pharmakokinetic drug interaction

8/22/2019 Pharmakokinetic Drug Interaction

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PHARMACOKINETIC

DRUG INTERACTIONSubmitted Vivek Paud

Ashok Bhus


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What is drug interaction?A drug interaction is a situation in which

substance (usually another drug) affectactivity of a drug when both are adminitogether. In other words, drug interactio

said to occur when the pharmacologicaactivity of a drug is altered by the conco

use of another drug or by the presence some other substance.


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This action can be synergistic (when the d

effect is increased) or antagonistic (whendrugs effect is decreased) or a new effec

produced that neither produces on its owdrug whose activity is affected by such a

interaction is called as the object druganagent which precipitates such an interac

referred to as the precipitant.


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Most of the interactions are undesirab(or harmful) whereas rare cases arefound to be desirable (beneficial): foe.g., enhancement of activity ofpenicillins when administered withprobenicid.


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Types of drug interaction:

Drug-drug interactions

Food-drug interactions

Chemical-drug interactions

Drug-laboratory test interaction

Drug-disease interactions


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Risk Factors:High risk patients

-Elderly, young, very sick, multiple disease

-multiple drug therapy

-Renal, liver impairment

High Risk Drugs

-Narrow therapeutic index drugs

-Recognized enzyme inhibitors or inducers


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Mechanism Of Drug Interactions

Pharmaceutical Interactions

Pharmacokinetic Interactions

Pharmacodynamic Interactions


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Pharmaceutical Interaction:Also called as incompatibility, it is a physicochemical interactiothat occurs when drugs are mixed in IV infusions causingprecipitation or inactivation of active principles. For e.g. ampicchlorpromazine and barbiturates interact with dextran in solutiosolutions and broken down or form chemical complexes.

Pharmacokinetic Interactions:Those interaction in which absorption, distribution, metabolism,

excretion of the drug is altered.

Pharmacodynamic Interaction:Those interaction in which the activity of the object drug at its sof action is altered by the precipitant. Such interactions may bedirect or indirect.


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Pharmacokinetic Interactions:

These interactions are those in which theabsorption, distribution, metabolismand/or excretion of the object drug arealtered by the precipitation.

Hence also called as ADME interactions.


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Pharmacokinetic interactions are those in

which one drug results in an alteration(increase or decrease) of the concentratanother drug in the system. The resultant ealters the plasma concentration of the ob

drug.


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Classification:

Absorption Interactions

Distribution Interactions

Metabolism Interactions

Excretion Interactions


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Absorption Interactions:

In this absorption of object drug is altered. Thiswill result in a reduction in the therapeutic effec

of the object drug.

This may result in:

1. Faster or slower drug absorption.2. More, or, less complete drug absorption.


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Major Mechanisms of absorptioninteractions are: Complexation and adsorption.

Alteration in GI pH.

Alteration in gut motility.

Inhibition of GI enzyme.

Alteration of GI microflora.

Malabsorption syndrome.


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ABSORPTIONA. Complexation/Chelation

Antacids (Mg2+, Al3+ ions)

Make complex with Tetracycline, ciprofloxacin

Reduced absorption of Tetracycline, ciprofloxac


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ABSORPTIONB. Altered GI Transit

Anticholinergics

Block M3 receptors

Reduce motility

Delays the absorption of Acetaminophen


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ABSORPTIONC. Altered gastric pH

H2 blockers (Ranitidine, cimetidine)

Reduce acid secretion

Increase PH

Reduce dissolution of Ketoconazole

Reduce absorption of ketoconazole


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ABSORPTIOND. Altered GI microflora

Antibiotics

Kills the microflora of GIT

Reduce the absorption of Oral contraceptives

Unwanted pregnancy


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Distribution Interactions

These are the interactions where the distribution patternof the object drug is altered.

The major mechanism for distribution interaction isalteration in protein-drug binding.


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DISTRIBUTIONAlteration In Plasma protein binding

Sulfonamides, Phenytoin (Highly protein bound)

Displaces the Warfarin from plasma protein binding

Elevates free Warfarin level

Increase anticoagulant effect

Increase the risk of bleeding


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Metabolism Interactions

Metabolism interactions are those where the metaboliof the object drug is altered.

Mechanism of metabolism interactions include:-

1. Enzyme Induction: increased rate of metabolism

2. Enzyme Inhibition: decreased rate of metabolism


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Metabolism InteractionsA. Enzyme Induction

Phenobarbital (CYP Enzyme inducer)

Increase the metabolism of Warfarin

Reduce the plasma level of Warfarin

Decreased anticoagulant effect


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METABOLISMB. Enzyme Inhibition

Metronidazole (CYP enzyme inhibitor)

Inhibits metabolism of Warfarin

Elevation of Plasma Warfarin levels

Raise the anticoagulant effect

Increased risk of Bleeding


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Excretion Interactions

In this the excretion pattern of the object drug is altered.

Major mechanism of excretion interactions are-

Alteration of renal blood flow : e.g. NSAIDs (reduce renal blood flowwith lithium.

Alteration of urine pH : e.g. antacids with amphetamine.

Competition for active secretion : e.g. probenicid and penicillin. Forced diuresis.


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EXCRETIONA. Increase in Renal blood flow

Hydralazine (Vasodilator)

Dilates the renal blood vessels

Increase the renal blood flow

Raise the clearance of Digoxin


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EXCRETIONB. Alteration of urine pH

Antacids

Reduce acid secretion

Increase the PH of urine

Reduced tubular reabsorption of Salicylates (Aspirin)

Increased Renal clearance of Aspirin


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EXCRETIONC. Competition for active secretion

Probenecid

Inhibits tubular secretion of Penicillins

Increase half life of Penicillins

Single dose therapy


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References:1. Biopharmaceutics and Pharmacokinetics- A Treatise

2. Katzungs Basic & clinical Pharmacology

3. Goodman & Gilmans The Pharmacological Basis ofTherapeutics

4. www.authorstream.com

5. www.Wikipedia.com
http://www.authorstream.com/http://www.wikipedia.com/http://www.wikipedia.com/http://www.authorstream.com/


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pharmakokinetic drug interaction

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