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ID: protein synthesis inhibitors Flashcards

1
Q

Jarish-Herxheimer rxn

A

is a transient clinical phenomenon that occurs in patients infected by spirochetes who undergo antibiotic treatment. The reaction occurs within 24 hours of antibiotic treatment of spirochete infections, including syphilis, leptospirosis, Lyme disease, and relapsing fever.

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2
Q

which is Quinupristin/Dalfopristin effective against:

  • E. Faecalis
  • E. Faecium
A

E. Faecium

**VRE

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3
Q

Aminoglycosides (5)

-list them

A

Amikacin

Gentamycin

Neomycin

Streptomycin

Tobramycin

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4
Q

resistance to tetracyclines?

A

develops by decreasing accumulation of the drug rather than altering chemical structure
**use of efflux pumps–>decreasing influx

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5
Q

Clindamycin

  • MOA
  • spectrum
  • cidal or static?
  • resistance?
  • indication
  • kinetics (abs, penetration, met, drug-drug, pregnancy/BF?)
  • adv rxn
A

MOA: binds to the 50S subunit–inhib protein synthesis–can potentiate phagocytosis of bacteria by opsonization
*similar to macrolides

  • Bacteriostatic
  • Bacteriocidal against some staph (toxin prod staph and MRSA), strep, anaerobes

Spectrum: NOT effective for most gram(-)s

  • *has post-antibiotic effect
  • *used for Gram+ infections–MRSA, streotococcus, anaerobes

-resistance is similar to Erythromycin

Kincetics:

  • abs: good after PO
  • Penetrates well into bone, poorly into CNS
  • metabolized by CYP3A4
  • Rifampin reduces levels of clinda

OK with pregnancy and BF

SE:

  • PO use is limited due to diarrhea
  • –diarrhea is possible up to 20%: Possible C. Diff/pseudomembranous colitis
  • skin rash
  • caution with neuromuscular blocking agents
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6
Q

which macrolides are ok to use in pregnancy

-which not ok?

A

Erythromycin
Azithromycin

Clarithromycin– cat C

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7
Q

Fidamoxin
-drug class

  • moa
  • Spectrum
  • Abs
A

considered macrolide

MOA: termintes protein synthesis and causes cel death

narrow spectrum: gram+ aerobes and anaerobes

NOT well abs…..so IND is C. Diff

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8
Q

list the abx that MOA target 50S subunit

A 
Macrolides 
Clindamycin 
Linezolid 
Chloramphenicol 
Streptogramins
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9
Q

Doxycyline
DOC for?
abs?
advantages compared to the other tetracyclines

A
  1. Chlamydia spp
  2. Mycoplasma pneumoniae
  3. Lyme Dz ****
  4. rocky mt spotted fever
  5. vibrio cholerae

Abs:
*ok with or w/o food

advantages

  1. twice daily dosing
  2. IV, Po and ok to take with food
  3. less likely to cause photosensitivity
  4. onlny tretracycline to be used in kids <8 because it does not bind to Ca as well
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10
Q

Streptomycin indications

A
  1. M. TB–active
  2. Plague
  3. Tularemia
  4. Brucellosis
  5. endocarditis
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11
Q

do aminoglycosides cross placenta?

A

YES

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12
Q

Clarithromycin

-which pathogens

A 
Legionella 
Moraxella 
H. Pylori 
Ureaplasma 
Mycoplasma pneumoniae **** FIRST LINE
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13
Q

erythromycin

-abs

A

poor abs after PO bc it is destroyed by stomach acid

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14
Q

MOA for macrolides

A

Bind irreversible to the 50S unit

  • -inhib protein synthesis
  • bacteriostatic BUT high doses=bactericidal

*can have some anti-inflammatory effects…. prevention of CF exacerbations

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15
Q

bacteria need ___ to survive

A

protein

*they synthesize it

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16
Q 
Lincosamide 
drug(s) in this class? -routes
A

Clindamycin
PO
IV
topical

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17
Q

tetracyclines are avoided in ____ trimester and contraindicated in ___trimester

A

avoid in 1st

contraindicated 2nd/3rd

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18
Q

SE macrolides (4)

A
  1. GI distress/motility
  2. Cholestatic jaundice
  3. Ototoxicity
  4. Prolonged QTc
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19
Q

Chloramphenicol

  • when do we use
  • moa
  • spectrum
  • route
  • abs
  • penetration
  • dose adjustments
  • pregnancy/BF?
  • adv rxn
A

ABX of LAST resort for LIFE THREATENING infections

*CHLOROX… CHLORamphenicol

MOA:
*binds irreversibly to 50s

  • broad spectrum
  • spirochetes
  • chlamydia
  • rickettsia
  • anaerobes

IV— wide distribution

  • yes CNS pen
  • liver dysfunction– needs dose adjustment
  • contra: BF

YES IN PREGNANCY !

