Protein Synthesis Inhibitors Flashcards
Macrolides MOA
Inhibition of protein synthesis, binds 50S ribosomal subunit, selective toxicity - no binding to mamillian ribosome. Bacteriostatic
Macrolide Examples
Erythromycin
Clarithromycin
Azithromycin
Macrolide distribution
Wide, except for CNS. Crosses placenta
Erythromycin Metabolism/excretion
Liver, excreted in bile. Avoid in liver disease.
Excreted in breast milk - check infants for thrush
Clarithromycin metabolism/excretion
Renally eliminated, may require adjustment
Excreted in breast milk - check infants for thrush
Macrolide uses, gram + cocci
alternative in penicillin allergic patients
Streptococci (phayngitis), pneumococci (pneumonia)
Macrolide uses, gram - cocci
Moraxella catarrhalis (otitis media, community acquired pneumonia)
Macrolide uses, gram - bacilli
H. influenzae –> upper respiratory infections, bronchitis
Azithromycin and Clarithromycin are the best
Macrolide uses, atypicals
Chlmydia (trachoma, community acquired pneumonia, urethritis) -- Azithromycin Mycoplasma pneumoniae (community-acquired pneumonia)
Azythromycin Metabolism
NOT metabolized, high tissue penetration
Excreted in breast milk, check infant for thrush
Macrolide drug interactions
Erythromycin and clarithromycin are inhibitors of cytochrome p450
Macrolide heart ADR
prolongs the QT interval – caution with other QT-prolonging drugs
Tetracycline MOA
Inhibition of bacterial protein synthesis, binds 30S ribosome, selective toxicity due to human cell ability to efflux the drug. Bacteriostatic
Tetracycline Examples
Doxycycline
Minocycline
Tetracycline Absorption
Give on an empty stomach, impaired by milk products
Tetracycline distribution
Tissue and fluid penetration is excellent - including placental and fetal circulation
Tetracycline Metabolism/excretion
Concentrates in liver, use with caution in liver impairement.
Doxycycline is choice for those with renal disease
Doxycycline use, gram + cocci
Methicillin resistant staphylococcus aureus (skin infection, pneumonia)
Most organisms are resistant
Doxycycline use, gram - cocci
Moraxella catarrhalis (otitis media, CAP) Most organisms are resistant
Doxycycline uses, gram - baccili
Heamophilis Influenzae (otitis media, CAP) Helicobacter pylori (peptic ulcer disease)
Doxycycline use, atypicals
Chlamydia (trachoma, urethritis, CAP) Mycoplasma pneumoniae (CAP)
Tetracycline ADR
Teeth and bones! Avoid in later half of pregnancy and in children under 8 years old.
Photosensitivity
Yeast overgrowth
Tetracycline DDI
Antacids or iron supplements - decreases bioavailability by forming insoluble salts in the stomach
Clindamycin MOA
Inhibition of protein synthesis by binding to 50S ribosome
Bacteriostatic
Clindamycin Distribution
Penetrates most tissues well, ESPECIALLY BONE
NOT into CSF,
Clindamycin metabolism
Hepatic.
Excreted in breast milk
Clindamycin use, gram + cocci
Streptococci ( pneumonia, pharyngitis)
MSSA
MRSA
Clindamycin use, anaerobes
Bacteroides fragilis (abcesses)
Clindamycin ADR
Pseudomembranous colitis - allows Clostridium difficile to become overgrown
Aminoglycoside MOA
Inhibits protein synthesis initiation, is transported into bacteria, requiring O2 so NOT effective against anaerobes
Bactericidal, concentration dependent.
Aminoglycoside Examples
Tobramycin
Gentamycin
Aminoglycoside Absorption
Not absorbed orally, too polar.
IM or IV
Aminoglycoside distribution
Limited to ECF, excluded from the CNS and eye but inflammation increases its penetration
Accumulates in renal cortex and inner ear
Aminoglycoside metabolism/ecretion
Not metabolized, purely excreted by kidneys - renal dosing necessary
Aminoglycoside uses, gram negative
Pseudomonas aeruginosa
E. coli (UTI*)
Aminoglycoside ADR
Ototoxic
Renal toxic