B&L: Antiviral Drugs

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B&L: Antiviral Drugs by Mind Map: B&L: Antiviral Drugs

1. Herpes viruses: HSV, zoster, CMV

1.1. Most drugs are nucleoside analogs (metabolite is TP)

1.1.1. TP competitively inhibs viral DNA polymerase

1.1.2. Express highly selective toxicity Initial conversion occurs via VIRAL kinase

1.2. Acyclovir

1.2.1. MOA acyclic guanosine analogs Phosphorylated by viral thymidine kinase

1.2.2. Use HSV-1, HSV-2, VZV HSV encephalitis (type I herpes) DOC: serious HSV infections!!! Famici-/valacyclovir: oral forms used to Tx genital herpes and shingles

1.2.3. Side effects Well tolerated po IV Acute renal failure Nuerotox

1.3. Ganciclovir

1.3.1. MOA Acyclic guanoside analog

1.3.2. Use Prv and Tx of CMV Prv of CMV reactivation in transplant pts

1.3.3. Side effects Greater tox than Acy- d/t less selectivity BMD Additive effect with AZT CNS: Headache, behavioral changes, convulsions, coma

1.4. Foscarnet

1.4.1. MOA NOT a nucleoside analog (i.e. does not require activation by kinases Pyrophosphate analog Blocks pyrophos binding site & inhib cleavage of pyrophos from dNTPs

1.4.2. Use Serious HSV and CMV infections

1.4.3. SE Renal insufficiency Hyopcalcemia Cardiac arrythmias d/t electrolyte imbalance

1.4.4. PK IV only Must titrate dose to Cr clearance

2. Resp. Virus Infections

2.1. Neuraminidase inhibitors

2.1.1. Zanamivir & Oseltamivir Use Influenza A & B MOA Competitive inhibitors of Flu A&B neuraminidases Effective against Avain and Swine flu (Flu A H5N1 and H1N1, resp) Zanamivir PK Use SE Osetlamivir PK Use SE

2.2. Viral uncoating inhibitors: Amantadine & Rimantadine

2.2.1. Use Influenza A Not effective against Avian and Swine flu Pre-exposure prophylaxis Like in a nursing home epidemic

2.2.2. MOA Prevents uncoating of viral RNA Inhib viral proton channel M2

2.2.3. PK Amantadine crosses BBB!!! Used in Parkinsonism

2.2.4. SE GI nausea, anorexia CNS nervousness, ADD, insomnia Worse with Amantadine

2.3. Resp. Syncytial Virus (RSV): Ribavirin

2.3.1. Use Severe RSV in infants and kids Hep C In combo w/ IF-alpha

2.3.2. MOA Guanosine analog

2.3.3. SE Inhalation: reversible decline in pulm fn Oral: Anemia

2.3.4. Teratogenic!!!

3. Hepatic Virus Infections

3.1. Ribavirin

3.2. Interferon-alpha

3.2.1. MOA Turns on gene expression of proteins w/ antiviral effects

3.2.2. SE BMD Flu-like Sx CNS: depression and suicidal behavior

3.2.3. Use Hep B (in combo w/ Ribavirin) Hep C

3.3. Nucleoside analogs

3.3.1. Lamivudine

3.3.2. Entecavir

4. Anti-HIV

4.1. Always used in combination Tx!!!

4.1.1. Triple combo = 2 nukes + 1 other class

4.1.2. Need to prevent resistance

4.1.3. Compliance is a major issue

4.2. Nucleoside analogs ("nukes")

4.2.1. MOA: Triphophate inhibits HIV reverse transcriptase selective for virus Also causes chain termination

4.2.2. Side effects Lactic acidosis Hepatic steatosis

4.2.3. PK Good bioavailability Renally cleared (mostly)

4.2.4. Lamivudine Good for pregnancy

4.2.5. Zidovudine (AZT) SE BMD anemia neutropenia Good for pregnancy Single dose at birth used to reduce MTCT

4.2.6. Stavudine

4.2.7. Didanosine

4.3. NNRTs ("non-nukes")

4.3.1. MOA Bind directly to HIV-RT

4.3.2. PK Both undergo hepatic metabolism (CYP3A4) Potent CYP3A4 inducers!

4.3.3. Efavirenz Advantages Potent antiviral activity Low pill burden SE Neuropsychiatric (dl) Teratogenic PK Metabolized by p450 - mixed inducer/inhibitor

4.3.4. Nevirapine Advantage Safe for pregnancy SE Rash, including rare hypersensitivity rxn Hepatitis PK Metabolized by p450 - 3A inducer

4.4. Protease Inhibitors

4.4.1. MOA Competative inhibition of viral protease Sits in the virus's active site Prevents immature virions from becoming mature, infections viruses

4.4.2. PK Eliminated by hepatic metab (CYP3A4) D-D interaxn potential

4.4.3. SE GI - NVD Hepatotox Metabolic Body fat redistribution Hyperlipidemia Insulin resistance

4.4.4. Ritonavir use Mostly used for PI boosting

4.4.5. Indinavir

4.4.6. Amprenavir

4.4.7. Nelfinavir

4.4.8. Saquinavir

4.5. Fusion inhibitor

4.5.1. Enfuvirtude

4.6. Entry inhibitor: CCR5 co-receptor antag

4.6.1. Maraviroc

4.7. Integrase inhib

4.7.1. Raltegravir