ADV RXN:
1. blood dyscrasias and risk of irreversible bone marrow suppression** BBW for the bone marrow suppresion****

  1. gray baby syndrome in neonates
  2. many drug-drug interactions due to inhibition of liver metabolizers (warfarin, phenytoin)
20
Q

which macrolides do you take without food

A

Erythromycin

Azithromycin

21
Q

list the abx that MOA target 30S subunit

A

tetracyclines
aminoglycosides–erythromycin
gentamycin, tobramycin
streptomycin

22
Q

name the new tetracyclines and routes

A

Eravacycline–IV–intraabdominal infections

Omadcycline–PO, IV—CAP, MSSA, MRSA

Sarecycline–PO—mod to sev acne in 9YO+

23
Q

Tetracyclines

  • list them and routes
  • moa
  • spectrum
  • not tx for?
  • abs–what can decrease it
  • which drug chelates the most
  • doisng? which drug in particular
  • drug-drug interactions
  • contra
A

tetracycline–PO
Minocycline–IV/PO
Doxycycline–IV/PO

MOA:

  • enter bacteria by both passive diffusion or active transport and [ ] intracellularlly in organisms
  • reversibly bind to 30S subunit of bacterial ribosome—inhib protein synthesis
  • bacteriostatic

Spectrum:

  • broad spectrum VERY
  • Aerobic gram+
  • Aerobic gram-
  • atypical pathogens: protoza, spirochetes, mycobacteria,

not tx for N. gonorrhoeae due to resistance

Absoprtion:

  • adequate
  • decreased by: dairy products, iron, aluminum, ca, magnesium

tetracycline chelates the most

doxycycline requires adjustment for severe hepatic dysfunciton

AVOID w. PCN

contra: kids under 8, pregnant (yes crosses placenta)
* doxycycline in special cases when benefits outweight the risk– can be used in preg and kids– bc it is not teratogeneic and does not cause dental staining

24
Q

aminoglycosides are generally combined with which other ABX?
-why?

