CHEMOTHERAPYHIGHLIGHTS

MOHAMED BAHR; MD, PHD

Antiviral Drugs

Mohamed Bahr; MD, PhD

ANTIVIRAL DRUGS

Mohamed Bahr; MD, PhD

Mohamed Bahr; MD, PhD

STEPS TARGETED BY ANTIVIRAL DRUGS1., 2., 3. Adsorption, penetration, and uncoating: viruses have no

metabolic machinery and have to enter host cell and use its metabolic

processes to replicate.

4. a. Early protein synthesis: synthesis of viral RNA and DNA

polymerases.

b. Synthesis of nucleic acids (RNA and DNA) and coat proteins:

by RNA and DNA polymerases in RNA and DNA viruses respectively. In

HIV, reverse transcriptase makes a DNA copy of viral RNA.

Late structural protein synthesis by viral protease (in HIV) → viral

protein processing → mature virion core.

Mohamed Bahr; MD, PhD

5. Assembly of the formed nucleic acid and coat proteins into

new viral particles.

6. Release of new viral particles from host cell, facilitated by

neuraminidase.

Mohamed Bahr; MD, PhD

Drug Mechanism Disease

Antiherpesvirus agents 

Inhibits DNA polymerase

 

A. Acyclovir   Herpes: H simplex - H zoster – chickenpox

B. Ganciclovir   CMV pneumonia and retinitis (immunocompromised).

Idoxuridine    

Mohamed Bahr; MD, PhD

Drug Mechanism Disease

Anti-influenza agents  RNA virus  

A. Amantadine Inhibits penetration and uncoating

Influenza A -parkinsonism

B. Oseltamivir C. Zanamivir

Inhibition of neuraminidase → inhibition of viral release

Influenza A (Avian) Influenza B → Prophylaxis – treatment.

Mohamed Bahr; MD, PhD

Antihepatitis agents  Inhibits DNA polymerase  

A. Adefovir dipivoxil    

B. Lamivudine    

C. Interferon-α and Peginterferon-α 2A, 2B

   

Other antiviral agents     

Ribavirin Inhibits RNA polymerase And mRNA synthesis

Hepatitis C (+ IFN) Respiratory syncytial VirusInfluenza A and B

     

Mohamed Bahr; MD, PhD

Retroviral    A. Nucleoside Reverse Transcriptase Inhibitors

   

Zidovudine Inhibit reverse transcriptase → inhibition of replication

 

B. Non-nucleoside Reverse Transcriptase Inhibitors

   

Nevirapine    C. Protease Inhibitors    IndinavirRitonavir

Inhibits protease → inhibition of viral protein processing

 

Entry Inhibitors    Enfuvirtide    

Mohamed Bahr; MD, PhD

IMMUNOGLOBULINS (GAMMA-GLOBULIN) • Pooled immunoglobulins (IgGs) containing antibodies

against virus envelope → inhibition of viral adsorption and

penetration.

• Used before symptoms (viremia) → attenuates or prevents

measles, infectious hepatitis, and poliomyelitis (passive

immunization, offers 3weeks protection).

Mohamed Bahr; MD, PhD

ADVERSE EFFECTS OF ANTIVIRAL DRUGS Acyclovir: N and V, headache, confusion, seizures, renal stones, eye stinging.

Ganciclovir: myelosupression - retinal detachment (with intraocular implants).

Amantadine: insomnia – hallucination.

Zanamivir/Oseltamivir: N and V – nose and throat irritation (inhaled

zanamivir).

Ribavirin: Anemia - upper airway irritation (with aerosol) – teratogenic.

Zidovudine: myelosupression -flu like syndrome - cholestatic hepatitis.

Indinavir: N and V, enzyme inhibitor, renal stones, central adiposity

(cushinoid).

Mohamed Bahr; MD, PhD

Types

IFN-α and and IFN-β: produced by B and T

lymphocytes, macrophages, and fibroblasts, in response to viruses and cytokines →

antiviral effect

IFN-γ: produced by T lymphocytes in response to

viruses, rickettsiae, protozoa →

immunostimulant effect

Pegylated IFN-α: higher efficacy and longer acting

than IFN-α → SC once/wk

Mohamed Bahr; MD, PhD

MECHANISMBind to specific cell membrane receptors → inhibition of viral

penetration, translation, transcription, protein processing,

maturation and release.

↑ Phagocytic activity of macrophages.

↑ Proliferation of cytotoxic T cells.

Mohamed Bahr; MD, PhD

USESHepatitis B and C.

Herpes: Disseminated infections in cancer patients.

HIV infection (AIDs).

Hairy cell leukemia (cytotoxic)

Mohamed Bahr; MD, PhD

ADVERSE EFFECTS1. Flu-like syndrome: fever, chills, myalgia and GIT upset.

2. CNS effects: dizziness - headache- confusion.

3. CVS effects: hypotension- arrhythmias.

4. Bone marrow depression.

5. Alopecia.

Mohamed Bahr; MD, PhD

TREATMENT OF CORONAVIRUS- Traditionally, there were no effective antiviral

agents for coronaviruses.

- Initial efforts focused on the use of currently

available drugs, either conventional antiviral

agents or non-antivirals with inhibitory

effects.

Mohamed Bahr; MD, PhD

REFERENCESLippincott’s Illustrated Reviews, 5th ed.

Color Atlas of Pharmacology, 2nd ed.

Goodman and Gilman's The Pharmacological Basis of

Therapeutics, 12th ed.