Bact protein synthesis inhibitor 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
–> preventing protein synthesis
tRNA
Tetracyclines should not be administered with dairy products or substances that contain divalent and trivalent cations (antacids) 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
broad spectrum activity against many
- Gram-negative
- Gram-positive bacteria
- atypical bacteria
- spirochetes
EXCEPT Pseudomonas & proteus
How are tetracyclines cleared?
Tetracycline- renal
Doxycycline & minocycline - hepatic (hepatic dysfn req dose adjustments)
Which drug is used in community acq penumonia (eg H influ, S pneumoniae) & MRSA?
Doxycycline
How are tetracyclines administered?
Usually oral
IV only on special requests
Can tetracyclines be used in pregnancy?
No,
cross placenta
concentrate in places w high calcium content- fetal bone & dentition
How is glycylcycline (tigecycline) administered?
IV (poor bioavailability)
Glycylcycline (tigecycline) was designed to overcome which two mechanisms of tetracycline resistance?
- Expression of efflux pumps
- Ribosomal protection (higher affinity to ribosome not easy to get dislodged by proteins)
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
What’s tigecycline not effective against?
pseudomonas + proteus (same as tetracycline)
How is tigecycline cleared?
Hepatic clearance– dose reduction for severe hep dysfn
Since tigecycline can treat resistant microbes, would it be a good option in bacteremia?
No, as tigecycline penetrates tissues well. Poor option for bloodstream infections.
Name at least 4 adverse effects associated with the use of tetracyclines & glycylcycline (tigecycline).
- Gastrointestinal distress (To reduce ulceration, drink plenty of fluids and do not take it before sleep)
- Phototoxicity (Like fluoroquinolones)
- Superinfection like thrush (fungal more common, CDAD only on prolonged use)
- Deposition in bone/primary dentition and may cause discoloration of teeth
The use of tetracycline and tigecycline is contraindicated in which populations of patients?
- Pregnant women,
- Breastfeeding women
- Children less than 7/8 years of age
What’s the difference b/n tetracycline VS aminoglycosides?
Tetracycline- bacteriostatic
Aminoglycosides- bacteriocidal (concentration dependent killing w PAE)
MOA of aminoglycosides
block formation of initiation complex, cause codon misreading, inhibit translocation
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
How is the action of aminoglycosides inhibited?
anaerobic conditions/ drop in pH
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)
as BL reduce cell wall and increase penetrance of aminoglycosides
Name an aminoglycoside that is used in the management of tuberculosis
Streptomycin (administered IM)
How are aminoglycosides cleared?
Renally (dose adj required w renal imp)
Indications of aminoglycosides
- Empiric therapy as broad spectrum– once pathogen isolated, discontinued and change to definitive tx
- Aerobic gram neg eg. pseudomonas
- Second line against MDR TB mycobacteria
If patient has a CSF infection of xx, do you give aminoglycosides?
No, as [ ] in CSF inadequate even w inflamed meninges
How are aminoglycosides commonly administered?
Parenterally (They have poor oral bioavailability)
Name an aminoglycoside that is administered orally
Neomycin – Given oral for bowel prep for surgery
IV severe nephrotoxicity
(like vancomycin also poor oral bioav but given orally for CDAD)
Which aminoglycoside has the widest spectrum?
Amikacin – but generally ineffective against anaerobic gram +ve strains
Name at least 2 adverse effects associated with aminoglycosides
- **Ototoxicity
- **Nephrotoxicity
* * do not combine w eg. vancomycin/amph B/NSAIDS - Neuromuscular paralysis (Especially when used with neuromuscular blockers– contraind in MG)
What are the 6 “NOs” in relation to aminoglycosides?
- No to protein synthesis
- Particularly active against aerobic Gram-“N”negative “O”rganisms
- No to use during pregnancy & myasthenia gravis
- No to oral administration
- No to CSF penetration
- “N”ephro- and “O”to- toxicities
How can bacteria become resistant to aminoglycosides?
- efflux pump
- amgs inactv enzymes
- alter 30 S ribosome
- note so antibiotics don’t affect humans as 60S 40S
Name 3 types of 50S protein synthesis inhibitors
Macrolides, clindamycin, linezolid
Name 3 macrolides
Erythromycin, clarithromycin, azithromycin
Are macrolides bacteriostatic or bactericidal antibiotics?
Bacteriostatic
Which of the macrolides cause the most GI distress?
Erythromycin
:( as also inhibit CYP 450 hence DDI
How can macrolides be administered?
Oral and IV
Name some of the microbial infections that the macrolides are useful against
- common sub for penicillin allergy
- *Atypicals (Mycoplasma, chlamydia, legioella)
- *Community acquired penumonia (S.pneumoniae, H. influenzae and Moraxella catarrhalis)
- STDs caused by Chlamydia trachomatis and Neisseria gonorrhoea
- *H.pylori infections (clarithro> azithro)
How are macrolides cleared?
Erythromycin and clarithromycin undergoes hepatic clearance (contraind hepatic dysfn)
Azithromycin – is mainly eliminated unchanged in faeces
Name 2 adverse effects associated with macrolides.
- Gastric Distress
- Hepatotoxicity
- Ototoxicity
- May prolong QT interval (aware if pt pro-arrthy)
Which drugs are useful in pregnancy?
- Beta lactams (penicillins)
- Macrolides (erythromycin & azithromycin)
- Clindamycin
Name 2 mechanisms via which bacteria may acquire macrolide resistance
ERM gene expression, efflux pumps
erythromycin methylase- ribosomal methylation, reduced binding
Which drug(s) can exhibit cross resistance with macrolides?
Clindamycin (if the microbes acquire resistance by expressing **erm methylases)
*thus if resistant to macrolide don’t give clindamycin
BUT if pt macrolide resistance due to efflux pump, can give clindamycin
Clindamycin is primarily used to treat _________ infections
anaerobic
What shld not be given w clindamycin?
Macrolides– antagonistic effect
How is clindamycin administered?
Oral / IV
Name an adverse effect associated with the use of clindamycin
Clostridium difficile associated diarrhoea
**highest risk!! (cannot use for CDAD)
Can clindamycin be used to treat MRSA?
Yes
What drugs can be given for MRSA?
- 5th gen cephalosporin (ceftobiprole/ceftaroline) IV
- vancomycin IV
- tigecycline IV
- clindamycin oral
- linezolid oral
- doxycycline oral/(IV special req)
Name 2 antibiotics that can be administered orally for MRSA
Linezolid and clindamycin
Indications for clindamycin
- pencillin resistant *ANAEROBIC eg bacteroides (w cefotetan, cefoxitin), clostridium perfringen
= good oral formulations ** - Gram +ve *MRSA/strep
- EXCEPT aerobic gram -ve + CDAD
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.
Linezolid is effective against Gram _________ bacteria?
positive
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
EXCEPT gram -ve
** only use if alternatives exhausted – LAST LINE
How is linezolid excreted?
nonenzymatic oxidation to inactive metabolites– no need adj dose in renal imp
Name at least 2 key adverse effects associated with prolonged use of linezolid
- Irreversible peripheral neuropathies
- Optic neuritis (>28d dose)
- Bone marrow suppression (>10d)
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)
Linezolid resistance
mutation of 23S ribosome
