Antivirals

Pharmacology Anti-Virals (College Sec)

1 week of 4th 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 host’s cell energy to synthesize protein, DNA and RNA (genetic parasites) Spread is fast • Viruses are difficult to kill because they live inside our cells • Any drug that kills a virus may also kill ourselves Viral Infections Competent immune system • Best response to viral infection • A well functioning immune system will eliminate or effectively destroy virus replication • Immunocompromised patients have frequent viral infections Cancer patients Transplant patients AIDS patients Viruses Affected by Current Antiviral Therapy

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Cytomegalovirus (CMV) retinitis

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Varicella Zoster Virus (VZV) Chickenpox, shingles

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Human Immunodeficiency Virus (HIV)

Herpes Simplex Virus (HSV) o HSV 1: oral aphthous ulcers o HSV 2: genital ulcers

Influenza A Virus (Flu) Respiratory Synctial Virus (RSV) Hepatitis B Virus (HBV)

Antivirals • Synthetic purine nucleoside analogs •

Two types of nucleosides a. Purine – Guanine, Adenosine b. Pyrimidine – Thymidine, Cytosine

Purine Nucleoside Analogs: Guanines Agent Antiviral Activity Acyclovir(prototype) HSV1, HSV2, VZV Ganciclovir CMV retinitis, systemic CMV infection Ribavirin Influenza A & B, RSV

malta aiko (yin) + mrose (yang)

MOA Acyclovir

Acyclovir monoPO4 Cellular enzymes

Acyclovir triPO4 Acyclovir triPO4 Competes with DGTP thereby inhibiting DNA synthesis and consequently viral replication Side 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 Activity Didanosine (ddI) HIV Vidaribine (Ara-A) HSV, VZV, CMV, EBV (prototype: zidavudine) MOA • Didanosine: Interferes with the HIV RNAdependent DNA polymerase (reverse transcriptase), thus preventing replication of the virus • Vidaribine: inhibits DNA polymerase Side Effects • Didanosine: Pacreatitis (9%), peripheral neuropathies (35%), seizures, retinal depigmentation • Vidaribine: Burning, itching, lacrimation, photophobia Pyrimidine Nucleoside Analogs: Cytosine Agent Antiviral Activity Lamovidine HIV, HBV Zalcitabine HIV (Prototype: zidovudine) MOA (Lamovidine) • Inhibition of HIV reverse transcriptase

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Pharma – Antivirals Dr. Biag

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The monophosphate is incorporated into the viral DNA by HBV polymerase resulting in DNA chain termination

Side Effects • Headache • •

Insomnia Malaise

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Pain Nausea & Vomiting

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Peripheral neuropathy

Pyrimidine Nucleoside Analogs: Thymidine Agent Antiviral Activity Zidovidine (AZT) HIV MOA • Converted to a triPO4 (the active form) by thymidine kinase and other cellular enzymes • Incorporated into growing DNA chain by viral reverse transcriptase, thereby terminating viral replication Side Effects • Bone marrow suppression • Nausea • •

Anorexia Headache

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Fever Cough

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Rash

Other Antivirals 1. Amantadine (Symmetrel) Indication: Influenza A Other Uses: Idiopathic Parkinson’s Disease Postencephalitic Parkinsonism Drug induced extrapyramidal reactions and symptomatic Parkinsonism associated with _______ MOA • As antiviral

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blocks uncoating of Influenza A virus preventing viral replication Antiparkinsonism activity: blocks reuptake of dopa into presynaptic neurons

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increased dopa release from presynaptic fibers

Side Effects • Orthostatic hypotension • •

Peripheral edema Insomnia

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Anorexia Nausea

• Xerostomia 2. Foscarnet (Foscavir) Indication: CMV (retinitis and systemic) MOA • Inhibits the replication of all known herpes virus in vitro Side Effects • Headache (26%), seizures (10%), acute renal failure (27%), nausea (47%), diarrhea (35%), anemia (33%) 3. Indinavir • Antiretroviral agent, protease inhibitor •

HIV-1

Side Effects • Nausea, dyslipedemia, mild discoloration indirect bilirubin

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MOA • Protease inhibitor • HIV protease is required for cleaving viral polyprotein precursors into individual final proteins found in infectious HIV. Inhibition prevents cleavage of these polyproteins resulting in the formation of immature noninfectious viral particles 4. Oseltamivir (Tamiflu) • Neuraminidase inhibitor Preventing the release of nearly formed virus form the surface of the infected cells • Indication: Influenza A & B Side Effects: • Fatigue • Dizziness • •

Headache Nausea & Vomiting

Pharma – Antivirals Dr. Biag

Just to let u know, 4 weeks na lang, end na ang school year 2007-2008 Wala lang, just so you have something to look forward to… (cause I am SURELY looking forward to see this year end, *sigh) Hapi bday ulit sa mga January celebrants 

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