Drug Antagonism

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Types of drug antagonisms, drug interactions and changes in DRC

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Pharmacology:

1 Pharmacology Jerin Jose Cherian Dept. of Pharmacology GMC Trivandrum Wednesday 28 th Septmeber, 2011

PowerPoint Presentation:

2 DRUG ANTAGONISM

Learning Objectives:

3 Learning Objectives Useful Definitions Drug Receptor interactions Graphical depiction (LDRC) Mechanisms of Antagonism

Definitions:

4 Definitions Ligand/Drug – a chemical that affects physiological function in a specific way Receptors – are chemicals which binds to the drug to exert a pharmacologic effect

Definitions contd.:

5 Definitions contd. R EFFECT D

Definitions contd.:

6 Definitions contd. Affinity – allows the ligand to bind to receptors. Intrinsic Activity – allows the bound agonist to activate or turn on its receptor function.

Definitions contd.:

7 Definitions contd. Affinity determines potency Intrinsic activity determines efficacy

:

8 AGONISTS – have affinity AND efficacy D + R = 1 ANTAGONISTS – have affinity but NO efficacy . 2 types B + R = 0 Definitions contd.

D-R interactions:

9 D-R interactions R NO EFFECT B B D B

D-R interactions:

10 D-R interactions Full Agonist – complete intrinsic activity= full efficacy D+R= 1 Partial Agonist – incomplete intrinsic activity = partial efficacy D+R = 0 1

Graphs – understand and learn!:

11 Graphs – understand and learn! Inc. dose of agonist

D-R interactions:

12 D-R interactions Antagonism wrt Drugs – D 1 & D 2 effect of D 1 + D 2 < effect of D 1 + effect of D 2 wrt Receptors – D & R Effect of D on R = 0

Mechanism of drug antagonism:

13 Mechanism of drug antagonism 4 types of drug antagonism – Pharmacodynamic/Receptor blockade Pharmacokinetic antagonism ADME Physiological antagonism Chemical antagonism

Pharmacokinetics:

14 Pharmacokinetics A bsorption D istribution M etabolism E xcretion Reduce drug availability No receptor level modulation

Physiological Antagonism:

15 Physiological Antagonism R 1 D 1 D 2 R 2 Directly opposite action Unrelated Receptors Signal transduction unhindered

Chemical Antagonism:

16 Chemical Antagonism D 1 + D 2 = Inert compound Dependant on their individual chem property

Pharmacodynamic Antagonism:

17 Pharmacodynamic/Receptor blockade Competitive Non Competitive Competition for Agonist Site Pharmacodynamic Antagonism

Non Competitive Antagonism :

18 Non Competitive Antagonism Via Allosteric Modulation Receptor-Effector pathway modulation (down-stream regulation) NO Competition for Agonist site

Competitive Antagonism:

19 Competitive Antagonism Reversible/Equilibrium Irreverible/Non-Equilibrium Pseudo-Reversible Competition for Agonist site Competition for Agonist site

Reversible-Competitive:

20 Reversible-Competitive B D R Weak bond Same agonist site LDRC shift to R Short duration

Reversible-Competitive:

21 B R D D D D D Reversible-Competitive Conc dependant  Dynamic Equilibrium

:

22 Irreversible antagonist + Agonist + Agonist Reversible Inc. dose of agonist

Irreverible - Competitive:

23 Irreverible - Competitive B D R Strong bond Same agonist site LDRC dec efficacy (flatten) Long duration

:

24 Irreversible antagonist + Agonist + Agonist Inc. dose of agonist

Pseudo-Reversible Competitive:

25 Pseudo-Reversible Competitive B D R R R R D D Strong bond Spare receptors  Agonist overcomes antagonist Same agonist site LDRC

PowerPoint Presentation:

26 Competitive Antagonism (equilibrium or reversible) Action of agonist is blocked if conc. of antagonist is  Antagonism can be overcome by  conc. of agonist Agonist can produce max.response in higher conc. Competitive antagonist shifts LDRC of agonist to right ED 50 of agonist  in presence of antagonist, e.g., Ach & atropine; Ad & Prop.; Morphine & naloxone Non-competitive (non-surmountable Antagonist) Antagonist binds to another site of receptor LDRC is flattened + max. response is  e.g.verapamil (noradrenaline)

PowerPoint Presentation:

27 Reversible Competitive Inc. dose of agonist

PowerPoint Presentation:

28 Irreversible Competitive Inc. dose of agonist

PowerPoint Presentation:

29 Pseudo reversible competitive Pseudo - Reversible Competitive Inc. dose of agonist

Non Competitive Antagonism :

30 Non Competitive Antagonism Via Allosteric Modulation Receptor-Effector pathway modulation (down-stream regulation) NO Competition for Agonist site

Allosteric Modulation:

31 Allosteric Modulation B D R Non agonist site DR interaction ineffective No Reversal LDRC flatten

Receptor-Effector pathway modulation (down-stream regulation):

32 Receptor-Effector pathway modulation (down-stream regulation) R D    EFFECT

PowerPoint Presentation:

33 Thank You ..

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