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Fundamentals of

Pharmacokineticsand Pharmacodynamics


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The science that deals with ,

the origin,

nature,chemistry,

effects and

uses of drugs;

It includes,

pharmacognosy,pharmacokinetics,

pharmacodynamics,

pharmacotherapeutics

and toxicology.

Definition

To understand all aspects of drug

action and efficacy-to develop

drugs/treatment regimes that have

selective actions without adverseeffects.

Goals

Pharmacology


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Properties of an Ideal Drug

Effectiveness:

A drug that elicits the response it was meant to. It is the mostimportant property.

Safety:

Safe even at high concentrations and for long periods ofadministration (no such thing as a safe drug)

Reduced by proper administration

No habit forming aspects

No side effects.

Selectivity

The drug should elicits only the response for which it is

given.

A chemical substance used in the treatment,

cure, prevention, or diagnosis of disease or used toenhance physical or mental well-being.

Drug


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Pharmacology:Science of drugs

Pharmacokinetics:Process related to how the

body acts on the drug.

Pharmacodynamics:Process related to how a drug

acts on the body


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Study of the relationship b/w administration ofthe drug, time-course of distribution and themagnitude of concentration at different sites of

action

The knowledge and quantification of pharmacokineticparameters are important for determining the dose,frequency of such doses and the routes of drugadministration.

Pharmacokinetics


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Bioavailability

Half life

Volume of distribution and

Clearance

Important

pharmacokineticparameters


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The fractionofanadministereddose of

unchangeddrugthatreachesthe systemic

circulation.

By definition, when a medication is

administered intravenously, its

bioavailability is 100 %. However, when a

medication is administered via

other routes(such as orally), itsbioavailability generally decreases

Bioavailabilty


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Absolute

bioavailability

It is the fraction of the drug absorbed through non-

intravenous administration compared with the corresponding

intravenous administration ofthe same drug

Relative

bioavailability

relative bioavailability measures the bioavailability ofa formulation (A)

of a certain drug when compared with another formulation (B) of the

same drug


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Bioequivalence

If two medicines are bioequivalent there is

no clinically significant difference in their

bioavailability

Acceptance Criteria for

Bioequivalence

Actual differences between observed mean

plasma concentrations of generic and

innovator medicines were no greater than 5%.


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Elimination/biological

halflife

The time ittakes forasubstance tolose halfof

itspharmacologic/physiologicactivity.

The time ittakes forthe bloodplasmaconcentration

ofadrugto halve ("plasma half-life").


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Clearance

Volume of body fluid sufficient to account for all the drug removed /unit time

Clearance describes the relationship between concentration and the rate of

elimination of drug from the body.

isthe massgenerationrate ofthe

substance.tisdialysistime ortime since

injectionofthe substance/drug

[min]or[s]

Kisthe clearance [mL/min]or

[m/s


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Volume ofdistribution(Vd)

Ratio of the total amount of drug in the body tothe concentration ofthe drug in the plasma

Vd

Plasma concentration(mg/l)

Total drug in the body (mg/kg)


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Absorption

The passage/transfer of drug molecules from its site of

administration into the blood/body fluids.

Mechanism of

Absorption of DRUG

Filtration Diffusion Carrier mediatedtransport

Flowofsolvent

alongwith

dissolved

substance

Substancesmove

fromanareaof

highertolower

concentration

Thepassage ofsubstance

againstthe concentration

gradient,usesspecific

carriers


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Factors affecting the

absorption of drugs

Route ofadministration

Solubilityandotherphysicalproperties

Characteristicofthe absorbingsurface

Disease statesaffectingabsorptiveprocesses


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First pass effect/ first-

pass metabolism

Phenomenonofdrugmetabolismwherebythe concentrationofadrug

isgreatlyreducedbefore itreachesthe systemiccirculation.


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DISTRIBUTION

The systemic circulation distributes drugs to various

body tissues or target sites

Dependent upon

Perfusion rate of the tissue-rate of blood flow

Plasma protein binding

Cellular binding

Concentration in any fatty tissue


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METABOLISM/

BIOTRANSFORMATION

Theprocessbywhich drugsare inactivatedandtransformedintoa form

thatcanbe eliminated fromthebodythrough aseriesofchemicalreactions.

Phase IandPhase IIReactions.

Phase I-Resultsinthe formationof

newmetabollite havingshortert1/2

Phase II-Conjugation.

Phase I-Resultsin watersoluble

conjugate


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Pharmacodynamics

Processrelatedto howadrugactsonthe body.

Aspectwhich involvesthe mechanismsbywhich adrugmolecule

bindstoaspecificsite/substrate andleadstoaresponse.

Drugtargets:

Receptors,Enzymes,ion channels & carriermolecule


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Drug-receptor

interactions


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Efficacy/therapeutic

efficacy

Efficacy, refers to the maximum response achievable from a drug. It is often described

by the parameterEmax.Intrinsic activity is a relative term which describes the efficacy

relative to a drug which has the highest observed efficacy.

LD50andED50

LD50

-The amount of a substance which causes the death of 50% of a

population of test animals.

ED50-The amount of a substance which causes the desired effect in 50% of a

population of test animals.


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Ratioofthe dose requiredtoproduce the toxic effectandthatrequiredto

produce desiredtherapeutic effect

Therapeuticindex


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Therapeuticwindow


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Factors that determinethe intensity of drug

response


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Personalizedmedicine

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