Bacterial Protein Synthesis Inhibitors

Question 1

Chloramphenicol

Answer 1

• Protein synthesis inhibitor
• Usually bacteriostatic
• Bind to bacterial 50S ribosomal subunit and inhibits peptidyl transferase - peptide at the donor site cannot be transferred to its amino acid acceptor
• Crosses the placental and blood-brain barriers
• Inactivated by hepatic glucuronosyltransferase
• A backup drug for severe infections caused by Salmonella
• Used in treatment of pneumococcal and meningococcal meningitis in beta-lactam sensitive persons.
• Used sometimes in rickettsial diseases and for Bacteroides fragilis
• Commonly used as a topical antimicrobial agent
• Gray baby syndrome

Question 2

Tetracyclins

Answer 2

• Tetracycline
• Demeclocycline
• Doxycycline
• Minocycline

Question 3

Tetracyclins: Mechanism of Action

Answer 3

• Protein synthesis inhibitor
• Bind to the 30S ribosomal subunit at a site that blocks the binding of amino acid-charged tRNA to the acceptor site of the ribosome-mRNA complex
• Wide tissue distribution and cross the placental barrier

Question 4

Tetracyclins: Clinical use

Answer 4

1) Primary use: Infections caused by Mycoplasma pneumonia, Chlamydia, Rickettsia, and Vibrio
2) Secondary use: Alternative drugs in the treatment of syphilis, respiratory infections, leptospirosis, acne. Used for prophylaxis against infection in chronic bronchitis
3) Selective use: GI ulcers cause by H. pylori (tetracycline), Lyme disease (doxycycline), meningococcal carrier state (minocycline)

Question 5

Macrolids

Answer 5

• Erythromycin
• Azithromycin
• Clarithromycin

Question 6

Macrolids: Mechanism of Action

Answer 6

• Protein synthesis inhibitor
• Considered to be bacteriostatic, at higher doses can be bactericidal
• Bind to 50S ribosome subunit, blocking translocation of peptidyl-tRNA from the acceptor site to the donor site

Question 7

Erythromycin

Answer 7

• Effective against many of the same organisms as penicillin G, therefor may be used in penicillin-allergic patients
• Used against M. pneumonia, Corynebacterium, C. jejuni, C. trachomatis, L. pneumophila, U. urealyticum, and Bordetella pertussis
• Active against gram-positive cocci - pneumococci (not PRSP) and beta-lactamase-producing Staphylococci (not MRSA)
• Inhibits hepatic P450 –> increase plasma levels of anticoagulants, carbamazepine, cisapride, digoxin, and theophylline

Question 8

Clarithromycin

Answer 8

• Activity same as erythromycin, but have also activity against H. influenza
• Have higher activity against Chlamydia, Legionella, Moraxella, Ureaplasma and H. pylori than erythromycin
• Approved for prophylaxis against and treatment of M. avium
• Used as a component of drug regiments for ulcers cause by H. pylori

Question 9

Azithromycin

Answer 9

• Similar spectrum of activity as erythromycin, but more active against H. influenza, Moraxella catarrhalis, and Neisseria.
• Preferred therapy in urethritis caused by C. trachomatis
• Effective against community-acquired pneumonia

Question 10

Telithromycin

Answer 10

• Protein synthesis inhibitor
• Bind to 50S ribosome subunit, blocking translocation of peptidyl-tRNA from the acceptor site to the donor site
• Some macrolide-resistant strains are susceptible to telithromycin because it binds more tightly to ribosomes and is poor substrate for bacterial efflux pumps
• Used in community-acquired pneumonia and other upper respiratory tract infections
• Inhibitor of the cytochrome CYP3A4

Question 11

Lincosamides

Answer 11

• Clindamycin

- Lincomycin

Question 12

Clindamycin, Lincomycin

Answer 12

• Bind to 50S ribosome subunit, blocking translocation of peptidyl-tRNA from the acceptor site to the donor site
• Treatment of severe infections caused by certain anaerobes such as Bacteroides
• Recommended for prophylaxis of endocarditis in valvular disease patients who are allergic to penicillin

Question 13

Streptogramins

Answer 13

• Quinupristin-dalfopristin

Question 14

Streptogramins: Mechanism of Action

Answer 14

• Bactericidal
• Protein synthesis inhibitor
• Bind to the 50S ribosomal subunit, constricting the exit channel on the ribosome through which nascent polypeptides are extruded
• tRNA synthetase activity is inhibited - decrease in free tRNA within the cell

Question 15

Quinupristin-dalfopristin

Answer 15

• Activity against PRSP, MRSA and vancomycin-resistant staphylococci (VRSA), and resistant Enterococcus faecium
• Inhibits CYP3A4 - increase plasma levels of many drugs, including cisapride, cyclosporine, diazepam, warfarin, etc.

Question 16

Linezolid

Answer 16

• Bacteriostatic
• Protein synthesis inhibitor
• Binds to a unique site (23S) on the 50S ribosome, inhibiting initiation by blocking formation of the tRNA-ribosome-mRNA ternary complex
• Active against drug-resistant gram-positive cocci, including strains resistant to beta-lactams and vancomycin

Question 17

Systemic aminoglycosides

Answer 17

• Gentamicin
• Amikacin
• Netilmicin
• Streptomycin
• Tobramycin

Question 18

Local aminoglycosides

Answer 18

• Neomycin
• Gentamicin
• Kanamycin

Question 19

Aminoglycosides: Mechanism of Action

Answer 19

• Bactericidal inhibitors of protein synthesis
• Penetration through cell wall can be enhanced by cell wall synthesis inhibitors - antimicrobial synergism
• Bind to the 30S ribosomal subunit;
  1) Block formation of the initiation complex
  2) Cause misreading of the codon on the mRNA template
  3) Inhibit translocation
• Can exert a post antibiotic effect –> their killing action continues when their plasma levels have declined below measurable levels (greater efficacy when administered as a single large dose than when given as multiple smaller doses)

Question 20

Gentamicin, Tobramycin, Amikacin

Answer 20

• Treatment of serious infections caused by aerobic gram-negative bacteria; E. coli, Enterobacter, Klebsiella, Proteus, Providence, Pseudomonas, and Serratia species

Question 21

Streptomycin

Answer 21

• Used in treatment of tuberculosis, plague, and tularemia

- Because of the risk of ototoxicity, streptomycin should not be used when other drugs will serve.

Question 22

Neomycin

Answer 22

• Only used topically or locally (e.g. in the GI tract) to eliminate bowel flora
• Can cause allergic skin reaction; contact dermatitis

Question 23

Netilmicin

Answer 23

• Usually reserved for treatment of serious infections caused by organism resistant to the other aminoglycosides