Protein Synthesis Inhibitors

Front 1

Name the 3 major macrolide antibiotics discussed in class.

Are these agents considered bacteriostatic or bacteriocidal?

Back 1

1) erythromycin
2) clarithromycin
3) azithromycin

These agents can be either bacteriostatic or bactericidal but are generally cosidered to be bacteriostatic.

Front 2

Describe the mechanism of action of the macrolides.

Back 2

The bacterial 50S ribosome has 2 RNA molecules, a 5S and a 23S species. The 23S rRNA contains 6 (I - VI)domains and the macrolides bind to domain V. Binding to this domain inhibits peptidyl transferase - or translocation.

Front 3

How do bacteria develop resistance to macrolides? (3 main mechanisms)

Back 3

1) efflux pump
2) mutation of ribosomal binding site
3) methylation of ribosomal binding site on domain V of 23S rRNA by methylases coded by erythromycin ribosome methylase genes.

Front 4

For each of the following statements, identify if it describes (a) erythromycin (b) clarithromycin or (c) azithromycin.

1) This macrolide is excreted by the kidney and inhibits P450 enzymes.

2) This macrolide is excreted in the bile and is effective against chlamydia, M. avium and H. influenzae.

3) This macrolide is used to treat Strep and Staph infections in patients who are allergic to penicillin. It may cause severe abdominal cramping.

4) This macrolide is active against Staph and Strep but may cause mania.

5) This macrolide is found in much higher concentrations in tissue compared to plasma, with tissues acting as a reservoir.

6) This macrolide is excreted in the bile and is a potent CYP34A inhibitor. It has a narrow spectrum and is fairly unstable in gastric acid.

Back 4

1) This macrolide is excreted by the kidney and inhibits P450 enzymes = CLARITHROMYCIN

2) This macrolide is excreted in the bile and is effective against chlamydia, M. avium and H. influenzae = AZITHROMYCIN

3) This macrolide is used to treat Strep and Staph infections in patients who are allergic to penicillin. It may cause severe abdominal cramping = ERYTHROMYCIN

4) This macrolide is active against Staph and Strep but may cause mania = CLARITHROMYCIN

5) This macrolide is found in much higher concentrations in tissue compared to plasma, with tissues acting as a reservoir = AZITHROMYCIN

6) This macrolide is excreted in the bile and is a potent CYP34A inhibitor. It has a narrow spectrum and is fairly unstable in gastric acid = ERYTHROMYCIN

Front 5

Three macroclides were discussed in class. Name the 2 agents that inhibit P450 metabolism of other drugs.

Back 5

1) erythromycin
2) clarithromycin

Front 6

While macrolides have a very low incidence of side effects, there a few documented adverse effects associated with their use (namely erythromycin).

What are these adverse effects?

Back 6

1)erythromycin can cause a cholestatic hepatitis

2) erythromycin stimulates motilin receptor and increases GI motility, leading to epigastric distress

3) erythromycin and clarithromycin can inhibit P450 metabolism of other drugs

Front 7

What is the differene in mechanism of action between macrolides and telithromycin?

Back 7

Macrolides (erythro-, clarithro-, azithromycin) bind to domain V on the 23S rRNA of the 50S ribosome and inhibit translocation.

Telithromycin binds to two sites: domain II and domain V of the 23S rRNA. This extra binding makes telithromycin a poor ligand for the microbial efflux pump and allows it to maintain activity against organism with "erm" genes.

Front 8

Telithromycin is approved for the treatment of (blank).

What are the contraindications for telithromycin administration?

Back 8

Telithromycin is approved for the treatment of COMMUNITY ACQUIRED PNEUMONIA.

It must not be given to those with a history of hepatitis or jaundice, as it can cause liver failure or injury. It should also not be given to those with myasthenia gravis.

Front 9

This macrolide derivative binds to the 50S ribosome and is effective against anaerobic infections such as B.fragilis, and has affinity for osseous tissue. It is also effective against community-acquired MRSA.

a) clindamycin
b) erythromycin
c) telithromycin

Back 9

This macrolide derivative is effective against anaerobic infections such as B.fragilis, and has affinity for osseous tissue. It is also effective against community-acquired MRSA.

a) clindamycin

Front 10

Pseudomembranous colitis is an adverse effect most often associated with this macrolide derivative...

Back 10

Pseudomembranous colitis is an adverse effect most often associated with the macrolide derivative CLINDAMYCIN.

