Type A and Type B drug reactions
→ Type A reaction = common, predictable + dose related.
→ Type B reaction = idiosyncratic, bizarre + unexpected, related to gene/host/environmental interactions.
Adverse drug reactions: ABx
Gentamicin + vancomycin = nephrotoxicity + ototoxicity.
Any antibiotic (commonly broad-spectrum e.g. cephalosporins or ciprofloxacin) = clostridium difficile colitis.
Adverse drug reactions: Antihypertensives
ACE-i e.g. lisinopril = hypotension, electrolyte abnormalities, acute kidney injury, dry cough.
B-blockers e.g. bisoprolol = hypotension, bradycardia, wheeze in asthmatics, worsens acute HF (but helps chronic HF).
CCBs e.g. diltiazem = hypotension, bradycardia, peripheral oedema, flushing.
Diuretics e.g. furosemide, benfroflumethiazide, spironolactone = hypotension, electrolyte abnormalities, acute kidney injury, subclass dependent effects.
Adverse drug reactions: Anticoagulants/antiplatelets
Heparin = haemorrhage (especially if renal failure or <50kg), heparin-induced thrombocytopenia.
Warfarin = haemorrhage (but initial pro-coagulant effect, takes ~days to become anticoagulant, prescribe with heparin until INR>2).
Aspirin = haemorrhage, peptic ulcers + gastritis, tinnitus in large doses.
Adverse drug reactions: antiarrhythmics
Digoxin = N&V&D, blurred vision, confusion + drowsy, xanthopsia (disturbed yellow including ‘halo’ vision).
NB: Low K+ augments digoxin effect. High levels limit its effect.
Amiodarone: pulmonary fibrosis, thyroid disease (both hyper/hypothyroidism), skin greying, corneal deposits.
Adverse drug reactions: Mood stabilizers
- late-arrhythmias, seizures, coma, renal failure, diabetes insipidus.
Adverse drug reactions: Antipsychotics
Haloperidol = dyskinesias e.g. acute dystonic reactions, drowsiness.
Clozapine = agranulocytosis = required intensive monitoring of FBC.
Adverse drug reactions: Corticosteroids
Dexamethasone + prednisolone = STEROIDS → stomach ulcers, thin skin, oedema, R + L HF, osteoporosis, infections, diabetes (hyperglycaemia more likely) + Cushing’s syndrome.
Fludrocortisone = HTN, Na+ & H2O retention.
Adverse drug reactions: NSAIDs
Ibuprofen = NSAID → no urine, systolic dysfunction (HF), asthma, indigestion (any cause), dyscrasia (clotting abnormality).
Adverse drug reactions: Statins
Simvastatin = myalgia, abdominal pain, +++ALT/AST (can be mild), rhabdomyolysis (can be just mildly increased CK though).
Clinically important drug interactions.
Spot drugs on list known to interact – generally 1 of 3 categories.
What are these categories?
1) Drugs with narrow therapeutic index e.g. warfarin, digoxin + phenytoin.
2) Drugs requiring careful titration of dose according to effect e.g. antihypertensives, antidiabetic drugs. drugs where an overtreatment may result in harm. e.g. , iodinated contrast media causing renal impairment risking metformin-induced lactic acidosis (note low GCS or acidotic behaviour) or ACE-i AKI.
3) Drugs affecting (or affected by) CP450 enzymes = inducers → PCBRAS; inhibitors = AODEVICES + ketoconazole + grapefruit juice.
Enzyme inducer = increase P450 enzyme activity = reduced levels of other drugs.
name some inducers
PC BRAS = phenytoin, carbamazepine, barbiturates, rifampicin, alcohol (chronic excess), sulphonylureas
Enzyme inhibitor = reduce P450 enzyme activity = increased levels of other drugs.
Name some inducers
AO DEVICES = allopurinol, omeprazole, disulfiram, erythromycin, valproate, isoniazid, ciprofloxacin, ethanol (acute intoxication), sulphonamides.
+Grape fruit juice!
Drugs with potent interactions with ETOH
Alcohol can cause:
→ GI bleeding with NSAIDs.
→ Lactic acidosis with metformin.
→ Hypertensive crisis by MAO-i.
→ Increased anticoagulation with warfarin (acute alcohol – chronic alcohol reduces warfarin effect).
→ Sweating, flushing, N&V - metronidazole + disulfiram.
→ Sedation by barbiturates, opioids + benzodiazepines.