protein synthesis inhibitors Flashcards
T or F
- tetracycline/glycylcyclines have bacteriostatic effect
True
T or F
- aminofgycosides are bacteriocidal
True
- group of antibiotics represented by naturally occurring streptomycin, gentamicin, tobramycin, neomycin and semisynthetic analogues amikacin and netilimicin
aminoglycosides
- structure of aminoglycosides
- amino sugars glycosidically linked to core aminocyclitol
- aminoglycosides w the broadest spectrum of coverage due to 2-hydroxy-4-amino butyl group resisting deactivating enzymes
- amikacin
- strong bases
- hydrophilic
- excist as polycations at physiological pH and poorly absorbed orally
- incompatible when mixed w beta lactams
aminoglyosides
aminoglycosides nomenclature:
- Streptomyces ending in ‘mycin’
- streptomycin
- tobramycin
- neomycin
aminoglycosides nomenclature:
- micromonospora ending in ‘micin’
- gentamicin
- netilmicin
3 main effects of aminoglycosides
- interference w initiation (ribosome is fixed to mRNA AUG start codon)
- premature termination (error recognition of mRNA misreads)
- incorporation of incorrect aa into proteins
aminoglycosides blocked by….
- low oxygen, low pH, elevated Ca or Mg, or an increase in osmolarity
- mostly active against aerobic gram neg bacilli
- not useful for anaerobes and poor activity against atypicals
aminioglycosides
gentamicin antibiotic map
- all of these are gram negs
- Proteus mirabilis
- E.coli
- klebsiella pneumonia
- serratia
- enterbacter spp
- psuedomonas
ADME of aminiglycosides
- poor oral bioavailability must be given IV or IM, some nebulizer forms such as tobra for CF
- distribute primarily in plasma and tissue interstitial fluid space
- poor distribution to human cells besides renal
- low CSF penetration
- don’t use in pregnant patients
- excreted primarily renally and metabolism is minimal
- monitor blood levels and half life is approx. 2-3 hrs
adverse rxn to aminoglycosides
- serious side ffets so limit use to important infections
- ototoxicity
- nephrotoxicity (usually reversible)
- neuromuscular paralysis (rare) but don’t use w succinyl choline
natural occurring tetracyclines
- tetracyclines
- chlorteteracycline
semisynthetic tetracyclines
- doxycycline
- minocycline
which generation of tetracyclines is this?
- unstable in acidic enviorments
- undergo 2 diff rxn:
1. acid promotes epimerization
2. acid induced dehydration w the loss of C6-OH group results in anhydritetracycline (nephrotoxic)
1st gen
which generation of tetracyclines is this?
- do not have C6-OH group and thus more stable at acidic pH
- food containing divalent and trivalent metal ions (Ca, Mg, Al) interact w tetracycline and forms insoluble complexes
- this causes poor absorption of ions and tetracyclines and causes tooth staining in kids
2nd gen
MOA of tetracyclines
- enter bacterial cells via passive diffusion though porins and by active transport across inner membrane
- bind to 30S subunit of bacterial ribosome and inhibit protein synthesis by preventing access of aminoacyl tRNA to the acceptor site of the mRNA ribosome complex
- broad spectrum antibiotics
- active against gram pos including MRSA aswell as gram neg excluding Psuedomonas, although typically not used for Enterococus, Psuedomonas, or UTI (E.coli)
- can be useful against atypicals such as Rickettsia, Mycoplasma pneumonia, chlamydia, spirochetes(lyme disease/syphillus), vibrio cholera, anthrax, leprosy
tetracyclines
ADME of tetracyclines
- GI absorption varies but oral absorption is impaired by ingestion of divalent and trivalent cations
diff in tetracyclines and minoyclines
- tetracyclines eliminated primarily unchanged in urine
- minocycline undergoes hepatic metabolism
- doxycycline preferred in renally compromised bc eliminated via bile
- tetracycline half life is 6-12 hrs
- minocycline is 16-20 hours
adverse effects of tetracyclines
- GI discomfort
- dermatologic issues such as pigment changes and photosensitivity
- bony structures and teeth issues
- renal toxicity
- don’t use in pregnancy
- semisynthetic analog of minocycline
- IV infused
- highly hydrophobic
- broad spectrum coverage and sensitive to tetracycline resistant strains due to C9 glycoamidio side chain
- ## inhibits protein synthesis by binding 30S subunit
glycylcycline (Tigecycline)
when are glycylcyclines (Tigecycline) indicated
- only in complicated SSTI and serious intra-abdominal infections
antibiotic map coverage of Tigecycline
- all but psuedomonas
ADME and Pk of tigecycline
- IV route
- large Vd
extensively distributed in the body - eliminated mainly via bile into feces
- dose adjust for HEPATIC diseases
adverse effects of tigecyline
- Black box warning to reserve for serious conditions due to higher mortality risk
- discoloration of teeth don’t use in pregnancy or children
