Pharm - Antibiotics and antifungals

Question 1

Describe gram + bacteria

Answer 1

Thick peptidoglycan cell wall e.g. s. aureus

Question 2

Describe gram - bacteria

Answer 2

Outer membrane with LPS e.g. e coli

Question 3

Describe mycolic bacteria

Answer 3

Outer mycolic acid layer

Question 4

All bacteria have a

Answer 4

Cell wall and membrane

Question 5

Explain nucleic acid synthesis in prokaryotes

Answer 5

1. PABA —- (DHOp synthase) —-> DHOp
2. DHOp —> DHF
3. DHF — (DHF Reductase) –> THF. THF important in DNA synthesis

Question 6

Explain DNA replication in prokaryotes

Answer 6

DNA Gyrase (aka topoisomerase) —> releases tension from DNA molecule by unwinding

Question 7

Explain RNA synthesis in prokaryotes

Answer 7

RNA Polymerase —> produces RNA from DNA template, differ from eukaryotic RNA polymerase

Question 8

Name and describe 2 antibiotics that interfere with nucleic acid synthesis

Answer 8

1. Sulphonamides - inhibit DHOp synthase

2. Trimethoprim - inhibits DHF reductase

Question 9

Name a antibiotic that inhibits DNA gyrase and topoisomerase 4 (i.e. inhibits DNA replication)

Answer 9

Fluoroquinolone (eg Ciprofloxacin)

Question 10

Name an antibiotic that interferes with RNA synthesis

Answer 10

Rifamycins (e.g. rifampicin) —> inhibits bacterial RNA polymerase

Question 11

Name 4 antibiotic types that inhibit protein synthesis/translation by ribosomes

Answer 11

1. Aminoglycosides
2. Chloramphenicol
3. Macrolides (e.g. erythromycin)
4. Tetracyclines

Question 12

Describe bacterial cell wall synthesis

Answer 12

1. Pentapeptide formed on NAM
2. NAG associates with NAM —> forms proteoglycan
3. PG moved across membrane by bactoprenol into periplasm
4. PG incorporated into cell wall when transpeptidase cross-links PG pentane-tides

Question 13

Which bacterial wall inhibitor antibiotics inhibit PG synthesis?

Answer 13

Glycopeptides (e.g. vancomycin) –> bind pentapeptide —> prevent PG synthesis

Question 14

Which bacterial wall inhibitor antibiotics inhibit PG transport

Answer 14

Bacitracin —> inhibits bactoprenol regeneration –> prevents PG transport

Question 15

Which bacterial wall inhibitor antibiotics prevent PG incorporation into cell wall

Answer 15

Beta-lactams —> bind covalently to transpeptidase —> inhibit PG incorporation into cell wall

e.g. carbapenems, cephalosporins, penicillin

Question 16

Which bacterial wall inhibitors affect cell wall stability

Answer 16

1. Lipopeptide (e.g. daptomycin) –> disrupt gram + cell walls
2. Polymyxins - binds LPS and disrupts gram - membranes

Question 17

What are the causes of AB resistance

Answer 17

1. Unnecessary prescription
2. Livestock farming
3. Lack of regulation
4. Lack of development

Question 18

What are the 5 resistance mechanisms

Answer 18

1. Destruction enzymes breakdown antibiotics
2. Additional targets (e.g. different DHF reductase made)
3. Enzyme alteration (e.g. mutations in DNA gyrase)
4. Hyperproduction (e.g. of DHF reductase)
5. Drug permeation - reduce drug influx, increase drug efflux systems

Question 19

What are the destruction enzymes that bacteria can make

Answer 19

Beta-lactamases hydrolyse the C-N bond of B-lactam ring of antibiotic

(1. Penicillins G and V originally used for gram + infections)
2. Flucloxacillin and temocillin are B-lactamase resistant –> can enter cell wall
3. Amoxicillin has broad spectrum activity —> but it is not beta-lactamase resistant (gram - activity, also coadministered with clavulanic acid to confer beta-lactamase resistance)

Question 20

How may bacteria use additional targets as a resistance mechanism

Answer 20

1. Bacteria make separate, alternative target which is unaffected by drug
   e. g. e coli makes a different DHF reductase –> giving it resistance to trimethoprim

Question 21

How may bacteria alter their target enzymes as a resistance mechanism

Answer 21

Enzyme is still effective but the drug is ineffective on it

e.g. s aureus develops mutation in ParC region of topoisomerase4, giving it resistance to quinolones

Question 22

How may bacteria hyper produce their target/enzyme as a resistance mechanism

Answer 22

e.g. e coli produce additional DHF reductases –> makes trimethoprim less effective

Question 23

How may bacteria reduce drug permeation as a means of drug resistance?

Answer 23

Reducing aquaporins and increasing efflux systems e.g. gram -ve

Question 24

Fungal infections can be classified by the tissues/organs affected. Elaborate

Answer 24

1. Superficial - outermost skin layers
2. Dermatophyte - skin/hair/nails
3. Subcutaneous - innermost skin layers
4. Systemic (mostly resp tract)

Question 25

What are the 2 most common anti-fungal drugs?

Answer 25

1. Azoles - e.g. fluconazole

2. Polyenes - amphotericin

Question 26

How do azoles work

Answer 26

Inhibit CYP450-dependent enzymes involved in membrane ergosterol synthesis

e.g. fluconazole for candidiasis and systemic infections

Question 27

How do polyenes work

Answer 27

Interact with cell membrane sterols —> forming membrane channels/pores —> bursts

e.g. amphotericin (4) —> systemic infections (but has bad SE)s

Question 28

Summarise the intracellular targets of antibiotics and drugs used

Answer 28

1. Nucleic acids - sulphonamides (DHOp), trimethoprim (DHFR)
2. DNA gyrase - fluoroquinolone e.g. ciprofloxacin
3. RNA polymerase - rifampicin
4. Bacterial ribosomes - macrocodes (aminoglycosides, tetracyclines)

Question 29

Summarise the cell membrane targets of antibiotics and drugs used

Answer 29

1. PG synthesis - vancomycin inhibits pentapeptide
2. PG incorporation - carbapenems, cephalosporins and penicillins inhibit transpeptidase
3. Membrane stability - lipopeptides and polymyxins