Chemotherapy 2

Question 1

What do anti-fungal drugs do?

Answer 1

Disrupt cell structure or division

Question 2

How do anti-fungal drugs target fungal cell membs?

Answer 2

Inhibits ergosterol (in fungi cell membs)

Question 3

Why do anti-fungal drugs targeting cell membs not affect human cell membs?

Answer 3

-Human cell membs = cholesterol is main sterol in cell memb
-Fungi = ergosterol

Question 4

Name anti-fungal drug that targets this ergosterol & how?

Answer 4

= Fluconazole
–> inhibits ergosterol synthesis - stops cell membs functioning as should

Question 5

Name 4 anti-fungal drugs that target ERs?

Answer 5

-Allylamines
-Benzylamines
-Imidazoles (impact energy metabolism)
-Triazoles

Question 6

Name anti-fungal drug that targets cell walls?

Answer 6

Echinocandins

Question 7

Name anti-fungal drug that targets cell membs?

Answer 7

Polyenes (amphotericin B)

Question 8

Name anti-fungal drug that targets DNA synthesis?

Answer 8

Flucytosine

Question 9

Name anti-fungal drug that targets mitotic spindle?

Answer 9

Griseofulvin

Question 10

What anti-bacterial drugs targeting folic acid metabolism also used as anti-fungals?

Answer 10

ALL
-Sulphonamides
-Trimethoprim
-Pyrimethamine
-5-Flurouracil/Flucytosine

Question 11

Why are anti-fungals targeting folate metabolism in fungi effective?

Answer 11

Stops nucleic acid synthesis

Question 12

How does flucytosine/5-FU work?

Answer 12

-Taken up by transporter in memb (selective)
-Pro-drugs = metabolised in cells - cytosine demonise converts to active form = 5-flurouracil
-Convert into base - is incorporated into RNA chain -> stopping further elongation OR inhibits thymidylate synthase - inhibits fungal DNA synthesis
—> both = cidal effects

Question 13

Why is flucytosine metabolism a useful target of anti-fungals?

Answer 13

Only occurs in fungi - cytosine delaminate only in fungi

Question 14

How do pro-drugs work?

Answer 14

-Take pro-drug
-Specific cell takes up
-Metabolises/converts & activates drug = anti-metabolite (false substrate - so can affect a target mimicking substrate)
. Selectivity here = as only surface cells can activate pro-drug

Question 15

What points in viral life cycle do anti-virals target?

Answer 15

-Entry into host cells
-Nucleic acid replication
-Viral protein synthesis
-Exit from host cells

Question 16

How do anti-virals target entry into host cells?

Answer 16

Inhibit fusion of virus w/ host cell memb after binding to surface rec

Question 17

How do anti-virals target nucleic acid replication?

Answer 17

-Inhibit DNA/RNA polymerases
OR
-Inhibit retroviral reverse transcriptase

Question 18

Name an anti-viral that inhibits DNA/RNA polymerases?

Answer 18

Aciclovir

Question 19

Name an anti-viral that inhibits retroviral reverse transcriptase?

Answer 19

Zidovudine

Question 20

How do anti-virals target viral protein synthesis?

Answer 20

Inhibit viral proteases involved in
processing large polyproteins

Question 21

How do anti-virals target exit from host cells?

Answer 21

Inhibit neuraminidase-catalysed
cleavage

Question 22

Name an anti-viral that targets exit from host cells?

Answer 22

Oseltamivir

Question 23

What is the basis of chemotherapy?

Answer 23

Selective toxicity - target system in infectious micro-organisms NOT in or exists in a different form – in host cells

Question 24

Why are basic biochemical processes NOT good targets for antimicirobials?

Answer 24

Common to most organisms - likely affect host cells (be toxic)

Question 25

Why are complex biochemical processes = good targets for antimicrobials?

Answer 25

More likely to differ between organisms - less likely to elicit toxic effects on host cells

Question 26

What limits antimicrobial use?

Answer 26

Drug resistance

Question 27

How do bacteria develop resistance? (to antimicrobials??)

Answer 27

-Random mutation
-Gene transfer OR transferred resistance

Question 28

How do random mutations lead to bacterial resistance?

Answer 28

-As cells replicate – in a pop is some bact w/ acquired resistance.
-Drug eliminates sensitive organisms & resistant ones proliferate

Question 29

How does gene transfer/transferred resistance lead to bacterial resistance?

Answer 29

Usually spread through conjugative transfer of R plasmid (may be virally mediated).

Question 30

What are the mechanisms responsible for resistance to antimicrobials - examples?

Answer 30

-Inactivating enzymes = destroy the drug (e.g., β-lactamases).
-Decreased drug accumulation (e.g., tetracyclines)
-Altering binding sites of targets - drugs can’t bind as well (e.g., aminoglycosides & erythromycin).
-Development of alternative metabolic pathways (sulphonamides (dihydropteroate synthase) & trimethoprim (dihydrofolate reductase)

& others in image

Question 31

Why limit use of antimicrobials?

Answer 31

Prevent resistance - as in presence of drugs - these bacteria divide/prolif faster BUT when no drug present non-resistant drugs divide/prolif faster

Question 32

How to slow the emergence & spread of antimicrobial resistance?

Answer 32

-Understanding the mechanisms
-Use of combination therapies
-Responsibilities of Physicians: must work to identify microbe and
prescribe suitable antimicrobials, must educate patients
-Responsibilities of Patients: need to carefully follow instructions

Question 33

Why combine 2 antibiotics/combination therapies?

Answer 33

-Use 2 antibiotics not 1 = reduce resistance - as use lower doses of each
-Manage pats - if have something unlikely bacterial (& if is to need to take drugs)
-Better as would need x2 mutations to occur for resistance

Question 34

What is co-amoxiclav & why use?

Answer 34

-Combination of:
Clavulanic acid + Amoxicillin
C = poor antimicrobial (have less of)
A = v. effective (have more of)
-Both = β-lactams
-Treat infections caused by β-lactamase producing bacteria (or if suspect this)

Question 35

How does co-amoxiclav work?

Answer 35

-B-lactamase binds to drug v. effectively - destroys clav acid - so clav acid becomes suicide substrate (if formulation right) - binds b-lactamase - kills b-lactamases - so amox can carry out its activities