BAP 12.Phar Mode of Drugs Action

8/10/2019 BAP 12.Phar Mode of Drugs Action

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Dr Ruzilawati Abu Bakar

Jabatan Farmakologi

Mode of Drugs Action(1)


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Outline of the lectureOverview- What is a drug?

- Route of drug administration

- PK - ADME

How do drugs work?Target for drug actionsDrug-Receptor Bond


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Overview


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What is a drug?

Drug is a chemical substance thatinteracts with a biological system toproduce a physiologic effect.

All drugs are chemicals but not allchemicals are drugs.

The goal of drug therapy is to prevent,cure or control various disease states.

To achieve this goal, adequate drugdoses must be delivered to the targettissues so that therapeutic levels areobtained.
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Routes of drug administration

IV- intravenous

IM intramuscular

SC - subcutaneous


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- the way the drug enters the body andreaches the bloodstream.

- where the drug goes in the body after

it has been absorbed.

- how it is changed by the body

- the route by which it, or its metabolites,leave the body

Pharmacokinetics


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Site of

ActionDosage Effects

Plasma

Concen.

Pharmacokinetics Pharmacodynamicswhat the body does

to the drugwhat the drug

does to the body

ADME Mechanisms of Drug Actions


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How do drug works


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Mechanism of drug action refer to drugseffect at the site of action

Drug molecules must be bound to particularconstituents of cells and tissues in order toproduce an effect/a pharmacological response

A drug will not work unless it is bound

It is important to be aware that not all drugexert their effects by interacting with a

target site

Mode of drug action


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Mode of drug action

Most drugs exert theireffects, both beneficial& harmful, byinteracting withreceptors

Receptors present onthe cell surface orintracellularly.

Receptors bind drugs &initiate events leadingto alterations inbiochemical activity of acell & consequently thefunction of an organ.


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Drug-Receptor complex

Drug + Receptor {DR} complex

Biologic ResponseThe binding of a drug to its

receptor initiates a series ofcellular response reactions inconsequences which cause a

biologic response
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Drugs act in the body by 2 principlesof mechanisms

HOW DO DRUGS WORK?

1)Non-specific mechanismof drug action

2)Specific mechanismofdrug action


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1) Non-specific mechanism

In this mechanism drugs do not bindwith any specific endogenous

substance within the body.

The effects are produced due tochemical and physical propertyofthe drugs.


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Due to chemical property

Antacids (magnesium trisilicate)

It is alkaline chemically &

reacts with gastric HClThere is acid-alkali reactionand production of salt andwater.

Acid + Alkali = Salt + WaterGastric acid neutralizes,acidity reduced and painsubsides.


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Due to physical property

General anaesthetic agents (Halothane)

This is highly lipid solublesubstance

It dissolves into lipid membraneof neuronsThere is disruption of normalionic exchanges within the nervoustissueLoss of excitability of neuronsDepression of CNS and

anesthesia produced.


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Mannitol an osmotic diuretic

Isphagula a bulk laxative

Dimercaprol a chelating agent used inheavy metal poisoning.


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B) Specific mechanism

drugs work by interacting with targetproteins.

this interaction leads to change ofbiochemical events within the cells

1. some activatetarget proteins2. some antagonize, block or inhibitthe

target proteins.


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The protein targets for drug action

Receptors Enzymes Ion channels Carrier molecules / transporter

Target for drug actions


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Target for drug action some activatetarget proteins

some antagonize, block or inhibitthe target proteins.

Activator/

substrate


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RECEPTOR


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Receptors are macromolecular substances,

protein in nature

present in the cell mainly on cell membrane

with which the drugs bind also present in the nucleus

produce Drug-Receptor complex,

induce changes in systems within cell produces drug responses

Definition of receptor


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Cell membrane Most commonly receptors are present on cell

membrane.

