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Introduction to Introduction to PharmacologyPharmacology

Pawitra PulbutrPawitra Pulbutr

B.Pharm (Hon.), M.Sc in B.Pharm (Hon.), M.Sc in Pharm (Pharmacology)Pharm (Pharmacology)

ppawitra@yahoo.comppawitra@yahoo.com

01-801791901-8017919

อ . ภญ . ปวิ�ตรา พู�ลบุ�ตร

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ObjectivesObjectives

• เข้�าใจควิามหมายข้องเภสั�ชวิ�ทยา• อธิ�บุายควิามหมายข้องเภสั�ชจลนศาสัตร!และเภสั�ช

พูลศาสัตร!• เข้�าใจถึ%งการออกฤทธิ�(ข้องยาโดยการจ�บุก�บุ

Receptor, ควิามหมายข้อง Affinity และ Efficacy

• เข้�าใจควิามหมายข้อง Agonist, Partial agonistและ Antagonist พูร�อมท�+งแยกควิามแตกต,างได�

• อธิ�บุายการเก�ด Antagonism และ Enhancement of drug effectsในร�ปแบุบุ

ต,างๆ• เข้�าใจ -Quantal dose re sponse curve และ

Graded dose response relations

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What is What is Pharmacology?Pharmacology?

Pharmacology can be defined as the study of the manner in which

the functions of the living systemsfunctions of the living systems is affected by chemical agentchemical agent

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Chemical agents

DRUGS

Living System

Pharmacologic effect

• Physiological

• Biochemical

Mechanism of drug actionMechanism of drug actionDrug fate in the bodyDrug fate in the body• Absorption

• Distribution

• Metabolism

• EliminationDesired

• Treatment

• Prophylaxis

Undesired

• Side effect

• Toxicity

InteractioInteractionn

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•Chemicals

•Alters biological functions

• Do not create new functions

• Interact with “specific molecule” “specific molecule”(target)(target) in the body

• Intrinsic substance OR Xenobiotics

What is What is drug?drug?

MedicineMedicineMedicineMedicine

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Drug - Body InteractionsDrug - Body Interactions

PharmacodynamicPharmacodynamicss

เภสั�ชพูลศาสัตร!What drug does to

the body

PharmacokineticsPharmacokinetics

เภสั�ชจลนศาสัตร! What body does

to the drug

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Pharmacodynamics

• What drug does to the body

• How do drugs act ?… Mechanism of action

• - Drug Target Interactions

• Dose response relationship

Desired effectsDesired effects

(Clinical (Clinical response)response)

Undesired effectsUndesired effects

(Adverse drug (Adverse drug reaction; ADRs)reaction; ADRs)

Mechanism of Mechanism of actionaction

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Target for drug Target for drug actionaction

Target for drug Target for drug actionaction

Protein

•ReceptorsReceptors

•Ion channelsIon channels

•EnzymesEnzymes

•Carrier Carrier moleculesmolecules

Other

eg. DNA

RNA, Tubulin

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PharmacokineticsPharmacokinetics

• What body does to the drug

• Drug fate in the body

•Absorption

•Distribution

•Metabolism

•Excretion

Drug concentration

at sites of actions

• Drug actionDrug action

• Onset & Duration of Onset & Duration of actionaction

EliminationElimination

Figure 1.1 Schematic representation of the pharmacokinetic and pharmacodynamic processes that link the administration of drugs to its effects

Dose of drug administered

Drug concentration In systemic circulation

Drug in tissues or distribution

Drug concentrationat site of action Drug metabolized or

excreted

Pharmacokinetics

Pharmacologic effect

Clinical response

Toxicity Efficacy

Pharmacodynamics

absorption

distribution

Eliminationdistribution

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Drug acts at receptor

Drug or Drug or LigandLigand

Receptor

Ligand can either stimulate or block

receptor

• Stimulate … “Agonist”

• Block … “Antagonist”

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KA = drug concentration which have 5 0 % occupancy at equilibrium

KA indicates Affinity; ความชอบจับของยากับ receptors

50 % occupancy

50 % occupancy

High KA ; Low Affinity

Low KA ; High Affinity

MODEL

Theoretical relationship between occupancy and ligand Theoretical relationship between occupancy and ligand concentrationconcentration

KA indicate affinity

KA = drug concentration which have 50% occupancy at

equilibrium

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Concentration Effect CurveConcentration Effect Curve• Concentration effect curve is not equal is not equal to occupancy concentr

ation curve

• Can not indicate the affinity … response is not related to response is not related to affinityaffinity

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Agonists VS AntagonistsAgonists VS Antagonists

Agonists

• Bind receptor Physiological response

• Maximal response “ Full agonist”

• Submaximal response“ Partial agonist”

Drugs act at receptor (one type of drug target)

LigandLigand = Agents that bind to = Agents that bind to receptorreceptor

Figure 1.4 Theoretical occupancy and response curve for full and partial agonist

Response full agonist

Response partial agonist

Resp

on

se

Concentration

Occu

pan

cy

Resp

on

seOccupancy

A= Full agonist

B= Partial agonist

0.5

1.0

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• A & C = Full agonistA & C = Full agonist

• B & D = Partial B & D = Partial agonistagonist

• A & C = Full agonistA & C = Full agonist

• B & D = Partial B & D = Partial agonistagonist

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Antagonist Antagonist

• Bind receptor No physiological response

• Block receptor

• Prevent endogenous ligand or agonist binding

Agonist has both “Affinity & Effica Agonist has both “Affinity & Efficacy”cy”

Antagonist has only “Affinity” Antagonist has only “Affinity”Agonist + Antagonist Pharmacolog

ic antagonism

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Drug antagonism

• Pharmacologic antagonism

• Physiologic antagonism

• Chemical antagonism

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Agonist + Competitive reversibleCompetitive reversible antagonist

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Agonist + Irreversible Irreversible antagonist

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Enhancement of drug Enhancement of drug effecteffect

Additive effect 1+1 = 2

Paracetamol + Ibuprofen

Synergism 1+1 > 2

Sulfamethoxazole + Trimethoprim

Potentiation 0+1 > 1

Penicillin + Probenecid

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Dose response curve

• Quantal response = All or none response

• Count the number of subjects who response

Quantal dose response curveQuantal dose response curve

Figure 1.6 Quantal dose effect curves

• Median effective dose = ED

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• Median lethal dose = LD

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• Therapeutic index Therapeutic index(T.I.)(T.I.) = LD = LD

5050 / ED / ED

5050

• More safety… High therapeutic index

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Graded dose response Graded dose response relationsrelations

• Different response when increasing the dose

Figure 1.7 Graded dose-response comparison of 2 sedative-hypnotic drugs

• EfficacyEfficacy ประสั�ทธิ�ภาพูประสั�ทธิ�ภาพู ……Maximum effect Maximum effect (E(Emaxmax))

• PotencyPotency ควิามแรงควิามแรง ...Dose ...Dose to giveto give the sa the sa me response (Lower dose; Higher pote me response (Lower dose; Higher pote

ncy)ncy)

sedation

Anesthesia

Respiratory arrest

Drug A

Drug B

dose

• Efficacy … A = BEfficacy … A = B

• Potency… A > BPotency… A > B

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Key words of the Key words of the dayday

Key words of the Key words of the dayday

Pharmacology Pharmacokinetics Pharmacodynamics Affinity … KA

Concentration – Occupancy curve Concentration response curve Ligand… Agonist-Antagonist Antagonism Enhancement Quantal dose response relationship Therapeutic index/ Standard margin of safety Efficacy VS Potency

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