Adverse Drug Reactions (ADRs) Flashcards
type A ADRs
Augmented
predictable, very common
dose/conc related
so inc dose = inc likelihood of occurring
eg NSAID-induced peptic ulceration results from predictable and dose-related pharmacological effects.
type B ADRs
Bizarre
unpredictable
not dose/conc related
what is exaggerated therapeutic effect (type A)?
give examples
exaggeration of intended therapeutic effect
eg dehydration with loop diuretics (furosemide)
low bp with DHP CCBs (amlodipine)
hypoglycaemia with insulin
what is unrelated therapeutic effect (type A)?
give examples
relate to other pharmacological action beyond the target tissues
eg ankle oedema with DHP CCBs
bronchospasm w Beta-blockers
What other factors could increase the risk of Type A ADRs?
dose
impaired elimination
genetics (eg some pts might not express hepatic enzymes which metabolise drugs)
What other factors could increase the risk of Type B ADRs?
genetic predisposition eg lucose-6-phosphate dehydrogenase (G6PD) deficiency
Immune factors that predispose to Type B reactions include allergy following small drug molecules acting as ‘haptens’ by combining with larger molecules (e.g. proteins) to activate an immune response.
how to manage type B ADRs?
Type B ADRs are not (in most cases) clearly related to dose and so it is not usually feasible or safe to manage them by dose reduction.
Although Type B ADRs are usually considered as unpredictable, a careful clinical and medicine history may alert prescribers to predisposing factors (e.g. a history of allergy or genetic factors).
type C ADRs
chronic
require prolonged exposure to develop
eg osteoporosis, pulmonary fibrosis with amiodarone
type D ADRs
delayed
do not occurs until prolonged period after exposure
eg lymphomas in pts who have had previous chemo for leukaemia
type E ADRs
end of use
medicine withdrawal
eg SSRIs, adrenal insufficiency after stopping corticosteroid therapy
3 factors of DoTS classification
Do: dose-related
T: Time-related
S: Susceptibility
Dose relatedness?
Hypersusceptibility: subtherapeutic (eg hypersensitivity)
Side FX: standard dose eg hyperkalemia with diuretics
Toxic FX: supratherapeutic (toxic plasma conc eg vomiting with digoxin)
Time relatedness
independent: ADR not related treatment timing
dependent: ADR related to timing of treatment
6 categories of time-relatedness?
1) Rapid: drug given too fast
2) 1st dose: ADR occurs after 1st dose (eg severe hypotension ACEi)
3) Early: early stage of treatment then subsides (eg headaches with nitrates)
4) Intermediate: not early stage, not late stage
5) Late: ADRs which worsen with duration/repeated exposure (eg osteoporosis with steroid use)
6) Delayed: ADRs which occur long time after initial exposure, eg withdrawals (Type D in ABCDE)
Name some susceptibility factors and give examples?
Age: neonates/elderly more prone to ADRs due to poor renal/hepatic function
Gender: women more prone to develop ADRs (eg torsade de pointes ventricular tachycardia with drugs that prolong QT interval
Pregnancy: increased hepatic enzyme activity, reduces the risk of ADRs as the drug is being cleared quicker, treatment less likely to work
Disease: renal impairment, reduced clearance, inc bioavailability, prolonged drug exposure (toxic FX) - eg rash w amoxicillin with EBV/IM
Drug interactions: inc risk of ADRs as precipitant drug can induce/inhibit metabolism of object drug
Environment: diet, alcohol, smoking
alcohol induces metabolism (eg warfarin)
Genetics: Some genetically inherited conditions such as glucose-6-phosphate dehydrogenase (G6PD) deficiency increase the risk of specific ADRs.