Example: -receptor of Adrenaline,Muscarinic receptor of Ach

Nucleus

Thyroxin receptor

Sites of Receptor

A receptor that is embedded in the cell membrane and functions

to receive chemical information from the extracellularcompartment and to transmit that information to

the intracellular compartment.


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Types of receptors

4 types of major receptors:

Type 1: Ligand-gated ion channels

(ionotropic receptors)Type 2: G-protein-coupled receptor

Type 3: Tyrosine Kinase-linked receptor

Type 4: Intracellular/nuclear receptor


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Type 1: Ligand-gated ion channels(ionotropic receptors)

Cell Membrane receptor

Coupled directly to anion channel


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Ligand-gated ion channelsLigand-gated ion channels are activated after binding to specific ligands ordrugs.

Many drugs activate membrane- bound ligand ion -gated channels.Eg. Benzodiazepines (psychoactive drug) enhance the stimulation of theGABA receptor , resulting in increased chloride influx & hyperpolarization ofthe cell - results in sedative, hypnotic (sleep-inducing), anxiolytic (anti-anxiety),


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Type 2: G-protein-coupled receptor

Cell Membrane receptor

Coupled with intracellular effectorsystems via a G-protein (signaling

protein)(have 3 subunits)

They are activated by hormones &neurotransmitters

A characteristic feature of thesereceptors they contain 7 membrane-spanning domains

The domain activation leads to thesubsequent synthesis of intracellular

second messengerThis will activate numerous proteinswithin cells.

e.g. Beta Adrenergic ReceptorMuscarinic ReceptorINTRACELLULAR EFFECTS

G-protein activation

Generation of Second

Messenger

Activation of Cell signaling


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-Unoccupied receptordoes not interact withG-protein

- G-protein bound with

GDP-Inactive adenylylcyclase

-Occupied receptorchanges shape andinteracts with G protein

-G protein releases GDP& binds GTP

-subunit of G proteindissociates & activatesadenylyl cyclase

-Biologic effect

GDP guanosine diphosphate

GTP guanosine triphosphate


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Type 3: Tyrosine Kinase-linked receptor

Cell Membranereceptors

Incorporateintracellular proteinkinase within theirstructure

e.g.: Insulin receptor,cytokines receptor& receptor for growthfactors


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-Ligand / drug binding tothe receptor on thesurface of the cell.

-formation of receptor

complexes (dimers &tetramer)

- phosphorylation oftyrosine residues onnumerous intracelullar

proteins.

-This triggers a cascadeof events leadingto cellactivation (eg theplatelet-derived growthfactor initiates the

proliferation of smoothmuscle).

-These proteins areinvolved in the regulationof cell growth,

differentiation andactivity.

Type 4: Intracellular/nuclear


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Type 4: Intracellular/nuclearreceptors

Within nucleus

Binding to receptor to form acomplexInfluence DNAtranscription

Result in mRNA encodes

for the synthesis of newprotein

Cellular / biologic effects

E.g.: oestrogen receptorSteroid hormones


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mRNA

A lipid soluble

substance drug/

hormone diffuse

across cell membrane

& moves to the nucleus

of the cell

Drug / hormonebinds to a nuclear

receptor

The drug- receptor

complex binds to

chromatin, activating

the transcription of

specific genesSpecific protein

Biologic effects


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Receptors - summary


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Receptor

1) Agonist of cell membrane receptors2)Antagonist of cell membrane receptors

3)Agonist of nuclear receptors

4)Antagonist of nuclear receptors


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Cell Membrane

Bound Endogenous Activator (Agonist) of Receptor

Active Cell Surface Receptor

Extracellular

Compartment

Intracellular

CompartmentCellular Response

Agonist of cell membrane receptors

- Receptor agonists

- bind to cell surfacereceptors & trigger aresponse

-Eg. Morphine agonists


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Cell Membrane

Displaced Endogenous Activator (Agonist) of Receptor

Inactive Cell Surface Receptor

Extracellular

Compartment

IntracellularCompartment

Bound Antagonist of Receptor (Drug)

