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Respiratory Medicine-Unit 1 > Protein Synthesis Inhibitors (Fitz) > Flashcards

Protein Synthesis Inhibitors (Fitz) Flashcards

1
Q

List aminoglycoside abx:

A 
Amikacin
GENTAMICIN
Kanamycin
NEOMYCIN
Streptomycin
TOBRAMYCIN
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2
Q

Brucellosis can be treated with this combo including an amino glycoside:

A

Gentamicin + doxycycline

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3
Q

Tularemia can be treated with this aminoglycoside

A

gentamicin

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4
Q

Yersinia pestis can be treated with this combo including an aminoglycoside

A

streptomycin + doxycycline

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5
Q

Pseudomonas aeruginosa can be treated with this combo including an amino glycoside:

A

Tobramycin + Pipericillin or ticarcillin

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6
Q

klebsiella can be treated with this combo including an aminoglycoside

A

Gentamicin + pipericillin or ticarcillin

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7
Q

What is the spectrum of activity of amino glycosides?

A

Pathogenic gram - rods:

  • Escherischia, Enterobacter, Serratia
  • Pseudomonas, Acinetobacter
  • Klebsiella spp., Yersinia pestis, Brucella spp., F tularensis
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8
Q

What are some indications for Aminoglycosides?

A
  • Gram - infx resistant to other safer antimicrobials (as 2nd line therapy)
  • Combo therapy for serious pseudomonas aeruginosa infx and brucellosis, tularemia, plague..
  • Synergistic tx with B lactam for streptococcal and enterococcal endocarditis
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9
Q

This oral amino glycoside can be used for sterilizing the bowel prior to colonoscopy or bowel surgery

A

Oral neomycin –> acts as topical abx in the gut where it eradicates flora

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10
Q

what is the MOA of amino glycosides?

A

Diffuse into gram - via porins (outer membrane) –> enter cytosol via O2-dependent active transporter –> bind 30s ribosome sub-unit and disrupt protein synthesis (alters AA sequence and eventually protein becomes defective and bacteria dies)

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11
Q

what are some mechanisms of resistance to amino glycosides?

A
  • depletion/deficit of porins (MDR)
  • O2 deficit/ anaerobic orgs
  • Enzymatic alteration of amino glycoside structure (acetylation, phosphorylation, adenylation)
  • mutation of 30s ribosome
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12
Q

___ are intrinsically resistant to aminoglycosides

A

anaerobes

Gram + rods: Clostridia
Gram - rods: bacteroides, fusobacteria

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13
Q

List adverse effects of amino glycosides:

A
  • Nephrotoxicity (accumulate in renal cortex)
  • Ototoxicity/vestibular toxicity (CN VIII defects) (accumulate in ear perilymph)
  • neuromuscular blockade
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14
Q

the risk of neuromuscular blockade by amino glycosides is greatest with:

A

intra-peritoneal administration or large doses, or rapid IV infusion. Can produce apnea or resp arrest

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15
Q

this tetracycline has a high potency, complete intestinal absorption, highly photo toxic, and is the preferred agent parenterally; preferred with renal impairment

A

Doxycycline

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16
Q

what is the spectrum of activity for tetracyclines?

A
  • broad spectrum
  • atypical orgs
  • intracellular orgs
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17
Q

What atypical orgs can be treated with Doxycycline?

A
  • Rickettsial (IC) –> tick-born RMSF, Q fever, typhus
  • Chlamydia trachomatis –> Major STD, urethritis, PID, lymphogranuloma venerum
  • Chlamydia psittaci –> psittacosis pneumonia
  • Mycoplasma pneumonia –> young adults, close quarters (alternate - erythromycin)
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18
Q

List the amino glycoside + tetracycline combo for the following:

  • Brucellosis
  • Tularemia
  • Plague
A

Brucellosis –> Gentamicin + doxycycline

Tularemia –> Gentamicin + a tetracyclne

Plague –> Streptomycin + doxycycline

19
Q

What is the MOA of tetracyclines?

A

passive diffusion into bacterial cytosol –> bind to 30s ribosomal unit –> BLOCK BINDING OF AMINOACYL-tRNA –> inhibit protein synthesis –> exert bacteriostatic effects

20
Q

what are mechanisms of resistance to tetracyclines?

