Tetracyclines Flashcards
Tetracyclines are bactericidal/bacteriostatic
bacteriostatic
Tigecycline is bactericidal/bacteriostatic
bacteriostatic
Tetracycline was developed from
oxytetracycline and chlrotetracycline
Doxycycline and minocycline are ____ derivatives of oxytetracycline
semisynthetic
____ and ____ are derived from minocycline
tigecycline; omadacycline
Tigecycline is a
glycylcycline
Tetracyclines include
tetracycline, doxycycline, minocycline, eravacycline, omadacycline, tigecycline
Structure of tetracyclines
4 benzene rings with hydronaphthacene nucleus
Doxycycline spectrum coverage
dark purple: s. pneumoniae, MSSA, MRSA
light purple: streptococcus, viridans
dark red: Neisseria, h. influenzae, klebsiella, mycoplasma, chlamydia, legionella
light red: b. pertussis, E. coli, enterobacter , citrobacter, serratia, acinetobacter
Minocycline spectrum coverage
dark purple: s. pneumoniae, MSSA, MRSA
light purple: streptococcus, viridans
dark red: Neisseria, h. influenzae, E. coli, klebsiella, serratia, acinetobacter, fusobacteria,clostridium, mycoplasma, chlamydia, legionella
light red: b. pertussis, enterobacter, citrobacter
Tigecycline spectrum coverage
dark purple: all gram + (strep, staph, enterococci)
dark red: Neisseria, h. influenzae, E. coli, klebsiella, enterobacter, citrobacter, serratia, acinetobacter, bacteroides, prevotella, fusobacteria, clostridium, mycoplasma, chlamydia, legionella
light red: b. pertussis
other: CRE, CRAB, ESBL, and VRE
Eravacycline spectrum coverage
dark purple: all gram + (strep, staph, enterococci)
dark red: Neisseria, h. influenzae, E. coli, klebsiella, enterobacter, citrobacter, serratia, acinetobacter, bacteroides, prevotella, fusobacteria, clostridium, mycoplasma, chlamydia, legionella
light red: b. pertussis, p. mirabilis, morganella
other: CRE, CRAB, ESBL, VRE
Omadacycline spectrum coverage
Same as tigecycline
dark purple: all gram + (strep, staph, enterococci)
dark red: Neisseria, h. influenzae, E. coli, klebsiella, enterobacter, citrobacter, serratia, acinetobacter, bacteroides, prevotella, fusobacteria, clostridium, mycoplasma, chlamydia, legionella
light red: b. pertussis
other: CRE, CRAB, ESBL, and VRE
All tetracycline don’t cover
p.aeruginosa
All tetracyclines also cover
spirochetes and rickettsiae, mycobacteria and nocardia, parasites, bacillus anthracis, vibrio cholerae
Tetracyclines MOA
Entry:
gram +: through the inner cytoplasmic membrane via an active transport system that depends on pH differential
gram-: become charged and enter through porin channels (OmpF and OmpC)
inhibits bacterial protein synthesis
binds reversibly to 30s ribosomal unit; inhibits the enzyme binding of aminoacyl-tRNA to the ribosomal acceptor site which prevents peptide elongation and protein synthesis
Tetracycline no longer has ___ formulation due to ____
IV; hepatotoxicity
Tetracycline should be ____ in renal impairment
AVOIDED
Tetracycline can cause ____ impairment
hepatic
Doxycycline comes in ____ formulations
IV and PO
Doxycycline is ___ in renal impairment
SAFE
Doxycycline has increased ___ excretion which allows it to have decreased serum accumulation and therefore safe for renal impairment
fecal
Doxycycline ____ cause(s) hepatitis
does not
Minocycline is available in
IV and PO formulations
Minocycline has ___ in hepatic impairment
no effect
Minimal amount of minocycine is excreted ___
renally
Tetracycline PO availability
77-88%
Tetracycline 1/2 life
7 hours
Doxycycline PO availability
100%
Doxycycline 1/2 life
12-16 hours
Minocycline PO availability
90%
Minocycline 1/2 life
16 hours
Tigecycline 1/2 life
37-67 hours
Eravacycline 1/2 life
20 hours
Omadacycline PO availability
35%
Omadacycline 1/2 life
16 hours
Protein binding for tetracycline
eravacycline> tigecycline> doxycycline> minocycline> tetracycline> omadacycline
Renal elimination for tetracycline
tetracycline> doxycycline> eravacycline> tigecycline> minocycline> omadacycline
Fecal elimination for tetracycline
doxycycline> omadacycline> tigecycline> eravacycline> tetracycline> minocycline
Tissue distribution for tetracycline
wide distribution except CSF, doxycycline is still used in some CNS infections
Tetracyclines indications
respiratory GI genitourunary spirochetal malaria treatment and chemiprophylaxis other: acne, bioterrorism
Tetracyclines adverse effects