Antagonist of cell membrane receptors

-Receptor antagonist

-Block the receptor & cannot trigger a response- eg. Angiotensin Receptor Blockers (ARBs) forhigh blood pressure, heart failure, chronic renalinsufficiency

(losartan , valsartan)


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Intracellular

Compartment

Nucleus

DNA

Modulation of

Transcription

Active Nuclear Receptor

Bound Endogenous Activator

(Agonist) of Nuclear Receptor

Agonist of nuclear receptors

e.g. HRT for menopausesteroids for inflammation


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Displaced Endogenous Activator

(Agonist) of Nuclear Receptor

Intracellular

Compartment

Nucleus

DNA

Bound Antagonist

of Receptor (Drug)

Inactive Nuclear ReceptorIn Cytosolic Compartment

Inactive Nuclear Receptor

In Nuclear Compartment

Antagonist of nuclear receptors

Eg. Estrogen Receptor Antagonists for the prevention and treatmentof breast cancer (tamoxifen [Nolvadex])

- tamoxifen competes with estrogen receptor in breast tissue


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Enzymes


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Enzymes catalyze the biosynthesis ofproducts from substrates

Drugs act by binding with enzymes

Usually inhibit the enzymatic activity

Bind reversibly or irreversibly toenzyme

Enzymes


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Binding

1) Aspirin (for pain relief) acts by binding with Cyclo-oxygenase enzyme (COX)irreversible binding Inhibits synthesis of prostaglandins

2) Physostigmineacts by binding with cholinesteraseenzyme (ChE).reversible binding

Inhibits metabolism of Ach & thus increases theconcentration of Ach in the body

Enzymes


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1) Enzyme inhibitors- Angiotensin Converting Enzyme (ACE)

Inhibitors for high blood pressure, heartfailure, and chronic renal insufficiency(captopril, ramipril)

2) Enzymes activators- e.g. nitroglycerine (guanylyl cyclase)


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Ion-channels


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There are two general classes ofion channels:

1) ligand gated ionotropic receptors.

2) voltage gated

Ion-channels


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Voltage-gated ion channels


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Voltage gated ion channels

Voltage-gated ion channels are activated by alterations in membrane voltage. For example,

voltage-gated Calcium (Ca+) channels open when the membrane is depolarized to athreshold potential and contribute to further membrane depolarization by

allowing Ca+ influx into the cell.


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Ligand-gated ion channels


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Blocker

Eg. Calcium Channel Blockersfor angina andhigh blood pressure

(amlodipine)

OpenerEg. Alprazolam (for management of anxiety

disorder)

Ion-channels


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Carrier molecules /

transporter

C i l l /


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Carrier molecules/Transporter

The transport of ions & small organic molecules across cellmembranes generally requires a carrier protein, since thepermeating molecules are often too polar to penetrate lipidmembranes on their own.

The carrier protein embody a recognition site that makes themspecific for a particular permeating species and these recognition

sites can also be targets for drugs that block the transport system.

C i l l /


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Some important example1) Selective Serotonin Reuptake Inhibitors

(SSRIs) for the treatment of depression

(fluoxetine, fluvoxamine)

2) Inhibitors of Na-2Cl-K Symporter (LoopDiuretics) in renal epithelial cells to increase

urine and sodium output for the treatment ofedema(furosemide, bumetanide)

Carrier molecules/Transporter


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Drug-Receptor

Bonds

D R t B d


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Drug-Receptor Bonds

Drugs interact with receptors by means ofchemical forces & bonds

any bond could be involved with the drug-

receptor interaction. There are 3 major types of chemical

forces/bonds

1) Covalent2) Electrostatic3) Hydrophobic


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Covalent bonds

Covalent bonds are very strong andwould be very tight.

Frequently, a covalent bond is described

as essentially "irreversible"underbiological conditions.

