Antivirus

Antivirus

Viruses are smallest microorganism consist of nucleic acid enclosed in a protein coat (Capsid). They do not have a cell wall and cell membrane. They do not carry out metabolic processes. They depend upon host metabolic processes. It is very difficult to treat virus infection. Antivirus drugs are used to treat viral infection. 

There are two types of viruses:

• DNA Viruses: Smallpox virus, Herpes virus
• RNA Viruses: Influenza virus (Orthomyxovirus)                                                                                                    Measles and mumps virus (Paramixo virus)

Classification: Antiviral drugs are classified depending upon their therapeutic uses.

·         

•        Respiratory tract viral infection treatment

o   Amantadine

o   Ribavirin

o   Rimantadine

• ·         Herpes and Cytomegalovirus infection

o   Acyclovir

o   Cidofovir

o   Famcicloviro   Penciclovir

o   Ganciclovir

o   Trifluridine

• ·         Hepatitis and leukemia due to viral infection

o   Interferon

•          HIV infection treatment

RESPIRATORY TRACT VIRAL INFECTION TREATMENT

Respiratory tract viral infections are caused by Influenza A virus, Influenza B virus and syncytial virus (RSV: Respiratory syncytial virus).Vaccines are available to prevent influenza A virus infection. Immunisation should be preferred. Antiviral drugs are used to prevent and control respiratory tract infections in non-immunized patients. Clinical symptoms of viral infections appear at a later stage of infection. Thus antiviral drugs the inhibit virus replication (virus growth) have very low efficacy. They are mostly used as prophylactic agents.

Amantadine: It is a water-soluble compound that inhibits virus matrix protein M_2. M₂ acts as an ion channel in the virus. Ion channels are used in acid-mediated dissociation of Ribonucleoprotein complex.  This helps fusion of virus in host cell membrane as endosomes. Endosomes have an acidic environment that causes un-coating of the virus and intracellular transport of virus. Amantadine blocks M₂ proteins that inhibit virus multiplication.

Pharmacokinetics: It is well absorbed from GIT, well distributed throughout the body including CSF. It can cross the blood-brain barrier. The unchanged active drug is excreted in urine. Thus it accumulates in a patient body suffering from renal dysfunction.

Adverse Reactions: Nervousness, Confusion, Hallucination, Seizure, and Coma, Loss of appetite, Nausea. It is contraindicated in lactating and pregnant women because it easily crosses the placental barrier and excreted unchanged in lactating mother milk.

Uses: Amantadine is only effective against influenza A virus infection. It is more useful as a prophylactic agent than therapeutic agent. It is used in the epidemic to prevent influenza A virus infection. It is also used as a supplement in vaccination to prevent influenza A virus infection.

As a therapeutic agent, it is particularly useful to treat influenza A virus infection in a nonimmunized patient.

   

Rimantadine: It is analog to amantadine. Its rate absorption from GIT is slower than amantadine but has a high volume of distribution and low CNS toxicity. It is extensively metabolized in the liver and excreted in urine. About 15% unchanged drug is also excreted in urine.

Ribavirin: It is broad-spectrum antiviral agent effective against both RNA and DNA viruse. Ribavirin acts at the various site to block virus replication. Enzyme adenosine kinase converts ribavirin to ribavirin 5 monophosphate (RMP). RMP is phosphorylated to ribavirin triphosphate (RTP). RTP compete with GTP and ATP to block GTP dependent enzymes necessary for mRNA synthesis.

 It is administered by an oral route and intravenous route. It is also used as an aerosol in respiratory tract viral infection. Unchanged drug and its metabolites are excreted in urine.

 Anemia, Increase in bilirubin and uric acid level in blood.

HERPES VIRUS INFECTION TREATMENT

Herpes virus produces various diseases like cold sores, viral encephalitis, genital infection etc.

Acyclovir: It is synthetic purine nucleoside analog. It is highly effective against the herpes virus. Herpes virus enzyme thymidine kinase converts acyclovir to acyclovir monophosphate. Host cells convert acyclovir monophosphate to acyclovir diphosphate and acyclovir triphosphate. Acyclovir triphosphate blocks DNA polymerase enzyme to act on Deoxyguanosine triphosphate. Acyclovir triphosphate incorporates itself to virus DNA. This causes premature DNA chain termination.

Acyclovir triphosphate is more sensitive to viral DNA polymerase enzyme than host cells polymerase enzyme. Virus cells activate acyclovir to acyclovir monophosphate. In absence of virus, acyclovir monophosphate will not be synthesized. Thus acyclovir will not produce its action. Due to these two factors, acyclovir is selective to infected host cells not healthy host cells.

Some viruses do not have enzyme thymidine kinase or polymerase. These viruses are resistant to acyclovir.

Pharmacokinetics: It is administered by intravenous route, oral route, and topical route. It is well distributed throughout the body including CSF. Metabolites are excreted in urine.

