Adverse drug reactions & Interactions

Question 1

Stats on ADRs

Answer 1

• 5% of hospital admissions are ADR-related
• 10-20% of hospital patients suffer ADR
• 0.1% of medical patient mortality
• Many patients receiving polypharmacy, increases chances of interactions/ADRs

Question 2

BNF definitions of incidence

Answer 2

Very common: 1 in 10

Common: up to 1 in 100

Less commonly: up to 1 in 1000

Rare: up to 1 in 10,000

Very rare: Less than 1 in 10,000

Question 3

Determinantsof drug toxicity

Answer 3

• Genetic
• Chemical
• Metabolic
• Drug interactions
• Altered microbial flora
• Hypersensitivity

Question 4

Describe ADR type A

Answer 4

• The normal pharmacological response is undesirable
• Dose-related
• Predictable
• Usually managed by dose adjustment

Question 5

Describe AB associated C. diff diarrhoea

Answer 5

• Antibiotic treatment = kills off other gut bacteria + allows C. difficile to proliferate
• Produces an enterotoxin (toxin A) and a cytotoxin (toxin B) which cause clinical disease
• Effects can range from mild diarrhoea to life-threatening pseudomembranous colitis

Question 6

Explain c.diff cycle

Answer 6

Question 7

ABs associated with CD diarrhoea

Answer 7

Common

Ampicillin

Amoxicillin

Co-amoxiclav

Cephalosporins

Clindamycin

Macrolides

Quinolones

Question 8

Define Type B ADR

Answer 8

Type B reactions are idiosyncratic, bizarre or novel responses that cannot be predicted from the known pharmacology of a drug and are associated with low morbidity and high mortality

Often related to genetics or immunology

Question 9

TYPE I-IV Hypersensitivity reactions

Answer 9

Question 10

Epidemiology of Penicillin allergy

Answer 10

• 1-10%
• 6-fold risk increase if previous reaction
• Risk greater for parenteral admin
• Significant proportion who develop anaphylaxis have no previous history of drug reaction

Question 11

B-lactam vs penicillin allergy considerations

Answer 11

• GI upset is common = Rx should continue
• Rash = no more penicillins; other B-lactams probably ok (risk of cross-over allergy low)
• Angioedema/anaphylaxis = no more B-lactams; use other class of agent

Question 12

Types of skin reactions

Answer 12

Urticaria

Erythematous eruptions: reddening, may resemble measles or maculopapular

Toxic epidermal necrolysis: rare but often fatal with blistering and skin peels off

• Sulphonamides
• Beta-lactams

Stevens-Johnson syndrome: fever, rash, blisters

• Vancomycin
• Penicillins
• Sulphonamides

Question 13

Possible consequences of drug interactions

Answer 13

May increase toxicity

Or

Reduce activity – failure of therapy

Question 14

Possible interaction mechanisms caused by CYP

Answer 14

Inhibition

Induction (CYP2D6 not inducible)

Question 15

Examples of CYP induced metabolism

Answer 15

Enzyme induction: increase activity of metabolising enzymes

• Rifampicin
• Griseofulvin

Reduce plasma conc of range of drugs E.g. rifampicin increase metabolism of OCs

May take a week or 2 for effect

Effect may persist on stopping inducer

Question 16

CYP enzyme inhibtion

Answer 16

Cy P450 inhibition

• antifungal agents (ketoconazole)
• erythromycin
• Rapid onset: 1-2 days
• Often reverse quickly on stopping

Macrolides and simvastatin

Question 17

Define therapeutic range

Answer 17

Therapeutic range =
[toxic concentration] – [therapeutic concentration]

Question 18

Aminoglycosides pros/cons

Answer 18

Question 19

Cephalosporins ADR

Answer 19

Question 20

Glycopeptides Pros/cons

Answer 20

Question 21

Quinolones pros/cons

Answer 21

Question 22

Tetracyclines pros/cons

Answer 22

Question 23

Lincosamides pros/cons

Answer 23

Question 24

Cloramphenicol pros/cons

Answer 24