A

beta-lactams

*synergy against serious gram+ infections

25
Erythromycin - specturm - simialr to?
similar to PCN G---- alternative if PCN allergy**** spectrum: * gram+ ----- strep, corynebacterium
26
are aminoglycosides generally used as monotherapy?
no | NEVER monotherapy for Gram+
27
Linezolid and Tedizolid - drug class? - routes - cidal or static - spectrum - indications - abs - distribution - dosing adjustents? - adv rxn
Oxazolidinones * Linezolid (PO, IV) * Tedizolid (IV, PO) * bacteriostatic * Linezolid bactericidal to streptococci spectrum: * Mainly used for resistant gram+ infections--MRSA, VRE * other: corynebacterium, Bacillus, Listeria, MSSA, coag. neg S aurea INDS: not first line bc they are bacteriostatic *gram+ infeections that are resistant *******MRSA ********VRE Tedizolid: limited to use in skin infections for PTs 12+ YO\ *Linezolid is alternative to daptomycin ABS: 100% after PO distribution: yes penetrates CNS, bone, alveoli, is bound to serum proteins No renal or hepatic dose adjustments* adv rxn: 1. MC: GI upset, HA, rash 2. myelosuppression 3. Peripheral or otic neuropathy (can be irreversible) 4. Serotonin syndrome if given with SSRIs, SNRIs, MAOIs Bupropion 5. Lactic Acidosis with prolonged used*** WHY WE WANT TO AVOID LONG TERM USE*******
28
Aminoglycosides -drugs? -routes MOA spectrum (not effective for?) - synergistic with? - indications
-mycin except for Amikacin IV ONLY*** because PO abs is poor -except for neomycin=topical only bc IV is too nephrotoxic MOA: - enter bacteria through porin channel - bind irreversible to 30S unit - inhibit protein synthesis * bactericidal * use is limited due to toxicity Spectrum: *mostly gram(-) aerobic bacilli EX: pseudomonas ****BUT these drugs are INFERIOR to beta-lactams NOT effective for: -anaerobics Synergistic with: PCNs for Gram+ infections: enterococci and streptococci INDS: - MC use=empiric tx for serious infections (combo with other agents) * *septicemia * *Hosp aquired resp infections * *complicated UTIs * *Osteomyelitis
29
protein give baceteria?
- structural integrity - ability to make energy - critical for bacteria to multiply
30
Pharmkinetics of Tigecycline - abs - penetrates what well? and what not so well? - any dose adjustments - durg-drug interations
- penetrates tissue well - but not plasma..... not good for bacteremia****** - dose adjustment for hepatic dz BUT not renal - may decr warfarin clerance
31
Quinupristin/Dalfopristin - drug class - route - MOA - cidal or static - Indications - penetration? - CYP ____ ____ - adv rxn
Streptogramin Quinupristin/Dalfopristin-- IV *combo of two streptogramins in ratio of 30:70 MOA: -binds to 50s subunit--- synergistic inhib of protein synthesis Bactericidal Inds: only gram+ *saved for severe infections **Vancomycin-resistant enterococcus faecium NOT FAECALIS does not penetrate CNS CYP 450 inhibitor adv rxns: * Venous irritation-->use central line* * Hyperbilirubinemia * Arthralgia/myalgia at high doses
32
why do we want to avoid long term use with Linezolid or Tedizolid?
lactic acidosis developement with LT use
33
Macrolides/Ketolides | -list them and routes
Azithromycin (PO, IV) Clarithromycin (PO) Erythromycin (PO)
34
which macrolide(s) are newer and more acid stables
Clarithromycin | Azithromycin
35
which macrolide(s) are better abs
Clarithromycin | Azithromycin
36
indication for Amikacin
useful when gentamycin or tobramycin resistance strains
37
adv rxns with tetracyclines (9)
- can accumulate in bones and teeth of growing kids - if allergic to one tetracycline-- allg to all**** - Photoxocitiy-- sunburn BAD - GI discomfort - esophageal erosion (avoid b4 bed) - hepatoxocitiy-- rare but fatal - nephrotoxicity can worsen it - vertigo with minocycline - Jarish-Herxheimer rxn for spirochete tx
38
pharmkinetics for aminoglycosides - abs after PO - penetration - __ dependent - synergistic? - why do we monitor the levels closely
poor abs after PO penetration: - tissues=variable - poor pen in CNS, lungs, eye, prostate, bile [ ] dep. with post-abx effect synergistic with beta-lactams have to monitor levels closey to avoid toxicity
39
Tigecycline - drug class? - route - derivative of? - why created - MOA - spectrum - indications - SE
``` Glycycline class IV ONLY ``` * derivative of minocycline * dev as a result of tetracycline resistance MOA: same as tetracyclines Broad spectrum - most gram+ - many multi-drug resistant aerobic gram (-)s INDS: * nosocomial soft tissue infections * *****MRSA * *****VRE * Anerobes * CAP * intra-abdominal infections SE * Similar to other tetracyclines EXCEPT: - BBW for increased mortality....... so use this drug only when alternative treatments are not available - coagulopathy - Safety not established for PT <18YO
40
Tetracycline and minocycline DOC for? | what happens to absoprtion when taken with or w/o food
acene Abs for tetracycline is 50% decreased if taken with food
41
which tetracycline is the only approved drug for use in peds
doxycycline
42
Inds for tobramycin
pseudomonas | aerosolized for CF
43
instructions to tell PT when they are on tetracycline tx (5)
1. Take tetracycline on empty stomach-- the others are ok to take with food 2. Avoid just before bed to preveent esophageal erosion 3. wear sunscreen 4. beware of risk with pregnancy 5. avoid dairy products, mag, aluminu, iron, ca
44
Indication for gentamycin
endocarditis
45
resistance to aminoglycosides?
- less resistance comapred to other classes of ABX | - more specific for each aminoglycoside
46
Azithromycin | -best against?
respiratory pathogens ** * H. flu * Moraxella * Mycoplasma pneumoniae (FIRST LINE) * Neisseria * mycobacterium avium STIs *chlamydia
47
contraindictions for aminoglyosides
PT with myasthenia gravis

Pharmacology (28 decks)

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