Antiviral

Antiviral Drugs

earlier treatment give best result

Classification of viral infections

Herpes simplex and varicella-zoster
Human immunodeficiency
Influenza A
Cytomegalovirus
Respiratory Syncytial virus (RSV)
Drugs that modulate the host immune system

Herpes simplex and varicella-zoster

Acyclovir
Valacyclovir
famciclovir

Acyclovir

Mechanism of action
Inhibits viral DNA synthesis only after phosphorylation by virus-specific thymidine kinase,this account for its high theraputic index.
The phosphorylated acyclovir inhibits DNA polymerase in the virus and so prevents virus DNA formation
It is effective against susceptible Herpes viruses if started early in the course of infection, but it does not eradicate persistent infection because viral DNA is integrated in the host genome.


Acyclovir
Clinical uses
Herpes simplex virus
Skin infections, including initial and recurrent labial and genital herpes
Ocular keratitis
Encephalitis, disseminated disease (IV)
Prophylaxis and Rx of immune compromised pt.
In shingles

Acyclovir (clinical uses)

Varicella-zoster virus
Chickenpox, particularly in the immunocompromised (IV) or in the immunocompetent with pneumonitis or hepatitis (IV)
Shingles in immunocompetent persons

Acyclovir

Adverse effects
Ophthalmic ointment causes a mild transient stinging sensation
gastrointestinal symptoms, headache, and neuropsychiatric reactions in large dose.

Human immunodeficiency

Nucleoside reverse transcriptase inhibitors
Protease inhibitors
Non- nucleoside reverse transcriptase inhibitors
Entry inhibitor


Nucleoside reverse transcriptase inhibitors
Zidovudine (Retrovir)
Didanosine
Lamivudine

Zidovudine (Retrovir)

Mechanism of action
HIV replicate by converting single strand RNA into double strand DNA which is incorporate to host DNA this conversion by enzyme reverse transcriptase,
ZIDOVUDINE Has a high affinity for HIV’s reverse transcriptase and is integrated by it into the viral DNA chain causing premature chain termination. The drug must be present continuously.

Zidovudine (Retrovir)

Clinical uses
Serious manifestations of HIV infection in patients with acquired immunodeficiency syndrome or AIDs related complex
Adverse effects
Anorexia, nausea, vomiting, Headache, dizziness, Malaise and myalgia
Anemia and neutropenia when tolerance develop.
Hepatic necrosis .

Protease inhibitors (amprenavir)

Mechanism of action
In its process of replication, 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


Protease inhibitors
Adverse effects
GIT disturbance nausea,vomitting,diarrhea, headache, dizziness, sleep disturbance, pancreatitis, neutropenia, and rashes, increase liver enzyme.hypertriglyceridemia ,hyperglycemia,hypercholesterolemia ,paresthesia ,accumelation of fat at the base of neck.

Non-nucleoside reverse transcriptase

Used in africa HIV1
Efavirenz treatment result in increase CD4+ CELL
And decrease in viral load ,oral absorption,well distri-
buted icluding CNS ,once day dosing T1/2 40 h,cause headache ,dizziness,rash.

Entry inhibitor

Enfuvirtide
is the first antiretroviral agent to target the host cell attachment/entry stage in the HIV replication cycle.
Given sub.cut,adverse effect related to injection pain
Erythema,induration,nodule,it is expensive.

Influenza A

Amantadine
Zanamivir
Oseltamivir (Tamiflu)


Amantadine
Is only effective only against influenza A; it acts by interfering with the uncoating and release of viral genome into the host cell.
Clinical Uses
Used orally for the prevention and treatment of infection with influenza A virus

Adverse effects

Dizziness, nervousness, and insomnia

Zanamivir

Is a viral neuraminidase inhibitor that blocks both entry of influenza A and B viruses to target cells.
Neuraminidase is enzyme important in life cycle of virus administer prior to exposure prevent release of new virions and spread from cell to cell, if we give it 24-48 hs of symptom appear decrease intensity and duration of disease.

Oseltamivir (Tamiflu)

Is an oral pro-drug of a viral neuraminidase inhibitor. it reduces the severity and duration of symptoms caused by influenza A or B
Is one option for treatment and prophylaxis of avian H5N1 influenza ,adverse effect GIT discomfort,so
Take with food,Zanamivir inhaled irritate R.T ,broncho
Spasm.

Cytomegalovirus

Ganciclovir
Resembles acyclovir in its mode of action, but is much more toxic,used in CMV retinitis in immunocomp-
Romised patient,given I.V.distribute in body,CSF,
Exc,in urine,it is carcenogenic,teratogenic,
neutropenia.


Respiratory syncytial virus (RSV)
Ribavirin is a synthetic guanosine nucleoside ,broad spectrum activity against RNA & DNA viruses used for RSV bronchiolitis in infants and children, inhaled by a special ventilator,used in chronic hepatitis infection C in combination with interferonα
it inhibit replication of RNA &DNA viruses ,it block RNA dependent RNA polymerase, used I.V
Orally,aerosol,cause anemia,increase bilirubin.

Drugs that modulate the host immune system

Interferons
Directly on uninfected cells to induce enzymes that degrade viral RNA
Indirectly by stimulating the immune system
To modify cell regulator mechanisms and inhibit neoplastic growth

Drugs that modulate the host immune system

Interferons
Interferons are cassified as alfa, beta, gamma according to their antigenic and physical properties.
Interferon alfa 2 a and 2b also improve the manifestations of viral hepatitis.it is used intralesional
,subcutaneous,IV.
Adverse effects
Are common and include an influenza-like syndrome

Drugs that modulate the host immune system

Imiquimod
is used topically for genital warts (caused by papillomaviruses). Treatment for 2-3 months results in gradual clearance of warts in about 50% patients.