Antiviral Drugs

Question 1

Tenofovir.

Answer 1

It is a monophosphate NUCLEOTIDE analogue.

Uses: Treatment of:

1) Hepatitis B (1st line drug)
2) HIV (1st line drug)

MOA:

• Used as prodrug Tenofovir Disoproxil Fumarate (TDF)
• Gets phosphorylated intracellularly
• Inhibits HBV DNA Polymerase or HIV Reverse Transcriptase
• Also gets incorporated into the proviral DNA to cause chain termination

Resistance to Tenofovir has not developed. It has good tolerability.

S/E:

1. Nephrotoxicity
2. GI intolerance
3. Fanconi syndrome
4. Bone resorption

Should be avoided in renal failure.

Question 2

Uses of interferon beta and gamma.

Answer 2

Beta: Multiple sclerosis
Gamma: Chronic granulomatous disease

Question 3

Uses of interferon alpha.

Answer 3

1. Chronic Hepatitis C
2. Chronic Hepatitis B
3. AIDS related Kaposi sarcoma
4. Condyloma acuninatum
5. HSV, CMV, VZV
6. CML
7. Hairy Cell Leukemia
8. Cutaneous T cell lymphoma

Question 4

Ribavarin- MOA, Uses, Side effects

Answer 4

MOA: Purine nucleoside analogue, gets phosphorylated intracellularly, inhibits viral RNA synthesis and GTP synthesis

Uses:

1) oral route- HCV along with INF alpha or DAA
2) inhalational- Treatment of RSV (DOC)
3) intravenous- severe influenza

Side effects:

1. Hemolytic amemia
2. Bone marrow suppression
3. Teratogenic

Contraindicated in pregnancy.

Question 5

Adverse effects and contraindications of Interferon alpha.

Answer 5

Adverse effects:

1. Flu like syndrome : Fever, malaise, aches and pains
2. Bone marrow suppression : Dose dependent neutropenia, thrombocytopenia
3. Neurotoxicity
4. Liver dysfunction
5. Hypothyroidism (sometimes hyper-)

Contraindications:

1. Pregnancy
2. Cirrhotic patients
3. Autoimmune disease patients

Question 6

Sofosbuvir— Classification, MOA, Use, Side effects, interaction.

Answer 6

Classification: It is an NS5B inhibitor which is a Directly Acting Anti-HCV (DAA) drug. Drugs belonging to this class have certain advantages over INF-alpha for Treatment of HCV.

• Can be given orally
• Much lesser toxicity

MOA of Sofosbuvir:
It inhibits NS5B which is an HCV RNA polymerase. It also gets incorporated into viral RNA and causes chain termination.

Use: As a Fixed Dose combination with Ledipasvir or Daclatasvir or Velpatasvi, it is effective against all genotypes of HCV.
SVR is achieved within 12 weeks in non-cirrhotics and 24 weeks of therapybin cirrhotic patients.

Side effects:

• Bradycardia and cardiac arrest (when used w Amiodarone)
• Joint pain, abdominal pain
• Anemia

Interactions: It is a PGP substrate, hence should not be used with PGP Inducer drugs.