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PHARMACODYNAMICS
Dr. Ab.Siddique.P.A
Associate Professor
Pharmacology & Therapeutics
Dr. sid
Associate Professor
Pharmacology
Introduction
• Study of actions of the drugs on the body &
their mechanisms of action
• Drugs produce their effects by interacting
with physiological systems of organisms
• Drugs only modify rate of functions of various
systems; they cannot change the basic
functions of any physiological system
PHARMACODYNAMICS
• What the drug does to the body.
• Study of drug effects. How? And What?
• Pharmacodynamics deals with the study of
biochemical and physiological effects of
drugs and their mechanisms of action.
Dose
Absorption
Distribution
Metabolism Pharmacokinetics
Excretion
Drug in the plasma
Drug at the site of action
Pharmacodynamics
MOA & Effect- Adverse and Beneficial
PRINCIPLES [Types] OF DRUG ACTION
1. Stimulation
– Adrenaline
– Pilocarpine
2. Depression
– Quinidine
– Morphine
– Barbiturates
3. Irritation
– Bitters
– Counter irritants
4. Replacement
• Insulin
• Iron
• Levodopa
5. Cytotoxic action
•Penicillin,
•Chloroquine
• cyclophosphamide
6. Modification of
immune status
•Vaccines
•Sera
Mechanism of Drug Action
Non-receptor mediated Receptor mediated
•Physical
•Chemical
•Enzymes
•Antibody
•Placebo
•Receptors on
the cell
membrane
•Receptors
inside the
cell
Mechanisms of drug action
Physical action:
• Physical property of the drug
is responsible
– E.g. mass: bulk laxatives
– Adsorptive : charcoal
– Osmotic activity: magnesium sulfate
– Radioactivity: radioactive iodine
– Radioopacity: barium sulfate
Mechanisms of drug action
Chemical action:
• Extracellular chemical interactions
–E.g. antacids neutralize gastric HCl
–Chelating agents used in poisoning
treatment
Mechanisms of drug action
Through enzymes:
• Stimulation: unusual
• Relevant to endogenous mediators
• E.g. adrenaline stimulates adenyl
cyclase
Mechanisms of drug action
• Enzyme inhibition:
–Non specific inhibition:
• Certain chemicals alter the tertiary
structure of any enzyme with which
they come in contact E.g. alcohol,
formaldehyde
Enzyme inhibition
–Specific inhibition:
• Competitive: Overcome by
increasing substrate conc.
– E.g. physostigmine &
neostigmine compete with
acetyl choline for
cholinesterase
• Non competitive: inhibitor
reacts with adjacent site &
not with catalytic site,
alters enzyme such that it
loses its catalytic activity
– E.g. aspirin & cyclooxygenase
Mechanism of Drug Action - Non-receptor
Mediated
Antibody production Examples
• Stimulation of
AB production
in body
• BCG against TB,
Polio vaccine
against Polio
Mechanism of Drug Action - Non-receptor
Mediated-Placebo effect
• Placebo: Dummy medicine without
Pharmacological effect
• Uses:
1. Relief of subjective symptoms- Eg .Anxiety
2. In Clinical trials to reduce bias
• Factors affecting
1. Pt factors-With neurotic symptoms
2. Drug factor-Injection, Capsules
3. Doctor factor-Personality, Fame, Dr - Pt
relationship
Mechanism of Drug Action - Receptor
Mediated
• Receptor:
 Protein macromolecules
 Present on cell wall or
 Inside the cell
 To which drug binds, interacts and
produces action
• Drug[D]+Receptor[R]↔D-R-Complex→Action
Eg. Adrenergic, Muscarinic
Drug
Receptor
Effect
RECEPTOR MEDIATED DRUG ACTION
D-R
Binding
Second messengers
Receptor Super Families
MEMBRANE BOUND RECEPTORS
• GPCR: Eg. Muscarinic, Adrenergic
receptors
• Ligand gated Ion channel: Eg. Nicotinic
receptors
• Enzymatic: Eg. Insulin receptor
 INTRACELLULAR RECEPTORS
• Nuclear Receptors: Eg. Steroid, Thyroid
hormone
endocrine and the sensory systems.
