Bacterial Protein Synthesis inhibitors Flashcards
Name 2 key targets of antimicrobials that work by inhibiting bacterial protein synthesis?
50S, 30S bacteria ribosomal subunits
Name at least 2 classes of antibiotics which are 30S protein synthesis inhibitors
tetracyclines, glycylcycline, aminoglycosides
Name 3 examples of tetracyclines
tetracycline, doxycycline, minocycline
Tetracycline prevents binding of ___________ to the A site of mRNA-ribosome complex
tRNA
Tetracyclines should not be administered with dairy products or substances that contain divalent and trivalent cations as this would lead to the formation of ___________, which would ___________ the absorption of the drugs.
non-absorbable chelates,
reduce
Comment on tetracycline’s antimicrobial coverage
It has broad spectrum activity against many Gram-negative and Gram-positive bacteria. It also has coverage against atypical bacteria. It does not have adequate coverage against Pseudomonas aeruginosa and Proteus
How is tigecycine administered?
Intravenously (It has poor oral bioavailability unlike the tetracyclines.)
Glycylcyclines (tigecycline) were designed to overcome which two mechanisms of tetracycline resistance?
Expression of efflux pumps, and ribosomal protection
Tigecycline is useful in targeting some of the resistant microbes including
- Methicillin resistant staphylococci (MRSA),
- Multidrug-resistant streptococci,
- Vancomycin-resistant enterococci (VRE),
- useful against carbapenem resistant strains of Extended-spectrum β-lactamase–producing gram-negative bacteria
Name at least 4 adverse effects associated with the use of tetracyclines
- Gastrointestinal distress (To reduce ulceration, drink plenty of fluids and do not take it before sleep)
- Phototoxicity (Like fluoroquinolones)
- Superinfection like thrush
- Deposition in bone/primary dentition and may cause discoloration of teeth
The use of tetracyline and tigecycline is contraindicated in which populations of patients?
- Pregnant women,
- Breastfeeding women
- Children less than 8 years of age
Aminoglycosides are transported across the inner membrane of Gram-negative bacteria by ___________ , which is an energy dependent process.
active transport
Aminoglycosides are particularly effective against _______ Gram-negative bacteria
aerobic
Name 5 examples aminoglycosides
gentamicin, streptomycin, tobramycin, amikacin, neomycin
Aminoglycosides demonstrate synergism when combined with which class of antibiotics? Name one class.
Beta lactams (e.g. gentamicin and ceftriaxone for the management of staphylococcus endocarditis)
How are aminoglycosides commonly administered?
Parenterally (They have poor oral bioavailability)
Name an aminoglycoside that is used in the management of tuberculosis
Streptomycin (administered IM)
How are aminoglycosides cleared?
Renally
Name at least 2 adverse effects associated with aminoglycosides
- Ototoxicity
- Nephrotoxicity (Do not combine with other nephrotoxicity)
- Neuromuscular paralysis (Especially when used with neuromuscular blockers)
Name an aminoglycoside that is administered orally
Neomycin (bowel prep)
Name 2 groups of patients in whom aminoglycosides would be contraindicated
- Pregnant women,
- Patients suffering from myasthenia gravis because of the risk of prolonged neuromuscular blockade
- Patients with severe renal Impairment
What are the 6 “NOs” in relation to aminoglycosides?
- No to protein synthesis
- Particularly active against aerobic Gram-Negative Organisms
- No to use during pregnancy
- No to oral administration
- No to CSF penetration
- Nephro- and Oto- toxicities
Name 3 types of 50S protein synthesis inhibitors
Macrolides, clindamycin, linezolid
Name 3 macrolides
Erythromycin, clarithromycin, azithromycin
25 Are macrolides bacteriostatic or bactericidal antibiotics?
Bacteriostatic
How can macrolides be administered?
Oral and IV
Name some of the microbial infections that the macrolides are useful against
Respiratory infections caused by S.pneumoniae, H. influenzae and Moraxella catarrhalis and those caused by atypical bacteria such as Legionella pneumophilia, Mycoplasma and Chlamydia
STDs caused by Chlamydia trachomatis and Neisseria gonorrhoea
H.pylori infections
Name 2 adverse effects associated with macrolides
- Gastric Distress
- Hepatotoxicity
- Ototoxicity
- May prolong QT interval
How are macrolides cleared?
Erythromycin and clarithromycin undergoes hepatic clearance
Azithromycin – is mainly eliminated unchanged in faeces
Which of the macrolides cause the most GI distress?
Erythromycin
Name 2 mechanisms via which bacteria may acquire macrolide resistance
ERM gene expression, efflux pumps
Which drug(s) can exhibit cross resistance with macrolides?
Clindamycin (if the microbes acquire resistance by expressing erm methylases)
Clindamycin is primarily used to treat _________ infections
anaerobic
Linezolid works by ___________
It binds the bacterial 23S ribosomal RNA of the 50S subunit and inhibits the formation of the initiation complex needed for protein synthesis.
How is clindamycin administered?
Oral / IV
Can clindamycin be used to treat MRSA?
Yes
Name an adverse effect associated with the use of clindamycin
Clostridium difficile associated diarrhoea
What is linezolid’s mechanism of action?
It binds the bacterial 23S ribosomal RNA of the 50S subunit and inhibits the formation of the initiation complex needed for protein synthesis.
Linezolid is effective against Gram _________ bacteria?
positive
Linezolid binds to bacterial _________ ribosomal RNA of 50S subunit
23S
Name 3 antibiotics that only covers Gram positives?
Vancomycin, penicillinase resistant penicillin, linezolid
How is linezolid administered?
Oral / IV
What does linezolid cover?
Many of the resistant Gram-positive strains such as MRSA, VRE, VRSA
Name at least 2 key adverse effects associated with prolonged use of linezolid
- Irreversible peripheral neuropathies
- Optic neuritis
- Bone marrow suppression
Linezolid can cause _________ if administered concomitantly with SSRI or MAO inhibitors?
serotonin syndrome
Can linezolid be used for the treatment of catheter-related bloodstream infections?
No, it is not approved. (Based on FDA recommendation)
Name 2 antibiotics that can be administered orally for MRSA
Linezolid and clindamycin
Which of the protein synthesis inhibitors are safe for use in pregnant women?
Macrolides, clindamycin
