23 - Antimicrobials

Question 1

Describe two antibiotics that target the folate pathway.
- Mechanism?

Answer 1

Sulfonamides:
- Compete w/ p-aminobenzoic acid so can’t perform pathway.
Trimethoprim:
- Purine and pyrimidine synthesis by inhibiting dihydrofolate reductase.

Note: co-trimoxazole is when given together

Question 2

List 3 types of beta-lactams
- Mechanism?

Answer 2

Penicillins, cephalosporins, and carbapenems
- bind to transpeptidase to prevent peptide side chain cross-links

Question 3

Name a glycopeptide.
- Mechanism?

Answer 3

Vancomycin
- Prevents next building block from transmembrane carrier to release.

Question 4

List 4 drugs that target ribosome of bacteria

Answer 4

• Aminogylcoside (30s)
• Tetracyclines (30s)
• Chloramphenicol (50s)
• Macrolides (50s)

Question 5

How do tetracyclines work?

Answer 5

Prevent tRNA accessing acceptor site (30s)

Question 6

How do aminoglycosides work?

Answer 6

Proof reading fails (30s)
- Rapidly bactericidal
- Minimal oral absorption due to large size
- Narrow therapeutic index

Question 7

How do chloramphenicols work?

Answer 7

Bind to 50s subunit to inhibit transpeptidation.

Question 8

How do macrolides work?

Answer 8

Inhibit translocation of peptide chain

Question 9

Name a drug that affects DNA synthesis. Mechanism?

Answer 9

Proflavine. Intercalate DNA to distort and cause misreading.

Question 10

Name two drugs that target DNA synthesis.

Answer 10

• Rifampicin inhibits RNA/DNA polymerase
• Quinolones e.g. ciprofloxacin inhibits DNA gyrase (topoisomerase II)

Question 11

1) How is B-lactam countered?
2) How is 1) countered by us?

Answer 11

1) Beta-lactamase degrades penicillins and cephalasporins
2)
- Some beta-lactam nuclei e.g. monobactams, carbapenems, are resistant to it
- Beta-lactamase inhibitors

Question 12

How can bacterias develop resistance?

Answer 12

• Deactivating antibacterial drug
• Altering binding site
• Increased drug elimination/reduced entry
• Bypass reactions

Question 13

What’s antimicrobial stewardship?

Answer 13

Intervention to improve use + measure use of antibiotics. Educate others on how to prescribe.

Question 14

5 types of antifungal drugs?

Answer 14

• Amphotericin – Creates ion pore
• Azoles – Inhibit ergosterol synthesis
• Terbinafine, naftifine, amorolfine – Inhibit squalene epoxidase. Blocks cell wall synthesis and cause toxic buildup of squalene
• Flucytosine – Inhibits thymidylate synthetase and DNA synthesis
• Griseofulvin – Inhibit microtubule system

Question 15

3 targets of virus-specific enzymes?

Answer 15

• DNA polymerase inhibitors
• Reverse Transcriptase Inhibitors (RTIs)
• Protease inhibitors

Question 16

1) Virus DNA polymerase inhibitor 2 examples?
2) Similarities/Difference?

Answer 16

1) Aciclovir and Ganciclovir
2) Both are guanosine analogues so inhibits DNA polymerase b
Aciclovir is a terminating nucleotide and highly specific for:
- Herpes SImplex Virus (HSV) type 1 and 3
- Varicella Zoster Virus (VZV)
- Cytomegalovirus (CMV)
Ganciclovir is not broken down fast and especially good against
- CMV

Question 17

How do nucleoside RTIs work?

Answer 17

Competes w/ triphosphates to become incorporated into DNA to cause chain termination.

Question 18

Describe non-nucleoside RTIs

Answer 18

Bind to reverse transcriptase to deactivate/denature it.

Question 19

Describe HIV protease inhibitors

Answer 19

Viral mRNA typically codes for 2 inactive proteins activated by viral protease. Inhibit viral protease.