Nonselective antiviral drugs

1. Antiviral drugs
Nonselective Antiviral drugs
Anti-Hepatitis virus
S. Parasuraman, M.Pharm., Ph.D.,
Associate Professor
Faculty of Pharmacy
AIMST University, Malaysia

2. Nonselective Antiviral drugs - Learning
Outcomes
• At the end of this session, the student would be able
to:
– classify nonselective antiviral drugs. (CLO1)
– describe the mechanism of action, pharmacological
actions, pharmacokinetic features, therapeutic uses,
adverse effects, interaction and contraindications of
nonselective antiviral drugs. (CLO1)

3. Nonselective Antiviral drugs
• Several antiviral drugs are relatively virus
nonselective and inhibit viruses belonging to
different classes, includes
– both DNA and RNA viruses.

4. Nonselective Antiviral drugs
Classification of anti-Hepatitis virus/ Nonselective
antiviral drugs
• Primarily for hepatitis B: Lamivudine, Adefovir
dipivoxil, Tenofovir
• Primarily for hepatitis C: Ribavirin, Interferon α

5. Nonselective Antiviral drugs (for hepatitis B)
• Lamivudine – Refer Anti-Retrovirus.
• Adefovir dipivoxil:
– Adefovir is a monophosphate analogue of AMP which is
active against HBV and some other DNA as well as RNA
viruses, but is used only for hepatitis caused by HBV.
Adefovir dipivoxil is an oral prodrug of the nucleotide
analogue adefovir.
– Adefovir is indicated in chronic hepatitis B, including
lamivudine-resistant cases and those having concurrent
HIV infection. There is no cross resistance between
adefovir and lamivudine.
• Tenofovir – Refer Anti-Retrovirus.

6. Nonselective Antiviral drugs (for hepatitis C)
• Ribavirin:
– Ribavirin is a purine nucleoside analogue has broad-
spectrum antiviral activity, including that against
influenza A and B, respiratory syncytial virus and many
other DNA and double stranded RNA viruses.
– Administered orally or i.v. ribavirin has been used in
severe influenza A/B and measles in
immunosuppressed patients as well as for herpes virus
infections, acute hepatitis, but is not a first line drug for
any of these.
– The most common therapeutic use of oral ribavirin is in
chronic hepatitis C.

7. Nonselective Antiviral drugs (for hepatitis C)
• Interferon α:
– Interferon receptors are JAK-STAT tyrosine protein
kinase receptors which on activation phosphorylate
cellular proteins.
– Three types of human IFNs (α, β and γ) are known to
have antiviral activity.
– Interferons (IFNs)are low molecular weight glycoprotein
cytokines produced by host cells in response to viral
infections, Tumor necrosis factor alpha (TNFα), and
Interleukin-1 (IL-1).

8. Nonselective Antiviral drugs (for hepatitis C)
• Interferon α:
– Interferon α have nonspecific antiviral as well as other
complex effects on immunity and cell proliferation.
– Interferons bind to specific cell surface receptors and
affect viral replication at multiple steps, viz. viral
penetration, synthesis of viral mRNA, assembly of viral
particles and their release.

9. Nonselective Antiviral drugs (for hepatitis C)
• Antiviral spectrum of Interferon α:
– Chronic hepatitis B: IFNα2Α 2.5−5 ΜU/m2 or IFNα2Β
5−10 ΜU given 3 times per week for 4–6 months causes
disappearance of HBV-DNA from plasma and
improvement in liver function tests/histology in nearly
half of the patients.
– Chronic hepatitis C: IFNα2Β 3ΜU 3 times weekly for 6–
12 months has produced remission in 50–70% patients.
– Condyloma acuminata: caused by papilloma virus is
usually treated with topical podophyllin.

10. Nonselective Antiviral drugs (for hepatitis C)
• Antiviral spectrum of Interferon α:
– AIDS-related Kaposi’s sarcoma: IFN is used to treat AIDS
related Kaposi’s sarcoma, but not to treat HIV as such.
However, interferon accentuates haematological toxicity
of zidovudine.
– H. simplex, H. zoster and CMV: For these infections in
immunocompromised patients, interferon is inferior to
acyclovir/ganciclovir.
– Chronic myeloid: Interferons are also used in chronic
myeloid leukaemia, follicular lymphoma, cutaneous T-
cell lymphoma and multiple myeloma.

11. Nonselective Antiviral drugs (for hepatitis C)
• Adverse effects of Interferon α:
– Flu-like symptoms: fatigue, aches and pains, malaise,
fever, dizziness, anorexia, nausea, taste and visual
disturbances develop few hours after each injection, but
become milder later.
– Neurotoxicity: numbness, neuropathy, altered behaviour,
mental depression, tremor, sleepiness, rarely convulsions.
– Myelosuppression: dose dependent neutropenia,
thrombocytopenia.
– Thyroid dysfunction: (hypo as well as hyper).
– Others: Hypotension, transient arrhythmias, alopecia and
liver dysfunction.