Adverse Drug Reactions Flashcards
what is an adverse drug reaction?
any undesirable reaction whether expected, predictable or not that results in a detriment to the wellbeing of the patient in any way whether symptomatic, detectable or not in the absence of another biologically plausible explanation that can be proven
who is adverse drug reaction most common in?
elderly and frail
multi-morbid (renal/hepatic clearance)
people on many drugs (polypharmacy)
how is therapeutic index calculated?
50% of toxic dose / 50% of effective dose
drugs with narrow therapeutic index?
theophylline warfarin digoxin gentamicin vancomycin cyclosporine levothyroxine carbamazepine phenytoin
stages where ADR can be detected?
pre-clinical phase = drug development (best time to detect any ADR) > phase 1-3 = clinical trials (often not picked up as only very small sample size and usually healthy people who take part in trials) > phase 4 = post marketing surveillance (most data available but highest cost, morbidity/mortality)
why do ADRs still occur?
some drugs have only very rare ADRs (e.g 1 in 60,000)
therefore 60,000 would need to be exposed before any ADR was seen
phase 1 drug metabolism?
usually via cytochrome P450
involves oxidation, reduction and hydrolysis
phase 2 drug metabolism?
conjugation (made water soluble to allow excretion in urine)
ADRs usually involve what phase?
1
type A ADR?
augmented pharmacological effects
dose dependant and predictable
type B ADR?
bizarre effects (or iridosynchratic)
unpredictable
dose independent
dangerous - high mortality
mechanisms for type A?
pre-renal failure (hypotension/hypovolaemia) can occur in overuse of diuretics or continued use of ACE inhibitors during D&V renal failure (AIN, acute tubular necrosis) can occur with gentamicin, sulphonamides and aspirin post renal failure (retroperitoneal fibrosis, crystaluria, urinary calculi) can occur with chemotherapy and methysergide drug interactions
how does gentamicin affects renal cells?
lysosomal enlargement and rupture
mitochondrial enlargement
loss of villi brush border
type A drug interactions?
drug - drug interactions
drug - disease interactions
drug - food interactions
can check interactions via drug interaction checker websites/apps
examples of drug-drug reactions (type A)?
theophylline and macrolides
statins and macrolides / statins and fibrates
TCAs and type 1 anti-arrhythmics
warfarin and multiple drugs
ACE inhibitors increase hypoglycaemic effect of SURs
clopidogrel and PPIs
drug - over counter/herbal medication interactions?
vit C - grapefruit juice (CP450 effect)
dementia - gingko biloba (anticoagulant effect)
BPH - saw palmento (anticoagulant effect)
OA - glucosamine (hyperglycaemia and anticoagulant)
depression - st John’s Wort (CoC)
drug - disease interactions?
higher risk of drug induced confusion in parkinsons disease
NSAIDs/COX-2 inhibitors/TZDs can worsen heart failure (due to sodium retention)
decongestants or anticholinergics can cause urinary retention in BPH patients
calcium, anticholinergics, CCBs worsen constipation
neuroleptics, tramadol and quinolones lower seizure threshold
beta blockers worsen asthma
drug food interactions?
potassium rich foods (green leafy veg, bananas, organges) interact with ACEi, ARBs, K-sparing diuretics)
Vit K/E rich foods (apples, chickpeas, spinach, nuts, kiwi, broccoli) interact with warfarin
pH altering foods (chicken, turkey, milk, soy, cheese, yoghurt) interacts with antibiotics, thyroid meds, digoxin and diuretics
foods with cytochrome P450 (grapefruit, apple, orange, cranberry) interact with statins and antihistamines
examples of type B reactions?
drug rash
bone marrow aplasia (chloramphenicol)
hepatic necrosis (halothane)
type C ADR?
chronic - due to prolonged therapy
eg
- steroid therapy = cushings disease, osteoporosis
- beta blockers = diabetes
- NSAIDs = hypertension
can be anticipated but patient must be warned before starting therapy so they can look out for first signs
type D ADRs?
delayed
can be remote from treatment, often many years after stopping
e.g teratogenic/carcinogenic effects (secondary malignancy after chemotherapy)
e.g abnormalities in children of women taken isotretonoin?
not as common these days
type E ADRs?
end of treatment
ADR from abrupt withdrawal of drug
e.g angina after beta blocker withdrawal, addisonion crisis after steroid withdrawal, epilepsy frequency changes after anticonvulsant withdrawal
what does black triangle indicate?
new medicine that has new active ingredient
biologics/vaccines
means you have to be vigilant when using due to some concern as to action of drug
status reviewed after 2 years and black triangle may be removed if established to be safe
what is yellow card scheme?
must be filled in when your patient has an unexpected drug reaction
even if its only expected to be a drug reaction
legal requirement
