W5 21 anti-viral and anti-fungal drugs Flashcards
Give samples of RNA viruses
Orthomyxo - influenza
Paramyxo- measles mumps rubella
Coronavirus - SARS CoV
RNA retrovirus - HIV
Give examples of DNA viruses
Herpes eg chickenpox, cold sores, glandular fever
Adenovirus - sore throat, conjunctivitis
Why are viruses difficult to target?
They replicate inside the host cell
They use host enzymes to make viral components
They get to an advanced stage before detection
When are anti-viral drugs used?
In systemic infection, immunocompromised, prophylaxis
Usually we just wait out the infection in healthy individuals
One method is to target the virus outside the host cell. What drugs can be given to target this?
Vaccine - virus (intact or extracts)
Neuraminidase inhibitors (oseltamivir - tamiflu)
What does a virus do?
Eg MMR
Prophylaxis
Generates a viral response to create immunity
What do neuraminidase inhibitors do?
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
What are the NICE guidelines for prophylaxis/treatment of influenza?
Vaccine most effective
Neuroaminidase inhibitors only for at-risk patients - treatment or post-exposure prophylaxis
What drugs target the inhibition of viral genetic replication and integration?
DNA polymerase inhibitors
Reverse transcriptase (RT) inhibitors
Integrate inhibition
What do DNA polymerase inhibits do and what are some uses for them?
They prevent viral DNA from making copies of itself
Used for DNA viruses - HSV1,2 VZV, cytomegalovirus (associated with AIDS)
What do reverse transcriptase (RT) inhibitors do and give a use?
They prevent RNA turning into DNA copies.
Used for RNA retrovirus (HIV), AIDS
What do integrase inhibitors do and give an example?
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
Side effects of integrase inhibitors
GI upset, rash
Rare: hepatitis
What mechanism do DNA polymerase inhibitors work by?
Pro-drug mechanism
Inhibits viral DNA-polymerase and terminates viral DNA chain extension
What DNA polymerase inhibitor is used for herpes viruses?
Acyclovir
What does reverse transcriptase inhibitor lamivudine do?
Analogue of cytosine. Inhibits RT (by competition) and terminates the viral DNA chain.
What do non-nucleoside RT inhibitors like Efavirenz do?
Active in the form that it is given, denatures the active site of RT.
What do protease inhibitors do?
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.
What is the drug regime for AIDS?
Highly active antiretroviral therapy (HAART)
2 nucleoside RT inhibits
Plus one of:
- non nucleoside RT inhibitors
- boosted protease inhibitor
- integrase inhibitor
What are the problems with AIDS drug regime?
Compliance, resistance
Unknown long term?
You can get superficial or systemic fungal disease. Give examples of superficial fungal diseases.
Dermatomycoses (Tinea) - skin, nails, scalp
Candidiasis - mucous membranes: oral, vaginal thrush, skin
You can get superficial or systemic fungal disease. Give examples of systemic fungal diseases.
Candidiasis (communist)
Esp, immunosuppressed (antibiotics)
Give some examples of antifungal drugs
Amphotericin, nystatin, azoles, terbinafine
What does amphotericin and nystatin do?
Binds to ergosterol in membranes (cholesterol). Forms an ion channel pore. Cells lose K+.
What is amphotericin used for and how is it administered?
GIT infection: oral
Systemic infection: i.v. (poor oral absorption)
What is nystatin used for?
C. Albicans
What do Azoles do?
Inhibition synthesis of ergosterol - decreases membrane fluidity so affects membrane-associated enzymes, replication and formation of hyphae (yeast)
Describe imidazoles for superficial infections
For tinea and candida infections
Treatment - usually topical
May cause hypersensitivity
Clotrimazole is common
Describe triazoles for systemic infections
Eg flucconazole
Oral or IV
Enters CSF
Side effects usually mild; hepatitis (rare)
Describe terbinafine
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
