Pharmaceutics - Guy

Question 1

What are the 2 clinical considerations that are taken in terms of how genetic variability can affect the drug response?

Answer 1

Therapeutic Response –> Non-response or Hyper-response

Adverse Response

a) Concentration-dependent
b) Idiosyncartic
c) Immunologic

Question 2

What are the 3 processes involved in absorption across the GI membrane?

Answer 2

Passive Diffusion

Transporter Mediated –> Influx (olgiopeptide transporter) and efflux (P-gp)

Pre-synaptic metabolism in the intestine and/or liver

Question 3

What’s the difference between Genotype and Phenotype?

Answer 3

Genotype –> An individuals full hereditory information (born with it)

Phenotype –> An individuals actual expressed properties

Question 4

What are the 4 types of metabolisers in terms of the CYP2D6 gene?

Answer 4

A –> Homozygous recessive

Slow metabolisers

B –> Heterozygous

Moderate metabolisers

C –> Homozygous dominant

Extensive metabolisers

D –> Duplication

Ultra rapid metaboliser

Question 5

What are the negative effects of being an Ultra-rapid Metaboliser?

Answer 5

Adverse effects –> due to high levels of metabolites

Lack of repsonse to antidepressents

Decreased levels of tramadol/morphine/metoprolol

Question 6

What type of metabolisers should the use of codeine be avoided?

Answer 6

Ultra-rapid –> Due to conversion to morphine occuring to rapidly

Poor –> As the morphine wont be formed quick enough

Question 7

What is the main function of P-gp?

Answer 7

Defence mechanism against xenobiotics (exogenous)

An efflux pump

Question 8

Thiopurine agents are activated/inactivated by what?

Answer 8

Activated –> Hypoxanthine phosphoribosyltransferase (HPRT), producing cytotoxic agents

Inactivated –> Thiopurine methyltransferase (TPMT), via S-methylation/oxidation