Antibacterial Agents 3: Protein Synthesis Inhibitors Flashcards
Macrolides Drug Types
Erythromycin, clathromycin, azithromycin
Macrolides MoA
Binding to 50S ribosome, blocking translocation of peptidyle RNA
Passive Diffusion
Bacteriostatic
Macrolide
Erythromycin
Absorption
Absorption varies depending on salt form
Estolate appears more bioavailable in children than ethyle succinate
Macrolides
Clarithromycin
Absorption
Can be taken without regards to food
Macrolides
Azithromycin
Absorption
Taken without food
Macrolides
Distribution
Wide distribution
except brain and CSF
Traverses placenta
Azi/Clathro= High tissue penentrance, low plasma levels
Macrolides
Erithromycin
Metabolism/Excretion
Liver and excreted in bile
Macrolides
Clarithromycin
Metabolism/excretion
Metabolized to active so renal excretion
Macrolides
Azithromycin
MEtabolism/Excretion
Not metabolized, high tissue penetrance
Gram Positive Cocci
Streptococci and pneumococci
Macrolide Atbx uses
All
Gram Negative Cocci
Moraxella catarrhalis
Macrolide Atbx use
All
Bordetella pertussis
Macrolide Atbx uses
All
Heamophillus influenzae
Macrolide Atbx use
Azithromycin, Clathrithromycin
Helicobacter pylori
Marolide Atbx Use
Clarithromycin with PPI or H2 antagonist
Legionella
Macrolide atbx uses
Azithromycin
Mycobacterium avium
Macrolide atbx use
Clarithromycin and Azithromycin
Chlamydia
Macrolide atbx use
Azithromycin
Mycoplasma pneumoniae
Macrolide atbx use
All
Macrolides
Adverse Efects
Direct stimulation of gut motility, increasing activity
with erithro
Hepatotoxic
Prolongs QT interval
E and C inhibits p450
Telithromycin
Erithromycin derivative
Use only for community-acquired pneumonia that is atbx resistant
Tetracyclines
Drugs
Tetracycline, Doxycycline, Minocycline
Tetracyclines
MoA
Bacteriostatic
Reversible binding to bacterial 30S ribo subunit
Resistance: Change influx, block binding
Tetracyclines
Absorption
Best without food
Milk, Al3+, Ca2+, Mg2+, and Fe2+ salts impair absorption
Doxy best absorped
Tetracycline
Destribution
Penetrant into most tissues, including fetus
variable protein binding
Tetracyclines
Metabolism/Excretion
Concentrated in liver, secreted by bile (care liver function pts)
Most into urine except Docy and Mino
Breast milk excretion
S. aureus
Tetracycline use
Doxy and tigecycline
Moraxella Catarrhalis
Tetracycline Use
Doxy
B. anthracis
Teracycline use
Doxy
H. influenzae
Tetracycline use
Doxy
H. pylori
Tetracycline use
Tetracycline
Vibrio cholera
Tetracycline use
Doxy
Propionobacterium acnes
Tetracycline use
Minocycline, doxycycline
Chlamydia
Tetracycline use
Doxy
Mycoplasma pneumoniae
Tetracycline use
Doxy
Richettsia
Tetracycline Use
Doxy
Borrelia burgdorferi
Tetracycline use
Doxy
Tetracyclines
Adverse reactions
Avoid use in latter half of pregnancy and <8yo
Contraindicaed with antacids/iron supplments as it decreases bioavailablity
Clindamycin
MoA
Inhibits protein synthesis by binding 50S ribosome
Bacteriostatic, cidal at high doses
Clinda
Pharmacokinetics
Oral ok
Penetrates well, especially bone, not into CSF
Excreted in breast milk, metab’d by liver
Clindamycin
Clinical use
Severe anaerobic infections
Streptococci, MSSA, MRSA, C. perfringens, B. fragilis
Clinda
Adverse reactions
Can cause pseudomembranous colitis
Aminoglycosides
Drugs
Streptomycin, tobramycin, gentamycin, amikacin, kanamycin, neomycin
Aminoglycosides
MoA
Bacterio static, cidal at high concentration
Not effective against anaerobes
Combines with 30S ribosome
Aminoglycosides
Absorption
Not Oral., best intramuscular
Aminoglycosides
Distribution
Lmited to extracellular fluid
Excluded from CNS (unless inflamed) and eye
Accumulates in renal cortex and inner ear
Aminoglycosides
Metabolism/excretion
Not metabolized, renal excretion
Post-antibiotic effect
Aminoglycoside
Spectrum
Gram negative bacilli
Gentamicin, tobramycin, amikacin
P. aeruginosa, , enterobacter, e. coli,
Can use neomycin topically or for bowel sterilization
Mycobacterium tuberculosis
Aminoglycosides
Streptomycin
Enterococci
Aminoglycoide uses
Gentamycin
Aminoglycosides
Toxicity
Very toxic
Eighth nerve damage
Chloramphenicol
MoA
Binds to 50S ribosome
Bacteriostatic
Also inhibits mitochondrial 70S
Cloramphenicol
Distrubution
Can readily enter CNS and CSF
Chloramphenicols
Metab and excre
In fetus and neonate, unable to conjugate the drug, so toxic
Excreted in breastmilk
Chloramphenicols
Adverse effects
Bone marrow toxixity (mitochondria)
Gray baby syndrome
Linezolid
MoA
Binds to 50S but on a different site so no cross resistance
Linezolids
Pharmacokinetics
Can be oral or IV
Readily distributed to tissue
Primarily metabolixed by nonenzymatic oxidation
Linezolid
Adverse reactions
Possible thrombocytopenia
Inhibits MAO (Monoamine oxidase)