Anti Viral Drugs

Dr Bikash Meher Asst. Prof AIIMS,Bhubaneswar

Contents

Introduction

Classification of antiviral drugs

Major site of action of antiviral drugs

Individual drugs

M.O.A

Uses

Adverse effects

Introduction

Steps of Viral replication

Antiviral therapy

Vaccination

Stimulating host immune mechanism

Antiviral drug therapy

Problems in antiviral drug therapy

Antiviral drug is toxic to host cells

Some viruses multiply in both cytoplasm as well as nucleus

Antiviral drugs most effective during rapid multiplications

Latent virus not affected by antiviral drugs

Ideal antiviral agents

Low toxicity to host

Greater selectivity

Should kill latent viruses as well

Classification of antiviral drugs

1.Based on

mechanism of

action

2.Based on type of virus

against which active

Based on mechanismInhibitors of attachment Enfuvirtide

Dosaconol

Inhibitors of un coating Amantadine

Inhibitors of Reverse transcriptase

ZidovudineLamivudine

Nucleic acid synthesis inhibitors

AcyclovirRibavarin

Inhibition of release of progeny virus

OseltamivirZanamivir

Other Interferons

Acyclovir

Guanine derivative pro drug

Mechanism of action

P/K

20% bioavailability

Bioavailability not affected by food

Widely distributed in most tissue

CSF conc. Is 50% of plasma conc.

T1/2- 3hr

Uses

Primary genital herpes

• 5% ointment locally 6 times a day for 10 days• 1gm/day in 5 divided doses

Recurrent genital herpes

• 5mg/kg IV infused over 1 hr• Repeated 8 hrly for 10 days

Mucocutaneous herpes Keratoconjuctivitis

• 5% ointment locally 6 times a day for 5days• 1gm/day in 5 divided doses

Chickenpox

• 15mg/kg/day for 7days

Varicella zoster

• 15mg/kg/day for 7days• 10mg/kg/8hr IV for 10 days

Herpes simplex encephalitis

• Acyclovir 10mg/kg/8hr IV for 10 days

Adverse effects

Stinging and burning sensation

Nausea,Vomiting,Diarrhea,Headache,Malaise

Vomiting,Rash,Sweating,Hypotension

Renal dysfunction,Nerotoxicity

Q.Tick the unwanted effects of intravenous acyclovir infusion

A. Renal insufficiency, tremors, delirium

B. Rash, diarrhea, nausea

C. Neuropathy, abdominal pain

D. Anemia, neutropenia, nausea, insomnia

Valcyclovir

L-Valyl ester of acyclovir

Bioavailability is 50-75%

More effective in herpes zoster

Dose -1gmBD for 1 week

Use in prevention CMV infection

A/E

GI intolerance in AIDS

Neurotoxicity,TTP,HUS in organ transplant pts

Ganciclovir

Guanine analogue of acyclovir

Poor bioavailability(8-10%)

More active against CMV

Accumulated in vitreous humor

Use in CMV infection,Acyclovir resistant HSV infection

For prevention of CMV in organ transplant patients

Dose 5mg/kg BD IV

A/E Myelosuppresion

Zidovudine potentiate myelosuppresion

Cyclosporine potentiate nephrotoxicity

Probencid increase ganciclovir level

Foscarnet Inorganic pyrophosphate derivative

Doesn't require phopsphorylation

Inhibits DNA polymerase activity

Poor bioavailability

Acyclovir resistant HSV infections,CMV retinitis

A/E

Renal toxicity

Electrolyte disturbance,anemia,lekopenia

Cidofovir Cytidine analogue

Cidofovir diphosphate Inhibits DNA polymerase

Poor bioavailability

Not metabolized significantly and excreted in urine unchanged

For CMV retinitis,HSV mucocutaneous reaction

PML,Molluscum contgiosom

A/E

Nephrotoxicity,↓IOP,Uveitis,Neutropenia

Adefovir dipivoxil Adenosine analogue

For HBV

Absorption is NOT affected by food

Active against lamivudine resistant strain of HBV

A/E

Sore throat,Headache,Abdominal pain, Flu syndrome

Nephrotoxicity,Lactic acidosis,Hepatomegaly

Dose 10 mg OD

Amantadine

Tricycline amine

Influenza A specific

No Cross resistance with zanamivir and oseltamivir

M.O.A

Adverse Effects

GI intolerance

CNS side effects

Anticholinergic effects

Teratogenic

CI in gastric ulcer and CNS disease

Uses

Prophylaxis of influenza A2

Treatment of influenza A2

Dose 100mg BD

Rimantadine

Methyl derivative of amantadine

More potent, Long acting

Less neurotoxic,High GIT intolerance

Dose 100mg BD

Zanamivir

Inhibits neuraminidase

Effective for both influenza A and B

Treatment should be started within 1-2 days

Poor bioavailability, Poor plasma protein binding

Used as inhalation

Dose -10mg BD a day for 5 days

Precipitate bronchospasm

Nasal and throat discomfort, GI disturbance

M.O.A

Oseltamivir

Prodrug

Oseltamivir carboxylate-active form

Dose

75 mg BD for treatment and 75 mg OD for prevention

A/E Nausea,Vomiting,Dirrhea,Abdominal pain,Seizures

Aggravation of diabetes

Telbivudine Thymidine nucleoside analogue Undergoes triple phophorylation Inhibits HBV DNA polymerase Bioavailability is NOT altered by food No known interaction with drugs affecting CYPp-450 More effective than lamivudine A/E Abdominal pain,headache Lactic acidosis,hepatomegaly,steatosis

Ribavarin

Purine nucleoside analogue

Broad spectrum antiviral activity

Bioavailability -50%

Inhibits Viral RNA polymerase

Uses

Influenza

Hepatitis C

Bronchiolitis

Dose 200mg QID

A/E

Anemia,BMD,Hemolysis

Teratogenic

Interferon

Low molecular weight glycoprotein

Nonspecific antiviral

Affect viral replication at multiple levels

Viral protein synthesis

Host specific

Uses

Chronic hepatitis B

AIDS related kaposi sarcoma

Chronic hepatitis C

Condyloma acuminata

H.simple,H zoster,CMV

Side effects

Flu like symptoms

Neurotoxicity

Myelosuppression

Thyroid dysfunction

Alopecia

Thank You

Fomivirsen

• Oligonucleotide• Anti CMV agent• Inhibits m-RNA synthesis• Selective accumulation in retina and vitreous humor• Use in CMV retinitis• A/E• Iritis vitreitis IOP• Cidofovir increase risk of occular inflammation