Antibacterial Antibiotics Continued Flashcards
Antibacterial Agents
Interfere with protein synthesis by: Interaction with bacterial ribosomes Block initiation Inhibition of tRNA synthesis Multiple mechanisms leading to disruption of RNA processing
Direct binding to 50S substrate
Drug blocks binding of aminoacyl moeity of charged tRNA molecule to acceptor site of complex.
Drug prevents translocation of peptidyl tRNA from acceptor site to donor site on the 50S ribosomal subunit
Direct binding to 30S subunit
Drug blocks binding of amino acid charged tRNA to acceptor site of ribosomes mRNA complex
Drugs can block formation of initiation complex b/w ribosomes and mRNA, misread mRNA, block translocation of mRNA.
Protein synthesis inhibitor class may be “-static” or “-cidal” depending on?
Drug concentration
Site of infection
Infecting organism
ie. linezolid is -static for enterococi and staph but -cidal for strept
Aminoglycosides
Basic structure= aminocyclitol ring
Different side groups; different glycosidic linkages.
Aminoglycosides- 2 effects on bacterial cell resulting in death
Bind (-) charges in outer phospholipid membrane displacing cations that link phospholipids together resulting in disruption of wall and leakage of contents
Irreversibly disrupt protein synthesis by blocking initiation, misreading mRNA, blocking translocation.
Aminoglycosides gain access to the cell membrane how?
Via porin channels
Inhibited by acidic pH and anaerobic conditions
Enhanced by cell wall active ABX (synergism)
3 known mechanisms of resistance
Modification of aminoglycoside molecule by enzyme
Binding of aminoglycosides on rRNA altered
Reduced uptake of aminoglycosides.
To combat resistance use agents that target cell wall in conjunction w/ aminoglycosides.
Aminoglycosides- spectrum of activity
Active against aerobic gram-negative bacilli (klebsiella species, enterobacter, psudeomonas aeruginosa)
Little activity against anaerobes due to lack of stability
Tx- UTI, respiratory tract, skin and soft-tissue infections
Aminoglycosides- combination w/ other agents
To broaden coverage in serious illness (bacteremia or sepsis and psuedomonal infections)
For synergism w/ vancomycin or penicillins in the tx of endocarditis
Aminoglycosides- spectrum of activity
Exhibit concentration-dependent killing and have a pronounced post-antibiotic effect
Aminoglycosides- streptomycin
Useful in treating enterococcal infections
Aminoglycosides- gentamicin, tobramycin, amikacin
Most widely used Aminoglycosides.
Cross-resistance b/w these drugs
Aminoglycosides- Neomycin, kanamycin
Limited to oral or topical due to neprhotoxicity
Aminoglycosides-Spectinomycin
Structurally related to Aminoglycosides but lack amino sugars and glycosidic bonds. Used to tx for gonorrhea in PCN allergy patients.
Aminoglycosides- Adverse Effects
otoxicity- may be irreversible (sterptomycin is the most ototocix; not reported w/ genatamicin)
Nephrotoxicity- usually reversible
Aminoglycosides- Adverse Effects Neuromuscular blockage
Aggravate muscle weakness; respiratory paralysis in myasthenia gravis or Parkinson’s disease due to curare-like effect
Aminoglycosides- hypersensitivity
Hypersensitivity rxn not common (rash, fever, urticaria, angioneurotic, edema, eosinophilia)
Aminoglycosides- Rare reactions
Optic nerve dysfunction, peripheral neuritis, encephalopathy, pancytopeniam exfoliative, dermatitis, amblyopia
Aminoglycosides- Adverse Effects tobramycin
Bronchospam and hoarseness with inhalation solution
Aminoglycosides- streptomycin
Contains metabisulfits avoid in sulfite allergies.
Aminoglycosides Phamacokinetics
No oral absportion (parenteral administration)
Widley distributed in ECF
Insoluble in lipid
Poor distribution in bile, aqueous humor, bronchial secretions, sputum, CSF
Clearance is proportional to creatinine clearance.
Gentamicin Dosing Strategies
Once daily dosing- Recommended for most clinical situations. Exclusion of Gram (+) infections, CrCl<30 ml/min, CF, spinal cord infections and burn patients
Multiple daily dosing- smaller amounts more times a day
Aminoglycoside drug interactions
Increased nephrotoxicity w/ loop diuretics
Respiratory depression when given w/ non-depolarizing muscle relaxants
Neomycin effects digoxin levels