How la?

My very first exams away from home (sounds so exciting like my first spoken words or something) are like in less than 3 weeks time (come to think of it, what were my first spoken words?hmmmmm..) Am finding it so hard to discipline myself (as always). I just hope that i would be able to find that inner will power to stay focus and not let my parents down. Sigh.

It's just so scary when your key lecture points for a topic in one of your courses is like this:

Pharmacogenetics

Students should appreciate the following
1. The principle of the relationship between genetics-environment-timing and human health/disease.
2. The broad concept of pharmacogenetics/pharmacogenomics (PGe) - the individualisation of drug therapy according to inter-patient genetic variability. The two terms are generally used interchangably.
3. The scenarios in which pharamcogenetics has the greatest value - eg. drug of low therpaeutic index, chronic treatment etc.
4. Types of genetic variation that may be investigated - single nucleotide polymorphisms (and small insertions/deletions). Patient can have 3 possible genotypes homozygous wildtype(w/w), homozygous mutant(m/m)or heterozygous (w/m). Potential impact of SNPs
coding versus non coding, synonymous (no change to amino acid sequence – also referred to as silent mutations) versus non synonymous (changes amino acid sequence – also referred to as missense mutations). Haplotypes - chromosomal phasing of SNPs
5. Utility of PGe to the pharmaceutical industry
- the need for the investigation of new drug targets for genetic variablity
- the ability of PGe to improve clinical trial process
6. Genetic variability in CYP450 - including specific drug examples such as warfarin and proton pump inhibitors. You DO NOT need to know all of the alleles for every SNP but instead those that were discussed in more detail in the lecture.
7. Genetic variability in UGT1A1 (GT1A1*28 TA promoter polymorphism) - including irinotecan example
8. Genetic variability in TPMT – you DO NOT need to know the specific amino acid changes but understand the consequences
9. Techniques to determine drug metabolising status - genotyping or phenotyping and the relative advantages/disadvantages of each. Have a superficial appreciation of the three steps in genotyping (PCR amplification to copy the desired region of DNA > allele discrimination reaction to determine which sequence is present > product detection). Phenotyping - administration of a probe compound. Determine ratio of parent drug:metabolite ratio. High ratio indicates poor metabolsim. eg. dextromethorphan (DM) CYP2D6 phenotyping. DM:DX greater than 0.30 indicates poor metaboliser (PM) status, DM:DX less than 0.3 indicates extensive metaboliser (EM)
10. The effect of Beta2 adrenergic receptor haplotype/ SNPs upon response to salbutamol
11. Whole genome scanning for candidate gene identification -used when traditional approach does not work. Exemplified by abacavir HLA-B57 example
12.Polygenic drug response - considering the impact of variation in more than one gene.
Exemplified by warfarin dose determination by CYP2C9 and VKORC1 (encodes for vitamin k reductase)
13. The application of gene expression profiling to pharmacogenetics - use of microarray transcription profiling to select patients requiring adjuvant chemotherapy to reduce unnecessary exposure to highly toxic drugs
14. The registration and potential problems with BiDil - the rationale for the company producing a drug for a single race (easy FDA approval, patentable) Problems with the study that lead to the registration (only in African Americans, people self identified race). Problems with the use of race as a marker for individualistion of drug therapy
15. Limitations of pharmacogenetics - in particular orphan patients (patient with a genetic profile that indicates poor response to available medicines). Problems with predicting rare events etc.

Die.