Front 11

This class of protein synthesis inhibitors treat VREF bloodstream infections as well as skin infection caused by methicillin-sensitive S.aureus or S.pyogenes.

Back 11

STREPTOGRAMIN class of protein synthesis inhibitors treat VREF bloodstream infections as well as skin infection caused by methicillin-sensitive S.aureus or S.pyogenes.

Quinupristin = streptogramin B
Dalfopristin = streptogramin A

Front 12

The streptogramin duo, quinupristin/dalfopristin, treat VREF as well as Staph and Strep skin infections.

For which infection is the duo bactercidial? bacteriostatic?

Back 12

Quinupristin/dalfopristin are bactericidal against Staph and Strep but static against VREF.

Front 13

This protein synthesis inhibitor is primarily active against Gm(+) bacteria that are often resistant to other drugs, like VRE, MRSA, VISA and GISA. It is active against all enterococci, even those that are vancomycin-resistant.

Back 13

LINEZOLID is a protein synthesis inhibitor that is primarily active against Gm(+) bacteria that are often resistant to other drugs, like VRE, MRSA, VISA and GISA. It is active against all enterococci, even those that are vancomycin-resistant.

Front 14

How is linezoild administered?
Does induce P450's?

Back 14

Linezolid is given IV or orally. It has nearly 100% oral bioavailability.

Linezolid does not inhibit or induce P450's.

Front 15

What are the adverse reactions associated with linezolid?

Back 15

--myelosuppression
--peripheral neuropathy
--linezolid has some MAOI activity which can lead to serotonin syndrome

Front 16

This protein synthesis inhibitor acts on the 50S ribosome. It is rapidly absorbed and is conjugated in the liver by glucuronosyl transferase. It is used only to treat infections that cannot be treated with other antibiotics.

Back 16

CHLORAMPHENICOL is a protein synthesis inhibitor acts on the 50S ribosome. It is rapidly absorbed and is conjugated in the liver by glucuronosyl transferase. It is used only to treat infections that cannot be treated with other antibiotics.

Front 17

What are the adverse effects associated with chloramphenicol?

Back 17

(1) aplastic anemia: not related to dosing size and not reversible

(2) bone marrow suppression: dose-dependent and reversible with immediate cessation of the drug

(3) gray-baby syndrome due to the neonate not being able to conjugate the drug and eliminate it

Front 18

Identify the specific protein synthesis inhibitor described by the following clinical uses:

1) treats VREF bloodstream infections and skin infections caused by Staph or Strep

2) treats community acquired pneumonia in those without a history of hepatitis or jaundice

3) effective against chlamydia, M.avium and H.influenzae

4) effective against community-acquired MRSA and the anaerobic B.fragilis

5) only used to treat infections that are not effectively treated with other antibiotics

6) active against rickettsiae, H.pylori adn chlamydia

7) active against MRSA and VRE but not very effective against Pseudomonas

8) three drugs that treat systemic infections due to Gm(-) enteric bacteria

9) active against Gm(+) bacteria that exhibit resistance to other drugs like VISA, GISA, VRE; also active against all enterococci

Back 18

1) treats VREF bloodstream infections and skin infections caused by Staph or Strep = QUINUPRISTIN / DALFOPRISTIN

2) treats community acquired pneumonia in those without a history of hepatitis or jaundice = TELITHROMYCIN

3) effective against chlamydia, M.avium and H.influenzae = AZITHROMYCIN

4) effective against community-acquired MRSA and the anaerobic B.fragilis = CLINDAMYCIN

5) only used to treat infections that are not effectively treated with other antibiotics = CHLORAMPHENICOL

6) active against rickettsiae, H.pylori adn chlamydia = TETRA-, MINO- DOXYCYCLINE

7) active against MRSA and VRE but not very effective against Pseudomonas = TIGECYCLINE

8) three drugs that treat systemic infections due to Gm(-) enteric bacteria = GENTAMICIN, TOBRAMYCIN, AMIKACIN

9) active against Gm(+) bacteria that exhibit resistance to other drugs like VISA, GISA, VRE; also active against all enterococci = LINEZOLID

Front 19

Name the three major tetracycline antibiotics.

What is their mechanism of action?

Back 19

1) tetracycline
2) minocycline
3) doxycycline

These agents bind to the 30S ribosome and are bacteriostatic. They achieve high intracellular levels in susceptible organisms due to the presence of an active transport system.

