Antivirals Flashcards
What type of drugs are anti-herpes virus drugs?
Nucleoside inhibitors of DNA polymerase
What type of molecules are anti-herpes virus drugs?
Purine or pyrimidine nucleoside analogues (guanosine)
Give 5 anti-herpes virus drugs
- Aciclovir
- Valaciclovir
- Ganciclovir
- Famciclovir
- Foscarnet
What is the mechanism of action of anti-herpes virus drugs?
They are converted to nucleoside triphosphate by viral and cellular kinases that are incorporated into viral DNA to decrease the rate of chain elongation, and so they are chain terminators
What is the antiviral spectrum of anti-herpes virus drugs?
- Herpes simplex virus
- Varicella zoster virus
- CMV
What is aciclovir used to treat?
- HSV-1
- HSV-2
- VZV
What is the mechanism of action of aciclovir?
First phosphorylation step is carried by a specific viral enzyme, thymidylate kinase, which leads to chain termination, directly inhibiting DNA polymerase
How are some viruses resistant to aciclovir?
- May lack thymidylate kinase (TK-)
- Possess mutations in the TK gene
- Mutations that prevent DNA polymerase from binding to acyclovir triphosphate
For what is aciclovir the treatment of choice?
- Herpes simplex encephalitis
- Varicella-zoster virus infections
- Fever blisters
- Genital herpes
How is aciclovir given when treating herpes simplex encephalitis?
IV
When is aciclovir given to treat VZV infections?
When the patient is >50 years old
What are fever blisters also known as?
Herpes labialis
How is aciclovir given when treating fever blisters?
Topically
How is aciclovir given when treating genital herpes?
- Topical
- Oral
- IV
What happens when aciclovir is given to patients with renal failure?
It accumulates
Does aciclovir have action against CMV?
No
What are the oral analogues of aciclovir?
- Valaciclovir
- Famciclovir
What is ganciclovir the treatment of choice for?
CMV infections, and its associated conditions
What conditions are associated with CMV infection?
- Retinitis
- Pneumonia
- Colitis
- Pneumonitis
In whom are CMV infections treated with ganciclovir?
Patients with AIDS, or are immunocompromised
How is the mechanism of action of ganciclovir like aciclovir?
It must be activated by phosphorylation, the triphosphate form of GCV inhibits the viral DNA polymerase
How is the mechanism of action of ganciclovir unlike aciclovir?
Phosphorylation of GCV is catalysed by phosphotransferase enzymes, both cellular and viral, and therefore GCV is activated in uninfected cells as well as infected cells, unlike aciclovir, which can only be activated by virally encoded TK
In whom is ganciclovir given as prophylaxis?
Transplant patients
Is the oral bioavailability of ganciclovir high or low?
Low
What is the result of the low oral bioavailability of ganciclovir?
It must be given IV, or valganciclovir given (much higher oral bioavailability)
What is the mechanism of action of foscarnet?
Prevents addition of nucleoside triphosphate dNTP to viral DNA, limiting the extension of the viral DNA strand
Does foscarnet phosphorylate?
No
What is foscarnet active against?
- HSV-1
- HSV-2
- CMV
- HIV
Why is foscarnet active against HIV?
Because it inhibits HIV reverse transcriptase
What are the anti-retroviral drugs (HAART)?
- Reverse transcriptase inhibitors (RTIs)I
- Integrase inhibitors
- Protease inhibitors
- Viral entry inhibitors
What are the types of RTIs?
- Nucleoside RTIS (NRTI)
- Non-nucleoside RTIs (NNRTI)
How do NRTIs and NNRTIs differ?
NRTIs have less activity on the host DNA polymerase
Give 5 NRTIs
- Zidovudine
- Didanosine
- Zalcitabine
- Zerit
- Tenofovir
Give 3 NNRTIs
- Nevirapine
- Delaverdine
- Efavirenz
What should NNRTIs not be used as?
Monotherapy
Why should NNRTIs not be used as monotherapy?
Because of resistant mutants
Give an example of a integrase inhibitor?
Raltegravir
Give 4 protease inhibitors
- Indinavir
- Saquinavir
- Lopinavir
- Aprenavir
Give two viral entry inhibitors?
- Fuzeon
- Maraviroc
What is fuzeon active against?
gp41
What is maraviroc active against?
CCR5
What are the types of anti-influenza drugs?
- Anti-influenza A drugs
- Anti-influenza B drugs
What are the types of anti-influenza A drugs?
- Inhibitors of early events
- Neuroaminidase inhibitors
What is the mechanism of action of anti-influenza A drugs that inhibit early events?
Adamantanes (M2 ion channel) inhibitors
Give two anti-influenza A drugs that are inhibitors of early events
- Amantadine
- Rimantadine
What type of drugs are anti-influenza B drugs?
Neuraminidase inhibitors
Give 2 neuraminidase inhibitors
- Zanamavir
- Oseltamavir
What is the trade name of zanamavir?
Relenza
What is the trade name of oseltamavir?
Tamiflu
Label this diagram
- A - NS2
- B - Lipid bilayer
- C - NA (Neurominidase)
- D - HA (Hemagglutinin)
- E - M2 (ion channel)
- F - M1 (matrix protein)
- G - NP (nucleocapsid)
- H - PB1, PB2, PA (transcriptase complex)
What is neuraminidase required for?
- For the virus to escape the infected cell
- To penetrate the mucus in the airway
What is the M2 ion channel important for?
Uncoating of the virus
