Adverse Drug Reactions

Question 1

what is an adverse drug reaction?

Answer 1

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

Question 2

who is adverse drug reaction most common in?

Answer 2

elderly and frail
multi-morbid (renal/hepatic clearance)
people on many drugs (polypharmacy)

Question 3

how is therapeutic index calculated?

Answer 3

50% of toxic dose / 50% of effective dose

Question 4

drugs with narrow therapeutic index?

Answer 4

theophylline 
warfarin
digoxin
gentamicin
vancomycin
cyclosporine
levothyroxine
carbamazepine
phenytoin

Question 5

stages where ADR can be detected?

Answer 5

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)

Question 6

why do ADRs still occur?

Answer 6

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

Question 7

phase 1 drug metabolism?

Answer 7

usually via cytochrome P450

involves oxidation, reduction and hydrolysis

Question 8

phase 2 drug metabolism?

Answer 8

conjugation (made water soluble to allow excretion in urine)

Question 9

ADRs usually involve what phase?

Answer 9

1

Question 10

type A ADR?

Answer 10

augmented pharmacological effects

dose dependant and predictable

Question 11

type B ADR?

Answer 11

bizarre effects (or iridosynchratic)
unpredictable
dose independent
dangerous - high mortality

Question 12

mechanisms for type A?

Answer 12

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

Question 13

how does gentamicin affects renal cells?

Answer 13

lysosomal enlargement and rupture
mitochondrial enlargement
loss of villi brush border

Question 14

type A drug interactions?

Answer 14

drug - drug interactions
drug - disease interactions
drug - food interactions
can check interactions via drug interaction checker websites/apps

Question 15

examples of drug-drug reactions (type A)?

Answer 15

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

Question 16

drug - over counter/herbal medication interactions?

Answer 16

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)

Question 17

drug - disease interactions?

Answer 17

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

Question 18

drug food interactions?

Answer 18

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

Question 19

examples of type B reactions?

Answer 19

drug rash
bone marrow aplasia (chloramphenicol)
hepatic necrosis (halothane)

Question 20

type C ADR?

Answer 20

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

Question 21

type D ADRs?

Answer 21

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

Question 22

type E ADRs?

Answer 22

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

Question 23

what does black triangle indicate?

Answer 23

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

Question 24

what is yellow card scheme?

Answer 24

must be filled in when your patient has an unexpected drug reaction
even if its only expected to be a drug reaction
legal requirement