Front 20

How do bacteria become resistant to tetracyclines?

Back 20

The major cause of clinical resistance is due to a pump that removes the drug from cells. There is often complete cross-resistance among the different tetracyclines.

Front 21

What is the major difference among the tetracyclines?

Which of the 3 tetracyclines is favored and why?

Back 21

The major difference among the tetracyclines is their half-lives.

Doxycycline is favored because of its long half life, nearly complete absorption, high tissue conc due to its high lipophilicity and lack of accumulation in patients with compromised renal function.

Front 22

What are the adverse effects associated with tetracyclines?

Back 22

1) hypersensitivity
2) GI irritation
3) phototoxicity
4) liver dysfunction
5) teeth discoloration and depressed bone growth in kids
6) minocycline causes vertigo and dizziness

Front 23

Why are the tetracyclines not given to children between the ages of two months and eight years?

Back 23

Discoloration of the permanent teeth can result from the administration of tetracyclines at any time between the ages of 2months and 8 years - the period of tooth calcification.

Front 24

What is the mechanism of action of tigecycline?

What is unique about tigecycline's antibacterial spectrum?

Back 24

Tigecycline has a higher affinity for the tetracycline ribosomal binding site, which allows tigecycline to overcome resistance due to changes in the binding site and allows to be relatively unaffected by the tetracycline efflux pump.

Tigecycline is unique in that it is effective against many multi-drug resistant pathogens. Examples: MRSA, VRE, penicillin-resistant S.pneumo, Acinetobacter

Front 25

Identify the protein cell wall inhibitor agent associated with the following adverse effects:

1) pseudomembranous coliits

2) cholestatic hepatitis and increased GI motility

3) vertigo and dizziness

4) aplastic anemia and bone marrow suppression

5) acute hepatic failure

6) serotonin syndrome and myelosuppression

7) teeth discoloration and phototoxicity

8) ototoxicity

9) gray baby syndrome

10) arthralgia and myalgia

Back 25

1) pseudomembranous colitis = CLINDAMYCIN

2) cholestatic hepatitis and increased GI motility = ERYTHROMYCIN

3) vertigo and dizziness = MINOCYCLINE

4) aplastic anemia and bone marrow suppression = CHLORAMPHENICOL

5) acute hepatic failure = TELITHROMYCIN

6) serotonin syndrome and myelosuppression = LINEZOLID

7) teeth discoloration and phototoxicity = TETRACYCLINES

8) ototoxicity = AMINOGLYCOSIDES

9) gray baby syndrome = CHLORAMPHENICOL

10) arthralgia and myalgia = QUINUPRISTIN/DALFOPRISTIN

Front 26

Describe the mechanism of action of aminoglycosides?

Back 26

Aminoglycosides inhibit protein synthesis by acting directly on the ribosome and are rapidly bactericidal. They interfere with teh attachment of mRNA to ribosomes, cause misreading and produce decreased or abnormal protein synthesis.

They are frequently synergistic with cell wall synthesis inhibitors.

Front 27

Name the aminoglycosides used to treat systemic Gm(-) enteric infections.

Back 27

1) Gentamicin
2) Tobramycin
3) Amikacin

Front 28

How do bacteria become resistant to aminoglycosides?

Back 28

Bacteria metabolize the AG's and convert them to inactive agents.

Front 29

Describe the pharmacokinetics of aminoglycosides..

1) administration & absorption
2) distribution
3) excretion

Back 29

1) AG's are poorly absorbed when given orally. They are, however, absorbed rapidly after IM or subQ administration.

2) AG's do not penetrate human cells very well. They are found in high concentrations in renal tubular cells and the hair cells of teh ear.

3) AG's are excreted by glomerular filtration.

Front 30

What are the adverse effects associated with aminoglycosides?

Back 30

1) ototoxicity

2) nephrotoxicity (proximal tubules affected the most)

3) neuromuscular blockade

Front 31

This class of protein synthesis inhibitors has a narrow therapeutic index. Monitoring is used to assure therapeutic drug levels are attained and to monitor for toxic drug levels. Toxic levels may result in ototoxicity or neuromuscular blockade.

a) tetracyclines
b) macrolides
c) aminoglycosides

Back 31

This class of protein synthesis inhibitors has a narrow therapeutic index. Monitoring is used to assure therapeutic drug levels are attained and to monitor for toxic drug levels. Toxic levels may result in ototoxicity or neuromuscular blockade.

c) aminoglycosides