pharmacogenetics

Question 1

people respond differently to drugs and doses and can be complex, they are influenced by:

Answer 1

1- environment ( nurture )
- age
- diet
- organ function ; underlying disease
- concomitant therapy ; drug interaction
2- genetics ( nature)
- as coded for by dna

Question 2

mercaptopurine ( purinethol ) and azathioprine
- inhibits —
- used to treat —-
- causes —-

Answer 2

• inhibits purine ( a/g) nucelotide synthesis which therefore inhibits the dna replication
• used to treat leukaemia and inflammatory bowel disease , organ transplant and rheumatoid arthritis
• causes myelosuppression : infection due to low wbc and anemia due to low rbc

Question 3

TMPT genotype influence —-

Answer 3

enzyme activity ( check graph )

Question 4

dosing by TPMT genotype greatly — the incidence of —

Answer 4

reduce , toxicity ( check graph )

Question 5

1.warfarin is an — and its used in prevention of —–
2. narrow therapeutic range:
- further complication by —-
- dosing is minotored by:

Answer 5

• anticoagulant
• thrombosis and embolism
  1. high dose leads to risk of bleeding and haemorrhage
  2. lose dose leads to thrombosis/embolism
• diet disease state and drug interaction
• international normalised ratio ( INR) clotting tendency of blood

Question 6

the azathioprine is the —- aka the — form and its converted to 6 mercaptopurine 6-MP and then will be removed by —- or —-

Answer 6

• prodrug
• inactive form
• XO and makes oxidised metabolites or by TPMT which produce 6MMP aka 6 methyl mercapropurine
• the 6 mercaptpurine will lead to 6 thioguanune nucleotide which is a major metabolite responsible for activity and is highly toxic

Question 7

warfin mode of action :
1- the action is through the inhibition of —- , and if you inhibit this the chemical reduction of it will —-
2- its metabolised by P450 in a particular —–
3. —- and —– are strong candidate genes

Answer 7

• vitamin k
• slow
• CYP2C9 ( genotype 6%)
• VKOR

Question 8

the VKORC1 is the —- of the drug and has — of dose variability
CYP2C9 is a —– of the drug and the genotype is —

Answer 8

• target
• 25%
• metaboliser
• 6%

Question 9

1.the HLA has —- gene region and —– reactions.
2. it contains many genes that are related to — system function

Answer 9

• candidate
• hypersensitivity
• immune

Question 10

class I presents —- from the inside of the cell as: —-
class II presents — from outside of the cell as: —-
class III is —- system , activation of response

Answer 10

• peptides
• viruses
• antigens
• from phagocytosis
• complement

Question 11

—– is the most diverse region of the human genome , rapidly evolving balancing selection , keeps diversity , combats evolving exposure to pathogens
has an important role in —– , many available genotype systems

Answer 11

• HLA
• transplantation

Question 12

true or false:
-stevens Johnsons syndrome is a severe adverse reaction involving separation of the epidermis from dermis
- early stages of toxic epidermal necrolysis
- incidence: 1-5 million population/year
- major cause is adverse effect of pharamacetucial

Answer 12

all trueeeee

Question 13

carbamazepine induced SJS is an —– drug targets — channels , the test is only effective in —- descent population

Answer 13

• anti-epileptic drug
• sodium channels
• asian
• more info:
• SJS = 1-6 cases per 10,000 new users.. (x10 in Asia)
• 2004: Strong link between HLA-B*1502 and SJS (100% sensitivity, 97% specificity).
• 2008 FDA makes labelling change for CBZ
  Advises all Asian descent individuals be typed by HLA-B*1502 prior to exposure to the drug

Question 14

read:
( carbamazepine induced SJS )

Answer 14

• 2011: Strong link between HLA-A3101 and CBZ-induced SJS. Sensitivity = 26%, Specificity = 96%
  (an RCSI discovery!) - McCormack et al, N Engl J Med. 2011 Mar 24;364(12):1134-43.
  Global frequency of HLA-A3101 allele – note it is more widespread than HLA- B*1502, therefore test is applicable across diverse populations

Question 15

read:
allopurinol induced SJS

Answer 15

• Used in treatment of hyperuricemia/gout
• Rare.. <1% new cases = SJS
• 2005 – Link to HLA-B*5801 established
• Strong predictive value in Asia (100% SJS), less good in Europe (50% carry)

Question 16

SJS tests can be — and — specific

Answer 16

population and drug

Question 17

interferon treatment of hepatitis :

Answer 17

• Hep C causes inflammation of the liver, a leading cause of cirrhosis
• Blood borne virus
• Chronic Hep C
  (>6 months)
  = 170million infections worldwide, leading cause of cirrhosis in 30% cases
• Treatment = 48 week course of interferon combined with ribavarin (anti viral)

Question 18

true or false:
- genotype correlates w reposes w population
- genotype held explain different rate of response across the population

Answer 18

true