adverse drug reactions

Question 1

absorption in the elderly

Answer 1

□ Decreased oral absorption

□ Small intestine surface area decreases

Question 2

distribution in the elderly

Answer 2

□ Increase in total body fat
□ Decrease in total body water
□ Vdist may increase for lipophilic drugs but decrease for hydrophilic drugs

Question 3

protein binding in elderly

Answer 3

□ Decrease serum albumin
□ Decreased drug binding
□ Increase in free drug fraction to cause therapeutic or toxic effects

Question 4

metabolism in the elderly

Answer 4

□ Old livers slow down
□ Decreased drug metabolism by CYP450
□ Hepatic clearance may decrease

Question 5

elimination in the elderly

Answer 5

□ Glomerulus filtration rate (GFR) decreases

□ Decreased clearance and increased half life for renally cleared drugs

Question 6

commonest ADRs

Answer 6

○ Commonest ADRs are skin rashes associated with antibiotics
§ Especially neonates and infants
§ Immature epidermis

Question 7

oxygen given to preterm infants

Answer 7

• develop blindness/retinopathy

- bronchopulmonary dysplasia - chronic lung disease

Question 8

sulphonamides in neonates

Answer 8

kernicterus
sulphonamide binds albumin and frees bilirubin
free bilirubin crosses blood brain barrier and causes a type of cerebral palsy

Question 9

dexamethasone

Answer 9

high dose causes neuronal apoptosis

cerebral palsy

Question 10

pregnancy

Answer 10

§ 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

Question 11

type A ADR

Answer 11

on target, predictable 
		○ Common, low mortality 
		○ Reduce dose to manage 
		○ Intolerant 
		○ Effects seen at site of the drug action

Question 12

type A ADR examples

Answer 12

○ Examples 
			§ Hypoglycaemia 
				□ Excessive insulin 
			§ Bleeding - anticoagulants 
			§ Postural hypotension 
				□ Anti hypertensives
			§ Drowsiness 
				□ Benzodiazepines and first gen anti histamines 
			§ Liver toxicity - paracetamol

Question 13

Type B ADR

Answer 13

○ Off target
○ Unpredictable, idiosyncratic
○ Not related to the drug pharmacological action
○ Often immunological component

Question 14

immediate Type B ADR

Answer 14

□ Usually less than an hour but may take up to 6 hours

□ Usually IgE mediates

Question 15

mechanism of IgE mediation

Answer 15

® 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

Question 16

delayed Type B ADR

Answer 16

□ 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

Question 17

pruritic

Answer 17

itchy

Question 18

◊ Morbilliform

Answer 18

} Erythematous maculopapular rash

Question 19

Severe cutaneous adverse reactions (SCARs)

Answer 19

• 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)

Question 20

low risk assessment in patients with reported history of allergies

Answer 20

○ Low risk
§ Isolated non allergic symptoms (e.g. diarrhoea) or pruritus without rash
□ Direct amoxycillin challenge

Question 21

medium risk assessment in patients with reported history of allergies

Answer 21

§ Urticaria
§ Other pruritis rash or other IgE mediated reaction
§ Evaluate with penicillin skin test

Question 22

high risk assessment in patients with reported history of allergies

Answer 22

§ Anaphylaxis
§ Positive penicillin skin test
§ Allergic to multiple beta lactam antibiotics (penicillins, cephalosporins etc.)