Since by definition the drug-receptor

interaction is reversible, covalent bondformation is rather rare

Covalent bonds cont


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Involves mutual sharing of orbital electrons

Covalent bonds.con t

C l t b d l


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A covalent bond is formed between the activatedform of phenoxybenzamine (a receptorantagonist)(antihypertensive drug) and the alphaadrenergic-receptor.

Results in blockade of the receptor The bonding is not readily broken The blocking effect of phenoxybenzamine

lasts long after the free drug has

disappeared from the bloodstream To overcome the alpha-adrenergic receptor

blockade, new alpha receptor protein mustbe synthesized.

This process may take 48 hours.

Covalent bonds.example

El t st ti B di


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Electrostatic Bonding Electrostatic bonds are weaker than covalent

bonds

Electrostatic interactions tend to be much morecommon than the covalent bonding in drug-

receptor interactions

The interaction strength is variable: Strong electrostatic interactions occur between

permanently charged ionic molecules (Ionic bonds) Weaker interactions all are due to hydrogen

bonding Very weak induced dipole interactions, e.g. van der

Waals forces

d


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Since many drugs contain acid or aminefunctional groups which are ionized atphysiological pH, ionic bonds are formed bythe attraction of opposite charges in thereceptor site

Electrostatic bonds that are formed between

two ions of opposite charge

Ionic bonds is relatively high stability

Ionic bonds

I i b d


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Ionic bonds

Positively charged drugs bind with negatively chargedreceptors (between cations and anions)

Complete transfer of electrons


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Hydrogen bonds

It is the electrostatic attractionbetween opposite partial charges

When a hydrogen atom bearing a partialpositive charge bridges 2 atoms bearingpartial negative charges, a hydrogenbond is created.

Weak bond


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Hydrogen bondscont

van der Waals bond


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van der Waals bond

Very weak induced dipole interactions. Bonding between two dipoles. non-specific attractions between two

atoms that are close to each other.

Hydrophobic Bonds


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Hydrophobic Bonds

Hydrophobic interactions referred tointeractions between molecules inwhich the interactions are less driven

by molecule to molecule attraction andmore by the tendency of molecules towish to avoid the aqueous (water)environments.

Hydrophobic Bonds


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Hydrophobic Bonds

Hydrophobic interactions are generally weak,but important.

Hydrophobic interactions are probablysignificant in driving interactions:

between lipid soluble drugs and the lipid

component of biological membranesbetween non-polar hydrocarbon groups on thedrug and non-polar receptor regions

Hydrophobic Bonds


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Hydrophobic Bonds

These bonds are not very specific but the

interactions do occur to exclude water molecules.

Outline of the lecture


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Outline of the lecture

Drug-receptor binding Dose-response relationship Factors governing drug action

affinity, potency, efficacy Effect of drugs on receptor

- agonist, antagonist Therapeutic Index Drug Reactions/Drug Interactions Factors influencing Drug Response Adverse Drug Reactions


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Drug receptor binding


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Drug-Receptor complex

Drug + Receptor {DR} complex

Biologic ResponseThe binding of a drug to its

receptor initiates a series ofcellular response reactions inconsequences which cause a

biologic response

Drug receptor binding
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Drug-receptor binding When a drug (D) combines with a receptor (R), itdoes so at a rate which is dependent on the

concentration of the drug and the concentration ofthe receptor.

This applies to the Law of Mass Action

k1[D] + [R] [DR]

k-1

D = drug

R = receptor,DR = drug-receptor complexk1= rate for association

K-1= rate for dissociation.

Effect

K2is a proportionality constant which relates to the maximal response or efficacy seenwhen all receptors are occupied

k2


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Drug-response relationship

Drug response relationship


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Drug-response relationship The relationship between dose of a drug

and response produced by that drug

The concentration of the drug would beplotted on the x-axis and the effect /response of the drug would be presentedon the y-axis.

