Anti Viral Agents
Antiviral Agents viral replication Adsorption
Penetration
Uncoating
Biosynthesis
Maturation
Release
Antiviral Drugs
Classification of Antiviral Drugs: Drugs directly impair viral replication
Drugs modulate the host I – system
Agents to treat HSV and VZV infections
(Acyclovir, Valacyclovir, and Famciclovir)Pharmacokinetic of Acyclovir
Oral, i.v, topical. Bioavailability is 15-20%.
Cleared primarily by glomerular filtration and tubular secretion.
T1\2=3hr
Cerebrospinal fluid concentrations are 50% of serum values.
Administration and metabolism of acyclovir
Indications for Acyclovir1. Herpes simplex virus
2. Varicella - zoster virus:
Chickenpox
Shingles
Adverse reactions
Stinging sensation and a diffuse superficial punctate keratopathy.
Gastrointestinal symptoms, headache and neuropsychiatric reactions, severe local inflammation with i.v.
Agents to treat cytomegalovirus (CMV)
Infections Ganciclovir, Valganciclovir, Cidofovir Ganciclovir Orall or i.v,
Poor bioavailability.
Eliminated in the urine, mainly unchanged (tl/2 4h).
Administration and metabolism of ganciclovir
Indications for Ganciclovir Include Life - threatening (CMV) infection
For maintenance suppressive treatment of retinitis in patients with AIDS
Prevention (CMV) following organ transplantation
Adverse Reactions of Ganciclovir
Neutropenia and thrombocytopenia fever, rash, gastrointestinal symptoms, confusion and seizure
Concomitant use of potential marrow - depressant drugs, e.g cotrimoxazole, zidovudine, should be avoided.
Antiretroviral Agents
Nucleoside reverse transcriptase inhibitors (NRTIs).
Non nucleoside reverse transcriptase inhibitors (NNRTIs).
Protease inhibitors (PIs).
Zidovudine (NRTIs)
Well absorbed
Distributed to most body tissues and fluids.
Eliminated primarily by renal excretion following glucuronidation in the liver.
Indications for Zidovudine
HIV infection in patients with acquired immunodeficiency syndrome (AIDS) or AIDS related complex.
Drug Interaction of Zidovudine
Myelosuppressive drugs such as ganciclovir, ribavirin, and cytotoxic
agent toxicity.
Probenecid, Serum levels of zidovudine acid through decreased its clearance.
(NNRTIs) Nevirapine
It used in combination with at least two other
antiretroviral
It penetrates the CSF
Hepatic metabolis m.
Rash and hepatitis are the commonest side effects.
Protease Inhibitors
(Ritronavir, Indinavir, Saquinavir)
HIV produces protein and also a protease which cleaves the protein into component parts that are subsequently reassembled into virus particles; protease inhibitors disrupt this essential process.
Some Adverse effect of HIV protease inhibitors
Drug Interactions with protease inhibitors
1. Enzyme inducer P450 ( e.g) rifampicin.
2. Enzyme inhibitors (e.g) ketoconazole, cimetidine.
Anti-influenza Agents
Amantadine
Active against influenza A virus
Mechanism of action: interfering with the uncoating and release of viral genome into the host cell.
PK:
Well absorbed from the GIT.
It Is eliminated in the urine.
Amantadine Adverse Reactions
Dizziness, insomnia, headedness and nervousness, Drowsiness, hallucinations, delirium, coma may occur in patients with impaired renal function. Convulsions may be induced, and amantadine should be avoided in epileptic patients.
Respiratory Syncytial Virus (RIBAVIRIN)
Interferons (Hepatic Viral Infection)
1. Directly on uninfected cells to induce enzymes that degrade viral RNA.2. Indirectly by stimulating the immune system.
Uses of Interferon
Alfa Interferon used for hairy cell leukaemia, recurrent or metastatic renal cell carcinoma, Kaposi's sarcoma in AIDS patients
Alfa-2α and -2b improve the manifestations of viral hepatitis, B and C. hepatitis C may need prolonged therapy.
Adverse reactions of interferon
An influenza-like syndrome
Fatigue &anoroxia
Convulsions, depression
Hypotension, hypertension, cardiac arrhythmias
Bone marrow depression.
It inhibit the metabolism of theophylline
Inosine Pranobex
Mucocutaneous herpes simplex and genital warts.
It is administered by mouth and metabolised to uric acid.
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