References:
G-Protein coupled[GPCR]
Ligand gated ion channels
Nuclear receptors
Enzymatic receptors
Receptor Super Families
Receptor Regulation
Downregulation Upregulation
• Prolonged use of agonists
[Salbutamol]
↓
Receptor no. and sensitivity
[β2 receptors] ↓ ↓
↓
Drug effect ↓ ↓
[Decreased effect on chronic
use]
• Prolonged use of
antagonists
[Propranolol]
↓
Receptor no. and sensitivity
[β2 receptors] ↑↑
↓
[Sudden withdrawal →
Increased sensitivity of
adrenoreceptors→ Angina
Receptor Mediated- Terms
Affinity: Ability of the drug to bind to
receptor
Intrinsic activity: Ability of drug to produce
pharmacological activity after binding
• Substance that binds & produces a
response similar to the physiological
signal molecule
Agonist
• Substance that binds to receptor &
prevents the action of agonist, but no
effect of its own
Antagonist
• Binds to receptor but has low intrinsic
activity, i.e. produces partial response
Partial agonist
Inverse agonist
•Activates receptor & produces a
response in the opposite direction to
that of agonist
Receptor mediated drug action
Dose response relationship
• Potency of drug: Amount of the drug required
to produce a response
– E.g 1 mg of bumetanide produces same diuresis as
50 mg of frusemide
– Less clinical significance
• Efficacy :
– Indicates maximum response that can be produced
by a drug
– E.g. Frusemide produces powerful diuresis which
cannot be produced by any dose of amiloride
– Great clinical significance
Dose response
• Dose-Response relationship: Relationship
between Pharmacological effect and dose
[Concn.of drug at site of action]
• Graded or quantitative: As the dose
administered in a single sub or tissue is
increased, response increases in a graded
fashion
Graded
• Quantal or all or none: frequency with
which any drug evokes a all or none
response in a population
Quantal
Therapeutic window phenomenon
• Optimal therapeutic effect exerted
only over a narrow range of plasma drug
conc.or drug doses; both below & above
this range, beneficial effects are
suboptimal
• E.g. Tricyclic antidepressants, Clonidine,
glipizide
Therapeutic index
Therapeutic index = median lethal dose
median effective dose
• Indicates safety margin of drug
• Drugs with low therapeutic index have
low safety margin
• E.g. digoxin, lithium
100→
50% →
50% →
0 →
ED50 LD50
TI Narrow TI WIDE
TI=10/5=2 TI=100/5=20
Combined effect of drugs
• When 2 drugs are administered together:-
1. They may be Indifferent to each other
2. One may increase the action of the
other- Synergism
3. Action may be decreased or abolished
Antagonism
Combined effect of drugs
Indifferent Synergism Antagonism
One facilitates
the action of
other
One opposes the
action of other
Additive
Supra-additive
[Potentiation]
Competitive
Non-
competitive
Physical
Chemical
Physiological
Receptor
Combined effect of drugs
Synergism : (Greek: Syn-together,
ergon-work)
• Action of one drug is facilitated or
increased by the other
• Additive: effect of drugs A + B = effect
of drug A + effect of drug B
– E.g. aspirin + paracetamol =
analgesic/antipyretic
Synergism
Supra additive: (potentiation)
• Effect is greater than individual
effects of components
• Effect of drug A+ B=> effect of drug A
+ effect of drug B
• E.g. acetyl choline + physostigmine
(inhibition of break down)
– Levodopa + carbidopa (inhibition of
peripheral metabolism)
Antagonism
• Drug decreases or inhibits the action of
another
• Effect of drug A + B< effect of drug A
+ effect of drug B
• Usually one drug is inactive as such;
decreases the effect of another
Physical antagonism
• Based on physical property of the drugs
• E.g. charcoal adsorbs alkaloids & can
prevent absorption
Chemical Antagonism:
Drugs react chemically & form inactive
product
e.g. KMnO4 oxidizes alkaloids: used for
gastric lavage in poisoning
In vitro chemical antagonism
• Drugs might react when mixed in same
syringe or infusion bottle
• E.g. thiopentone sodium + succinyl
choline
• Penicillin + succinyl choline
• Heparin + penicillin/
tetracycline/streptomycin
Physiological/ functional antagonism
• Two drugs act on different receptors or
by different mechanisms, but have
opposite effects on the same
physiological function
• Pharmacological effects in opposite
direction
• E.g. Histamine & adrenaline on bronchial
muscles & BP
Receptor mediated antagonism
• Antagonist interferes with the binding
of agonist with its receptor or inhibits
generation of response as a result of
binding
• Competitive & non-competitive
• E.g. acetyl choline & atropine
– Morphine & naloxone
– Diazepam & bicculline
Competitive[Surmountable] Noncompetitive[Unsurmountable]
