11 pd drug interaction eng

8/13/2019 11 PD Drug Interaction Eng

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713 311 PRINCIPLES OF VETERINARY PHARMACOLOGY

Dr. Korawuth Punareewattana

Pharmacodynamics: Drug Interaction

Topic11

Faculty of Veterinary Medicine, Khon Kaen University


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Topics on Drug Interactions Definition

Effects of drug interaction

Types of drug interaction

Pharmaceutical interaction

Pharmacodynamic interactionPharmacokinetic interaction


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Definition Drug interactioncan be defined as the

modifications of the effects of one drug by the

prior or concomitant of another drug (poly-

pharmacy)

A drug interaction is a situation in which a

substance affects the activity of a drug, i.e. the

effects are increasedor decreased, or they produce a

new effect that neither produces on its own.


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Effects of drug interaction Drug interaction can result in

Increased effect Additive or Synergistic effect

Increased therapeutic effect good

Increased toxic or adverse effect bad

Decreased effect Antagonistic effect

Decreased therapeutic effect bad

Decreased toxic effect good

Drug interactions usually happen unexpectedly and result in

adverse drug reactions

Drug interactions for good therapeutic effects are usually used

intentionally and their results are already known by physicians


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Drug-Drug interaction may alter drug effect by

Additive effect : 1 + 1 = 2

Synergistic effect : 1 + 1 > 2

Potentiation effect : 1 + 0 = 2

Antagonism : 1 - 1 = 0 or 0.5


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Effect of Drug interactionTherapeutic drug interaction could be used in 2 objectives

1. To produce synergistic therapeutic effects

Examples are found by several antibiotic combinations Penicillin-Sreptomycin

Penicillin-Probenecid

Sulfa-trimethoprim2. To detoxify or lower toxic effects

Examples are those antidotes of certain toxic agents

Xylazine-Yohimbine


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Types of drug interactionThere are at least 3 types of drug interaction

Pharmaceutical interaction minor

Pharmacodynamic (PD) interaction major

Pharmacokinetic (PK) interaction major


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Pharmaceutical interaction Interactions that occur prior to systemic administration

At manufacturing process

At clinical process by mixing 2 or more drugs in the same

container

Drug incompatibility having drug interaction

Drug compatability no interaction

Chemical or Physical interactions

Usually result in pharmacological loss


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Pharmacodynamic interaction Definitioninteraction that one drug may cause changes in another

drug action, effect or response without PK alteration

Pharmacodynamic interaction could result in either

Additive effect

Synergistic effect

Antagonistic effect

Pharmacodynamic interaction can happen at these levels

Level of drug action

Level of drug effect

Level of drug response

At this level, it could be called Physiological interaction


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Pharmacokinetic interaction Pharmacokinetic (PK) interactions sometimes are also referred to as

dispositional interactions.

These interactions are characterized by the alteration of the PK or

disposition (ADME) of one drug by another.

Change in absorption

Change in distribution

Change in Metabolism

Change in Excretion

Important PK interactions are those associated with

Altered drug metabolism

Drug transporters

Protein binding


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PK interaction associated with

altered drug metabolism

Altered phase I metabolism

CYP induction

CYP inhibition

Altered phase II metabolism

Induction of phase II enzyme

UDP-glucuronyl transferases (UGTs)

Inhibition of phase II enzyme

Competitive use of conjugate molecules


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drug transporters TransportersPlaying Key Roles in Drug Absorption and Excretion

Important drug transporters

P-glycoproteins (PgP)

very important for excretion processes

Other transporters

Interaction usually result in

Inhibit function of transporters

And inhibit drug excretion

And finally cause AUC of a drug to increase or more drug in the body


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Examples of Clinically Significant Drug interactions Associated with

Inhibition of Transporters Other Than PgP


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Protein binding The major plasma proteins to which most drugs bind are albuminand

a1-acid glycoprotein; the former typically binds acidic, anionic drugs

whereas the latter typically favors basic drugs

Competitive protein binding by another drug will result in increase

concentration of free drug, and that will yield more drug response

11 pd drug interaction eng

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