CPTP 3.11 Pharmacology of Antimicrobials 2

Question 1

What structure involved in protein synthesis is different in eukaryotic and prokaryotic cells, and thus can be selectively targeted by antimicrobial drugs?

Answer 1

Ribosomes

Question 2

In what direction is RNA read?

Answer 2

5’ to 3’

Question 3

What is the first ‘start’ codon always used?

Answer 3

AUG

Question 4

What are the three sites on a ribosome?

Answer 4

A, P and E:
• Activation
• Propagation
• Exit

Question 5

Where does tRNA bind to mRNA?

Answer 5

At the A (‘activation’) site

Question 6

Describe what happens during translation in the ribosome

Answer 6

• tRNA binds to mRNA at the A site of the ribosome
  
  • The ribosome moves the mRNA along, transferring the tRNA into the P site, freeing up the A site so another tRNA molecule can match the next codon.
  • The amino acids of both tRNA molecules form a peptide bond
  • The confirmation of this bond breaks the bond between the tRNA in the P site and its amino acid
  • This tRNA moves along to the E site and is released
  • Its amino acid is still attached to the amino acid held by the subsequent tRNA molecule, which now moves across to the P site
  • A site is freed up and the chain continues

Question 7

Name the classes of antibiotics which bind to bacterial ribosomes. Name the formulary example of this drug and its route of administration. State whether each is bacteriostatic or bacteriocidal.

Answer 7

Tetracyclines (bacteriostatic)
• Doxycycline, oral

Aminoglycosides (bacteriocidal)
• Gentamicin, IV or IM

Macrolides (bacteriostatic)
• Clarithromycin (Oral, parenteral, IM)
• Erythromycin (Oral, parenteral)

Question 8

What can impede oral absorption of doxycycline?

Answer 8

• Calcium
  
  • Magnesium
  • Aluminium salts

Question 9

How do tetracyclines work? How is it selectively toxic?

Answer 9

• Bacterium pumps tetracycline into its cell
  
  • This transport is only present in bacterial cells
  • Binds to the 30s subunit of the bacterial ribosome (the bottom one)
  • This inhibits the formation of the complex between the tRNA (in the 50s subunit) and the mRNA (in the 30s subunit)

Question 10

Outline the spectrum of the tetracyclines and aminoglycosides

Answer 10

Tetracyclines:
• Broad spectrum

Aminoglycosides:
  •  Broad spectrum
  •  Low activity against:
        > Anaerobes 
        > Streptococci
        > Pneumococci

Macrolides:
• Narrow spectrum
• Gram negative bacteria

Question 11

How can you tell a drug is:

1) a cephalosporin?
2) a macrolide?
3) an aminoglycoside?
4) a penicillin?
5) a sulfonamide?
6) a tetracycline?

Answer 11

1) begins with ‘cefa-‘
2) ends with ‘-mycin’
3) Ends with ‘-micin’
4) ends with ‘-illin’
5) begins with ‘sulfa-‘
6) ends with ‘-cycline’

Question 12

How do aminoglycosides work?

Answer 12

• Irreversibly binds to the 30s subunit of the bacterial ribosome
  
  • Causes more frequent misreading of prokaryotic genetic code
  • This creates malformed protein, which is discarded

Question 13

Which drug has high effectiveness against Haemophilus influenzae and Helicobacter pylori?

Answer 13

Clarithromycin

Question 14

How do macrolides work?

Answer 14

REVERSIBLY binds between the A and P sites of the 50s bacterial ribosome subunit, preventing movement of the ribosome along mRNA

Causes a blocked ribosome

Question 15

Which drug classes inhibit the enzymes used to package DNA? What is the formulary example? Is it bacteriocidal or bacteriostatic?

Answer 15

The quinolones (bacteriocidal)
  •  Ciprofloxacin

Metronidazole (Bacteriocidal)
• Metronidazole

Question 16

How do quinolones and metronidazole work? Which of these comes in a predrug form?

Answer 16

• Bacteria (prokaryotes) do not have chromosomes, and instead use one DNA supercoil
  
  • DNA gyrase is the enzyme that packages DNA into supercoils (to protect it)
  • Quinolones bind the two elements (which usually spin separately to create the coiling) of DNA gyrase together
  • This leaves DNA separated and prone to attack and interaction from cell contents such as lysosomes

metronidazole = predrug

Question 17

What is the enzyme with the reverse action of DNA gyrase?

What does this do?

Answer 17

Bacterial Topoisomerase IV

UNWINDS DNA

Question 18

What pathogens cause tuberculosis?

Answer 18

Mycobacteria

Question 19

What is the mechanism of action of rifampicin?

Answer 19

Inhibits bacterial DNA-dependent RNA polymerase

Question 20

What must be considered with rifampicin? What is it metabolised by? What is its route of administration? Is it bacteriostatic or bacteriocidal?

Answer 20

Reduces the effectiveness of hormonal contraceptives

The liver

Oral, bacteriocidal

Question 21

What are the stages of TB treatment?

Answer 21

Initial treatment: ‘RIPE’ (2 months)

Rifampicin
Isoniazid
Pyrazinamide
Ethambutol

Continuation phase (4 months)