A
  • tetracycline efflux pump (Tet A efflux pump)

- ribosome protection (methylation of ribosome)

21
Q

___ is the only tetracycline safe to use in renal impairment because it is cleared almost entirely by biliary excretion

A

doxycycline

22
Q

List some adverse effects of tetracyclines:

A
  • GI disturbance –> superinfx; can disrupt commensal flora of gut and allow pathogenic orgs to thrive; C diff thrives; Pseudomembranous colitis occurs-can be life-threatening
  • Accumulation in teeth and bone –> chelate Ca and Mg in calcified tissues; contraindicated < 8 yrs old
  • Fatal hepatotoxicity –> fatty liver, esp during pregnancy; Contraindicated in pregnancy and breast feeding and children < 8 yrs of age
  • Phototoxicity
  • Vestibular problems–> minocycline
  • Diabetes insipidus –> demeclocycline
23
Q

this improved relative of tetracyclines has no drug interactions, is excreted biliary, and safe in pts with renal impairment. It has decreased susceptibility to resistance by yet A efflux pumps and ribosomal protection. Its has a broad spectrum of activity including Gram + aerobes including MRSA, VRE, Gram -, Anaerobes such as C perfringens, bactericides spp

A

Tigecycline

24
Q

List some macrocodes and ketolides:

A

Erythromycin
Clarithromycin
Azithromycin

Telithromycin (ketolide)

25
Q

a major indication for macrolide/ ketolides is ___

A

URT-CAP

Covers atypicals such as Legionella pneumophila, Chlamydiphila pneumonia, Mycoplasma

26
Q

__, a once-daily, 5 day regimen is as effective as 10 day courses of other macrolides

A

azithromycin

27
Q

What is the MOA of macrolides?

A

bind to 50s subunit –> inhibit translocation step of protein synthesis –> ribosome cannot ratchet forward to the next codon –> inhibit bacterial protein synthesis

28
Q

what are mechanisms of resistance to macrolides?

A
  • methylation of ribosome –> erm genes confer high level macrolide resistance
  • macrolide efflux pumps –> mef E pump macrolides out of cytosol
29
Q

___ are intrinsically resistant to macrolides due to decreased permeability to the outer cell envelope

A

Enterobacteriaceae
Pseudomonas spp
Acinetobacter spp

30
Q

What are some adverse effects and clinical complications of macrolides and ketolides?

A
  • GI–> nausea, vomiting, diarrhea
  • Hepatotoxicity (rare, serious) –> cholestatic jaundice- erythromycin estolate (hypersensitivity), fatal hepatotoxicity (telithromycin)
  • Cardiac–> QTc interval prolongation, blockade of Ikr channel (inward rectifying K channel), increases risk for Torsades; QT prolongation Erythromycin > clarithro/azithromycin
  • Drug-drug interactions –> CYP3A interaction
  • Reversible hearing loss
31
Q

This macrolide is associated with ~2fold increase in risk of sudden cardiac death overall and 5fold increase in pts taking drugs that are CYP3A4 inhibitors-which causes elevations in this drugs circulating levles

A

Erythromycin

32
Q

These macrolides are the safest in pregnancy:

A

Erythromycin and Azithromycin

33
Q

Name a Lincosamide:

A

Clindamycin

34
Q

What are some Clindamycin distinctions from erythromycin?

A

-Anaerobes-Primary clinical use (e.g., abdominal anaerobic infx with bactericides fragilis associated with trauma such as gunshot or stabbing)

35
Q

what is the main adverse event associated with Clindamycin?

A

Pseudomembranous colitis caused by overgrowth of C diff (manage with metronidazole, vancomycin PO)

36
Q

The antimicrobial spectrum of this Abx is wide but clinical use is rare. Its clinical use is restricted to life-threatening infx for which there is no alternative (some meningitis infx)

A

Chloramphenicol

37
Q

Name some lethal toxicities of Chloramphenicol

A
  • Aplastic anemia –> idiosyncratic
  • Gray baby syndrome –> can penetrate human cells and disrupt their mt protein synthesis; drug concentration dependent caused by impaired glucuronidation in neonates and impaired renal clearance
38
Q

List ontogenic and pediatric catastrophes associated with:

  • Sulfonamides: __
  • Chloramphenicol: __
A

Sulfonamides –> kernicterus

Chloramphenicol –> gray baby syndrome

39
Q

What does the OTC diarrhea drug Intestinomicine contain that should be a concern for people with anemia and other low blood cell counts?

A

Chloramphenicol

40
Q

What is the MOA of Chloramphenicol?

A

Bind 50s ribosomal subunit –> inhibits peptidyl transferase step of protein synthesis

Can enter host cells and impair host mt protein synthesis –> produces toxicity

41
Q

chloramphenicol resistance involves its enzymatic modification by ___

A

Acetyltransferase (CAT)

42
Q

Name an oxazolidinone

A

Linezolid

43
Q

This oxazolidinone is used when orgs are vancomycin resistant:

A

Linezolid

44
Q

Describe Linezolid clearance and toxicity

A
  • Non enzymatic oxidation
  • Not a CYP450 substrate, inhibitor, or inducer
  • Renal clearance
  • Long term use: Increase ALT
  • decreases platelets, MAO interaction
  • Peripheral neuropathy

Respiratory Medicine-Unit 1 (6 decks)

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