Physical action
• Absorption: Kaolin absorbs bacterilal toxin
and thus acts as antidiarrhoeal agent.
• Protectives:- Various dusting powders.

86. • Antagonist:- Which have only the affinity
no intrinsic activity (IA=0). IA=0 so no
pharmacological activity.
• Rather these drug bind to the receptor
and produce receptor blockade.
• Atropine blocks the effects of Ach on the
cholinergic muscarinic receptors.

87. Physical Action
• Osmosis:- MgSo4 acts as a purgative by
exerting osmatic 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

88. 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.

89. Protoplasmic poison
• Germicides and antiseptics like phenol
and formaldehyde act as non specifically
as protoplasmic poison causing the death
of bacteria

90. 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

91. 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.

92. Physiological antagonism
• Two antagonists, acting at different sites,
counter balance each other by producing
opp. effect on same physiological system.
• Histamine –Vasodilatation
• Nor epinephrine – Vasoconstriction

93. 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 are trap the heavy
metals. Ex:-EDTA, BAL.