adverse drug reactions Flashcards
absorption in the elderly
□ Decreased oral absorption
□ Small intestine surface area decreases
distribution in the elderly
□ Increase in total body fat
□ Decrease in total body water
□ Vdist may increase for lipophilic drugs but decrease for hydrophilic drugs
protein binding in elderly
□ Decrease serum albumin
□ Decreased drug binding
□ Increase in free drug fraction to cause therapeutic or toxic effects
metabolism in the elderly
□ Old livers slow down
□ Decreased drug metabolism by CYP450
□ Hepatic clearance may decrease
elimination in the elderly
□ Glomerulus filtration rate (GFR) decreases
□ Decreased clearance and increased half life for renally cleared drugs
commonest ADRs
○ Commonest ADRs are skin rashes associated with antibiotics
§ Especially neonates and infants
§ Immature epidermis
oxygen given to preterm infants
- develop blindness/retinopathy
- bronchopulmonary dysplasia - chronic lung disease
sulphonamides in neonates
kernicterus
sulphonamide binds albumin and frees bilirubin
free bilirubin crosses blood brain barrier and causes a type of cerebral palsy
dexamethasone
high dose causes neuronal apoptosis
cerebral palsy
pregnancy
§ Maternal fat increases
§ Total body water increases
§ In crease in maternal blood volume and cardiac output
§ Increase blood flow to kidneys and uteroplacental unit
§ Decreased plasma protein levels, especially motility
§ Altered drug metabolising capacity in the liver
type A ADR
on target, predictable ○ Common, low mortality ○ Reduce dose to manage ○ Intolerant ○ Effects seen at site of the drug action
type A ADR examples
○ Examples § Hypoglycaemia □ Excessive insulin § Bleeding - anticoagulants § Postural hypotension □ Anti hypertensives § Drowsiness □ Benzodiazepines and first gen anti histamines § Liver toxicity - paracetamol
Type B ADR
○ Off target
○ Unpredictable, idiosyncratic
○ Not related to the drug pharmacological action
○ Often immunological component
immediate Type B ADR
□ Usually less than an hour but may take up to 6 hours
□ Usually IgE mediates
mechanism of IgE mediation
® Allergen picked up by a dendritic cell of macrophage
® Peptide mounted in MHC cleft
® Activates Th2 helper cell which activates a B cell to produce IgE antibodies to the allergen
® Plasma cells maintains memory
® IgE molecules picked up by mast cells and basophils
® The next time the person is exposed to the allergen there is a quick response/degranulation
delayed Type B ADR
□ Usually days but can be less than a day with re exposure
□ T cell mediated delayed hypersensitivity
□ Can be due to development of toxic metabolites in genetically predisposed individuals
pruritic
itchy
◊ Morbilliform
} Erythematous maculopapular rash
Severe cutaneous adverse reactions (SCARs)
- AGEP
○ Acute generalised exanthematous pustulosis- DRESS
○ Drug reaction with eosinophilia and systemic symptoms - SJS
○ Stevens-Johnson syndrome (<10% skin affected) - TEN
○ Toxic epidermal necrolysis (>30% skin affected)
- DRESS
low risk assessment in patients with reported history of allergies
○ Low risk
§ Isolated non allergic symptoms (e.g. diarrhoea) or pruritus without rash
□ Direct amoxycillin challenge
medium risk assessment in patients with reported history of allergies
§ Urticaria
§ Other pruritis rash or other IgE mediated reaction
§ Evaluate with penicillin skin test
high risk assessment in patients with reported history of allergies
§ Anaphylaxis
§ Positive penicillin skin test
§ Allergic to multiple beta lactam antibiotics (penicillins, cephalosporins etc.)