A plot of drug concentration ([D]) versuseffect / response is a rectangularhyperbola.

The drug effect reaches a plateau or

maximum.

This is because there are a finite numberof receptors. Hence, the response musteventually reach a maximum - reaches anequilibrium (the amount of drug bound to

the receptor is constant)

Response


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Drug-response relationship

The hyperbolic plot is acumbersome graph becausedrug concentrations oftenvary over 100 to 1000-fold.

This needs a long X-axis.

To overcome this problem,the log of the drugconcentration is plotted

versus the effect.

A plot of the log of [D]versus response is a sigmoidcurve.

Response

SEMILOG DOSE-RESPONSE CURVE


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Drug Concentration

SEMILOG DOSE RESPONSE CURVE

EC50

50% Effect

Maximal Effect

Effect

or


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Affinity

Potency

Intrinsic activity (efficacy)

F G D


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Factors Governing Drug Action

Factors that determine the effect of adrug on physiologic processes are

1)Affinity

2) Potency

3) Intrinsic activity (efficacy)

Affinity


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Affinity

Affinity is a measure of the tightness that adrug binds to its receptor.

The affinity of a drug for its receptor is

described by the equilibrium constant (KD)

The higher the affinity (low KDvalue) themore likely it is that the receptor will beoccupied by drug.

P


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Potency

A measure of the amount of drugneeded to produce an effect / aresponse

The concentration producing an effectthat is 50% of the maximum is used to

determine potency; it is commonlydesignated as the EC50

EC Half maximal effective


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EC 50 Half maximal effective

concentration(EC50)the concentration of

the drug that producesa response equal to 50%of the maximalresponse.

It is commonly used as ameasure of drug'spotency.

The smaller the value ofEC50the more potent isthe drug.


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25

100

50

75

0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8

Drug A

Muscle

Contraction

Response (mm)

Log [Drug] nM

Drug B

80

40

Drug A is more potentth D B bP t


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than Drug B becauseless Drug A is needed toobtain 50% effect

Eg. Candesartan &irbesartanangiotensin-receptor

blockers that are usedalone or in combinationto treat hypertension

Candesartan is more

potent than irbesartanbecause the dose rangefor candesartan is 4 to32 mg, as compared to adose range of 75 to 300mg for irbesartan.

Potency..cont

SEMILOG DOSE-RESPONSE CURVE


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RANK ORDER OF POTENCY: A > B > C > D

A B C D

Log [Dose]

Effi


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Efficacy

Efficacy or Intrinsic activityis ameasure of the ability of a drug-receptor complex to produce a

functional response.

Efficacy is dependent on the number ofdrug-receptor complexes formed

Potency & Efficacy


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POTENCY

EFFICACY

EC50

Maximal Effect

Log [Dose]

Potency & Efficacy

P t & Effi


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Potency & Efficacy

Potency andefficacy betweendrugs can be

compared by usingdose-responsecurve

Potency & Efficacy


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y y

RANK ORDER OF POTENCY: A > B > C > D

RANK ORDER OF EFFICACY: A = C > B > D

A

B

C

D

EC50


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AgonistAntagonist

Eff t f d pt


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Effect of drugs on receptors

Drug that act on a specific receptor canbe classified by their effect on thereceptor

1) Agonist

2) Antagonist

Agonist


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A drug that combines with receptors andinitiates a sequence of biochemical and

physiological changes Once bound to the receptor an agonist activates

or enhances cellular activity.

Agonists have both affinity & intrinsic activity It has intrinsic activity = 1

- - -

+ + +

Depolarization

Agonist


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Agonist

Examples of agonist action:-

Epinephrine an agonist at betaadrenergic receptor

Increase in force of contraction of theheart

Agonist


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Agonists can be further divided into :

1) Full Agonists

2) Partial Agonists

Agonist

Full A nist


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Full Agonist

Compounds that areable to elicit themaximal responseof the tissue

following receptoroccupation andactivation.

