W5 21 anti-viral and anti-fungal drugs

Question 1

Give samples of RNA viruses

Answer 1

Orthomyxo - influenza
Paramyxo- measles mumps rubella
Coronavirus - SARS CoV
RNA retrovirus - HIV

Question 2

Give examples of DNA viruses

Answer 2

Herpes eg chickenpox, cold sores, glandular fever
Adenovirus - sore throat, conjunctivitis

Question 3

Why are viruses difficult to target?

Answer 3

They replicate inside the host cell
They use host enzymes to make viral components
They get to an advanced stage before detection

Question 4

When are anti-viral drugs used?

Answer 4

In systemic infection, immunocompromised, prophylaxis
Usually we just wait out the infection in healthy individuals

Question 5

One method is to target the virus outside the host cell. What drugs can be given to target this?

Answer 5

Vaccine - virus (intact or extracts)
Neuraminidase inhibitors (oseltamivir - tamiflu)

Question 6

What does a virus do?

Answer 6

Eg MMR
Prophylaxis
Generates a viral response to create immunity

Question 7

What do neuraminidase inhibitors do?

Answer 7

Virus released from cell remained attached via sialic acid residues.
Neuraminidase is an enzyme produced by a virus, it breaks bonds and releases viruses to infect other cells. So the drug prevents virus infecting other cells.
Used for influenza A and B

Question 8

What are the NICE guidelines for prophylaxis/treatment of influenza?

Answer 8

Vaccine most effective
Neuroaminidase inhibitors only for at-risk patients - treatment or post-exposure prophylaxis

Question 9

What drugs target the inhibition of viral genetic replication and integration?

Answer 9

DNA polymerase inhibitors
Reverse transcriptase (RT) inhibitors
Integrate inhibition

Question 10

What do DNA polymerase inhibits do and what are some uses for them?

Answer 10

They prevent viral DNA from making copies of itself
Used for DNA viruses - HSV1,2 VZV, cytomegalovirus (associated with AIDS)

Question 11

What do reverse transcriptase (RT) inhibitors do and give a use?

Answer 11

They prevent RNA turning into DNA copies.
Used for RNA retrovirus (HIV), AIDS

Question 12

What do integrase inhibitors do and give an example?

Answer 12

Viral DNA is incorporated into chromosomal DNA using the viral integrase enzyme, so stops this.
Eg raltegravir.
Eg for HIV
Used in combination with nucleoside RT inhibitors

Question 13

Side effects of integrase inhibitors

Answer 13

GI upset, rash
Rare: hepatitis

Question 14

What mechanism do DNA polymerase inhibitors work by?

Answer 14

Pro-drug mechanism
Inhibits viral DNA-polymerase and terminates viral DNA chain extension

Question 15

What DNA polymerase inhibitor is used for herpes viruses?

Answer 15

Acyclovir

Question 16

What does reverse transcriptase inhibitor lamivudine do?

Answer 16

Analogue of cytosine. Inhibits RT (by competition) and terminates the viral DNA chain.

Question 17

What do non-nucleoside RT inhibitors like Efavirenz do?

Answer 17

Active in the form that it is given, denatures the active site of RT.

Question 18

What do protease inhibitors do?

Answer 18

For AIDS. HIV mRNA cleaved into functional proteins by viral protease. Post-translational modification.
Atazanir - inhibits HIV protease to reduce formation of structural proteins and enzymes. Combined with low dose ritonavir - inhibits liver enzyme that metabolises protein inhibitors.

Question 19

What is the drug regime for AIDS?

Answer 19

Highly active antiretroviral therapy (HAART)
2 nucleoside RT inhibits
Plus one of:
- non nucleoside RT inhibitors
- boosted protease inhibitor
- integrase inhibitor

Question 20

What are the problems with AIDS drug regime?

Answer 20

Compliance, resistance
Unknown long term?

Question 21

You can get superficial or systemic fungal disease. Give examples of superficial fungal diseases.

Answer 21

Dermatomycoses (Tinea) - skin, nails, scalp
Candidiasis - mucous membranes: oral, vaginal thrush, skin

Question 22

You can get superficial or systemic fungal disease. Give examples of systemic fungal diseases.

Answer 22

Candidiasis (communist)
Esp, immunosuppressed (antibiotics)

Question 23

Give some examples of antifungal drugs

Answer 23

Amphotericin, nystatin, azoles, terbinafine

Question 24

What does amphotericin and nystatin do?

Answer 24

Binds to ergosterol in membranes (cholesterol). Forms an ion channel pore. Cells lose K+.

Question 25

What is amphotericin used for and how is it administered?

Answer 25

GIT infection: oral
Systemic infection: i.v. (poor oral absorption)

Question 26

What is nystatin used for?

Answer 26

C. Albicans

Question 27

What do Azoles do?

Answer 27

Inhibition synthesis of ergosterol - decreases membrane fluidity so affects membrane-associated enzymes, replication and formation of hyphae (yeast)

Question 28

Describe imidazoles for superficial infections

Answer 28

For tinea and candida infections
Treatment - usually topical
May cause hypersensitivity
Clotrimazole is common

Question 29

Describe triazoles for systemic infections

Answer 29

Eg flucconazole
Oral or IV
Enters CSF
Side effects usually mild; hepatitis (rare)

Question 30

Describe terbinafine

Answer 30

New drug
Targets superficial infections
Topical and oral preparations (absorbed through skin)
Inhibits ergosterol synthesis (affecting squalene which is toxic when accumulates)
Averse effects - GI disturbance, rash