Adverse Effects: the Topical application may produce local irritation. Oral administration may develop nausea, vomiting, diarrhea, and headache. High dose of intravenous route develops renal dysfunction.

Therapeutic Uses: It is used in herpes simplex virus type I and II infection. It is more effective in the initial stage of infection. It is the drug of choice to treat herpes simplex encephalitis, genital herpes infection. It is also used as the prophylactic agent.

Famciclovir and Penciclovir: Famciclovir is a prodrug. It is metabolized to active penciclovir. It is used to treat acute herpes zoster. It is administered orally.

Ganciclovir: It is similar to acyclovir. Ganciclovir is more 
than acyclovir. It has very low oral bioavailability thus it is administered by intravenous route. It is well distributed throughout the body and excreted unchanged in urine. Its half-life is about 3-4 hours. Ganciclovir is carcinogenic, embryotoxic and teratogenic.

Foscarnet: It has broad antiviral activity. It inhibits herpes virus DNA polymerase and HIV reverse transcriptase. It is poorly absorbed by oral route thus it is administered by intravenous route. It is well distributed throughout the body. The highest concentration is found in the bone matrix. Unchanged drug is excreted in urine by glomerular filtration.

Adverse Effect: Nephrotoxicity, anemia, nausea, and fever.

Uses: It is used to treat rhinitis in HIV patient. It is also useful in acyclovir-resistant herpes simplex virus.

Vidarabine (Adenine Arabinose): It is adenine nucleoside analog. It has the least toxicity. However, acyclovir is preferred than vidarabine. It is phosphorylated in cells to form vidarabine 5 triphosphate that inhibits viral DNA polymerase i.e. inhibition of viral DNA synthesis. It acts on both host cells and viral DNA polymerase. But it has more affinity for virus DNA polymerase.

Vidarabine is administered by intravenous route. It is quickly metabolized by adenine diamine to hypoxanthine arabinoside. It produces a synergistic effect with vidarabine. It is slightly soluble in water thus it is administered with a large volume of water by the intravenous route. It penetrates into CNS thus it is used to treat encephalitis due to the herpes virus. Vidarabine ointment is used to treat hepatic and vaccinial keratitis. Vidarabine with acyclovir is used in life-threatening virus infection. 

HUMAN DEFICIENCY VIRUS (HIV) INFECTION TREATMENT

Purine and pyrimidine nucleoside forms are used against HIV as an antiretroviral agent. HIV protease inhibitors are also used against HIV.

Zidovudine: It is thymidine analog referred as AZT (Azidothymidine). It is used in HIV 1 virus infection to improve immunity. It also helps to prevent and cure the related infection.

Enzyme thymidine kinase phosphorylates zidovudine to zidovudine triphosphate that competitively inhibits DNA polymerase enzyme (i.e. a reverse transcriptase). Zidovudine has higher affinity with virus DNA polymerase than human DNA polymerase. Zidovudine also terminate chain formation during DNA synthesis. Thymidine and ribavirin antagonize action zidovudine.

Pharmacokinetics: It is well absorbed by the oral route. Food contents slow down the rate of drug absorption but do not affect total absorption of the drug. Drugs are completely absorbed from GIT even in presence of food. It is well distributed in the body including CNS. It is metabolized by glucuronidation into inactive metabolites. It has 1 hr of half-life. Glucoronide metabolites are excreted in urine.

Adverse Effect: Anemia, granulocytopenia, severe headache, seizure.

Didanosine: It belongs to the dideoxynucleoside. It is used to treat Zidovudine resistant HIV infection. It is not used in the initial stage of resistant. It acts as zidovudine. It is metabolized to didanosine adenosine triphosphate (ddATP) by various phosphorylation reaction. ddATP incorporate into DNA to terminate DNA chain elongation (just like zidovudine).

Pharmacokinetics: It is rapidly absorbed from GIT. Alkaline media favor its absorption. Thus it is administered with an antacid or chewable buffered tablet or in a buffered solution. Food in GIT reduces the rate of absorption. Thus it is advisable to administer drug under fasting condition. It is well distributed in the body including CNS. But CNS penetration is less than zidovudine. It is rapidly excreted in urine.  55% of the unchanged drug is also excreted in urine.

Zalcitabine: It is analog of deoxycytidine. Its mechanism of action is similar to Zidovudine. Zalcitabine is well absorbed from GIT, food reduces the rate of absorption. It is well distributed in the body including CNS. But its penetration into CNS is less than Zidovudine. It is metabolized into inactive deoxyuridine. It is excreted in fecal matter. Unchanged zalcitabine is excreted in urine also. Both active and metabolites are excreted in fecal matter.

Adverse Effects: Rash stomatitis peripheral neuropathy, headache mouth ulcer and edema.

Stavdine:

एक छोटी सी कोशिश ... कुछ गलतियाँ है, माफ़ कीजियेगा ...