50s Protein Synthesis Inhibitors ic8 Flashcards
MOA of Macrolides
Reversibly bind to 50s ribosomal subunit
Inhibit translocation step
Examples of Macrolides
Azithromycin
Clarithromycin
Erythromycin
Characteristics of Macrolides (static or cidal, Administration, Metabolism, Caution, Pregnancy?)
Bacteriostatic
Alternative to Penicillins
Oral administration (enteric coated)
Hepatic metabolism
Cause alot of DDI (inhibit CYP450)
Suitable for Pregnancy
Indication of Macrolides (usually used for?)
Which other class also?
Atypicals (MCL)
similar to Tetracyclines, Fluoroquinolones (except ciprofloxacin)
Adverse effects of Macrolides (4 points)
Gastric discomfort
More common for Erythromycin
Hepatotoxicity
Ototoxicity
Prolong QT interval
2 resistance mechanisms against Macrolides
Which mechanism can use Clindamycin, which cannot?
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
Administration of Clindamycin
IV and Oral
Topical gel, solution
Indication of Clindamycin
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
Adverse effects of Clindamycin
1) Esophageal irritation
Take with a full glass of water
2) GI related (Diarrhea, vomiting)
3) Associated with CDAD
Coverage of Linezolid
Only Gram (+)
MOA of Linezolid
Bind to 23s ribosomal RNA of 50s subunit
Even more specific than Macrolides and Clindamycin
Spectrum of activity of Linezolid
Gram (+) eg. Staph, Strep, Enterococci, Listeria
More resistant strains also eg. MRSA, Penicillin resistant Strep
PK of Linezolid (Administration, CSF, CNS penetration, Metabolites)
Oral and IV
Good penetration into CSF and CNS
Unlike Clindamycin and Macrolides
Produces inactive metabolites
Accumulation wont be an issue
Caution for use of Linezolid
Should not be used if there are alternative options
Reserve as an alternative agent
Will hasten resistance
Which patient populations should not use Linezolid (2 points)
Contraindicated in Pregnancy
Do not use in Catheter Related BloodStream Infections (CRBSI)
Adverse effects of Linezolid (4 points)
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)
Counselling points of Linezolid (related to adverse effects)
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
