Chapter 16 – part II

Virus: parasitic microbe

Virion: RNA/DNA covered w/protein• Inserts genetic material healthy cell

Viruses

Antivirals available for many viral infectionsViruses controlled by current antiviral therapy

• Cytomegalovirus (CMV)• Hepatitis viruses• Herpes viruses• Human immunodeficiency virus (HIV)• Influenza viruses (the “flu”)• Respiratory syncytial virus (RSV)

• Retrovirus: Subdivision of viruses, includes HIV

Antiviral Key Terms• Mutable – the mutation of a single nucleotide is sufficient to

render drug ineffective

• Prodrug: A drug that is converted in the body to the active drug

• Nucleoside: A building block of DNA/RNA

Antiviral Drugs

• Prevent viruses from reproducing• Block viral entry into cell – must

work inside of cell• Most agents are pyrimidine or purine

nucleoside analogs• 2 major types• Retrovirus• Non-retrovirus

Classifications of Antivirals

•Non-retroviral Antiviral Agents•Anti-herpesvirus agents•Anti-influenza agents•Anti-hepatic agents

Anti-herpesvirus Agents “-cyclovir”• Nucleoside Analogues • Fool virus into using them instead of nucleoside to construct RNA/DNA.• Halt construction d/t lack of 3’ hydroxyl group

• Acyclovir: • inibitory activity against herpes simplex virus types 1 (HSV-1), 2 (HSV-2), and

varicella-zoster virus (VZV).

• Ganciclovir, Penciclovir: • inhibits viral DNA synthesis

• Valaciclovir: • Prodrug of acyclovir

Anti-influenza Agents “-tadine, -mivir”• Amantadine, (Symmetrel) Rimantadine

• Inhibit protein in early stage of replication (Influenza A)• Tx: sx of Parkinson’s disease

• Zanamivir, (Relenza) Oseltimivir (Tamiflu)• Inhibits neuraminidases (Influenza A + B)• with milk protein allergy

• Ribavirin • (ART) – Antiretroviral therapy:

• serious life-threatening flu ONLY

Anti-hepatitis virus agents – “-fovir, -vudine”• Nucleoside analogs• Hepatitis B• Adefovir, tenofovir • Clevudine, lamivudine, telbivudine

• Hepatitis C• Interferons: boost natural immunity

• Serious infections ONLY • Ribavirin: Category X

• Adverse: fatigue, flu-like sx, anxiety, rash, diarrhea

Classifications of Antivirals

•Antiretroviral AgentsDeveloped for treatment of HIV

*5 types* • NRTIs - Nucleoside reverse transcriptase inhibitors• NNRTIs – Non-nucleoside reverse transcriptase inhibitors• Protease inhibitors• Entry inhibitors/fusion inhibitors• Integrase strand transfer inhibitors

Nucleoside reverse transcriptase inhibitors (NRTIs)

• NRTIs, sometimes called "nucleoside analogues" or "nukes," contain faulty versions of the building blocks (nucleotides) used by reverse transcriptase to convert RNA to DNA. • When reverse transcriptase uses these faulty building blocks, the new

DNA cannot be built correctly. • In turn, HIV's genetic material cannot be incorporated into the

healthy genetic material of the cell and prevents the cell from producing new virus.

NRTIs “-vudine”Prevents protein synthesis in the retroviral cell, which in turn stops reproduction.

• Abacavir, didanosine• Transient risk cardiovascular events

• Stavudine, zidovudine• lipid levels, glucose tolerance

• Prolonged exposure linked to:• Non-cirrhotic portal hypertension• Esophageal varices

• Serious potential risk: Lactic acidosis• Females/Obese• Mortality = 50%

Nucleoside Analog (NRTI)

Non-nucleoside reverse transcriptase inhibitors (NNRTIs)“-virine, -virdine”

• NNRTIs are antiretroviral drugs used in the treatment of HIV. • Inhibit reverse transcriptase (RT)• enzyme that controls the replication of HIV genetic material.

• Reduces ability of enzyme to perform its function• May cause liver damage

Protease Inhibitors

Protease Inhibitors “-navir”

• Suppress viral enzyme protease – needed for replication• Tripanavir, Nelfinavir, Ritonavir, Fosamprenavir

• Associated with:• risk hematuria/bleeding• Intracranial hemorrhage• risk kidney stones (Atazanavir)

Antifungal Agents

Mechanism of action:• Changes permeability of the fungal cell wall• Results in:• Death to cell• Failure to reproduce

Classifications of Antifungal Agents

Divided into 3 groups:• Systemic antifungals

• Polyene macrolides (amphotericin B)• Unclassified systemic antifungals (griseofulvin, fluctosine)

• Azole antifungals• Imidazoles (ketoconazone)• Triazoles (itraconazone, flucanozole) **best broad-spectrum agent**• Echinocandins (caspofungin, micafungin)• Allylamines (terbinafine)

• Topical antifungals

Antiparasitic Agents

• Protozoal infections

• Malaria

• Toxoplasmosis

• Leishmaniasis

• Giardiasis

• Thichomoniasis

• Trypanosomiasis

• Amebiasis

Antiparasitic Agents “-quine”

Individuals with Susceptibility to parasites:• Pregnant women• People with HIV/AIDS

• Antimalarials: work against Plasmodium• Quinine: Preg. Code X • Chloroquine: cross-reacts w/antacids/laxatives• Mefloquine: risk of cardiac arrhythmias• Metronidazole (Flagyl) antiprotozoal/antibiotic

Anthelmintic Agents “-dazole”

Destroys specific wormsTapeworms Round worms Flukes

Protype drug: Mebendazole

**Treat all people in household**