Clinical Use of Antiviral Drugs

Question 1

HERPES VIRUS:
What are the 4 types?
——————–

Aciclovir (ACV):
What is it used for?

What does it do?
→ What are the steps it takes to do this?
→ Why does it only kill the viral DNA?

What is Valaciclovir?
→ What is it used for?
——————–

Ganciclovir:
What is it used for?

What does it do? How does it do it?

What is Valaganciclovir?
→ What is it used for?
——————–

Foscarnet:
What is it used for?

What does it do?

Who is it not used in? Why? When can it only be used?

Cidofovir:
What is it used for? How does it differ from Foscarnet?

Resistance:
What are the 2 ways Herpes virus can develop resistance?
→ In who does it rarely happen?

Answer 1

• • Herpes Simplex (HSV) - Cold sores, Genital ulcers
  • Varicella Zoster (VZV) - Chickenpox, Shingles
  • Cytomegalovirus (CMV)
  • Epstein-Barr (EBV) - Infectious mononucleosis (Glandular fever)
  ——————–
• HSV treatment, ZSV treatment and prophylaxis, and CMV/EBV prophylaxis
• Inhibits Viral DNA synthesis
  → • ACV phosphorylated by a HSV Thymidine Kinase (TK) and a cellular TK into ACV Triphosphate
  • ACV Triphosphate competes with dGTP to bind to growing DNA - Once it binds, it stops any further growth = Cell death
  → ACV Triphosphate has more affinity for the viral DNA polymerase compared to the cell’s DNA polymerase = Selective Toxicity
• Prodrug of Aciclovir (Valine ester attached)
  → VSV in Immunocompromised patients or CMV
  prophylaxis in transplant patients
  ——————–
• CMV - Treatment of reactivated infection after organ transplant, Congenital infection in a Newborn, and Prophylaxis after organ transplant
• Inhibits Viral DNA synthesis by doing the same thing as Aciclovir
• Prodrug of Ganciclovir (Valine ester attached)
  → Treatment and prophylaxis of CMV
  ——————–
• CMV infection in Immunocompromised patients
• Inhibits Viral DNA synthesis
• Renal Transplant patients with CMV reactivation due to its Nephrotoxicity - Only used if there’s Ganciclovir resistance
• CMV, but is much more Nephrotoxic than Foscarnet
• Inhibits Viral DNA synthesis
• 1. Thymidine Kinase mutants - Drugs that don’t need to be phosphorylated are still effective e.g. Foscarnet, Cidofovir
     
     2. DNA Polymerase mutants - All drugs become less effective
        → Immunocompetent patients

Question 2

INFLUENZA:
What does Zanamivir and Oseltamivir do? How?

How does Amantadine work?

Why does this virus become resistant so quickly?

Answer 2

• Inhibits virus release from infected cells by inhibiting Neuraminidase
• Inhibits virus uncoating by blocking the M2 protein when inside cells and the assembly of Haemagglutinin
• Only needs 1 amino acid change to become resistant

Question 3

VIRAL HEPATITIS:
What does Chronic infection of Hep B and C lead to?

What can be given for treatment of Hep B?
→ Does this cure the patient?

What can be given for treatment of Hep C?
→ Does this cure the patient?

Answer 3

• Cirrhosis and Liver Cancer (Hepatocellular Carcinoma)
• Lamivudine, Tenofovir, Entecavir, Adefovir - Used by itself or in combination
  → Not curative but reduces risk of cirrhosis and cancer
• Pegylated Interferon + Ribavirin, Sofosbuvir + Velpatsavir
  → Curable in many patients

Question 4

HIV:
What are the steps of its infection?

What is used to reduce the risk of resistance? Why is this used?

What are the different Anti-retrovirals?

Answer 4

• • GP120 binds to CD4 receptor and CCR5 coreceptor for Penetration and Uncoating
  • RNA then reverse transcribed into DNA = Production of viral proteins
• Combination therapy as it evolves very quickly
• Reverse Transcriptase Inhibitors, Protease Inhibitors, CCR5 Inhibitors and Integrase Inhibitors - All combined into 1 pill