Pharmacogenetics Flashcards
what is pharmacogenetics?
science of understanding how different individual genotypes relate to diff drugs. Can find out which drugs will be safe and effective.
this applied to the entire genome= pharmacogenomics
example of patient’s concurrent illness which can cause increased risk of drug toxicity/ reduced efficacy?
nausea or malabsorption syndrome
why are smoking and alcohol consumption important factors relating to drug toxicity and/or efficacy?
can affect enzyme systems in liver, so interfere with drug metabolism
e.g. binge drinking causes CYP450 inhibition
chronic alcohol intake causes CYP450 induction
potential risk factors for drug toxicity/ poor efficacy?
age reduced renal/CVS/liver function DDIs smoking and alcohol concurrent illness genetic variation
why are ACEI/AngII receptor antagonists not given 1st line for tment of hypertension in ALL individuals?
some individuals have less RAAS activity, so drugs would be less effective in lowering BP e.g. people aged 55 or older, and people of afro-caribbean origin. These people would achieve better BP lowering with a Ca2+ channel blocker or thiazide diuretic.
younger caucasions have higher RAS activity, so will experience a greater lowering of their BP.
in what 3 ways can absent or reduced CYP activity increase risk of ADRs?
decreased 1st pass met and drug elimination
drug accumulation due to reduced metabolism
re-routing of metabolism e.g. with paracetemol
TPMT is used to eliminate azathioprine from the body. What is it,m and why is its susceptibility to genetic polymorphism important?
thiopurine methyltransferase= phase 2 drug metabolising enzyme
if reduced activity, drug won’t be metabolised, so can produce toxicity= myelotoxicity
if increased activity, drug may be ineffective as an immunosuppressant.
if a ptnt has G6PDD, what drugs may cause an adverse reaction of haemolytic anaemia?
antimalarials e.g. primaquine
sulphonamides e.g. nitrofurantoin
as these drugs can induce rbc oxidative stress, and G6PDD means ptnts lack enzyme necessary for prod of NADPH via pentose phosphate pathway for protecting against free O2 radicals in rbc.
which drugs can cause hepatic porphyrias?
antipsychotics
OCP
analgesics
alcohol
examples of type B ADRs occurring with certain drugs due to HLA associations?
clozapine= agranulocytosis carbamazepine= hypersensitivity reactions gold= thrombocytopenia