Full agonists havehigh efficacy

Partial Agonist


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Partial Agonist

Compounds thatproduce an agonistaction, but areunable to elicit thefull response of thetissue.

DRC full & partial agonist


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DR full & part al agon st

Antagonist
http://en.wikipedia.org/wiki/File:Agonist.png


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g Antagonistshave the ability to bind to the

receptor but do not initiate a change incellular function.

Because they occupy the receptor, they can

prevent the binding and the action ofagonists.

Antagonists are also referred to as blockers.

Antagonist


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Antagonist

Antagonists, only have affinity for thereceptor. This property allowsantagonists to bind to the receptor.

However, antagonists do not haveintrinsic activity at the receptor, NO

EFFECTis produced (zero efficacy)

Antagonist


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Antagonist

Antagonist


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Antagonists can be further divided into :

1) Competitive Antagonists

2) Noncompetitive Antagonists

Antagonist

Competitive Antagonist


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Agonists and antagonists"compete" for the samebinding site on the

receptor.

Once bound, anantagonist will block

agonist binding. They bind in a reversible

manner



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Because competitive antagonists bind in a reversiblemanner, agonists, if given in high concentrations, candisplace the antagonist from the receptor and the

agonist can then produce its effect.

The antagonist can be completely displaced,therefore, the agonist is still able to produce thesame maximal effect observed prior to antagonisttreatment.

Competitive Antagonistcont


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p g The presence of a competitive antagonist will shift

the dose response curve for an agonist to the right

The maximum possible effect of the agonist does notchange

Competitive Antagonistcont


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p g

Eg. Prazosinantihypertensive drugcompetes with the endogenous ligand,

norephinephrineat

1-adrenoceptors

Decreasing vascular smooth muscle tone

Reducing blood pressure

Noncompetitive antagonist


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Noncompetitive antagonist is referred to as an irreversible antagonist.

They are chemically reactive compounds andcovalently binds with the receptor

It remains attached to the receptor for a long periodof time.

Because the antagonist is covalently bound to thereceptor, the binding of agonists & their

pharmacologic activity, are blocked.

Unlike competitive antagonists, the blocking activityof noncompetitive antagonists can not be overcome byincreasing the agonist concentration.

Noncompetitive antagonist cont


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Noncompetitive antagonistcon t

Noncompetitive antagonist always decreasesthe maximal response

Response



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Eg. Irreversible binding of antagonist

Aspirin inhibition of cyclooxygenase

Blocks production of prostaglandins fromarachidonic acid

Requires synthesis of new protein to overcome This mechanism is important for the use of aspirin in

preventing recurrence of myocardial infarction


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Therapeutic Index

Therapeutic Index


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Therapeutic Index

therapeutic effect-desirable and beneficialeffect.

toxic effect- harmful and undesired effect.

Therapeutic Index of a drug

Is the ratio of the dose that producestoxicity to the dose that produces a clinicallydesire or effective response in a population

Therapeutic Index cont


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Therapeutic Indexcon t

TD50= the drug dose that produces a toxiceffect in half the population

ED50= the drug dose that produces atherapeutic or desired response in half thepopulation


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Log concentration drugin plasma

Percentage ofpatient

Therapeutic Index cont


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Therapeutic Indexcon t

Therapeutic index is a measureof a drugs safety, because a

larger value indicates a widemargin between doses that areeffective & doses that are toxic

Narrow Therapeutic Index


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Narrow Therapeutic Index

Warfarin oral anticoagulant

- When the therapeutic index issmall, it is possible to have range ofconcentration where the effective &toxic response overlap

WarfarinLithiumDigoxinPhenytoin

GentamycinAmphotericin B5-fluorouracilAZT (zidovudine)

Large Therapeutic Index


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Large Therapeutic Index

Penicillin antimicrobial drug

- It is safe & common to give doses in excess (oftenabout ten-fold excess) of that what which is minimallyrequired to achieve a desired response


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Drug interactions

Drug-drug interactions


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A drug-drug interaction occurswhen one drug interacts with orinterferes with the action ofanother drug.

