antiviral drugs(non retro-viral)
TRANSCRIPT
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Anti Viral Drugs
Dr Bikash Meher Asst. Prof AIIMS,Bhubaneswar
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Contents
Introduction
Classification of antiviral drugs
Major site of action of antiviral drugs
Individual drugs
M.O.A
Uses
Adverse effects
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Introduction
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Steps of Viral replication
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Antiviral therapy
Vaccination
Stimulating host immune mechanism
Antiviral drug therapy
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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
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Ideal antiviral agents
Low toxicity to host
Greater selectivity
Should kill latent viruses as well
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Classification of antiviral drugs
1.Based on
mechanism of
action
2.Based on type of virus
against which active
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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
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Acyclovir
Guanine derivative pro drug
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Mechanism of action
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P/K
20% bioavailability
Bioavailability not affected by food
Widely distributed in most tissue
CSF conc. Is 50% of plasma conc.
T1/2- 3hr
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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
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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
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Adverse effects
Stinging and burning sensation
Nausea,Vomiting,Diarrhea,Headache,Malaise
Vomiting,Rash,Sweating,Hypotension
Renal dysfunction,Nerotoxicity
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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
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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
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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
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A/E Myelosuppresion
Zidovudine potentiate myelosuppresion
Cyclosporine potentiate nephrotoxicity
Probencid increase ganciclovir level
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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
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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
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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
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Amantadine
Tricycline amine
Influenza A specific
No Cross resistance with zanamivir and oseltamivir
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M.O.A
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Adverse Effects
GI intolerance
CNS side effects
Anticholinergic effects
Teratogenic
CI in gastric ulcer and CNS disease
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Uses
Prophylaxis of influenza A2
Treatment of influenza A2
Dose 100mg BD
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Rimantadine
Methyl derivative of amantadine
More potent, Long acting
Less neurotoxic,High GIT intolerance
Dose 100mg BD
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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
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M.O.A
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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
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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
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Ribavarin
Purine nucleoside analogue
Broad spectrum antiviral activity
Bioavailability -50%
Inhibits Viral RNA polymerase
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Uses
Influenza
Hepatitis C
Bronchiolitis
Dose 200mg QID
A/E
Anemia,BMD,Hemolysis
Teratogenic
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Interferon
Low molecular weight glycoprotein
Nonspecific antiviral
Affect viral replication at multiple levels
Viral protein synthesis
Host specific
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Uses
Chronic hepatitis B
AIDS related kaposi sarcoma
Chronic hepatitis C
Condyloma acuminata
H.simple,H zoster,CMV
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Side effects
Flu like symptoms
Neurotoxicity
Myelosuppression
Thyroid dysfunction
Alopecia
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Thank You
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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