pharmacogenetics Flashcards
people respond differently to drugs and doses and can be complex, they are influenced by:
1- environment ( nurture )
- age
- diet
- organ function ; underlying disease
- concomitant therapy ; drug interaction
2- genetics ( nature)
- as coded for by dna
mercaptopurine ( purinethol ) and azathioprine
- inhibits —
- used to treat —-
- causes —-
- 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
TMPT genotype influence —-
enzyme activity ( check graph )
dosing by TPMT genotype greatly — the incidence of —
reduce , toxicity ( check graph )
1.warfarin is an — and its used in prevention of —–
2. narrow therapeutic range:
- further complication by —-
- dosing is minotored by:
- 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
the azathioprine is the —- aka the — form and its converted to 6 mercaptopurine 6-MP and then will be removed by —- or —-
- 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
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
- vitamin k
- slow
- CYP2C9 ( genotype 6%)
- VKOR
the VKORC1 is the —- of the drug and has — of dose variability
CYP2C9 is a —– of the drug and the genotype is —
- target
- 25%
- metaboliser
- 6%
1.the HLA has —- gene region and —– reactions.
2. it contains many genes that are related to — system function
- candidate
- hypersensitivity
- immune
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
- peptides
- viruses
- antigens
- from phagocytosis
- complement
—– 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
- HLA
- transplantation
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
all trueeeee
carbamazepine induced SJS is an —– drug targets — channels , the test is only effective in —- descent population
- 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
read:
( carbamazepine induced SJS )
- 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
read:
allopurinol induced SJS
- 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)
