PCH 201 : Clinical Biochemistry

Basic Biochemistry

Lecture Notes 15 : Drug metabolism polymorphisms

Pharmacogenetic treatment of gout

Mr Willmore Chingwena
Room 146, Dept Biotechnology and Biochemistry
University of Zimbabwe
By the end of these Lecture, you will be able to know the
following :

Define Drug metabolism Polymorphism

Describe the gout as an example for a condition which expresses drug
polymorphism
Factors affecting response to pharmacotherapy,

age,
weight,
liver
renal function,
co-medication,
heterogeneity in the disease,
nutritional state
smoking.
inherited variants - drug metabolism Polymorphism
Problem statement : Failures of modern pharmacotherapy

I.adverse drug reactions,

II.reactions which are serious or even lethal,
III.nonresponsive to standard therapy
WHY IS IT SO ?

interindividual variation of drug effects influenced by genetic variation of

drug metabolism.

Genetic polymorphisms of drug-metabolizing enzymes give rise to distinct

subgroups in the population that differ in their ability to perform certain
drug biotransformation reactions.
inherited variants that may have a major impact on drug
response

drug-metabolizing enzymes (DMEs),

transporters,

receptors and,

molecules of signal transduction cascades

Pharmacogenetics/pharmacogenomics
tries to define the influence of genetic factors on drug efficacy and
adverse drug reactions
What does it help ?
This field allowed us to come up with modern technologies in

genetic testing.

personalized medicine (considering patients’ individual genetic

profile)
The genetics of gout: towards personalised
medicine?

hyperuricaemia

pharmacogenetics of urate-lowering therapy

Serum urate levels and the risk of gout are influenced by a
combination of inherited genetic variants and the environment.