Lecture 8 - Adverse Reactions to Antibiotics

Question 1

Describe the Augmented adverse drug response? how do we manage this?

Answer 1

an undesirable response to a drug usually related to the dosage (predictable)
-usually managed by dose adjustment

Question 2

Describe the problem with antibiotic treatment and c. difficile

Answer 2

c. difficile is gram positive anaerobic and grows in bowel. antibiotics kills off other gut flora allowing c.diff to proliferate. c diff produces an enterotoxin (toxin A) and cytotoxin (toxin B) which causes clinical disease. range from mild to life threatening

Question 3

What other things pre dispose c. diff infections

Answer 3

antacids, bowel surgery, PPI

Question 4

Describe idiosynratic or bizarre antibiotic reactions

Answer 4

unrelated pharmacology, unpredictable, rare and often severe often unrelated to genetics or immunology

Question 5

What causes a penicillin allergy? How do you treat?

Answer 5

penicillins couple to proteins forming immunogens - hypersensitivity reaction
- treat with h1 antagonists (antihistamine) + steroids and adrenaline

Question 6

Which antibiotic has common cross reactivity with penicillin ?

Answer 6

cephalosporins - not as bad as first thought

Question 7

Name the type 1 drug hypersensitivity reactions

Answer 7

anaphylactic shock, urticaria, laryngral oedema and asthma

Question 8

Name the type 2 drug hypersensitivity reactions

Answer 8

leucoytopenia, agranulocytosis, thrombocytopenia, haemolytic anaemia

Question 9

Name the type 3 drug hypersensitivity reactions

Answer 9

allergic vasculitis, drug fever, serum sickness

Question 10

Name the type 4 drug hypersensitivity reactions

Answer 10

contact dermatitis

Question 11

Name the drug hypersensitivity reactions that have an uncertain mode of response

Answer 11

Exfoliative dermatitis, Steven-Johnson Syndromes, Encephalitis, neuritis, hepatitis, rash with viral infection

Question 12

Who is at risk of penicillin reaction? What factors affect this risk?

Answer 12

1-10% of people taking it, risk increased if prev history. BUT can develop anaphylaxis with no history. risk increased with parenteral administration

Question 13

if a patient has previously responded to penicillin with
1) GI upset
2) a rash
3) anaphylaxis
and you need to prescribe ABs, what should you do?

Answer 13

1) give penicillin still
2) no penicillin but a diff beta lactam
3) dont prescribe penicillin or beta lactam

Question 14

describe

1) erythematous eruption
2) toxic epidermal necrolysis

Answer 14

1) reddening of the skin - may resemble measels or maculopapular
2) rare but often fatal with blistering, skin peels off

Question 15

what is stevens- johnson syndrome?

Answer 15

a form of toxic epidermal necrolysis - fever, skin rash and blisters

Question 16

If a patient was experiencing an ADR to co-amoxiclav then what would you do?

Answer 16

obtain a drug history, usually stop the drug

treat the symptoms with antihistamine and soothing cream

Question 17

Define a drug interaction

Answer 17

effects of one drug are changed by presence of another drug, food, drink, environmental chemical agent

Question 18

what are the two possible consequences of drug interactions?

Answer 18

increased toxicity or reduced activity

Question 19

which condition can increase drug interactions?

Answer 19

renal impairment

Question 20

why would warfarin have a higher chance of interacting with other drugs

Answer 20

narrow therapeutic window

Question 21

Which drugs cause enzyme induction?

Answer 21

rifampicin, ethanol, st johns wart, carbamezepine, phenytoin, griseofulvin, barbiturates

Question 22

What effect do enzyme inducers have on other drugs taken?

Answer 22

reduce plasma conc of other drugs as increases metabolism of other drugs e.g. pill - may take week or 2 for effect and may persist on stopping inducer

Question 23

Which drugs cause enzyme inhibition? How long does it take to occur? What does it do to levels or other drugs taken?

Answer 23

1) cimetidine, antifunglas, erythromycin, ciclosporin
2) 1-2 days and reverses quickly on stopping
3) toxic levels of other drug

Question 24

What is the the therapeutic range? Give an example of a drug with a wide and narrow range?

Answer 24

window between toxic and therapeutic concentrations

wide - penicillin and narrow - gentamicin

Question 25

Name some antibiotics that can cause c diff associated diarrhoea

Answer 25

Clindamycin
Cephalosporins
Broad spec penicillins (co-amoxiclav)
Quinolones
Erythromycin (via motility stim)

Question 26

How does the amount of CYPs needed to metabolise a drug effect the drug interactions?

Answer 26

is only metabolised by one CYP then more likely to have clinically relevant interactions