Antibiotics and Anti-fungals

Question 1

What are the membrane properties of gram positive bacteria and give an example of one

Answer 1

Prominent peptidoglycan cell wall

E.g. Staphylococcus Aureus

Question 2

What are the membrane properties of gram negative bacteria and give an example of one

Answer 2

Outer membrane with lipopolysaccharide

E.g. Escherichia Coli

Question 3

What are the membrane properties of mycolic bacteria and give an example of one

Answer 3

Outer mycolic acid layer

E.g. Mycobacterium Tuberculosis

Question 4

Describe the process of nucleic acid synthesis in bacteria

Answer 4

1. Paraaminobenzoate (PABA) converted to Dihydropteroate (DHOp) via DHOp synthase
2. DHOp converted to dihydrofolate (DHF)
3. DHF converted to tetrahydrofolate (THF) by DHF reductase
4. THF used in DNA synthesis

Question 5

Describe the process of DNA replication in prokaryotes

Answer 5

Occurs using DNA gyrase

Topoisomerase - releases tension

Question 6

Describe RNA synthesis in prokaryotes

Answer 6

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

Question 7

Describe protein synthesis in prokaryotes

Answer 7

Ribosomes
Produce protein from RNA templates
Differ from eukaryotic ribosomes

Question 8

Give two drugs that target nucleic acid synthesis in prokaryotes and state the action in which they target

Answer 8

Sulphonamides inhibit DHOp synthase

Trimethoprim inhibits DHF reductase

Question 9

Give examples of drugs that target DNA replication and RNA synthesis in prokaryotes and state the action in which they target

Answer 9

Fluoroquinolones (e.g. Ciprofloxacin) inhibit DNA gyrase + topoisomerase IV

The rifamycins (e.g. Rifampicin) inhibits bacterial RNA polymerase

Question 10

Give examples of drugs that target protein synthesis in prokaryotes

Answer 10

Macrolides (e.g. Erythromycin)

Aminoglycosides
Chloramphenicol
Tetracyclines

Question 11

Explain the process of bacterial wall synthesis

Answer 11

1. A pentapeptide is created on N-acetyl muramic acid (NAM)
2. N-acetyl glucosamine (NAG) associates with NAM forming Peptidoglycan (PtG)
3. PtG is transported across the membrane by bactoprenol
4. PtG is incorporated into the cell wall when transpeptidase enzyme cross-links PtG pentapeptides

Question 12

Give examples of drugs that might target Peptidoglycan synthesis

Answer 12

Glycopeptides (e.g. Vancomycin) bind to the pentapeptide preventing PtG synthesis

Question 13

Give examples of drugs that might target peptidoglycan transportation

Answer 13

Bacitracin inhibits bactoprenol regeneration preventing PtG transportation

Question 14

Give examples of drugs that might target peptidoglycan incorporation

Answer 14

beta-lactams bind covalently to transpeptidase inhibiting PtG incorporation into cell wall

Question 15

Give examples of beta lactams

Answer 15

Carbapenems
Cephalosporins
Penicillins

Question 16

Give examples of drugs that might target cell membrane stability and explain how they work

Answer 16

Lipopeptide - (e.g. daptomycin) disrupt Gram +ve cell membrane

Polymyxins - binds to LPS and disrupts Gram -ve cell membrane

Question 17

What are the causes of antibiotic resistance

Answer 17

Unnecessary prescription
Livestock farming
Lack of regulation
Lack of development

Question 18

What are the types of resistance

Answer 18

Destruction enzymes
Additional target
Alteration of target 
Alteration in drug permeation
Hyperproduction

Question 19

Explain of how resistance arises from destruction enzymes

Answer 19

beta-lactamases in the cell membrane hydrolyse C-N bond of the beta-lactam ring

Question 20

Give examples of drugs that bacteria may be resistant against due to production of destruction enzymes

Answer 20

Penicillins G + V - Gram +ve

Flucloxacillin + Temocillin - beta-lactamase resistant

Amoxicillin - Broad spectrum
Gram -ve activity
Co-administered with Clavulanic acid - resistant

Question 21

Explain the resistance mechanism of Additional targets and give an example

Answer 21

Bacteria produce another target that is unaffected by the drug

Example
E Coli produce different DHF reductase enzyme making them resistant to trimethoprim

Question 22

Explain the resistance mechanism of alteration in target enzymes and give an example

Answer 22

Alteration to the enzyme targeted by the drug. Enzyme still effective but drug now ineffective

Example
S Aureus - Mutations in the ParC region of topoisomerase IV confers resistance to quinolones

Question 23

Explain the resistance mechanism of alteration in drug permeation and give an example

Answer 23

Reductions in aquaporins and increased efflux systems

Examples
Primarily of importance in gram –ve bacteria

Question 24

Explain the resistance mechanism of hyper production and give an example

Answer 24

Bacteria significantly increase levels of DHF reductase

Example
E Coli produce additional DHF reductase enzymes making trimethoprim less effective

Question 25

Give the classifications of fungal infections

Answer 25

in terms of tissue/organs:

Superficial - Outermost layers of skin
Dermatophyte - Skin, hair or nails
Subcutaneous - Innermost skin layers
Systemic - Primarily respiratory tract

Question 26

How many anti-fungal drugs are licensed in the UK and what are the two most common categories

Answer 26

15 anti-fungal drugs licensed in the UK

Two most common categories:
Azoles: Fluconazole
Polyenes: Amphotericin

Question 27

What is the mechanism of azoles

Answer 27

Inhibit cytochrome P450-dependent enzymes involved in membrane sterol synthesis

Question 28

What is the mechanism of polyenes

Answer 28

Interact with cell membrane sterols forming membrane channels

Question 29

What are azoles used for

Answer 29

Fluconazole (oral) - candidiasis and systemic infections

Question 30

What are polyenes used for

Answer 30

Amphotericin (I-V) - systemic infections