L05 - Adverse Reactions to Antibiotics Flashcards

1
Q

Define ADR

A

Adverse Drug Reactions are injuries caused by taking medication

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2
Q

What are the six main determinants of toxicity?

A
Genetic
Chemical
Metabolic
Drug Interactions
Altered Microbial Flora
Hypersensitivity
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3
Q

Define Type A Reactions

A

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

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4
Q

Define Type B Reactions

A

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

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5
Q

Describe Penicillin allergies

A

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)

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6
Q

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

A

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

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7
Q

What is the most commonly affected organ in ADRs?

A

Skin

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8
Q

Give four examples of ADRs affecting the skin

A

Urticaria
Erythematous Eruptiosn
Toxic Epidermal Necrolysis
Stevens-Johnson Syndrome

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9
Q

Define Drug Interactions

A

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

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10
Q

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

A

Polypharmacy

Renal Impairment

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11
Q

What are CYP450 enzymes?

A

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

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12
Q

What are the two possible interaction mechanisms of CYPs

A

Inhibition

Induction (CYP2D6 not inducible)

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13
Q

Describe enzyme induction - Give an example

A

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

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14
Q

Describe enzyme inhibition

A

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

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15
Q

Define the Therapeutic Range

A

The window between Toxic and Therapeutic drug concentrations

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16
Q

Give three examples of the most common ADRs for Cephalosporins

A

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

17
Q

Describe the Pros of Aminoglycosides (Gentamycin)

A

Strong Gram-ve activity
Rapidly bactericidal
Synergistic w/ Penicillin

18
Q

Describe the Cons of Aminoglycosides (Gentamycin)

A

Poor lipid solubility
pH dependent
No oral formulation

19
Q

Describe the ADRs of Aminoglycosides (Gentamycin)

A

Ototoxic/Nephrotoxic

TDM req.

20
Q

Describe the Pros of Glycopeptides (Vancomycin)

A

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

21
Q

Describe the Cons of Glycopeptides (Vancomycin)

A

Oral formulation NOT absorbed - cannot treat systemic infections

22
Q

Describe the ADRs of Glycopeptides (Vancomycin)

A

Ototoxic/Nephrotoxic
Red-man syndrome
TDM req.

23
Q

Describe the Pros of Quinolones (Ciprofloxacin)

A

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

24
Q

Describe the Cons of Quinolones (Ciprofloxacin)

A

Interactions - Theophylline, Amiodarone

25
Q

Describe the ADRs of Quinolones (Ciprofloxacin)

A
High risk of C. diff diarrhoea
Selective for MRSA
CNS toxicity
Tendon damage
Photoxicity/Skin eruptions
26
Q

Describe the Pros of Tetracyclines (Doxycyline)

A

Strong activity against intra-cellular/atypical organisms

27
Q

Describe the Cons of Tetracyclines (Doxycycline)

A

Oral formulation only

28
Q

Describe the ADRs of Tetracyclines (Doxycyline)

A

GI disturbance
Photosensitivity
Dental staining
Hepatotoxicity

29
Q

Describe the Pros of Lincosamides (Clindamycin)

A

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

30
Q

Describe the ADRs of Lincosamides (Clindamycin)

A

High risk of C. diff diarrhoea
Rash
GI upset

31
Q

Describe the Pros of Sulphonamides/Co-trimoxazole

A

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

32
Q

Desribe the Cons of Sulphonamides/Co-trimoxazole

A

Serious adverse effects

33
Q

Describe the ADRs of Sulphonamides/Co-Trimoxazole

A

Rash
Blood disorders
Crystalluria

34
Q

For which two infections is Co-trimoxazole reserved?

A

Pneumocystis carinii pneumonia

Toxoplasmosis

35
Q

Describe the Pros of Chloramphenicol

A

Broad spectrum
Resistance rare
Excellent CSF penetration

36
Q

Describe the Cons of Chloramphenicol

A

Bacteriostatic (cidal to H.influenzae)

37
Q

Describe the ADRs of Chloramphenicol

A

Bone marrow toxicity (suppression/aplasia)