L05 - Adverse Reactions to Antibiotics

Question 1

Define ADR

Answer 1

Adverse Drug Reactions are injuries caused by taking medication

Question 2

What are the six main determinants of toxicity?

Answer 2

Genetic
Chemical
Metabolic
Drug Interactions
Altered Microbial Flora
Hypersensitivity

Question 3

Define Type A Reactions

Answer 3

Type A = Augmented Response
Normal pharmacological response is undesirable
Dose related, predictable, managed by adjustment

Question 4

Define Type B Reactions

Answer 4

Type B = Bizzare or Idiosyncratic
Unrelated to pharmacology
Unpredictable, rare, often severe
Related to genetics/immunology

Question 5

Describe Penicillin allergies

Answer 5

Penicillins couple to proteins, form immunogens (Type 1 hypersensitivity)
Ranges from mild rashes to anaphylaxis
Occurs in 1-10% (risk 6x if prev. reaction or parenteral administration)

Question 6

What is the time course of ADRs to Beta Lactam antibiotics?

Answer 6

0-60 mins = Acute
1-24 hours = Subacute
1 day to several weeks = Latent

Question 7

What is the most commonly affected organ in ADRs?

Answer 7

Skin

Question 8

Give four examples of ADRs affecting the skin

Answer 8

Urticaria
Erythematous Eruptiosn
Toxic Epidermal Necrolysis
Stevens-Johnson Syndrome

Question 9

Define Drug Interactions

Answer 9

When the effects of one drug are changed by the presence of another:
drug/food/drink/environmental chemical agent
(increase toxicity OR reduce activity)

Question 10

Give two examples of factors that may increase the risk of drug interactions

Answer 10

Polypharmacy

Renal Impairment

Question 11

What are CYP450 enzymes?

Answer 11

Enzymes involved in metabolism of toxic compounds. Drugs may be metabolised my multiple/single CYPs

Question 12

What are the two possible interaction mechanisms of CYPs

Answer 12

Inhibition

Induction (CYP2D6 not inducible)

Question 13

Describe enzyme induction - Give an example

Answer 13

Increased activity of metabolising enzymes, thereby reducing the plasma concentration of drugs
May take 1/2 weeks for effect and may persist
Rifampicin is a potent inducer

Question 14

Describe enzyme inhibition

Answer 14

Decreased activity of metabolising enzymes, thereby increasing the plasma concentration of drugs
Rapid onset (1-2 days) and reverses quickly
Ketoconoazole (antifungal agents) and Erythromycin are potent inhibitors

Question 15

Define the Therapeutic Range

Answer 15

The window between Toxic and Therapeutic drug concentrations

Question 16

Give three examples of the most common ADRs for Cephalosporins

Answer 16

Hypersensitivity (Rash, Eosiniophilia, Fever, Anaphylaxis)
Gastrointestinal (Diarrhoea, Pseudomembranous Colitis)
Haematological (Anaemia, Leukopenia, Platelet Dysfunction)

Question 17

Describe the Pros of Aminoglycosides (Gentamycin)

Answer 17

Strong Gram-ve activity
Rapidly bactericidal
Synergistic w/ Penicillin

Question 18

Describe the Cons of Aminoglycosides (Gentamycin)

Answer 18

Poor lipid solubility
pH dependent
No oral formulation

Question 19

Describe the ADRs of Aminoglycosides (Gentamycin)

Answer 19

Ototoxic/Nephrotoxic

TDM req.

Question 20

Describe the Pros of Glycopeptides (Vancomycin)

Answer 20

Strong Gram+ve activity
Used for line infections
PO formulation can treat c. difficile

Question 21

Describe the Cons of Glycopeptides (Vancomycin)

Answer 21

Oral formulation NOT absorbed - cannot treat systemic infections

Question 22

Describe the ADRs of Glycopeptides (Vancomycin)

Answer 22

Ototoxic/Nephrotoxic
Red-man syndrome
TDM req.

Question 23

Describe the Pros of Quinolones (Ciprofloxacin)

Answer 23

Strong Gram-ve activity
Oral/i.v. formulations
Good tissue penetration

Question 24

Describe the Cons of Quinolones (Ciprofloxacin)

Answer 24

Interactions - Theophylline, Amiodarone

Question 25

Describe the ADRs of Quinolones (Ciprofloxacin)

Answer 25

``` High risk of C. diff diarrhoea Selective for MRSA CNS toxicity Tendon damage Photoxicity/Skin eruptions ```

Question 26

Describe the Pros of Tetracyclines (Doxycyline)

Answer 26

Strong activity against intra-cellular/atypical organisms

Question 27

Describe the Cons of Tetracyclines (Doxycycline)

Answer 27

Oral formulation only

Question 28

Describe the ADRs of Tetracyclines (Doxycyline)

Answer 28

GI disturbance Photosensitivity Dental staining Hepatotoxicity

Question 29

Describe the Pros of Lincosamides (Clindamycin)

Answer 29

Anti-toxin (binds to 50S subunit) Excellent oral bioavailability Good tissue penetration Anaerobic activity

Question 30

Describe the ADRs of Lincosamides (Clindamycin)

Answer 30

High risk of C. diff diarrhoea Rash GI upset

Question 31

Describe the Pros of Sulphonamides/Co-trimoxazole

Answer 31

Broad spectrum Good CSF penetration (sulph.) i.v./oral formulations

Question 32

Desribe the Cons of Sulphonamides/Co-trimoxazole

Answer 32

Serious adverse effects

Question 33

Describe the ADRs of Sulphonamides/Co-Trimoxazole

Answer 33

Rash Blood disorders Crystalluria

Question 34

For which two infections is Co-trimoxazole reserved?

Answer 34

Pneumocystis carinii pneumonia | Toxoplasmosis

Question 35

Describe the Pros of Chloramphenicol

Answer 35

Broad spectrum Resistance rare Excellent CSF penetration

Question 36

Describe the Cons of Chloramphenicol

Answer 36

Bacteriostatic (cidal to H.influenzae)

Question 37

Describe the ADRs of Chloramphenicol

Answer 37

Bone marrow toxicity (suppression/aplasia)