1. Binds with the same site
on the receptor
2. Resembles the agonist
3. Surmountable by
incresing the concn. Of
agonist
4. Rightward shift of DRC
5. Eg.
Ach – atropine
Morphine - Naloxone
1. Binds to another site or
same site covalently
2. No resemblance
3. Not surmountable
4. Flattening of DRC
5. Eg.
Diazepam –Bicuculline
Phenoxybenzamine-
Noradrenaline
Antagonism

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PHARMACODYNAMICS-1

  • 1. PHARMACODYNAMICS Dr. Ab.Siddique.P.A Associate Professor Pharmacology & Therapeutics Dr. sid Associate Professor Pharmacology
  • 2. Introduction • Study of actions of the drugs on the body & their mechanisms of action • Drugs produce their effects by interacting with physiological systems of organisms • Drugs only modify rate of functions of various systems; they cannot change the basic functions of any physiological system
  • 3. PHARMACODYNAMICS • What the drug does to the body. • Study of drug effects. How? And What? • Pharmacodynamics deals with the study of biochemical and physiological effects of drugs and their mechanisms of action.
  • 4. Dose Absorption Distribution Metabolism Pharmacokinetics Excretion Drug in the plasma Drug at the site of action Pharmacodynamics MOA & Effect- Adverse and Beneficial
  • 5. PRINCIPLES [Types] OF DRUG ACTION 1. Stimulation – Adrenaline – Pilocarpine 2. Depression – Quinidine – Morphine – Barbiturates 3. Irritation – Bitters – Counter irritants 4. Replacement • Insulin • Iron • Levodopa 5. Cytotoxic action •Penicillin, •Chloroquine • cyclophosphamide 6. Modification of immune status •Vaccines •Sera
  • 6. Mechanism of Drug Action Non-receptor mediated Receptor mediated •Physical •Chemical •Enzymes •Antibody •Placebo •Receptors on the cell membrane •Receptors inside the cell
  • 7. Mechanisms of drug action Physical action: • Physical property of the drug is responsible – E.g. mass: bulk laxatives – Adsorptive : charcoal – Osmotic activity: magnesium sulfate – Radioactivity: radioactive iodine – Radioopacity: barium sulfate
  • 8. Mechanisms of drug action Chemical action: • Extracellular chemical interactions –E.g. antacids neutralize gastric HCl –Chelating agents used in poisoning treatment
  • 9. Mechanisms of drug action Through enzymes: • Stimulation: unusual • Relevant to endogenous mediators • E.g. adrenaline stimulates adenyl cyclase
  • 10. Mechanisms of drug action • Enzyme inhibition: –Non specific inhibition: • Certain chemicals alter the tertiary structure of any enzyme with which they come in contact E.g. alcohol, formaldehyde
  • 11. Enzyme inhibition –Specific inhibition: • Competitive: Overcome by increasing substrate conc. – E.g. physostigmine & neostigmine compete with acetyl choline for cholinesterase • Non competitive: inhibitor reacts with adjacent site & not with catalytic site, alters enzyme such that it loses its catalytic activity – E.g. aspirin & cyclooxygenase
  • 12. Mechanism of Drug Action - Non-receptor Mediated Antibody production Examples • Stimulation of AB production in body • BCG against TB, Polio vaccine against Polio
  • 13. Mechanism of Drug Action - Non-receptor Mediated-Placebo effect • Placebo: Dummy medicine without Pharmacological effect • Uses: 1. Relief of subjective symptoms- Eg .Anxiety 2. In Clinical trials to reduce bias • Factors affecting 1. Pt factors-With neurotic symptoms 2. Drug factor-Injection, Capsules 3. Doctor factor-Personality, Fame, Dr - Pt relationship
  • 14. Mechanism of Drug Action - Receptor Mediated • Receptor:  Protein macromolecules  Present on cell wall or  Inside the cell  To which drug binds, interacts and produces action • Drug[D]+Receptor[R]↔D-R-Complex→Action Eg. Adrenergic, Muscarinic
  • 15. Drug Receptor Effect RECEPTOR MEDIATED DRUG ACTION D-R Binding Second messengers
  • 16. Receptor Super Families MEMBRANE BOUND RECEPTORS • GPCR: Eg. Muscarinic, Adrenergic receptors • Ligand gated Ion channel: Eg. Nicotinic receptors • Enzymatic: Eg. Insulin receptor  INTRACELLULAR RECEPTORS • Nuclear Receptors: Eg. Steroid, Thyroid hormone
  • 17. endocrine and the sensory systems. References: G-Protein coupled[GPCR] Ligand gated ion channels Nuclear receptors Enzymatic receptors Receptor Super Families
  • 18.
