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Antivirals

Antivirals

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Published by sarguss14

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Published by: sarguss14 on Jan 06, 2009
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03/18/2013

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PharmacologyAnti-Virals (College Sec)
1 week of 4
th
Shift
Understanding Viruses
:
 
Viral replication:-A virus cannot replicate on its own-It must attach to and enter a host cell-It then uses the hosts cell energy tosynthesize protein, DNA and RNA (geneticparasites)-Spread is fast
Viruses are difficult to kill because they live insideour cells
Any drug that kills a virus may also kill ourselvesViral InfectionsCompetent immune system
Best response to viral infection
A well functioning immune system will eliminateor effectively destroy virus replication
Immunocompromised patients have frequent viralinfections-Cancer patients-Transplant patients-AIDS patientsViruses Affected by Current Antiviral Therapy
Cytomegalovirus (CMV) retinitis
Herpes Simplex Virus (HSV)
o
HSV 1: oral aphthous ulcers
o
HSV 2: genital ulcers
Varicella Zoster Virus (VZV)-Chickenpox, shingles
Human Immunodeficiency Virus (HIV)
Influenza A Virus (Flu)
Respiratory Synctial Virus (RSV)
Hepatitis B Virus (HBV)
Antivirals
Synthetic purine nucleoside analogs
 Two types of nucleosidesa.Purine – Guanine, Adenosine
b.
Pyrimidine – Thymidine, Cytosine
Purine Nucleoside Analogs: Guanines
Agent Antiviral ActivityAcyclovir(prototype)HSV1, HSV2, VZVGanciclovirCMV retinitis, systemic CMVinfectionRibavirinInfluenza A & B, RSVMOAAcyclovir Acyclovir monoPO4Acyclovir triPO4Acyclovir triPO4-Competes with DGTP thereby inhibiting DNAsynthesis and consequently viral replicationSide Effects
Acyclovir: rash, nausea & vomiting, headache,lethargy, dizziness, seizures, confusion, agitation,impaired renal function
Ganciclovir: bone marrow toxicity, fever, nausea,anorexia, vomiting
Purine Nucleoside Analogs: Adenosine
Agent Antiviral ActivityDidanosine (ddI)HIVVidaribine (Ara-A)HSV, VZV, CMV, EBV(prototype: zidavudine)MOA
Didanosine: Interferes with the HIV RNA-dependent DNA polymerase (reversetranscriptase), thus preventing replication of thevirus
Vidaribine: inhibits DNA polymeraseSide Effects
Didanosine: Pacreatitis (9%), peripheralneuropathies (35%), seizures, retinaldepigmentation
Vidaribine: Burning, itching, lacrimation,photophobia
Pyrimidine Nucleoside Analogs: Cytosine
Agent Antiviral ActivityLamovidineHIV, HBVZalcitabineHIV(Prototype: zidovudine)MOA
 
(Lamovidine)
Inhibition of HIV reverse transcriptase
 
malta aiko
(yin) +
mrose
(yang)1 of 3
Cellular enzymes
 
Pharma
– Antivirals
 Dr. Biag
Page
2
of 3
 The monophosphate is incorporated into the viralDNA by HBV polymerase resulting in DNA chainterminationSide Effects
Headache
Insomnia
Malaise
Pain
Nausea & Vomiting
Peripheral neuropathy
Pyrimidine Nucleoside Analogs: Thymidine
Agent Antiviral ActivityZidovidine (AZT)HIVMOA
Converted to a triPO4 (the active form) bythymidine kinase and other cellular enzymes
Incorporated into growing DNA chain by viralreverse transcriptase, thereby terminating viralreplicationSide Effects
Bone marrow suppression
Nausea
Anorexia
Headache
Fever
Cough
Rash
Other Antivirals1.Amantadine (Symmetrel)
Indication: Influenza AOther Uses:-Idiopathic Parkinson’s Disease-Postencephalitic Parkinsonism-Drug induced extrapyramidal reactionsand symptomatic Parkinsonism associatedwith _______ MOA
As antiviral
-
blocks uncoating of Influenza A viruspreventing viral replication
Antiparkinsonism activity:-blocks reuptake of dopa into presynapticneurons-increased dopa release from presynapticfibersSide Effects
Orthostatic hypotension
Peripheral edema
Insomnia
Anorexia
Nausea
Xerostomia
2.Foscarnet (Foscavir)
Indication: CMV (retinitis and systemic)MOA
Inhibits the replication of all known herpesvirus in vitroSide Effects
Headache (26%), seizures (10%), acute renalfailure (27%), nausea (47%), diarrhea (35%),anemia (33%)
3.Indinavir
Antiretroviral agent, protease inhibitor
HIV-1Side Effects
Nausea, dyslipedemia, mild discoloration of indirect bilirubinMOA
Protease inhibitor
HIV protease is required for cleaving viralpolyprotein precursors into individual finalproteins found in infectious HIV. Inhibitionprevents cleavage of these polyproteinsresulting in the formation of immature non-infectious viral particles
4.Oseltamivir (Tamiflu)
Neuraminidase inhibitor-Preventing the release of nearly formedvirus form the surface of the infected cells
Indication: Influenza A & BSide Effects:
Fatigue
Dizziness
Headache
Nausea & Vomiting

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