Antimicrobial Chemotherapy 2

Question 1

What can fungi be divided into

Answer 1

Yeasts
Filamentous fungi (moulds)

Question 2

What can be used to treat fungi

Answer 2

Anti-fungal drugs

Question 3

What are the categories of anti-fungal drugs

Answer 3

Polyenes
Azoles
Allylamines
Echinocandins

Question 4

What is the mechanism of action for polyenes

Answer 4

They bind to ergosterol that is present in the fungal cell wall but not in the bacterial cell wall
This results in an increase in the permeability of the cell wall

Question 5

What are polyene drugs active against

Answer 5

Yeasts

Filamentous fungi

Question 6

What is a disadvantage of polyene drugs

Answer 6

They bind to other sterols (e.g. cholesterol) in mammalian cell membranes and this is the reason for their toxicity

Question 7

Which polyene can be used intravenously and what is it used for

Answer 7

Amphotericin B

Used for serious systemic fungal infection

Question 8

Describe amphotericin B

Answer 8

It is exteremely toxic and has a wide range of side effects (e.g. renal, hepatic and cardiac toxicity)
The lipid complexed formulations of this drug offer a reduced incidence of such side effects

Question 9

What is nystatin

Answer 9

A polyene drug available for topical use only

Question 10

What do azoles do

Answer 10

Inhibit ergosterol synthesis

Question 11

Name some azoles

Answer 11

Old:
Miconazole
Ketoconazole
Newer:
Fluconazole
Voriconazole
Itraconazole

Question 12

Describe fluconazole

Answer 12

Used for oral and parenteral treatment of yeast infections
Has no serious toxicity problems
Resistance among some Candida species is emerging
Resistance can emerge during treatment

Question 13

Describe itraconazole

Answer 13

Active against both yeasts and filamentous fungi, including Aspergillus spp. and dermatophytes.

Question 14

What does voriconazole treat

Answer 14

Aspergillosis

Question 15

Describe the mechanism of action for allylamines

Answer 15

They suppress ergosterol synthesis but act at a different stage of the synthetic pathway from azoles

Question 16

Name an allylamine

Answer 16

Terbinafine (only one in common use)

Question 17

What are allylamines active against

Answer 17

Dermatophyte infections of the skin
(e.g. ringworm, athlete’s foot) and nails (onychomycosis)

Mild infections will be treated topically and more serious infections
(including onychomycosis) orally

Question 18

Describe the mechanism of action for echinocandins

Answer 18

They inhibit the synthesis of glucan polysaccharide in several types of fungi

They are fungicidal against the Candida species and inhibit the growth of several Aspergillus species

Question 19

Name some echinocandins

Answer 19

Micafungin
Caspofungin
Anidulafungin

Question 20

What does virustatic agents

Answer 20

Those that inhibit growth and/or replication

Question 21

What are virucidal agents

Answer 21

Those that will kill the virus

Question 22

Are anti-viral drugs virucidal or virustatic

Answer 22

Virustatic

Question 23

How do anti-viral drugs tend to work

Answer 23

Many are nucleoside analogues which

interfere with nucleic acid synthesis

Question 24

How can the treatment of herpes be effective

Answer 24

If started early

Will not erdicate any of the viruses

Question 25

What do anti-herpes virus drugs treat

Answer 25

Herpes simplex virus Cytomegalovirus Varicella-zoster virus Epstein-Barr virus

Question 26

What is aciclovir

Answer 26

An anti-herpes virus drug | A nucleoside analogue

Question 27

What is aciclovir active against

Answer 27

Herpes Simplex | Varicella Zoster

Question 28

What must occur for aciclovir to become active

Answer 28

Be converted into its active form by an enzyme (thymidine kinase) coded for by the virus genome

Question 29

What is an advantage of aciclovir

Answer 29

It's specific for virus-infected cells and | has very low toxicity for uninfected host cells

Question 30

When is the IV and oral forms of aciclovir used

Answer 30

IV: treats severe infections (e.g. herpes encephalitis and VZV pneumonitis) Oral: cold sores (caused by HSV reactivation)

Question 31

Name some anti-herpes virus drugs (at least 3)

Answer 31

``` Valaciclovir Famciclovir Valganciclovir Foscarnet Ganciclovir Cidofovir ```

Question 32

Describe valaciclovir | and famciclovir

Answer 32

Oral agents related to aciclovir | They can treat HSV and shingles

Question 33

What is foscarnet used for

Answer 33

HSV, VZV and CMV infections Highly nephrotoxic Only given through IV

Question 34

Describe ganciclovir

Answer 34

Active against CMV Toxic and given by IV infusion Use is largely restricted to treating life or sight threatening infections in the immunocompromised (e.g. AIDS, transplant recipients)

Question 35

What is valganciclovir

Answer 35

Pro-drug of ganciclovir Oral alternative for some CMV situations Bone marrow toxicity so close blood count monitoring required

Question 36

When is cidofovir used

Answer 36

For CMV retinitis | when other anti-viral drugs are inappropriate

Question 37

What is zidovudine

Answer 37

First Treatment for HIV (1987) A nucleoside analogue which interferes with the action of reverse transcriptase. It is virustatic

Question 38

What can zidovudine cause

Answer 38

Anaemia and neutropaenia

Question 39

How is a HIV patients response to treatment monitored

Answer 39

Their viral load and CD4+ cell count

Question 40

How is chronic hepatitis B and C treated

Answer 40

With pegylated interferon-a | Hep C also uses oral ribavirin

Question 41

What has limited the use of pegylated interferon-a

Answer 41

Its low response rate, serious side effects and | the high cost of treatment

Question 42

What can be used for the treatment of influenza A and B

Answer 42

Zanamivir and Oseltamivir

Question 43

What can be used for the treatment of severe respiratory syncytial virus

Answer 43

Ribavirin is occasionally used | It must be inhaled as a fine spray to reach the site of infection in the lungs as administration is difficult

Question 44

What is genotypic analysis

Answer 44

Helps in choosing rational treatment in selected patients (e.g. in HIV infection, where the viral load is rising despite adherence to treatment, or for HSV, VZV or CMV not responding clinically to apparently adequate dosage).

Question 45

When is drug monitoring used

Answer 45

To ensure therapeutic, but not toxic, serum levels are achieved For aciclovir, this is usually restricted to patients with significant renal impairment