Ribosome Stuff Flashcards

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1
Q

Aminoglycosides

A
  1. Gentamicin
  2. Neomycin
  3. Amikacin
  4. Tobramycin
  5. Streptomycin
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2
Q

Aminoglycoside mechanism

A

Bactericidal.

Irreversible inhibition of initiation complex through binding of the 30S subunit. Can cause misreading of mRNA. Also block translocation.

Require O2 for uptake; therefore ineffective against anaerobes.

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3
Q

Aminoglycoside clinical use

A

Severe gram-negative rod infections. Synergistic with β-lactam antibiotics.

Neomycin for bowel surgery.

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4
Q

Aminoglycoside toxicity

A
  1. Nephrotoxicity
  2. Neuromuscular blockade
  3. Ototoxicity (especially when used with loop diuretics)
  4. Teratogen.
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5
Q

Aminoglycoside resistance

A

Bacterial transferase enzymes inactivate the drug by

  • acetylation
  • phosphorylation
  • or adenylation
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6
Q

Tetracyclines

A
  1. Tetracycline
  2. Doxycycline
  3. Minocycline
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7
Q

Tetracycline mechanism

A

Bacteriostatic.

Bind to 30S and prevent attachment of aminoacyl-tRNA.

Limited CNS penetration. Doxycycline is fecally eliminated and can be used in patients with renal failure.

Do not take tetracyclines with

  • milk (Ca2+),
  • antacids (Ca2+ or Mg2+),
  • or iron-containing preparations

because divalent cations inhibit drugs’ absorption in the gut.

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8
Q

Tetracycline clinical use

A
  • Borrelia burgdorferi
  • M. pneumoniae

Drugs’ ability to accumulate intracellularly makes them very effective against Rickettsia and Chlamydia. Also used to treat acne.

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9
Q

Tetracycline toxicity

A
  1. GI distress
  2. discoloration of teeth
  3. inhibition of bone growth in children
  4. photosensitivity
  5. Contraindicated in pregnancy.
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10
Q

Tetracycline resistance

A

↓ uptake or ↑ efflux out of bacterial cells by plasmid-encoded transport pumps.

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11
Q

Chloramphenicol mechanism

A

Blocks peptidyltransferase at 50S ribosomal subunit. Bacteriostatic.

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12
Q

Chloramphenicol clinical use

A

Meningitis

  • Haemophilus influenzae
  • Neisseria meningitidis
  • Streptococcus pneumoniae

Rocky Mountain spotted fever

  • Rickettsia rickettsii

Limited use owing to toxicities but often still used in developing countries because of low cost.

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13
Q

Chloramphenicol toxicity

A
  1. Anemia (dose dependent)
  2. aplastic anemia (dose independent)
  3. gray baby syndrome (in premature infants because they lack liver UDP-glucuronyl transferase).
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14
Q

Chloramphenicol mechanism of resistance

A

Plasmid-encoded acetyltransferase inactivates the drug.

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15
Q

Lincosamide

A

Clindamycin

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16
Q

Clindamycin mechanism

A

Blocks peptide transfer (translocation) at 50S ribosomal subunit. Bacteriostatic.

17
Q

Clindamycin clinical use

A

Anaerobic infections (e.g.,

  • Bacteroides spp.
  • Clostridium perfringens

in

  • aspiration pneumonia
  • lung abscesses
  • oral infections.

Also effective against invasive group A streptococcal infection (strep pyogenes).

[Treats anaerobic infections above the diaphragm vs. metronidazole (anaerobic infections below diaphragm)]

18
Q

Clindamycin Toxicity

A
  1. Pseudomembranous colitis (C. difficile overgrowth)
  2. fever
  3. diarrhea
19
Q

Oxazolidinones

A

Linezolid

20
Q

Oxazolidinones mechanism

A

Inhibit protein synthesis by binding to 50S subunit and preventing formation of the initiation complex.

21
Q

Oxazolidinones clinical use

A

Gram-positive species including MRSA and VRE

22
Q

Oxazolidinones toxicity

A
  1. Bone marrow suppression (especially thrombocytopenia)
  2. peripheral neuropathy
  3. serotonin syndrome
23
Q

Oxazolidinones resistance

A

Point mutation of ribsomal RNA.

24
Q

Macrolides

A
  1. Azithromycine
  2. Clarithomycin
  3. Erythromycin
25
Q

Macrolide mechanism

A

(Azithromycin, clarithromycin, erythromycin)

Inhibit protein synthesis by blocking translocation; bind to the 23S rRNA of the 50S ribosomal subunit. Bacteriostatic.

26
Q

Macrolide clinical use

A
  1. Atypical pneumonias
    1. Mycoplasma
    2. Chlamydia
    3. Legionella
  2. STIs
    1. Chlamydia
  3. gram-positive cocci
    1. streptococcal infections in patients allergic to penicillin
  4. B. pertussis
27
Q

Macrolide toxicity

A
  1. Gastrointestinal motility issues
  2. Arrhythmia caused by prolonged QT interval
  3. acute cholestatic hepatitis
  4. rash
  5. eosinophilia.
  6. Increases serum concentration of theophyllines, oral anticoagulants.
  7. Clarithromycin and erythromycin inhibit cytochrome P-450.
28
Q

Macrolide resistance

A

Methylation of 23S rRNA-binding site prevents binding of drug