Clinical Pharmacogenetics – subjects, aim, tasks and clinical

Question 1

define Clinical Pharmacogenetics

Answer 1

study of genetically determined variations in drug response commonly reffered to pharmacogenetics

Question 2

Objectives: of pharmacogenetics

Answer 2

identification of genetically controlled variations in responses to drugs

The study of the molecular mechanisms causing variations in drug response

evaluation of the variaton’s clinical significance

development of simple methods to identify individuals who may be susceptible to variable responses before drug are administered

Question 3

define Polymorphism:

Answer 3

monogenic trait caused by the presence in
a set population of more than one allele at the same locus causing more than one phenotype in regard to drug interaction with the organism.

Question 4

how does Polymorphism affect drug interaction

Answer 4

differences in enzyme activity or receptor structures

differences are expressed in different ethnic groups e.g

Protein structure, configuration and concentration may alter action of the drug in multiple ways.

Question 5

how genetic differences affect phk/

Answer 5

changes in drug intensity

changes in drug duration of action

Question 6

how genetic differences affect phD

Answer 6

abnormal effectsw/ genetic transmitted disorders

Question 7

Acetylation: is done by what ez

Answer 7

N-acetyltransferase

fast and slow acetylators depend on the amount of N-acetyltransferase

Question 8

genes of fast acylators

Answer 8

autosomal dominant character

Question 9

genes of slow acylators

Answer 9

recessive

enhanced response to treatment, but also at increased toxicity

require lower doses

Question 10

Acetylator status: assessment

Answer 10

give orally sulfonamide

measure the relative proportion of acetylated and total sulfonamide in a sample of urine 5-6 hours later.

Question 11

categorisatino according to oxydation

Answer 11

extensive metabolizer
-normal

poor metabolizer
impaired
autosomal recessive defect

Question 12

location of defect in cytochrome CYP2D6 for hydroxylation of debrisoquine
poor metabolizers

Answer 12

chromosome 22

Question 13

Drugs affected in defect of CYP2D6

Answer 13

captopril,
codeine,
metoprolol,

Question 14

drug inhibiting oxydation

Answer 14

Quinidine

Question 15

factors affecting the Clinical relevance of pharmacokinetic defects

Answer 15

importance of the affected metabolic pathway to the overall elimination of the drug

therapeutic index of the drug

how easily the variable drug response can be monitored in clinical trials

Question 16

clinical imprtance of CYP2D6 polymorphism

Answer 16

Considerable as several drugs rewuire this ez in their metabolic PW

antidepressants
antipsychotics
antiarrythmics

Question 17

Pharmacodynamic defects consequences

Answer 17

increase or decreases pt sensitivity to a drugn

Question 18

Red cell enzyme defects

Answer 18

erythrocytes are deficient in

1) glucose-6-phospathe dehydrogenase
2) glutathione reductase and
3) methemoglobin reductase

Question 19

G6PD

Answer 19

diminished production of NADPH

causes accum of
METHAEMOGLOBIN

leads to hemolysis

Question 20

black variety

Answer 20

G6PD production is probably normal, but its degradation is accelerated

haemolysis occurs on first administration of the drug and lasts a few days after drug is discontinued

in continued use mild hemolysis occurs

Question 21

Mediterranean variety

Answer 21

enzyme is abnormal

severe haemolysis occurs on first administration and is maintained with continued administration.

Question 22

Glutathione reductase deficiency

autosomal DOMINANT inheritance

Answer 22

deficiency of reduced glutathion

hemoylisis d/2 increased oxidising agents

Question 23

drugs causing hemolysis in Glutathione reductase deficiency

Answer 23

Warfarin

Question 24

Methemoglobin reductase

autosomal recessive inheritance.

Answer 24

Normally methaemoglobin is continuously reduced to heamoglobin

dficiency causes accum of met heam

impaired oxygen delivery to the tissues thus, hypoxemia

Question 25

rx of methamogoglobin induced hypoxia

Answer 25

methylene blue.