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,, thereby inhibiting bacterial protein synthesis
tRNA
How is tetracycline administered?
Oral, best on empty stomach.
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
Can tetracyclines be used in pregnancy?
No. It is contraindicated as all tetracyclines cross the placental barrier and concentrate in fetal bones and dentition
Comment on tetracycline’s antimicrobial coverage
Bacteriostatic antibiotics (avoid administering with beta-lactams)
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?
A
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 ( bacteria produce protein that dislodge tetracycline from 30s ribosome)
What class of drug is tigecycline?
Glycylcycline
The use of tetracyline and tigecycline is contraindicated in which populations of patients?
- Pregnant women,
- Breastfeeding women
- Children less than 8 years of age
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
Not active against pseudomonas, proteus
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: sever sunburn ( avoid going in the sun)
- Superinfection like thrush
- Deposition in bone/primary dentition and may cause discoloration of teeth
- Superinfection: prolonged use may cause fungal or bacterial superinfection (CDAD)
Aminoglycosides are transported across the inner membrane of Gram-negative bacteria by ___________ , which is an energy dependent process. There, what do they do?
active transport; Aminoglycosides bind to the 30s subunit,distorting its structure and causing misreading of the mRNA
Aminoglycosides are particularly effective against _______ Gram-negative bacteria; what is it not effective against?
aerobic; anaerobic
Name 5 examples aminoglycosides
gentamicin, streptomycin, tobramycin, amikacin, neomycin
Aminoglycosides demonstrate synergism when combined with which class of antibiotics? Name one class. Why?
Beta lactams. to expand empiric spectrum of activity of the antimicrobial regimen to ensure the Prescence of at least one drug active against a suspected pathogen.
How are aminoglycosides commonly administered? Any exceptions?
Parenterally (They have poor oral bioavailability) EXCEPT FOR Neomycin which is given orally due to severe nephrotoxicity if given parenterally.
Name an aminoglycoside that is used in the management of tuberculosis
Streptomycin (administered IM)
How are aminoglycosides cleared?
Renally. Dose adjustment is needed with renal impairment
Name at least 3 adverse effects associated with aminoglycosides
- Ototoxicity
- Nephrotoxicity (Do not combine with other nephrotoxicity)
- Neuromuscular paralysis (Especially when used with neuromuscular blockers)
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
How do bacteria develop resistance to aminoclycosides
- Increased efflux pumps can reduce effective intracellular concentration
- inhibition of the aminoglycoside uptake
- Production of aminoglycoside inactivating enzymes by Gram Negative Bacteria
- 30S subunit alteration
Name 3 macrolides
Erythromycin, clarithromycin, azithromycin
Are macrolides bacteriostatic or bactericidal antibiotics?
Bacteriostatic
What are erythromycin an alternative for?
Penicillin; can use din patient with penicillin allergy
Why are Azithromycin and Clarithromycin a better option than Erythromycin?
Compared to erythromycin, clarithromycin and azithromycin has improve acid stability, tissue penetration and broaden spectrum of activity.
Azithromycin has less DDI (less inhibitory effect on CYP450 enzyme)
How can macrolides be administered? High or low CNS penetration>
Oral and IV. Poor CNS penetration
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 feces.
Which of the macrolides cause the most GI distress?
Erythromycin
Can macrolides be used in pregnancy?
Yes ; they are widely used for a variety of bacterial infection in pregnancy
Name 2 mechanisms via which bacteria may acquire macrolide resistance
ERM (erythromycin resistance methylase gene) gene expression, efflux pumps
Which drug(s) can exhibit cross resistance with macrolides?
Clindamycin (if the microbes acquire resistance by expressing erm methylases) DONT GIVE THESE TWO ANTIBIOTIC TGT
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
What are the clinical indication for clindamycin?
MRSA and streptococcus and penicillin resistance anaerobic bacteria
Name an adverse effect associated with the use of clindamycin
Clostridium difficile associated diarrhoea; CI in pts with pseudomembranous colitis or ulcerative colitis
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
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 (Methicillin-resistant Staphylococcus aureus), VRE (vancomycin-resistant Enterococci), VRSA (Vancomycin resistant Staphylococcus aureus)
Name at least 4 key adverse effects associated with prolonged use of linezolid
- Irreversible peripheral neuropathies
- Optic neuritis
- Bone marrow suppression
- Most common: GI effects: nausea, headache, diarrhea
Linezolid can cause _________ if administered concomitantly with SSRI or MAO inhibitors? What food to avoid?
serotonin syndrome as it inhibits Monoamine inhibitory activity. Avoid Tyramine-containing and histamine rich food.
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
Which antibiotics are bactericidal and bacteriostatic?
Bactericidal: aminoglycoside
Bacteriostatic: tetracycline, macrolides
Which antibiotic targets aerobic? What about anaerobic?
Aerobic: aminoglycoside
Anaerobic: clindamycin
