50s Protein Synthesis Inhibitors ic8

Question 1

MOA of Macrolides

Answer 1

Reversibly bind to 50s ribosomal subunit
Inhibit translocation step

Question 2

Examples of Macrolides

Answer 2

Azithromycin
Clarithromycin
Erythromycin

Question 3

Characteristics of Macrolides (static or cidal, Administration, Metabolism, Caution, Pregnancy?)

Answer 3

Bacteriostatic
Alternative to Penicillins
Oral administration (enteric coated)
Hepatic metabolism
Cause alot of DDI (inhibit CYP450)
Suitable for Pregnancy

Question 4

Indication of Macrolides (usually used for?)
Which other class also?

Answer 4

Atypicals (MCL)
similar to Tetracyclines, Fluoroquinolones (except ciprofloxacin)

Question 5

Adverse effects of Macrolides (4 points)

Answer 5

Gastric discomfort
More common for Erythromycin

Hepatotoxicity

Ototoxicity

Prolong QT interval

Question 6

2 resistance mechanisms against Macrolides

Which mechanism can use Clindamycin, which cannot?

Answer 6

1) Efflux pumps
Use Clindamycin instead

2) Result of ERM gene
ERM gene causes ribosomal methylation → Reduced binding affinity of Macrolides to 50s ribosomal subunit
Cannot use clindamycin too

Question 7

Administration of Clindamycin

Answer 7

IV and Oral
Topical gel, solution

Question 8

Indication of Clindamycin

Answer 8

Mainly used for serious Anaerobic oral infections

Gram (+) and (-), but more (+)
Eg. MRSA, Strep, Penicillin resistant Anaerobes

Alternative for serious Penicillin allergies

Can be used during pregnancy

Question 9

Adverse effects of Clindamycin

Answer 9

1) Esophageal irritation
Take with a full glass of water

2) GI related (Diarrhea, vomiting)

3) Associated with CDAD

Question 10

Coverage of Linezolid

Answer 10

Only Gram (+)

Question 11

MOA of Linezolid

Answer 11

Bind to 23s ribosomal RNA of 50s subunit
Even more specific than Macrolides and Clindamycin

Question 12

Spectrum of activity of Linezolid

Answer 12

Gram (+) eg. Staph, Strep, Enterococci, Listeria

More resistant strains also eg. MRSA, Penicillin resistant Strep

Question 13

PK of Linezolid (Administration, CSF, CNS penetration, Metabolites)

Answer 13

Oral and IV

Good penetration into CSF and CNS
Unlike Clindamycin and Macrolides

Produces inactive metabolites
Accumulation wont be an issue

Question 14

Caution for use of Linezolid

Answer 14

Should not be used if there are alternative options
Reserve as an alternative agent
Will hasten resistance

Question 15

Which patient populations should not use Linezolid (2 points)

Answer 15

Contraindicated in Pregnancy

Do not use in Catheter Related BloodStream Infections (CRBSI)

Question 16

Adverse effects of Linezolid (4 points)

Answer 16

1) GI effects

2) Bone marrow suppression (> 10 days)
Thrombocytopenia (Platelet deficiency)

3) Serotonin syndrome
Linezolid has MAOi (Monoamine Oxidase inhibitory) activity
MAO helps to get rid of excess neurotransmitters eg. Acetylcholine and Adrenaline / Epinephrine
MAOi will cause excess adrenergic activity
If given with other SSRi (Selective Serotonin Reuptake inhibitor) or MAOi
Avoid Tyramine and Histamine rich food

4) Irreversible Peripheral neuropathy and Optic neuritis (> 28 days)

Question 17

Counselling points of Linezolid (related to adverse effects)

Answer 17

1) Not approved for CRBSI

2) Do not use within 2 weeks of MAOi

3) Avoid tyramine-rich foods and serotonergic drugs
Tyramine rich food: Cheese, smoked meats, draft beer