Adverse drug reactions

Question 1

What is the difference between intrinsic and idiosyncratic adverse drug reactions

Answer 1

Intrinsic - predictable based on drug concs e.g. liver toxicity in paracetamol overdose

Idiosyncratic - not predictable. More serious

Question 2

3 examples of idiosyncratic ADRs

Answer 2

Hypersensitivity from Abacavir

Hepatotoxicity from Flucloxacillin

Myopathy from statins

Question 3

Polymorphisms in what gene are related to adverse drug reactions

Answer 3

HLA

Question 4

What is the most common cause for abacavir hypersensitivity

Answer 4

One or two HLAB*57:01 alleles

Question 5

What is the MOA involved in abacavir sensitivity

Answer 5

Activated abacavir binds directly to B*57:01 leading to inappropriate recognition of “self peptides” and inappropriate T cell response

Question 6

Carbamazepine causes skin rash in the Chinese population due to what poly

Answer 6

HLAB*15:02

Question 7

Allopurinol causes a skin rash in the Chinese population due to what poly

Answer 7

HLAB*58:01

Question 8

What is DILI

Answer 8

Drug-induced liver injury
Iodiosyncratic

Question 9

What is one cause of DILI and what poly causes this

Answer 9

Flucloxacillin
HLAB*57:01 - as seen with a manhattan plot

Question 10

What poly causes statin induced myopathy

Answer 10

SLCO1B1*5 with simvastatin
Due to reduced hepatic uptake

Question 11

What effect do ion channel polys have of cardiovascular responses

Answer 11

Some drugs can prolong repolarisation (longer QT interval) due to blockage in of K+ channel
K+ channel polys cause increased risk of sudden death due to drug-induced ventricular fibrillation