Pharmacogenetics

CONTENTS

 Introduction
 Divisions of pharmacogenetics
 Drug disposition pharmacogenetics
 Drug target pharmacogenetics

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 What is pharmacogenetics?

People can metabolize drugs quickly, slowly

or normally.
Pharmacogenetics-the combination of
pharmacology & genetics-uses information
about a person’s genetic make-up to help
guide drugs and their doses for a particular
person.

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 What is pharmacogenetics?

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 Introduction

 It is the study of influences of a gene on therapeutic and

adverse effect of drugs.
 It is also defined as the study of inherited variation in drug-
metabolizing enzyme & drug response
 The term ‘pharmacogenetics’ was coined by Vogel.

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 Examples

 G-6-PD deficiency causes hemolysis with primaquine and

other oxidizing drugs like sulfonamides, dapsone, quinine,
nalidixic acid, etc.
 Overexpression of P-gp transporters results in tumor
resistance to many chemotherapeutic drugs due to greater
pumping out of drug from tumor cells.
 Malignant hyperthermia after halothane is due to abnormal
Ca2+ channel(ryanodine receptor) in the sarcoplasmic
reticulum of skeletal muscles.
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 Division of Pharmacogenetics

Drug Disposition Pharmacogenetics

-the pharmacokinetics of a drug can be altered by
sequence variation in drug disposition genes

Pharmacogenetics
Drug Target Pharmacogenetics
-the pharmacodynamics of a drug can be altered by
sequence variation in drug target genes

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 Drug Disposition
Pharmacogenetics

 A drug disposition includes its absorption, metabolism,

distribution and excretion.
 The plasma concentration of a drug or its active metabolites
may be affected by genetic variation.

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 Drug Disposition
Pharmacogenetics Example:

if genetic variation leads to

lower activity of metabolizing
enzyme

Plasma Plasma
concentration concentration
of metabolites of parent drug
decreases increases

 -If only parent drug exhibits pharmacologic activity, the effect is increased which may lead to its
adverse effects.
 -If only the metabolite exhibits pharmacologic activity, the effect is decreased which may lead to its
therapeutic failure.
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 Drug Target
Pharmacogenetics

 Pharmacologic effects of drugs are exerted by modulating

activities of enzyme or receptor.
 Genetic polymorphism of drug-target enzyme or receptor
may alter the drug response.

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 Pharmacogenetics Vs
Pharmacogenomics

• Focused on patient variability

• One drug in different patients with inherited gene
Pharmacogenetics variants
• Predicts drug toxicity
• Useful in patient/disease-specific healthcare

• Focused on drug variability

• Many drugs and one genome
Pharmacogenomics •
•
Predicts drug efficacy
Useful in drug discovery and development or drug
selection

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 THANKS!
Any questions?

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