  • 19. Receptor Regulation Downregulation Upregulation • Prolonged use of agonists [Salbutamol] ↓ Receptor no. and sensitivity [β2 receptors] ↓ ↓ ↓ Drug effect ↓ ↓ [Decreased effect on chronic use] • Prolonged use of antagonists [Propranolol] ↓ Receptor no. and sensitivity [β2 receptors] ↑↑ ↓ [Sudden withdrawal → Increased sensitivity of adrenoreceptors→ Angina
  • 20. Receptor Mediated- Terms Affinity: Ability of the drug to bind to receptor Intrinsic activity: Ability of drug to produce pharmacological activity after binding
  • 21. • Substance that binds & produces a response similar to the physiological signal molecule Agonist • Substance that binds to receptor & prevents the action of agonist, but no effect of its own Antagonist • Binds to receptor but has low intrinsic activity, i.e. produces partial response Partial agonist Inverse agonist •Activates receptor & produces a response in the opposite direction to that of agonist Receptor mediated drug action
  • 22. Dose response relationship • Potency of drug: Amount of the drug required to produce a response – E.g 1 mg of bumetanide produces same diuresis as 50 mg of frusemide – Less clinical significance • Efficacy : – Indicates maximum response that can be produced by a drug – E.g. Frusemide produces powerful diuresis which cannot be produced by any dose of amiloride – Great clinical significance
  • 23. Dose response • Dose-Response relationship: Relationship between Pharmacological effect and dose [Concn.of drug at site of action] • Graded or quantitative: As the dose administered in a single sub or tissue is increased, response increases in a graded fashion Graded • Quantal or all or none: frequency with which any drug evokes a all or none response in a population Quantal
  • 24. Therapeutic window phenomenon • Optimal therapeutic effect exerted only over a narrow range of plasma drug conc.or drug doses; both below & above this range, beneficial effects are suboptimal • E.g. Tricyclic antidepressants, Clonidine, glipizide
  • 25. Therapeutic index Therapeutic index = median lethal dose median effective dose • Indicates safety margin of drug • Drugs with low therapeutic index have low safety margin • E.g. digoxin, lithium
  • 26.
  • 27. 100→ 50% → 50% → 0 → ED50 LD50 TI Narrow TI WIDE TI=10/5=2 TI=100/5=20
  • 28. Combined effect of drugs • When 2 drugs are administered together:- 1. They may be Indifferent to each other 2. One may increase the action of the other- Synergism 3. Action may be decreased or abolished Antagonism
  • 29. Combined effect of drugs Indifferent Synergism Antagonism One facilitates the action of other One opposes the action of other Additive Supra-additive [Potentiation] Competitive Non- competitive Physical Chemical Physiological Receptor
  • 30. Combined effect of drugs Synergism : (Greek: Syn-together, ergon-work) • Action of one drug is facilitated or increased by the other • Additive: effect of drugs A + B = effect of drug A + effect of drug B – E.g. aspirin + paracetamol = analgesic/antipyretic
  • 31. Synergism Supra additive: (potentiation) • Effect is greater than individual effects of components • Effect of drug A+ B=> effect of drug A + effect of drug B • E.g. acetyl choline + physostigmine (inhibition of break down) – Levodopa + carbidopa (inhibition of peripheral metabolism)
  • 32. Antagonism • Drug decreases or inhibits the action of another • Effect of drug A + B< effect of drug A + effect of drug B • Usually one drug is inactive as such; decreases the effect of another
  • 33. Physical antagonism • Based on physical property of the drugs • E.g. charcoal adsorbs alkaloids & can prevent absorption Chemical Antagonism: Drugs react chemically & form inactive product e.g. KMnO4 oxidizes alkaloids: used for gastric lavage in poisoning
  • 34. In vitro chemical antagonism • Drugs might react when mixed in same syringe or infusion bottle • E.g. thiopentone sodium + succinyl choline • Penicillin + succinyl choline • Heparin + penicillin/ tetracycline/streptomycin
  • 35. Physiological/ functional antagonism • Two drugs act on different receptors or by different mechanisms, but have opposite effects on the same physiological function • Pharmacological effects in opposite direction • E.g. Histamine & adrenaline on bronchial muscles & BP
  • 36. Receptor mediated antagonism • Antagonist interferes with the binding of agonist with its receptor or inhibits generation of response as a result of binding • Competitive & non-competitive • E.g. acetyl choline & atropine – Morphine & naloxone – Diazepam & bicculline
  • 37. Competitive[Surmountable] Noncompetitive[Unsurmountable] 1. Binds with the same site on the receptor 2. Resembles the agonist 3. Surmountable by incresing the concn. Of agonist 4. Rightward shift of DRC 5. Eg. Ach – atropine Morphine - Naloxone 1. Binds to another site or same site covalently 2. No resemblance 3. Not surmountable 4. Flattening of DRC 5. Eg. Diazepam –Bicuculline Phenoxybenzamine- Noradrenaline Antagonism