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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
a major indication for macrolide/ ketolides is ___
URT-CAP | Covers atypicals such as Legionella pneumophila, Chlamydiphila pneumonia, Mycoplasma
26
__, a once-daily, 5 day regimen is as effective as 10 day courses of other macrolides
azithromycin
27
What is the MOA of macrolides?
bind to 50s subunit --> inhibit translocation step of protein synthesis --> ribosome cannot ratchet forward to the next codon --> inhibit bacterial protein synthesis
28
what are mechanisms of resistance to macrolides?
- methylation of ribosome --> erm genes confer high level macrolide resistance - macrolide efflux pumps --> mef E pump macrolides out of cytosol
29
___ are intrinsically resistant to macrolides due to decreased permeability to the outer cell envelope
Enterobacteriaceae Pseudomonas spp Acinetobacter spp
30
What are some adverse effects and clinical complications of macrolides and ketolides?
- 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
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
Erythromycin
32
These macrolides are the safest in pregnancy:
Erythromycin and Azithromycin
33
Name a Lincosamide:
Clindamycin
34
What are some Clindamycin distinctions from erythromycin?
-Anaerobes-Primary clinical use (e.g., abdominal anaerobic infx with bactericides fragilis associated with trauma such as gunshot or stabbing)
35
what is the main adverse event associated with Clindamycin?
Pseudomembranous colitis caused by overgrowth of C diff (manage with metronidazole, vancomycin PO)
36
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)
Chloramphenicol
37
Name some lethal toxicities of Chloramphenicol
- 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
List ontogenic and pediatric catastrophes associated with: - Sulfonamides: __ - Chloramphenicol: __
Sulfonamides --> kernicterus Chloramphenicol --> gray baby syndrome
39
What does the OTC diarrhea drug Intestinomicine contain that should be a concern for people with anemia and other low blood cell counts?
Chloramphenicol
40
What is the MOA of Chloramphenicol?
Bind 50s ribosomal subunit --> inhibits peptidyl transferase step of protein synthesis Can enter host cells and impair host mt protein synthesis --> produces toxicity
41
chloramphenicol resistance involves its enzymatic modification by ___
Acetyltransferase (CAT)
42
Name an oxazolidinone
Linezolid
43
This oxazolidinone is used when orgs are vancomycin resistant:
Linezolid
44
Describe Linezolid clearance and toxicity
- 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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