Ribosome Stuff

Question 1

Aminoglycosides

Answer 1

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

Question 2

Aminoglycoside mechanism

Answer 2

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.

Question 3

Aminoglycoside clinical use

Answer 3

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

Neomycin for bowel surgery.

Question 4

Aminoglycoside toxicity

Answer 4

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

Question 5

Aminoglycoside resistance

Answer 5

Bacterial transferase enzymes inactivate the drug by

• acetylation
• phosphorylation
• or adenylation

Question 6

Tetracyclines

Answer 6

1. Tetracycline
2. Doxycycline
3. Minocycline

Question 7

Tetracycline mechanism

Answer 7

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.

Question 8

Tetracycline clinical use

Answer 8

• Borrelia burgdorferi
• M. pneumoniae

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

Question 9

Tetracycline toxicity

Answer 9

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

Question 10

Tetracycline resistance

Answer 10

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

Question 11

Chloramphenicol mechanism

Answer 11

Blocks peptidyltransferase at 50S ribosomal subunit. Bacteriostatic.

Question 12

Chloramphenicol clinical use

Answer 12

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.

Question 13

Chloramphenicol toxicity

Answer 13

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

Question 14

Chloramphenicol mechanism of resistance

Answer 14

Plasmid-encoded acetyltransferase inactivates the drug.

Question 15

Lincosamide

Answer 15

Clindamycin

Question 16

Clindamycin mechanism

Answer 16

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

Question 17

Clindamycin clinical use

Answer 17

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)]

Question 18

Clindamycin Toxicity

Answer 18

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

Question 19

Oxazolidinones

Answer 19

Linezolid

Question 20

Oxazolidinones mechanism

Answer 20

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

Question 21

Oxazolidinones clinical use

Answer 21

Gram-positive species including MRSA and VRE

Question 22

Oxazolidinones toxicity

Answer 22

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

Question 23

Oxazolidinones resistance

Answer 23

Point mutation of ribsomal RNA.

Question 24

Macrolides

Answer 24

1. Azithromycine
2. Clarithomycin
3. Erythromycin

Question 25

Macrolide mechanism

Answer 25

(Azithromycin, clarithromycin, erythromycin) Inhibit protein synthesis by blocking translocation; bind to the 23S rRNA of the 50S ribosomal subunit. Bacteriostatic.

Question 26

Macrolide clinical use

Answer 26

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

Question 27

Macrolide toxicity

Answer 27

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.

Question 28

Macrolide resistance

Answer 28

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