Tetracyclines Flashcards by India Auchey

Tetracyclines are bactericidal/bacteriostatic

bacteriostatic

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Tigecycline is bactericidal/bacteriostatic

bacteriostatic

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Tetracycline was developed from

oxytetracycline and chlrotetracycline

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Doxycycline and minocycline are ____ derivatives of oxytetracycline

semisynthetic

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____ and ____ are derived from minocycline

tigecycline; omadacycline

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Tigecycline is a

glycylcycline

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Tetracyclines include

tetracycline, doxycycline, minocycline, eravacycline, omadacycline, tigecycline

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Structure of tetracyclines

4 benzene rings with hydronaphthacene nucleus

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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

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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

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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

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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

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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

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All tetracycline don’t cover

p.aeruginosa

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All tetracyclines also cover

spirochetes and rickettsiae, mycobacteria and nocardia, parasites, bacillus anthracis, vibrio cholerae

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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

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Tetracycline no longer has ___ formulation due to ____

IV; hepatotoxicity

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Tetracycline should be ____ in renal impairment

AVOIDED

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Tetracycline can cause ____ impairment

hepatic

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Doxycycline comes in ____ formulations

IV and PO

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Doxycycline is ___ in renal impairment

SAFE

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Doxycycline has increased ___ excretion which allows it to have decreased serum accumulation and therefore safe for renal impairment

fecal

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Doxycycline ____ cause(s) hepatitis

does not

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Minocycline is available in

IV and PO formulations

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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?

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