Pharmacogenomics

Question 1

What is pharmacogenetics

Answer 1

the study of the relationship between individual gene variants and variable drug effects

Question 2

What is pharmacogenomics?

Answer 2

describes the relationship between variants in a large collection of genes, up to the whole genome, and variable drug effects

Question 3

Potential causes for variability in drug effects include factors such as…

Answer 3

• environment
• age
• gender
• ethnic group
• liver and kidney function
• concomitant illnesses
• nutritional status

Question 4

What are the two types of population dose curves?

Answer 4

unimodal and bimodal

Question 5

What is the most common type of genetic variation?

Answer 5

change in a single nucleotide pair (termed Single Nucleotide Polymoprhism, SNP)

Question 6

Why do some patients have a prolonged response to succinylcholine of hours instead of minutes?

Answer 6

presence of an atypical plasma cholinesterase (type of enzyme)

• due to SNP in gene for human plasma cholinesterase
• SNP changes acidic amino acid to a neutral amino acid; which reduces affinity of cholinesterase for choline esters

Question 7

Some people are susceptible to the antimalarial drug primaquine, causing hemolytic anemia - what is this condition associated with?

Answer 7

amino acid substitutions in the G6PD enzyme that result from SNPs
(G6PD deficiency)

Question 8

Polymorphisms in Cytochrome P450 Genes

Answer 8

• polymorphism of the cytochrome P450 (CYP) enzymes for CYP2D6
• poor metabolizers and extensive meetabolizers
• CYP2D6 enzyme is responsible for the metabolism of drugs such as beta-blockers and tricyclic antidepressants, and for the metabolism of codeine to morphine

Question 9

Polymorphisms in Thiopurine Methyltransferase

Answer 9

• azathioprine and mercaptopurine used in the treatment of various autoimmune, dermatologic, and hematologic disorders may cause fatal myelosuppression in persons deficient in thiopurine methyltransferase (TPMT)

Question 10

Genetic Polymorphisms in Drug Targets

Answer 10

ex: polymorphisms of the B2AR results in differences in responsiveness of airways to the inhaled beta2-agonist (bronchodilator) albuterol

Question 11

What are the major mechanisms through which genetic variation can alter responses to drug?

Answer 11

• increased/decreased drug absorption
• increased/decreased drug metabolism
• increased/decreased drug excretion
• increased/decreased drug efficacy through altered receptor-target affinity
• adverse drug reactions

Question 12

What are four potential new clinical activities to overcome genetic variation?

Answer 12

• genotyping before treatment
• adjustment of dosing regimens according to genotype
• earlier selection of patients for alternative (or second-line) therapy
• prescription of concomitant medication to ensure intended effects