Antifungals and antivirals

Question 1

What are the four important stages of the viral lifecycle?

Answer 1

Enveloped virus invades the host cell.
The viral nucleic acid is released and replicated
Viral nucleic acid is repackaged
Envelope proteins are used to package the caspid protein and nucleic acid, and release them from the cell

Question 2

Name some common acute/relapsing viral infections.

Answer 2

Influenza
Herpesviruses (HSV, VZV and CMV)
RSV

Question 3

Name some chronic active viral infections.

Answer 3

These are the most commonly treated.
HIV
Herpes viruses (Hep B and C)

Question 4

What is the principle drug used against herpes infections?

Answer 4

Aciclovir - principally HSV and VZV

- useful in treatment and prophylaxis

Question 5

How does Aciclovir work?

Answer 5

It requires activation by an enzyme which is only found within virally active cells.
The ACV molecule is then inserted into DNA replication (nucleotide analogue), which disrupts viral multiplication

Question 6

Describe the possible toxic effects of Aciclovir.

Answer 6

Low doses - well tolerated
High doses - when treating herpes simplex encephalitis
- renal tubular crystalosis
- seizures

Question 7

What are neuroaminidase inhibitors?

Answer 7

A class for acute viral infections that prevent the action of neuroaminidase in viral budding

Question 8

When should neuroaminidas inhibitors be used?

Answer 8

In the elderly to shorten the duration of influenza symptoms
- young people can survive with symptoms for a few days
Can be used as post-exposure prophylaxis

Question 9

What are the possible toxic side effects of neuroaminidase inhibitors?

Answer 9

Usually well tolerated
GI upset
Neuropsychiatric symptoms (especially in Japan)
Probably safe in pregnancy

Question 10

What are the efficacy concerns in regards to neuraminidase inhibitors?

Answer 10

Not as good as antibiotics

Can’t achieve cure in a chronic active infection

Question 11

Fungal infections can come in which two forms?

Answer 11

Yeasts - mostly candida’s

Moulds - commonly arising in immunocompromised patients

Question 12

Describe the components of a fungal cell wall?

Answer 12

Proteins
Beta-glucans
Chitin
Cell membrane bilayer

Question 13

Why is targeting antifungal treatment hard?

Answer 13

Fungal cells are very similar to human cells, and we don’t want treatments to attack the healthy cells in a patient

Question 14

List some antifungal treatments that are applied topically.

Answer 14

Clotrimazole
Miconazole
Terbinafine
Nystatin

Question 15

How do topical antifungals work?

Answer 15

They all inhibit the synthesis and function of ergosterol.

- a component of the plasma cell membrane bilayer in fungi

Question 16

What are the pros and cons of topical therapy?

Answer 16

Pros - relatively non-toxic

Cons - limited efficacy for anything other than a mild infection

Question 17

When would terbinafine given orally instead of topically?

Answer 17

In more serious fungal infections as it achieves much higher doses in the skin and nails than

Question 18

Describe oral terbinafine.

Answer 18

A highly lipophilic drugs that accumulates in the skin and nails after systemic administration

Question 19

What are some of the toxic effects of oral terbinafine?

Answer 19

Relatively non-toxic

Can cause hepatic upset and SJS

Question 20

What are the systemic agents used for severe fungal infections?

Answer 20

Azoles
Echinocandins
Polyenes

Question 21

What do azoles do?

Answer 21

They inhibit synthesis of ergosterol - important components of the plasma membrane on fungal cells

Question 22

What is the most common Azole to prescribe?

Answer 22

Fluconazole is the most common, but there are other more broad spectrum agents available

Question 23

What fungi are Fluconazole active against?

Answer 23

Yeasts (candida)

Other Azoles however, are active against moulds

Question 24

Give an example of an Echinocandin?

Answer 24

Caspofungin

Question 25

Describe Caspofungin, including its spectrum, mechanism of action, resistance and toxicity.

Answer 25

Broad spectrum antifungal agent
Inhibits glucan formation in the fungal cell walls
Excellent sepctrum against candida and aspergillus
Minimal resistance
Relatively non-toxic

Question 26

Describe Amphotericin B, including its spectrum, mechanism of action and toxicity.

Answer 26

The boradest spectrum anti-fungal agent
Forms membrane attack complexes and permeabilises fungal membrane
Very toxic
Limited to specialist use

Question 27

Give an example of a Polyene?

Answer 27

Amphotericin B