B&L: Antiviral Drugs

Comienza Ya. Es Gratis
ó regístrate con tu dirección de correo electrónico
Rocket clouds
B&L: Antiviral Drugs por Mind Map: B&L: Antiviral Drugs

1. SE

1.1. BMD

1.2. Flu-like Sx

1.3. CNS: depression and suicidal behavior

2. NNRTs ("non-nukes")

2.1. MOA

2.1.1. Bind directly to HIV-RT

2.2. PK

2.2.1. Both undergo hepatic metabolism (CYP3A4) Potent CYP3A4 inducers! MAJOR D-D interaxns!!!

2.3. Efavirenz

2.3.1. Advantages Potent antiviral activity Low pill burden

2.3.2. SE Neuropsychiatric (dl) Teratogenic

2.3.3. PK Metabolized by p450 - mixed inducer/inhibitor

2.4. Nevirapine

2.4.1. Advantage Safe for pregnancy

2.4.2. SE Rash, including rare hypersensitivity rxn Hepatitis

2.4.3. PK Metabolized by p450 - 3A inducer

3. Eliminated by hepatic metab (CYP3A4)

3.1. D-D interaxn potential

4. Serious HSV and CMV infections

5. Herpes viruses: HSV, zoster, CMV

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

5.1.1. TP competitively inhibs viral DNA polymerase

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

5.2. Acyclovir

5.2.1. MOA acyclic guanosine analogs Phosphorylated by viral thymidine kinase

5.2.2. 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

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

5.3. Ganciclovir

5.3.1. MOA Acyclic guanoside analog

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

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

5.4. Foscarnet

5.4.1. 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

5.4.2. Use

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

5.4.4. PK IV only Must titrate dose to Cr clearance

6. Resp. Virus Infections

6.1. Neuraminidase inhibitors

6.1.1. Zanamivir & Oseltamivir Use Influenza A & B Effective against Avain and Swine flu (Flu A H5N1 and H1N1, resp) Zanamivir PK Use SE Osetlamivir PK Use SE

6.2. Viral uncoating inhibitors: Amantadine & Rimantadine

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

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

6.2.3. PK Amantadine crosses BBB!!! Used in Parkinsonism GI nausea, anorexia nervousness, ADD, insomnia

6.2.4. SE CNS Worse with Amantadine

6.3. Resp. Syncytial Virus (RSV): Ribavirin

6.3.1. MOA Competitive inhibitors of Flu A&B neuraminidases Prevents the release of progeny from the host cell

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

6.3.3. MOA Guanosine analog

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

6.3.5. Teratogenic!!!

7. Hepatic Virus Infections

7.1. Ribavirin

7.2. Interferon-alpha

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

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

7.3. Nucleoside analogs

7.3.1. Lamivudine

7.3.2. Entecavir

8. Anti-HIV

8.1. Always used in combination Tx!!!

8.1.1. Triple combo = 2 nukes + 1 other class

8.1.2. Need to prevent resistance

8.1.3. Compliance is a major issue

8.2. Nucleoside analogs ("nukes")

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

8.2.2. Side effects Lactic acidosis Hepatic steatosis

8.2.3. PK Good bioavailability Renally cleared (mostly)

8.2.4. Lamivudine

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

8.2.6. Stavudine

8.2.7. Didanosine

8.3. Protease Inhibitors

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

8.3.2. PK

8.3.3. Good for pregnancy

8.3.4. SE At low dose (50mg) just inhib CYP3A4 to improve bioavailability of other PI in combo GI - NVD Hepatotox Metabolic Body fat redistribution Hyperlipidemia Insulin resistance

8.3.5. Ritonavir use Mostly used for PI boosting

8.3.6. Indinavir

8.3.7. Amprenavir

8.3.8. Nelfinavir

8.3.9. Saquinavir

8.4. Fusion inhibitor

8.4.1. Enfuvirtude

8.5. Entry inhibitor: CCR5 co-receptor antag

8.5.1. Maraviroc

8.6. Integrase inhib

8.6.1. Raltegravir