Lecture 8: Pharmacogenetics Flashcards
What is the effect of alterations to DNA at the gene leve?
Affect transcription, translation and the final protein product (e.g. drug metabolising enzyme (DME), which can lead to adverse drug reactions (ADRs) or therapeutic failure.
What is an ADR?
Adverse Drug Reaction
What leads to ADRs?
Variation in how people react to drugs due to underlying genetic differences.
What are DMEs?
Drug Metabolising Enzymes
What is the affect of polymorphism in the tatse receptor 2 member 38 (TAS2R38) gene?
Protein is unresponsive to Phenylthiocarbamide due to 3 possible single nucleotide polymorphins (SNPs).
What are SNPs?
Single nucleotide polymorphins; change in a single nucleotide base.
What are the SNPs that trigger TAS2R38 to be unresponsive to Phenylthiocarbamide?
Amino acid change of G to C
Amino acid change of T to C
Amino acid change of A to G
Describe the inheritance of Phenylthiocarbamide
Autosomal dominant dominant (taster) and recessive (non-taster) inheritance
What is Primaquine?
Primaquine is a drug used for the treatment of malaria.
What is the affect of Primaquine on individuals that have certain glucose-6-phosphate dehydrogenase (G6PD) variants?
Can induce hemolytic anemia (ie. RBC burst)
Describe the inheritance of Glucose-6-phosphate dehydrogenase (G6PD) deficiency
X-linked recessive disorder
What is the affect of What is the affect of Primaquine and how can this affect vary?
Primaquine interacts with CYP450 enzymes within the body to metabolise it, but gene changes can alter the CYP450 enzyme proteins produced, meaning that there is an increase or decrease of transcription of CYP450 enzymes which can cause an increase or decrease in the amount of the drug in the blood plasma that can either lead to adverse drug reactions (ADRs) or therapeutic failure.
How do CYP450 enzymes work?
CYP450 enzymes work by oxidizing the drug so it can be more easily removed from the body.
How can gene alterations affect drugs within the body?
Alter the metabolism of drugs which can lead to therapeutic failure or ADRs.
Cause variation is drug transporters which can affect drug interactions within the body.
What are the role of drug transporters in the body?
Drug transporters govern drug absorption, excretion, and, in many cases, extent of drug entry into target organs.
