Pharmacodynamics MBBS 2013-Class-1.pptx

8/22/2019 Pharmacodynamics MBBS 2013-Class-1.pptx

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PharmacodynamicsDr.U.P.Rathnakar

MD.DIH.PGDHM


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Pharmaco dynamics

Principles & mechanism of drug action

Receptor & Non- rec. mediated drug action

Dose response relationships

Therapeutic Index-Drug potency and efficacy

Factors modifying drug action

Drug interactions

Adverse drug reactions- Bioassay-


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Pharmaceutical process

Drug reaches the patient

Pharmacokinetic process What body does to the drug

Pharmacodynamic process

What drug does to the body Pharmacotherapeutic process

Therapeutic effect on the patient


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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


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Mechanism of Drug Action

Non-receptor mediated

Physical

Chemical

Enzymes

Ion channels

Transporters

Immune status

Receptor mediated

Receptors on the cell

membrane

Receptors inside the cell


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Non-receptor Mediated

Osmosis

Adsorption

Demulcent

Radioactivity

Examples

20% Mannitol in Glaucoma

Activated charcoal inpoisoning

Soothing effect of cough

lozenges

I131 in Hyperthyroidism

Physical


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Non-receptor Mediated

Antacids

Chelation

Enzymes

Enzyme inhibition

[Specific or non specific]

Enzyme Stimulation-

Activation

Induction

Examples

Neutralize acid in stomach

BAL in Arsenic poisoning

ACE inhibitors in HTN

[specific]

Phenol, formaldehyde[non

specific]- [no therapeutic value]

Pralidoxime in OP

poisoning

Enzyme inducers[Rifampicin]

Chemical


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Mechanism of Drug Action - Non-

receptor Mediated

Stimulation of AB

production in body

Ion channels

Na channels

Ca channelsTransporters

Serotonin transporter

GABA transporter

Examples

BCG against TB, Polio

vaccine against Polio

Quinidine in heart

Nifedipine

Blocked by Fluoxitine

Blocked by Tiagabine

Antibody production

[Immune]


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Non-receptor mediated

Physical

Chemical

Enzymes

Ion channels

Transporters

Immune status

Receptor mediated

Receptors on the cell

membrane

Receptors inside the cell

M h i f D A i R


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Mechanism of Drug Action - Receptor

Mediated [Eg.Adrenergic Receptors, Muscarinicreceptors]

Receptor:

Protein macromolecules

Present on cell wall or Inside the cell

To which drug binds, interacts, produces

action Drug[D] + Receptor[R] D-R-Complex Action


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Receptor Mediated drug action

Terms

Affinity: Ability of the drug to bind to receptor

Intrinsic activity: Ability of drug to produce pharmacological activity

after binding

Agonist: Drug which binds and Affinity + Intrinsic activity

produces pharmacological action Eg. Morphine, Adrenaline

Antagonist: Binds but no action. Affinity + NO Intrinsic activity

[But blocks receptors] Eg. Naloxone, AtropinePartial agonist: Binds BUT Affinity + LESS intrinsic

less Action activity-Pindolol

Inverse agonist:Binds BUT Affinity + opp. Activity to agonist

Produces action opp.of agonist [b-carboline & GABA Rec]


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Receptor super families

Minutes to

Hours to Days

Intracellular

receptors


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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


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Second Messengers[Effectors]

Binding of a hormone or drug to its receptor does not

instantly produce clinical effects. Instead, a series of

rapid biochemical events couples receptor binding to

ultimate clinical effects. These biochemical events arecalled second messengers.

cAMP

Ca++

Second messengers

Amplify signal

Binding

Biochemical events


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Functions of receptors

To carry signal into the cell

To amplify signal


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CONCEPT OF SPARE

RECEPTORS

Some agonists could elicit maximal

physiological effects by occupying only a

small fraction of the total receptor population

suggested that there were "spare receptors.

Quick response for low concn of drug and fast

dissociation [100% effect is produced when less than 100% of receptorsare occupied]

Eg.Neurotransmission EC50=Kd50-No spare receptors

EC50


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Receptor Regulation

Down regulation

Prolonged use of agonists

[salbutamol 2]

Receptor no.

[ 2 receptors]

Decreased efficacy

Up regulation

Prolonged use of antagonists

[Propranolol]

Receptor no. [ receptors]

[Sudden withdrawal

Increased sensitivity of

adreno-receptorsAngina


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Drug potency & Efficacy

Potency- Amount of drug required to obtain a

particular response[More potent less dose]

Efficacy-The ability of a drug to elicit a maximal

response Aspirin is less potent[300mg] & less efficacious than

morphine[10mg]

Pethidine is less potent[100mg]equally efficacious

as morphine[10mg]


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Dose-response curves determine how much of

a drug (X-axis) causes a particular effect, or a

side effect, in the body (Y-axis).

Dose-response [potency & effect]curve[DRC]

100%

50%

EC50

E max


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Graded dose response curves[Single subject- Continuous]

Advantages of Log-dose curve

Large no.of doses can be plotted on a small graph paper

Comparison of two or more drugs easier as middle portion is

straight line

Linear [Simple]dose response curve Log dose response curve


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Quantal dose response curve

Quantal or all or none: frequency with which any drug evokesa all or none response in a population

LD50

&

ED50

35% 35%

12%

3%

11%

4%

4%

15%

50%

85%

97% 100%

1

0

0

2

0

0

3

0

0

4

0

0

5

0

0

6

0

0

Cumulative DRC


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Therapeutic index [TI]

LD50=Dose which kills 50% of sample population

ED50=Dose which produces desired effect in 50% of

sample

TI= Median lethal dose[LD50]or Toxic Dose50]Median effective dose[ED50]

Wider the TI-More safe the drug

Eg.Penicillin -wide TI , Digoxin narrow TI

Certain safety factor = LD1/ED99

LD1=Lethal dose for 1% population

ED99=Effective dose for 99% of population


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Therapeutic range

Therapeutic range: Range between dose which

produces minimal Th.effect and Max.acceptable

adverse effect

Therapeutic range

Max.ADE

Acceptable-ADE

Min.Th.Effect


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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

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Pharmacodynamics MBBS 2013-Class-1.pptx