GI: nausea, vomiting, diarrhea, heartburn, epigastric pain
pill esophagitis with doxycycline (patients should drink 8 oz of water and stand upright for 30 min)
reduced risk of c. diff
photosensitivity and hyperpigmentation: blue/black discolorations where scars or inflammation, muddy/brown discoloration on sun-exposed area; USE SUNSCREEN AND PROTECTIVE CLOTHING WHEN EXPOSED TO SUN
blue/black discoloration of gums secondary to bone pigmentation that is visible through non-pigmented oral mucosa occurs with long term use of minocycline and is permanent
nephotoxicity if impaired renal function
neurotoxicity with minocycline causing vertigo, dizziness, tinnitus, lack of concentration (reversible), vestibular effects higher in women
psuedotumor cerebri
Tetracyclines are generally ___ in pregnancy
avoided
Tetracyclines can cross the placenta, found in fetal tissues, and can have ____ effects on the developing fetus
toxic
___ has been noted in animals treated early in pregnancy
embryotoxicity
Tetracycline should be taken with/without food
without; can reduce absorption by 50%
Doxycycline and minocycline should/should no be taken with food
food doesn’t not have effect that is clinically significant
divalent and trivalent cations: Al, Ca, Mg, Fe, Zn interaction with tetracyclines
significant reduction of all tetracycline absorption
should not be administered concurrently
give tetracycline 1-2 hours before or 2 hours after divalent/trivalent cations
Interaction of doxycycline with carbamazepine, phenytoin, barbiturates
decreased 1/2 life by 44-52%; increases hepatic metabolism, monitor for decreased therapeutic effect. avoid using at the same Time.
oral anticoagulants with tetracyclines
increased risk of bleeding; tetracyclines impair utilization of prothrombin and decrease vit K production by intestinal bacteria
Tigecycline decreases warfarin ___
clearance
Oral contraceptives with tetracyclines
reduced levels when administered with tetracyclines; women should use additional form of birth control
reduction in bacterial hydrolysis of conjugated estrogen in intestine
Tetracycline should be taken____. Doxycycline and minocycline should be taken ____.
on an empty stomach; with/without food
Directions for taking tetracyclines (mostly doxycycline)
take with full 8 oz of water and stand up for at leaSt 30 min to reduce risk of esophageal irritation and ulceration
Wear___ to prevent sunburn
sunscreen
tigecycline is a ___ derivative of minocycline
semisynthetic
the 9-glycyl substitution results in ___ which enables tigecycline to overcome 2 major types of resistance:
steric hindrance; tetracycline-specific efflux pumps and ribosomal protection
Tigecycline spectrum coverage
no coverage against p. aeruginosa
reduced activity against proteus mirabilis, Providencia, morganella (over expressed multi drug efflux pumps)
Tigecycline adverse effects
GI: nausea and vomiting dose related
transient elevations in transaminases and alkaline phosphatase levels
Tigecycline does/does not need renal adjustment
does not
Tigecycline has ___ protein binding
increased
Can tigecycline be used in bacteremia?
no
Tigecycline primary route of elimination
liver via biliary excretion
Tigecycline indications
CA pneumonia
complicated intra-ab infections
complicated skin and skin structure infections
should only be used when other treatment is not available
Tigecycline mechanism of resistance
tet genes mediate resistance (plasmids and transposons) efflux pumps (gram+ and gram -) ribosomal protection proteins enzymatic degradation decreased drug permeability target mutations
Omadacycline was approved in
2018
Omadacycline indication
Community acquired bacterial pneumonia or acute bacterial skin and skin structure infections
Omadacycline is available in
PO and IV
Omadacycline adverse effects
trasaminitis, hypertension, insomnia, GI upset
Eravacycline approved in
2018
Eravacycline indications
intra-ab infections
Eravacycline need adjustment for severe ____ impairment
hepatic
If eravacycline is used with a strong CYP 3A inducer:
need to increase the dose to 1/5mg/kg q12h
Eravacycline adverse efffects
infusion related reactions, nausea, vomiting, diarrhea, hypotension, wound dehiscence
Eravacycline is not indicated for treatment of complicated urinary tract infections because it
did not show statistical non-inferiority to ertapenem for treatment of complicated UTI