Antibiotics-Protein Synthesis Inhibitors Flashcards
Gentamicin
- Aminoglycosides – IM or IV administration (not well distributed but high concentrations in inner ear and renal cortex)
- Bind irreversibly to the 30S ribosomal subunit and inhibit protein synthesis (blocks initiation and translation, elicits termination, and incorporates incorrect amino acids) – concentration dependent killing with significant PAE
- Resistance is very slow to develop (poor drug uptake)
Ototoxicity (tinnitus, irreversible hearing loss), vestibular toxicity, and renal toxicity (reversible)
*BACTERICIDAL – mostly severe Gram – aerobic bacilli (Pseudomonas) – combine with penicillin or vancomycin (synergistic) for Staph aureus and S. epidermidis – topical for burns, wounds, and skin lesions
Spectinomycin
- Aminocyclitol – IM, rapid absorption
- Binds 30S ribosomal subunit, bacteriostatic (no misreading of mRNA)
- Mostly Gram- but also many Gram+ (used against MRSA, enterococci, and antibiotic resistant gonorrhea (MAIN USE))
Tigecycline
- Glycylglycine – IV ONLY
- Binds with higher affinity to 30S ribosome – blocks aminoacyl tRNAs from enter the A site of the ribosome
- Effective against strains that are tetracycline resistant and MRSA – skin and intra-abdominal infections
Tetracycline
- Tetracyclines (less oral absorption)
- Reversible binding to 30S subunit – block aminoacyl tRNAs from entering the A site of the ribosome, wide distribution (liver, spleen, bone, teeth, CNS, placenta)
- Causes superinfections, GI irritation (pseudomembranous colitis), hepatotoxicity, renal toxicity, vestibular disturbances, discoloration of teeth (fetus and kids) – DON’T give to pregnant women or children < 8
- Very broad (more active against gram+ than gram-), bacteriostatic – Acne, drug of choice for rickettsial diseases (Chlamydia, Mycoplasma, pneumonia, Borrelia)
Doxycycline
Minocycline
- Tetracyclines (less resistance than tetracycline and increased oral absorption)
- Reversible binding to 30S subunit – block aminoacyl tRNAs from entering the A site of the ribosome, wide distribution (liver, spleen, bone, teeth, CNS, placenta)
- Causes superinfections, GI irritation (pseudomembranous colitis), photosensitivity (doxy) hepatotoxicity, renal toxicity, vestibular disturbances, discoloration of teeth (fetus and kids) - DON’T give to pregnant women or children < 8
- Very broad (more active against gram+ than gram-), bacteriostatic – Acne, drug of choice for rickettsial diseases (Chlamydia, Mycoplasma, pneumonia, Borrelia)
Azithromycin
Clarithromycin
*Macrolides – acid stable – wide distribution (crosses placenta)
*Bind reversibly to 50S subunit – block tRNA/peptide movement from A to P site – competitively inhibit ribosome binding of streptogramins, clindamycin, and chloramphenicol
*C: metabolized by liver, secreted in kidney
*Bacteriostatic (dosing and pH considerations – can be bactericidal)
Narrow spectrum (more gram+), effective against anaerobes – use as alternative to penicillins – respiratory infections from atypical microbes, acne
Erythromycin
- Macrolides – unstable in acid so given as salt, ester, or enteric coated tablet – wide distribution (crosses placenta)
- Bind reversibly to 50S subunit – block tRNA/peptide movement from A to P site – competitively inhibit ribosome binding of streptogramins, clindamycin, and chloramphenicol
- Excreted in bile (so okay in renal disease)
Oral – GI disturbances, hepatotoxicity (cholestatic hepatitis with estolate, reversible) *Bacteriostatic (dosing and pH considerations – can be bactericidal) Narrow spectrum (more gram+), penetrates into abscesses – use as alternative to penicillins – respiratory infections from atypical microbes, acne
Telithromycin
- Macrolide – semi synthetic derivative of erythromycin – oral administration (unaffected by food)
- Increased acid stability, increased affinity for 50S subunit, reduced induction of resistance – binds 50S ribosome at 2 sites and blocks protein synthesis
No cross reactivity via methylase expression – S. aureus and S. pyogenes with MLSbR are resistant
*Hepatic metabolism, hepatic and renal elimination (reduce dose for renal insufficiency)
Diarrhea, nausea, abdominal pain, visual effects (blurred vision), liver damage/failure
Exacerbation of disease symptoms in myasthenia gravis patients (DON’T USE)
*Concentration-dependent bactericidal activity against susceptible S. pneumoniae (otherwise bacteriostatic) – H. influenza, M. catarrhalis, S. aureus – community acquired RTIs (pneumonia), sinusitis, bronchitis
Clindamycin
*Lincomycins – oral or parenteral (wide distribution including bone but not CNS)
*Binds exclusively to 50S subunit of bacterial ribosomes (X-resistance is an issue) – bacteriostatic
Resistance is slow due to ribosomal methylase that modifies the target (doesn’t induce methylase expression in microbes)
*Impaired in patients with hepatic failure
Diarrhea, pseudomembranous colitis (C. dificile), skin rash, Stevens-Johnson syndrome, anaphylaxis
*Most gram+ are susceptible, better than macrolides against anaerobes (B. fragilis), not aerobic gram- → drug of choice for respiratory tract infections, abscess, severe GroupA strep, MRSA, sin and soft tissue infections, osteomyelitis
Quinupristin: 30
Dalfopristin: 70
- Streptogramins – IV admin
- Q: Binds the 50s subunit
D: Binds nearby and synergistically enhances binding of Q
*Pain and phlebitis at IV site, deregulation of levels of drugs metabolized by CYPs
Resistance: methylases (so no MLSbR), lactonases, acetyltransferases, increased efflux
*Bactericidal combined (static alone) – MRSA, serious vancomycin resistant gram+ infections (VRE, VRSA, Strep pneumonia)
Chloramphenicol
- Other – oral, parenteral, or topical (wide distribution – CNS and placenta)
- Bind novel site in 23S ribosomal RNA of the 50S subunit – no cross resistance with other protein synthesis inhibitors
- Resistance primarily due to acetyltransferases that modify the drug
Hematological toxicities, aplastic anemia, gray baby syndrome (vomiting, cyanosis, loose green stools, flaccid, hypothermic, death)
*Bacteriostatic (cidal in HIB and Neisseria) – broad spectrum, inhibits most anaerobics and gram- bacilli – only very severe infections normally treated with tetracycline, VRE
Linezolid
- Oxazolidinones – oral, 100% bioavailability
- Bind novel site in 23S ribosomal RNA of the 50S subunit – no cross resistance with other protein synthesis inhibitors
- Bacteriostatic (cidal against S. pneumonia) – used for serious infections (MRSA, multidrug resistant S. pneumonia, VRE)
Mupirocin
- Other – topical use only
- Inhibits isoleucyl tRNA synthetase – rapidly metabolized to inactive form
- Resistance is rare
- Impetigo caused by MRSA or Group A strep
