Antibiotics and antifungals

Question 1

state some general features of bacteria

Answer 1

• single cell microorganisms: cell wall, cell membrane
• entire phylogenetic domain
• 1/3 are pathogenic

Question 2

describe the properties of gram +ve bacteria

Answer 2

• prominent peptidoglycan cell wall

e. g. S Aureus

Question 3

describe gram -ve bacteria

Answer 3

outer membrane with LPS

e.g. E Coli

Question 4

describe mycolic bacteria

Answer 4

e.g. M. tuberculosis

outer mycolic acid layer

Question 5

what are 4 important steps in prokaryotic protein synthesis?

Answer 5

• nucleic acid synthesis
• DNA replication
• RNA synthesis
• protein synthesis

Question 6

describe nucleic acid synthesis

Answer 6

1. PABA –> DHOp (by DHOp synthase)
2. DHOp –> DHF
3. DHF –> THF (by DHF reductase)
   THF important in DNA synthesis

Question 7

what enzymes are important in DNA replication?

Answer 7

• DNA gyrase/ topoisomerase

- unwinds bacterial DNA, released tension

Question 8

describe RNA synthesis

Answer 8

• RNA polymerase

- produces RNA from DNA template

Question 9

describe protein synthesis

Answer 9

• produce protein from RNA templates

- differ from eukaryotic ribosomes

Question 10

what drugs target nucleic acid synthesis?

Answer 10

• sulphonamides inhibit DHOp synthase

- trimethoprim inhibits DHF reductase

Question 11

what drugs target DNA replication?

Answer 11

• flurorquinolones inhibit DNA gyrase and topoisomerase

Question 12

what drugs target RNA synthesis?

Answer 12

Rifamycins inhibit bacterial RNA polymerase

Question 13

wjat drugs inhibit ribosomes in protein synthesis?

Answer 13

• aminoglycosides
• chloramphenicol
• macrolides
• tetracyclines

Question 14

what are the 3 steps to bacterial wall synthesis?

Answer 14

1. peptidoglycan (PtG) synthesis
2. PtG transportation
3. PtG incorporation

Question 15

describe PtG synthesis

Answer 15

• pentapeptide created on N-acetyl muramic acid (NAM)

- N-acetyl glucosamine (NAG) associates with NAM forming PtG

Question 16

describe PtG transportation

Answer 16

PtG transported across membrane by bactoprenol

Question 17

describe PtG incorporation

Answer 17

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

Question 18

what drugs inhibit PtG synthesis

Answer 18

glycopeptides bind to pentapeptide preventing PtG synthesis

Question 19

what drugs inhibit PtG transportation?

Answer 19

• bacitracin inhibits bactoprenol regeneration

- prevents PtG transportation

Question 20

what drugs inhibit PtG incorporation?

Answer 20

• beta lactams bind covalently to transpeptidase
• inhibits PtG incorporation into cell wall
  e. g. carbapenems, cephalosporins, penicillins

Question 21

what 2 drugs affect cell wall stability (but target cell membrane)?

Answer 21

• lipoprotein - disrupt gram +ve cell membranes

- polymyxins - binds to LPS and disrupts gram -ve cell membranes

Question 22

what are the causes of antibiotic resistance?

Answer 22

• unnecessary prescription
• livestock farming
• lack of regulation
• lack of development

Question 23

state the 5 resistance mechanisms

Answer 23

• production of destructive enzymes
• additional target
• alterations in target enzymes
• hyperproduction
• alterations in drug permeation

Question 24

describe the production of destruction enzymes

Answer 24

• beta lactamases hydrolyse C-N bond of beta lactam ring
• e.g. Pencillins G and V = gram +ve
• flucloxacilin and temocilin are beta lactamase resistant

Question 25

describe additional target mechanism

Answer 25

- bacteria produce another target that is unaffected by drug

Question 26

give an example of the additional target mechanism

Answer 26

E coli produce different DHF reductase enzyme making them resistant to trimethoprim

Question 27

describe alterations in target enzymes

Answer 27

- alteration to enzyme targeted by drug - enzyme still effective but drug now ineffective e. g. S Aureus

Question 28

describe hyperproduction

Answer 28

- bacteria significantly inc. levels of DHF reductase

Question 29

give an example of a bacteria that uses the hyperproduction method

Answer 29

E coli produce additional DHF reductase enzymes making trimethoprim less effective

Question 30

describe alterations in drug permeation

Answer 30

- reductions in aquaporins and inc. efflux systems | - primarily of importance in gram -ve bacteria

Question 31

how can fungal infections be classified?

Answer 31

- superficial: outermost layers of skin - dermatophyte: skin, hair, nails - subcutaneous: innermost skin layers - systemic: primarily resp tract

Question 32

what are the 2 most common categories of anti-fungals?

Answer 32

- azoles: fluconazole | - polyenes: amphotericin

Question 33

what do azoles do?

Answer 33

- inhibit cytochrome P450-dependent enzymes involved in membranes sterol synthesis

Question 34

what is the azole, flucanazole used to treat?

Answer 34

candidiasis and systemic infections

Question 35

what do polyenes do?

Answer 35

- interact with cell membrane sterols forming membrane channels

Question 36

what is the polyene, amphotericin used to treat?

Answer 36

systemic infections