Protein Synthesis Inhibitors

Question 1

What is selective toxicity?

Answer 1

Drug blocks a reaction that is vital to both the microbe and host, but has greater impact on the microbe

Question 2

Tetracycline

1) Mechanism of action
2) Use

Answer 2

1) Protein synthesis inhibitor - Bind to the 30S subunit

2) Acne, Rickettsial diseases (typhus, RMSF), Lyme disease

Question 3

Doxycycline

1) Mechanism of action
2) Use
3) Elimination

Answer 3

1) Protein synthesis inhibitor - Bind to the 30S subunit
2) Acne, Rickettsial diseases (typhus, RMSF), Lyme disease
3) **eliminated as an inactive chelate in feces which reduces GI complications because less impact on normal flora

Question 4

Minocycline

1) Mechanism of action
2) Use

Answer 4

1) Protein synthesis inhibitor - Bind to the 30S subunit

2) Acne, Rickettsial diseases (typhus, RMSF), Lyme disease

Question 5

What decreases absorption of tetracyclines?

Answer 5

Divalent and trivalent cations (esp. iron and calcium), when gastric pH is elevated (ex: H2 blockers, antacids, PPIs)

Question 6

1) What spectrum of bacteria do tetracyclines work on?

2) How do microbes become resistant to tetracyclines?

Answer 6

1) very broad, Gm + > Gm -
2) Decreased intracellular drug levels due to decreased influx OR increased efflux via the plasmid-encoded Tet efflux pump
* *widespread resistance has much limited their clinical use

Question 7

What are the important adverse effects of tetracyclines?

Answer 7

superinfection (C. diff), discoloration of teeth and impaired bone development –> **don’t give to pregnant women or to children under the age of 8

Question 8

Tigecycline

1) Mechanism of action
2) Use

Answer 8

1) glycylcycline (relative of tetracycline) that is bacteriostatic
2) MRSA, effective for strains that are pet-resistant
* *Black box warning: increased risk of mortality so only use when there are no other drugs suitable

Question 9

Gentamicin

1) Mechanism of action
2) Use

Answer 9

1) Aminoglycoside that binds IRREVERSIBLY to 30s subunit to inhibit protein synthesis–> lingers for a long time, bactericidal
* *concentration-dependent
2) SEVERE Gm - infections and in combination with PCN or vanco, OR topically for burns and wounds

Question 10

Streptomycin

1) Mechanism of action
2) Use

Answer 10

1) Aminoglycoside that binds IRREVERSIBLY to 30s subunit to inhibit protein synthesis–> lingers for a long time, bactericidal
* *concentration-dependent
2) High resistance limits use –> Mycobacterial infections (TB)
* *Can cause deafness in newborns, don’t give during pregnancy

Question 11

Aminoglycosides

1) Spectrum
2) How do organisms become resistant?

Answer 11

1) primarily Gm - rods, but used in combination with PCN or Vanco which act synergistically to extend coverage to Gm +
2) enzymatic inactivation of the drug

Question 12

What are the adverse effects of aminoglycosides?

Answer 12

toxicities to inner ear leading to tinnitus, permanent hearing loss and renal cortex leading to reversible renal failure

Question 13

Azithromycin

1) Mechanism of action
2) Use

Answer 13

1) Macrolide antibiotic: Bind reversibly to 50S subunit –> bacteriostatic
2) An alternative to PCN (allergy), or prophylaxis against bacterial endocarditis in patients with PCN/Ampicillin allergy

Question 14

Clarithromycin

1) Mechanism of action
2) Use

Answer 14

1) Macrolide antibiotic: Bind reversibly to 50S subunit –> bacteriostatic
2) An alternative to PCN (allergy), or prophylaxis against bacterial endocarditis in patients with PCN/Ampicillin allergy

Question 15

Erythromycin

1) Mechanism of action
2) Use

Answer 15

1) Macrolide antibiotic: Bind reversibly to 50S subunit –> bacteriostatic
2) An alternative to PCN (allergy), or prophylaxis against bacterial endocarditis in patients with PCN/Ampicillin allergy
* *unstable in acidic environments so given enteric ally coated or delayed-release orally

Question 16

What antibiotics should not be used with a macrolide antibiotic? Why?

Answer 16

Streptogramins, clindamycin, chloramphenicol, because macrolide competitively inhibit ribosomal binding of these drugs so they are antagonistic in combination

Question 17

What are the three ways organisms can become resistant to macrolide antibiotics?

Answer 17

Resistance develops rapidly
Three ways:
1) efflux pump
2) ***MLS-type B resistance (methylase modifies the bacterial ribosome so unable to bind drug)
3) hydrolysis of macrolide by esterases

Question 18

What are the adverse effects associated with macrolide antibiotics?

Answer 18

GI disturbances, hepatotoxicity
**Drug interactions: Erythromycin and clarithromycin inhibit CYP3A4 activity –> warfarin levels increase with erythromycin

Question 19

Quinupristin/dalfopristin

1) Mechanism of action
2) Use

Answer 19

1) Streptogramins: quinupristin binds 50S subunit and dalfopristin binds nearby, synergistically enhancing quinupristin binding
* *Individually they are bacteriostatic, but combined they are bactericidal
2) serious/life-threatening MDR infections like VREf
* *MLS-type B and erm-encoded resistance can occur

Question 20

Linezolid

1) Mechanism of action
2) Use

Answer 20

1) Oxazolidinone: binds to 30S and 50S to block protein synthesis
2) reserve for treatment of resistant infections (MRSA, S. pneumoniae, VREf)
* *No cross-resistance with other protein synthesis inhibitors

Question 21

Clindamycin

1) Mechanism of action
2) Use
3) Adverse effects

Answer 21

1) Lincosamide: binds to 50S subunit
2) Gm +, **better than macrolide against anaerobes
Abscesses, prophylaxis against bacterial endocarditis in patients with PCN allergy, and osteomyelitis
3) MLS-type B resistance, diarrhea, colitis

Question 22

Mupirocin

1) Mechanism of action
2) Use

Answer 22

1) inhibits isoleucyl tRNA synthetase (indirect protein synthesis inhibitor)
2) topical use only, helpful for treating MRSA impetigo