Antibacterial Agents: Protein Synthesis 50s

Question 1

What drugs act on the 50S subunit?

Answer 1

Chloramphenicols and Macrolides

Question 2

What type of drug is chloramphenicol?

Answer 2

Bacteriostatic, bactericidal at high levels

Question 3

What is chloromphenicol’s mechanism of action?

Answer 3

Prevents binding of tRNA to A site, prevents transpeptidation process, inhibits protein production, prevents protein production

Question 4

How is chloramphenicol administered?

Answer 4

Oral, topical and I.V.

Question 5

How is choloramphenicol absorbed?

Answer 5

Oral drug is abosorbed in GIT (2hrs)
I.V. levels vary (2-3hrs)

Question 6

Where is chloramphenicol distributed?

Answer 6

Everywhere

Question 7

How is chloramphenicol metabolized?

Answer 7

It is a prodrug.
Oral prodrug hydrolyzed in small intestine
IV prodrug hydrolyzed in circulation
Active drug metabolized by hepatic glucuronyl transferase

Question 8

How is chloramphenicol excreted?

Answer 8

Via the renal tubule

Question 9

What is chloramphenicol used against?

Answer 9

Gram-ve and gram+ve bacteria
aerobic and anaerobic
reserved for life threatening illnesses

Question 10

What are chloramphenicol’s clinical uses?

Answer 10

Typhoid fever, cholera and bacterial conjunctivitis

Question 11

What are chloramphenicol’s side effects?

Answer 11

Anemias, Grey baby syndrome, prevents other drugs; metabolism, GIT disturbances, ocular irritation and toxicity and CNS effects

Question 12

How can bacteria be resistant to chloramphenicol?

Answer 12

Enzymatic inactivation through acetylation by CAT gene, decreased drug permeability, ribosomal protection and presence/increased presence of efflux pumps

Question 13

Give two examples of Macrolides

Answer 13

Erythromycin and clarithromycin

Question 14

What type of drug are macrolides?

Answer 14

Bacteriostatic but bactericidal at high concentrations

Question 15

What is the mechanism of action for macrolides?

Answer 15

Binds to 50s subunit, blocks relocation of tRNA with polypeptide chain from A to P site, inhibits translocation blocking further translation of protein

Question 16

How are macrolides administered?

Answer 16

Oral and I.V. Food has an affect on uptake

Question 17

How are macrolides distributed?

Answer 17

Extensive tissue and cellular distribution. Does not cross BBB

Question 18

How are macrolides metabolized?

Answer 18

In the liver

Question 19

How are macrolides excreted?

Answer 19

Azithromycin and erythromycin excreted in bile. Clarithromycin excreted in urine

Question 20

What bacteria are macrolides effective against?

Answer 20

G+ve cocci and bacilli and some G-ve cocci and bacilli

Question 21

What are macrolides clinical uses?

Answer 21

Whooping cough, community acquired pneumonia, Heliobacter pylori infection, STIs, acute non-specific urethritis, campylobacteriosis, anti-inflammatory effects

Question 22

What are the side effects of macrolides?

Answer 22

GIT disturbances, ototoxicity, inactivates digoxin, inhibits cytochrome p450, cholestatic jaundice, QTe prolongation

Question 23

What are mechanisms of resistance against macrolides?

Answer 23

Target modification of a guanine residue, active efflux system, drug inactivation