Pharmacogenetics

Question 1

Pharmacogenetics

Pharmacogenomics

Answer 1

• genetics: Study of genetic variation (usually in single gene) that influences drug response
• genomics: broader application of high-throughput methods to analyse: several genes, epigenetic markers etc

Question 2

Precision (personalized) medicine

Answer 2

Find optimal dosage dependent on patient-specific (genetic) properties > dosage adjustment based don genotype

Question 3

PharmG-KB

Answer 3

Pharmacogenomics Knowledgebase.
Database for effect of genetic variation on drug response. Information on genetic variants, genes, drugs, phenotypes and literature references.

Question 4

CYP2D6

Answer 4

Strongly involved in drug metabolism and first pass effect (also antidepressants and antihypertensive drug debrisoquine).
Multiple genetic variants > poor metabolisers have stronger effect/adverse reactions

Question 5

OATP1B1 influx transporter

Answer 5

Membrane transporter expressed in liver: transports drugs (incl lipid-lowering simvastatin) into liver.
SNP > reduced hepatic statin uptake > increased risk for myopathy.

Question 6

TPMT deficiency

Answer 6

Methylates metabolite of immunosuppresive prodrug azathioprine to prevent conversion into cytotoxic metabolites.
Deficiency > accumulation of cytotoxic metabolites >leukocyte reduction

Question 7

G6PD deficiency

Answer 7

Involved in biosynthesis of reduced glutathione (scavenges free radical).
Deficiency problematic when antimalarial drug primaquine is given (forms reactive species).
Deficiency > reduced glutathione in erys > increased reactive primaquine metabolites > ery breakdown

Question 8

UGT1A1 deficiency

Answer 8

Catalyses glucuronidation of lipophilic substances.

Irinotecan cancer treatment in patient with UGT1A1 deficiency > decreased elimination of drug > increased risk for adverse effects

Question 9

CYP2D6 UM mother

Answer 9

Codeine is transformed to morphine by CY2D6 in liver.

UM mother > high amounts of morphine passed to child via breast milk > death

Question 10

OATP1B1 influx transporter polymorphism

Answer 10

Membrane transporter expressed in liver: transports drugs (incl atorvastatin) into liver. Low activity > increased statin conc and risk for myopathy.

Question 11

CYP2C19 deficiency, CYP3A4 interaction

Answer 11

Matabolises pantoprazole. Deficiency > increased levels of pantoprazole > inhibits CYP3A4 (statin metaboliser) > increased risk for myopathy

Question 12

CYP2C191/1 genotype

Answer 12

Increased metabolism of of proton pump inhibitor lansoprazole.
Decreased repsonse to amoxicillin and clarithromycin in people with Helicobacter infections.