Antibiotics and antifungals

Question 1

Describe the membrane properties of a gram positive bacteria

Answer 1

Thick peptidoglycan cell wall

eg in staph aureus

Question 2

Describe the membrane properties of a gram negative bacteria

Answer 2

Outer membrane has LPS (liposaccarides)

Question 3

Describe the membrane properties of a mycolic bacterai

Answer 3

They have an outer mycolic acid layer eg mucobacterium tuberculosis

Question 4

What are the steps of protein synthesis by antibiotics

Answer 4

1. nucleic acid synthesis
2. DNA replication
3. RNA synthesis
4. Protein synthesis

Question 5

What are examples of drug intracellular targets in antibiotics that are involved in nucleic acid synthesis

Answer 5

1. dihydropterate synthase converts PABA to DHOp
   Sulphonamide inhibits DHOp synthase
2. dihydrofolate (DHF) reductase converts DHF -> THF
   Trimerthoprim inhibits DNF reductase

Question 6

What are examples of drug intracellular targets in antibiotics that are involved in DNA replication

Answer 6

DNA gyrases (topoisomerases) release the tension in DNA 
Fluoroquinolones inhibit DNA gyrases and topoisomerase IV

Question 7

What are examples of drug intracellular targets that are involved in RNA synthesis

Answer 7

a. RNA polymerase produces RNA from DNA template
b. Prokaryotic RNA polymerase differs to eukaryotic ones
Rifamycins inhibit bacterial RNA polymerase

Question 8

What are examples of drug intracellular targets that are involved in protein synthesis

Answer 8

a. ribosomes produce the protein from RNA templates

b. prokaryotic ribosomes differ from eukaryotic ribosomes.

Question 9

What are examples of drugs that inhibit the ribosome

Answer 9

aminoglycosides
chloramphenicol
macrolides
tetracyclines

Question 10

What are the different targets for extracellular gram +ve drug antibiotics

Answer 10

1. peptidoglycan synthesis
2. PtG transportation
3. PtG incorporation
4. Cell wall stability

Question 11

What happens in peptidoglycan synthesis and what antibiotics target this step?

Answer 11

Pentapeptide is created on NAm and NAG associates with NAM forming the peptidoglycan
Glycopeptides bidn to pentapeptide and prevent PtG synthesis

Question 12

What happens in PtG transportation and what antibiotics target this step

Answer 12

Bacteroprenol transports the PtG across the membrane

Bacitracin inhibits Bactoprenol regeneration

Question 13

What happens in PtG incorporation and what antibiotics target this step

Answer 13

Transpeptidase enzyme cross links PtGs and creates wall

Beta lactams eg carbapenems, cephalosportins bind covalently to transpeptidase and inhibits it’s action

Question 14

What antibiotics target the cell wall stability step of peptidoglycan synthesis

Answer 14

Lipopeptides disrupt the gram +ve walls

Polymyxin binds to liposaccarides and disrupts gram -ve membranes

Question 15

What are causes of antibiotic resistance

Answer 15

Unnecessary prescription
Livestock farming
Lack of regulation
Lack of developmenet

Question 16

What are different antibiotic resistance mechanisms

Answer 16

1. additional targets - different DHFR enzyme
2. hyperproduction - more DHFR enzyme
3. alternations in target enzymes - alterations to enzyme to make drugs ineffective whilst the enzyme still works
4. alterations in drug permeation - reductions in AQAs and increased efflux systems to reduce AB entry
5. Production of destruction enzymes eg beta lactamases that hydrolyse C-N bonds of beta lactam ring

Question 17

What are examples of antibiotics that are resistant to production of destruction enzymes therefore are an example of antibiotic resistance

Answer 17

Flycloxacillin and temocillin

Amoxicillin combats gram -ve bacteria and is resistant to beta lactamases only when co administered with clavulanic acid

Question 18

What are different classifications of a fungal infection

Answer 18

• superficial (outer most layer of skin)
• dermatophyte (skin, hair or nails)
• subcutaneous (inner most skin layers)
• systemic (primarily respiratory tract)

Question 19

What are examples of antifungal drugs used

Answer 19

Azoles eg fluconazole

Polyenes eg amphortericin

Question 20

What does fluconazole do

Answer 20

Inhibit CYP450 enzymes involved in membrane ergosterol synthesis

Question 21

What does amphortericin do

Answer 21

Binds to ergosterol and creates channel pores

Question 22

What does fluconazole treat

Answer 22

Candidiasis, systemic infections

Question 23

What does amphortericin treat

Answer 23

Systemic infections