Drug-drug interactions canproduce effects that are:-

1. Additives2. Synergistic3. Antagonistic

Additive drug reactions


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Additive drug reactions

Occurs when the combined effect oftwo drugs is equal to the sum of eachdrug given alone.

Eg. taking drug heparin with alcohol willincrease bleeding

The equation to illustrate the additiveeffect of drugs 1 + 1 = 2


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Antagonistic drug reactions


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Occurs when one drug interferes with theaction of another causing neutralization or adecrease in the effect of one drug.

Eg. Protamine sulfate is a heparin antagonist

The administration of protamine sulfatecompletely neutralizes the effects of heparin

in the body

The equation to illustrate the antagonisticeffect of drugs 1 + 1 = 0

Drug-drug interactions


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g g

Factors influencing Drug Response


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Factors influencing Drug Response

Certain factors may influence drugresponse

1. Body weight and size2. Age and Sex

3. Genetics - pharmacogenetics4. Condition of health / Disease

AGE


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AGE The age of the patient may

influence the effects of adrug.

Infants & children usuallyrequire smaller doses of a drugthan adults

Immature organ function,particularly of the liver &kidneys, can affect the abilityof infants & young children to

metabolize drugs

AGEcont


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AGEcon t

Elderly patients may also requiresmaller doses, although this maydepend on the type of drugadministered.

Changes that occur with agingaffect the pharmacokinetics of a

drug because of the physiologicchanges that occur with aging.

Weight


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Weight

In general, dosages are based ona weight of approximately 150 lb(~ 68 kg), which is calculated tobe the average weight of menand women.

A drug dose may sometimes beincreased or decreased because

the patients weight issignificantly higher or lowerthan this average.

SEX
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SEX

The sex of an individual mayinfluence the action of some drugs

Women may require a smaller dose ofsome drugs than men.

This is because many women aresmaller & have a different body fat-to-water ratio than men.

Disease


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D sease

The presence of disease may influence theaction of some drugs.

Sometimes disease is an indication for notprescribing a drug or for reducing the dose ofa certain drug.

Both hepatic (liver) & renal (kidney) diseasecan greatly affect drug response

Diseasecont


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D seasecon tIn liver disease

The ability to metabolize ordetoxify a specific type ofdrug may be impaired

If the average or normaldose of the drug is given, theliver may be unable tometabolize the drug at anormal rate.

The drug may be excreted from the body at much slower rate than normal prescribe

a lower dose & lengthen the time between doses because liver function is abnormal.


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Adverse Drug Reactions

Adverse Drug Reactions


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Adverse Drug React ons

Patients may experience one or more adversereactions when they are given a drug at anormal dose

Adverse reactions are undesirable drugeffects

May be common or may occur infrequently

May be mild, severe or life-threatening.

May occur after the first dose, after severaldoses or after many doses

Adverse Drug Reactions.cont


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rs Drug act ons.con t

Often, an adverse reaction is unpredictable, althoughsome drugs are known to cause certain adversereactions in many patients

Eg. drugs used in treating cancer are very toxic & are

known to produce adverse reactions in many patientsreceiving them.

Other drugs produce adverse reactions in fewerpatients

Some adverse reactions are predictable, but manyadverse reactions occur without warning.

Adverse Drug Reactionseg


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D g g

Common adverse effects of oral iron therapy:-

Black stools

Nausea

Constipation

Diarrhea

References


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1) Pharmacology, Rang & Dale, Churchill Livingstone, 5thed., 2003

2)Introductory Clinical Pharmacology, Roach & Ford,Lippincott Williams & Wilkins, 8thed., 2008.

3)Pharmacology: Lippincotts Illustrated Review, 4thed.,2009.

BAP 12.Phar Mode of Drugs Action

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