Drug Safety and Side Effects

Question 1

What are Type A adverse drug reactions?

Answer 1

• Pharmacological
• Consequence of drug action - predictable of you know the pharcokinetics and pharmacodynamics of drug
• often dose dependent
• can be resolved by lowering dose or withdrawing treatment
• generally picked up during drug testing

Question 2

What are type B adverse drug reactions?

Answer 2

• Idiosyncratic or bizarre
• unrelated to drug’s pharmacology - difficult to predict
• Often involves immune system and/ or genetic abnormality
• can be fatal
• need to withdraw drug
• need longer term and widespread use before it is detected

Question 3

Give 3 examples of type A ADRs

Answer 3

• NSAIDs –> GI bleeds, peptic ulcer, renal impairment - caused by the COX inhibition and so reduction of prostaglandins
• Diuretics –> hypotension, dehydration, electrolyte changes - due to vasodilation effects and fluid excretion
• Opioids –> vomiting, confusion, constipation, urinary retention, respiratory depression - due to stimulation of opiate receptors
• Insulin/oral hypoglycaemic drugs –> hypoglycaemia - due to poor control of blood glucose, excess glucose uptake/storage

Question 4

34 year old, suffers from allergic rhinitis, woke up with nosebleed

Answer 4

Takes antihistamines - therefore more prone to nosebleeds

Question 5

67 year old, suffers from AF, had a subconjunctival bleed

Answer 5

Stroke from thrombosis - take Warfarin

Question 6

Elderly lady, being treated for heart failure with a diuretic, collapsed at home

Answer 6

Postural hypotension

Question 7

Man with arthritis takes Aspirin and NSAIDs, presents with haematemesis (vomiting blood)

Answer 7

GI Bleed

Question 8

Lady on St John’s Wort for depression, becomes pregnant despite being on pill

Answer 8

SJW is an enzyme inducer - stimulates CYP enzymes - reduces pill’s efficacy

Question 9

Name a possible type B ADR example

Answer 9

Hypersensitivity reactions –> anaphylactic shock

Question 10

What is Steven Johnson Syndrome?

Answer 10

• Very severe Type B ADR
• linked to genetics, infections, poorl liver metabolism
• Flu like symptoms, blistering of skin which falls off
• organ damage and possibly blindness
• 5% mortality rate

Question 11

How do drugs induce hypersensitivity reactions?

Answer 11

Chemical reaction between penicillin and plasma proteins forms an immunogenic penicilloyl hapten

• Triggers immune response
• Mast cells release histamine –> Anaphylaxis

Question 12

Name some ADRs due to prolonged drug administration

Answer 12

• thinning of skin
• osteoporosis
• buffalo hump
• some drugs have to be taken long term for arthritis, lupus, IBS etc - have to balance benefits and risk

Question 13

How can we reduce or avoid ADRs

Answer 13

• Continue to treat, but treat ADR with another drug
• Accept more severe ADRs because of the benefit (e.g. alopecia with chemo)
• be aware of drug interactions
• pharmacovigilance - monitor the safety of drugs

Question 14

Give 2 examples of withdrawn drugs

Answer 14

Thalidomide

Rofecoxib - COX-2 selective inhibitor, increased risk of MI, stroke

Question 15

What is Thalidomide?

Answer 15

• A drug that was used for morning sickness
• Had teratogenic effects - caused polydactyly, syndactyly and phocomelia (short arm/leg bones)
• wasnt initially tested on pregnant animals so missed the tertogenic effects

Question 16

How do we report ADRs?

Answer 16

• pharmacovigilance
• yellow card - form anyone can fill out about reactions to a specific drug
• black triangle
• green form - limited to a small number of new drugs - record any significant medical event that occurs whilst a patient is taking a drug