Antibiotics and antifungals COPY

Question 1

What are the main classes of antibiotic drugs?

Answer 1

1. Sulphonamides 2. Trimethoprim 3. Fluoroquinolones 4. Rifamycins 5. Macrolides 6. Glycopeptides 7. Carbapenems, cephalosporins, penicillins 8. Polymyxins 9. Lipopeptide

Question 2

What are the 4 main steps in prokaryotic protein synthesis? What drugs target each step?

Answer 2

1. Nucleic acid synthesis - sulphonamides, trimethoprim 2. DNA replication - fluoroquinolones 3. RNA synthesis - rifamycins 4. Protein synthesis - macrolides

Question 3

What drugs are used to treat fungal infections and how do they work?

Answer 3

1. Azoles(e.g. fluconazole) - inhibit ergosterol production (in fungal CM) 2. Polyenes(e.g. amphotericin) - bind to ergosterol and make pores in CM

Question 4

What mechanisms are commonly used by bacteria to become resistant to drugs?

Answer 4

1. Changes to target - change DNA gyrase 2. Hyperproduction - make more DHFR enzyme 3. Additional target - make diff. DHFR enzyme 4. Destruction enzymes - B-lactamases 5. Alter permeation - increase efflux mechanisms

Question 5

How do sulphonamides work?

Answer 5

Targets DHOp synthase to inhibit NA synthesis

Question 6

How does trimethoprim work?

Answer 6

Targets DHF reductase to inhibit NA synthesis

Question 7

How do macrolides work?

Answer 7

Target ribosomes to inhibit protein synthesis

Question 8

How do fluoroquinolones work?

Answer 8

Target DNA gyrase/topoisomerase IV to inhibit DNA synthesis

Question 9

How do rifamycins work?

Answer 9

Target RNA polymerase to inhibit RNA synthesis

Question 10

How do glycopeptides work?

Answer 10

Target pentapeptide to inhibit peptidoglycan synthesis

Question 11

How do carbapenems, cephalosporins + penicillins work? WHat group of drugs are they?

Answer 11

Target transpeptidase enzyme involved in PtG incorporation into cell wall. The group of drugs they are is beta-lactams

Question 12

How do polymyxins work?

Answer 12

Target LPS to disrupt Gm-ve CMs

Question 13

How does lipopeptide work?

Answer 13

Disrupts Gm+ve cell walls

Question 14

How is tuberculosis treated?

Answer 14

1. RNA-polymerase inhibitor - rifampicin 2. Mycolic acid synthesis inhibitors 3. Pyrazinamide - reduces availability of ribosomes required for protein translation

Question 15

What are mycobacteria?

Answer 15

• Gram positive w/more complex outer wall - Wall contains a PtG-arabinogalactan polymer that binds mycolic acids, pore forming proteins and a number of extractable lipids - Gives bacteria a ‘waxy’ outer layer - E.g. mycobacteria tuberculosis, mycobacteria leprae

Question 16

What does bacitracin do

Answer 16

•Bacitracin inhibits bactoprenol regeneration preventing PtG transportation

Question 17

Describe structure of mycolic bacteria, and what other types of bacteria are there

Answer 17

Mycolic Bacteria

• Outer mycolic acid layer
• E.g. Mycobacterium Tuberculosis

other types : gram negative and positive

Question 18

Describe process of bacteria l protein synthesis

Answer 18

1.Nucleic Acid Synthesis

Dihydropteroate (DHOp)

• Produced from paraaminobenzoate (PABA)
• Converted into dihydrofolate (DHF)

Tetrahydrofolate (THF)

• Produced from DHF by DHF reductase
• THF ® Important in DNA synthesis

2.DNA replication

DNA gyrase

•Topoisomerase ® releases tension

3.RNA synthesis

RNA polymerase

• Produces RNA from DNA template
• Differ from eukaryotic RNA polymerase

4.Protein synthesis

Ribosomes

• Produce protein from RNA templates
• Differ from eukaryotic ribosomes

Question 19

Describe the process of bacterial cell wall synthesis

Answer 19

1.Peptidoglycan (PtG) synthesis

• A pentapeptide is created on N-acetyl muramic acid (NAM)
• N-acetyl glucosamine (NAG) associates with NAM forming PtG

2.PtG transportation

•PtG is transported across the membrane by bactoprenol

3.PtG incorporation

•PtG is incorporated into the cell wall when transpeptidase enzyme cross-links PtG pentapeptides

Question 20

List the causes of antibiotic resistance

Answer 20

Unnecessary prescription,Livestock farming,Lack of regulation,

Lack of development(Very few antibiotics in recent years)

Question 21

Mechanism of antibiotic resistance

Answer 21

•Desctruction enzymes(b-lactamases hydrolyse C-N bond of the b-lactam ring)

Additional target(Bacteria produce another target that is unaffected by the drug[•E Coli produce different DHF reductase enzyme making them resistant to trimethoprim])

Alterations in target enzymes(Alteration to the enzyme targeted by the drug. Enzyme still effective but drug now ineffective[•S Aureus - Mutations in the ParC region of topoisomerase IV confers resistance to quinolones])

Hyperproduction

•Bacteria significantly increase levels of DHF reductase(e.g.Coli produce additional DHF reductase enzymes making trimethoprim less effective)

Alterations in drug permeation(.Reductions in aquaporins & increased efflux systems[•Primarily of importance in gram –ve bacteria])

NOTE:

Difference between ‘Additional target’ and ‘Alterations in target enzymes’ is that in the former we still have the first enzyme working but another has been added which is unaffected by the drug; and in the latter, there is a replacement , withthe replacement being unaffected by the drug

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