antivirals

Question 1

name some antiviral drugs

Answer 1

Aciclovir & valaciclovir
Ganciclovir & valganciclovir
Foscarnet
Ribavirin
CoVID antivirals

Question 2

Aciclovir

Answer 2

Anti-herpesvirus drug, tried and trusted due in most part to its high selective toxicity.

Typically used to treat or prevent HSV1 HSV2 VZV infection.

Few side effects (accumulation causes neurotoxicity, and maintain hydration/dose adjust in renal dysfunction)

used to treat:
- genital herpes (HSV1 or 2)
- herpes labialis / stomatitis (HSV1)
- disseminated herpes
- herpes keratitis
- chickenpox and shingles

Question 3

aciclovir Mechanism of Action

Answer 3

Pro-drug, activated to a monophosphate by the viral thymidine kinase only in herpesvirus infected cells
Host cell kinases then adds a second and third phosphate group
Aciclovir triphosphate competitively inhibits herpesvirus specific DNA polymerases
Further viral DNA synthesis is inhibited without affecting other normal cellular functions

Question 4

when do we use IV acyclovir?

Answer 4

Oral aciclovir-relatively poor oral bioavailability, necessitating frequent dosing
Severe herpes virus infections
Herpes virus encephalitis
Disseminated herpes (neonatal or congenital herpes)
Severe shingles/opthalmic zoster
Herpes viruses in immunocompromised patients
Extensive eczema herpeticum

Question 5

Valaciclovir and its benefits

Answer 5

L-Valyl ester pro-drug of aciclovir
Tablet with better oral absorption Improves plasma concentration of acyclovir
3-5 x better bioavailability than oral aciclovir
Twice or three times a day dosing versus 4 or 5 times daily
Useful step down after initiation of IV therapy
Patients less likely to forget a dose

Question 6

Ganciclovir

Answer 6

• treats CMV
  Treatment and prophylaxis of CMV infection in immunosuppressed patients such as SOT or HSCT recipients.
  Ganciclovir (9-[(1,3-dihydroxy-2-propoxy)methyl]guanine) is a potent inhibitor of most members of the herpesvirus family.
  Ganciclovir 5’ triphosphate is a selective and potent inhibitor of viral DNA polymerase. Ganciclovir is metabolized to the active triphosphate form.
  3 phosphorylation steps:
  a deoxyguanosine kinase induced by CMV-infected cells (encoded by UL97 region)
  guanylate kinase (cellular)
  phosphoglycerate kinase (cellular) Other nucleotide-metabolizing enzymes may be involved as well.

Question 7

Valganciclovir

Answer 7

• L-Valyl ester of ganciclovir
• VGCV has better absorption in the intestines and better oral bioavailability than oral GCV.
• Valine side chain cleaved by gut esterases, converting it to GCV

Question 8

primary cmv infection

Answer 8

• viral disease
  presents with:
• rash
• atypical white blood cells, sticking rbc together
• swollen lymph nodes

usually isnt problematic and treatment isnt required

Question 9

cmv reactivation

Answer 9

• inflammation of bowel
• pneumonitis