Antiviral Drugs

Harindu Udapitiya.Temporary Lecturer,Division Of Pharmacology,Department of Oral Medicine & Periodontology.

Overview

• 1.Introduction to virus and replication.• 2.Targets of Antivirals.• 3.Antiviral Drugs.

– Mode of Action– Pharmacokinetics– Clinical Use– Adverse effects

1.Introduction to virus and replication.

Structure of a virus

Viral Replication

Targets of Antiviral Drugs

• 1.Inhibition of penetration & attachment to host cells.

• 2.DNA polymarase inhibitors• 3.Reverse Transcriptase inhibitors• 4.Protease inhibitors• 5.Inhibitors of virus release.

Antiviral Drugs

• 1.Inhibition of penetration & attachment to host cells.

I. Amantidine

II. Immunoglobulin

2.DNA polymarase inhibitors.III. Aciclovir

IV. Ganciclovir

V. Tribavirin

• 3.Reverse Transcriptase inhibitorsI. Zidovudine

II. Lamivudine

• 4.Protease inhibitorsI. Saquinavir

II. Ritonavir

• 5.Inhibitors of virus release.I. Oseltamivir

II. Zanamivir

• 6.Interferones(INF)

• 1.Inhibition of penetration & attachment to host cells

Amantidine

• Mode of actionBlocks M2 receptors

• PharmacokineticsWell absorbed orallyT1/2=3hElimination-renally

• Adverse Effects Anxiety Insomnia Hallucination

Immunoglobulin

• Contains antibodies which are directed against the virus envelope and can 'neutralise' some viruses and prevent their attachment to host cells.

• Use in,– Measles– infectious hepatitis– German measles– Rabies– poliomyelitis

• 2.DNA polymarase inhibitors.

Aciclovir

•Mechanism of action Aciclovir viral thiamidine kinase Aciclovir monophosphate

DNA polymarase Aciclovir triphosphate

• Pharmacokinetics Oral,IV,Topical oral BA 10-20% Plasma T1/2-2-3h Distribute 50% to CSF Elimination-Renal

• Adverse EffectsReversible nephropathyHeadache,nauseaEncephalopathy

• Clinical Use Varicella zoster-shingells,chikenpox Herpes zoster Prophylactically for immunocompramised patients.

Gangcyclovir

• MOASame as aciclovir

• Pharmacokinetics IV,oral T1/2=4h Elimination-renal

• Adverse Effects Bone marrow suppresion Potential carcinogenicity

• Clinical Use– CMV infection

3.Reverse Transcriptase inhibitors

Zidovudine

• Necleoside analog• Oral,iv,rectal• Oral BA=75%• T1/2=05-3h• Elimination=renal• Use in treatement for HIV infection & as

post exposure prophylactic.

4.Protease inhibitors

Saquinavir

• Uses with combination of ritonavir.• Oral• Protein binding 98%• T1/2=9-15 h• Use in HIV therapy.

5.Inhibitors of virus release.

Oseltamivir

• Oral BA=75%• Oseltamivr hepatic estarase oseltamivir

carboxylase• Widely distributed through body• T1/2=6-10h• Elimination=renal• Use in Influenza A,B• Adverse effects

– Nausea,vomiting,abdominal pain

Zanamivir

• Oral,inhalation• Oral BA=2%• T1/2=2.5-5h• Elimination-renal• Use in infl A & B• Adverse effects

– Broncospasms– Cough

Interferones

• Interferons are a family of inducible proteins synthesised by mammalian cells

• They induce, in host cell ribosomes, the production of enzymes that inhibit the translation of viral mRNA into viral proteins, thus halting viral replication.

• Wide sprectum of use.

• Iv,Im• T1/2=2-4h• Clinical use

Hepatitis B & C

• Adverse effecctsFeverMyelgiaBM suppression Rashes

Summery• 1.Introduction to virus and replication.• 2.Targets of Antivirals.• 3.Antiviral Drugs

– Amantidine– Immunoglobulin– Aciclovir– Gangcyclovir– Zidovudine– Saqunavir– Oseltamivir– Zanamivir

• Interferones

Furthur reading…

1. Viral vaccines

2. DNA & RNA Viruses

3. HIV treatment.