Flashcards in Micro - Antimicrobials (Antimicrobials inhibiting Protein Synthesis) Deck (38):
How do protein synthesis inhibitors affect bacteria and spare humans?
Specifically target smaller bacterial ribosome (70S, made of 30S and 50S subunits), leaving human ribosome (80S) unaffected
Which antimicrobials affecting protein synthesis are 30S versus 50S inhibitors?
30S inhibitors: A = Aminoglycosides [bactericidal], T = Tetracyclines [bacteriostatic]; 50S inhibitors: C = Chloramphenicol, Clindamycin [bacteriostatic}, E = Erythromycin (macrolides) [bacteriostatic], L = Linezolid [variable]; Think: "Buy AT 30, CCEL (sell) at 50"
Again, what are the 30S inhibitors? Which are bacteriostatic versus bactericidal?
Aminoglycosides (bacteriocidal), Tetracyclines (bacteriostatic)
Again, what are the 50S inhibitors? Which are bacteriostatic versus bactericidal?
Chloramphenicol [bacteriostatic], Clindamycin [bacteriostatic], Erythromycin (macrolides) [bacteriostatic], Linezolid [variable]
What are 5 examples of aminoglycosides?
(1) Gentamicin (2) Neomycin (3) Amikacin (4) Tobramycin (5) Streptomycin; Think: "'Mean' (aMINoglycoside) GNATS caNNOT kill anaerobes"
Are aminoglycosides bacteriostatic or bactericidal? What is their specific mechanism?
Bactericidal; Inhibit formation of initiation complex and cause misreading of mRNA. Also block translocation; Think: "A initiates the Alphabet"
What do aminoglycosides require for uptake, and what is a clinical implication/consequence of this?
Require O2 for uptake; therefore ineffective against anaerobes
What is the coverage/clinical use of aminoglycosides?
Severe gram-negative rod infections
With what other type of antimicrobials are aminoglycosides synergistic?
Synergistic with Beta-lactam antibiotics
Which aminoglycoside is used for bowel surgery?
Neomycin for bowel surgeryh
What are 4 toxicities to associate with aminoglycosides?
(1) Nephrotoxicity (especially when used with cephalosphorins) (2) Neuromuscular blockade (3) Ototoxicity (especially when used with loop diuretics) (4) Teratogen; Think: "'Mean' (aMINoglycoside) GNATS caNNOT kill anaerobes"
Using aminoglycosides along with what other antimicrobials makes them especially nephrotoxic?
Nephrotoxicity (especially when used with cephalosporins)
Using aminoglycosides along with what other drug class makes them especially ototoxic?
Ototoxicity (especially when used with loop diuretics)
What is the mechanism of resistance against aminoglycosides?
Bacterial transferase enzymes inactivate the drug by acetylation, phosphorylation, or adenylation
What are 3 examples of tetracyclines?
(1) Tetracycline (2) Doxycycline (3) Minocycline
Are tetracyclines bacteriostatic or bactericidal? What is their specific mechanism?
Bacteriostatic; Bind to 30S and prevent attachment of aminoacyl-tRNA
What part of the body has limited penetration of tetracyclines?
Limited CNS penetration
In what particular patient population can tetracycline be used, and why?
Doxycycline is fecally eliminated and can be used in patients with renal failure
What are 3 things that you should not take with tetracyclines, and why?
Do not take with milk (Ca2+), antacids (Ca2+ or Mg2+), or iron-containing preparations because divalent cations inhibit its absorption in the gut
What is the bacterial coverage of tetracyclines? For what medical condition are tetracyclines also used?
Borrelia burgdorferi, M. pneumoniae. Drug's ability to accumulate intracellularly makes it very effective against Rickettsia and Chlamydia. Also used to treat acne.
What are 4 toxicities associated with tetracylines?
(1) GI distress (2) Discoloration of teeth in children (3) Inhibition of bone growth in children (4) Photosensitivity
In what medical condition/patient population are tetracyclines contraindicated?
Contraindicated in pregnancy
What is the mechanism of resistance against tetracyclines?
Decreased uptake or increased efflux out of bacterial cells by plasmid-encoded transport pumps
What are 3 examples of macrolides?
(1) Azithromycin (2) Clarithromycin (3) Erythromycin
What is the specific mechanism of macrolides? Are they bacteriostatic or bactericidal?
Inhibit protein synthesis by blocking translocation ("macroSLIDES"); bind to the 23S rRNA of the 50S ribosomal subunit. Bacteriostatic
What is the coverage/clinical use of Macrolides?
Atypical pneumonias (Mycoplasma, Chlamydia, Legionella), STDs (for Chlamydia), and gram-positive cocci (streptococcal infections in patients allergic to penicillin)
What are 5 toxicities to associated with macrolides?
MACRO: Gastrointestinal Motility issues, Arrhythmia caused by prolonged QT, acute Cholestatic hepatitis, Rash, eOsinophlia
What 2 substances increase in serum concentration upon macrolide use?
Increases serum concentration of the theophyllines, oral anticoagulants
What is the mechanism of resistance against macrolides?
Methylation of 23 rRNA-binding site prevents binding of drug
What is the specific mechanism of chloramphenicol? Is it bacteriostatic or bactericidal?
Blocks peptidyltransferase at 50S ribosomal subunit; Bacteriostatic
What are clinical uses for chloramphenicol?
Meningitis (Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae) and Rocky Mountain spotted fever (Rickettsia rickettsii)
What are the limitations of chloramphenicol? Where is it used, and why?
Limited use owing to toxicities but often still used in developing countries because of low cost.
What are 3 toxicities associated with chloramphenicol? What are details to remember about each of these?
(1) Anemia (dose dependent) (2) Aplastic anemia (dose independent) (3) Gray baby syndrome (in premature infants because they lack liver UDP-glucuronyl transferase)
What is the mechanism of resistance against chloramphenicol?
Plasmid-encoded acetyltransferase inactivates the drug
What is the specific mechanism of clindamycin? Is it bacteriostatic or bactericidal?
Blocks peptide transfer (translocation) at 50S ribosomal subunit. Bacteriostatic.
What is the clinical use/coverage of clindamycin?
Anaerobic infections (e.g., Bacteroides spp., Clostridium perfringens) in aspiration pneumonia, lung abscesses, and oral infections. Also effective against invasive Group A streptococcal (GAS) infection.
Compare/Contrast clindamycin and metronidazole in terms of clinical use/coverage.
Clindamycin treats anaerobes above the diaphragm vs. metronidazole (anaerobic infections below diaphragm)