Antiviral Agents and Mechanisms
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Questions and Answers

What are the two main ways antiviral agents can be effective against viruses?

Antiviral agents can block viral entry into or exit from the cell, or they can be active inside the host cell.

Why are non-selective inhibitors of virus replication concerning?

They may interfere with host cell functions, which can lead to toxicity.

List one antiviral drug used in monotherapy for herpes simplex virus.

Acyclovir is used in monotherapy for herpes simplex virus.

Identify the three steps involved in viral replication.

<p>The steps are adsorption and penetration, synthesis of viral nucleic acid, assembly of viral particles, and release from the host cell.</p> Signup and view all the answers

What is the significance of the capsid in a virus?

<p>The capsid protects the viral nucleic acid and aids in its infection of host cells.</p> Signup and view all the answers

What type of viruses do acyclovir and its related drugs specifically target?

<p>They specifically target Herpes Simplex Virus (HSV-1 and HSV-2) and Varicella-Zoster Virus.</p> Signup and view all the answers

What are the implications of using dual therapy for prolonged periods in treating HCV?

<p>Dual therapy, like interferon alfa/ribavirin, may improve treatment efficacy but can also increase the risk of side effects.</p> Signup and view all the answers

Why are viruses classified as obligate intracellular parasites?

<p>Because their replication solely depends on the synthetic processes of a host cell.</p> Signup and view all the answers

What is the role of reverse transcriptase in retroviral replication?

<p>Reverse transcriptase serves as an RNA-dependent DNA polymerase that synthesizes a double-stranded DNA copy from the retroviral genomic RNA.</p> Signup and view all the answers

Name the two different classes of reverse transcriptase inhibitors.

<p>The two classes are nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs).</p> Signup and view all the answers

What combinations of NRTIs are recommended for most treatment-naïve patients?

<p>A regimen typically includes two different NRTIs combined with an integrase strand transfer inhibitor (INSTI).</p> Signup and view all the answers

Identify two specific NRTIs commonly used in HIV treatment.

<p>Tenofovir alafenamide (TAF) and Emtricitabine (FTC) are two commonly used NRTIs.</p> Signup and view all the answers

Describe the mechanism of action of NRTIs.

<p>NRTIs inhibit reverse transcriptase by mimicking nucleotides, causing early termination of the viral DNA strand.</p> Signup and view all the answers

What is the significance of integrating the provirus into host DNA?

<p>Integration allows the retrovirus to replicate and produce new viral particles as the host cell divides.</p> Signup and view all the answers

State a potential requirement for dosage adjustment of NRTIs.

<p>Most NRTIs require dosage adjustment in cases of renal dysfunction.</p> Signup and view all the answers

What is the significance of drug combinations like Truvada in HIV treatment?

<p>Drug combinations like Truvada provide a synergistic effect, enhancing the efficacy of HIV treatment.</p> Signup and view all the answers

What is the primary indication for the use of acyclovir?

<p>Acyclovir is primarily indicated for severe HSV infections like encephalitis and severe outbreaks among HIV patients.</p> Signup and view all the answers

In what scenarios is cytomegalovirus (CMV) particularly concerning?

<p>CMV is especially concerning during pregnancy and for individuals with weakened immune systems.</p> Signup and view all the answers

What is the mechanism of action for ganciclovir?

<p>Ganciclovir acts by being integrated into viral DNA and inhibiting DNA polymerase, thereby halting viral replication.</p> Signup and view all the answers

How does the potency of ganciclovir compare to acyclovir for treating CMV?

<p>Ganciclovir's activity against CMV is up to 100 times greater than that of acyclovir.</p> Signup and view all the answers

What is the bioavailability of oral ganciclovir and how does it affect its use?

<p>The bioavailability of oral ganciclovir is poor, limiting its effectiveness in outpatient treatment.</p> Signup and view all the answers

What drugs are mentioned as agents for cytomegalovirus treatment?

<p>Ganciclovir, valganciclovir, and cidofovir are the drugs mentioned for treating cytomegalovirus.</p> Signup and view all the answers

What is the typical half-life of ganciclovir in the body?

<p>The typical half-life of ganciclovir is approximately 4 hours.</p> Signup and view all the answers

How is the clearance of ganciclovir related to kidney function?

<p>The clearance of ganciclovir is linearly related to creatinine clearance.</p> Signup and view all the answers

What are protease inhibitors used for in relation to hepatitis C virus (HCV)?

<p>Protease inhibitors are used to treat HCV but are not active against HIV.</p> Signup and view all the answers

Which protease inhibitor can be used unboosted, and under what conditions is this recommended?

<p>Atazanavir can be used unboosted, and this is recommended only for selected patients.</p> Signup and view all the answers

What is the role of ritonavir in the administration of protease inhibitors?

<p>Ritonavir acts as a booster to inhibit drug-metabolizing enzymes, enhancing the efficacy of other protease inhibitors.</p> Signup and view all the answers

How do entry inhibitors like Maraviroc function in blocking HIV infection?

<p>Maraviroc targets the CCR5 receptor, a coreceptor for HIV entry into the host cell.</p> Signup and view all the answers

What is the primary mechanism of action (MOA) of HIV protease inhibitors?

<p>HIV protease inhibitors prevent the cleavage of polyproteins by inhibiting the HIV protease enzyme, leading to immature viral particles.</p> Signup and view all the answers

Name one combination of protease inhibitor with a booster agent, and provide its commercial name.

<p>Darunavir/cobicistat is a combination, known commercially as Prezcobix.</p> Signup and view all the answers

What type of adverse effects are associated with protease inhibitors, particularly regarding cardiovascular health?

<p>Protease inhibitors can have adverse cardiovascular effects, requiring patients to make appropriate lifestyle changes.</p> Signup and view all the answers

What is the significance of conducting tropism testing before initiating treatment with Maraviroc?

<p>Tropism testing ensures that the CCR5 receptor is being targeted since Maraviroc only works against HIV that utilizes CCR5 for entry.</p> Signup and view all the answers

What is the primary mechanism of action of Adefovir Dipivoxil in treating hepatitis B?

<p>It competitively inhibits HBV DNA polymerase and causes chain termination after incorporation into the viral DNA.</p> Signup and view all the answers

List the four classes of direct-acting antiviral agents (DAAs) used in hepatitis C treatment.

<ol> <li>NS3/4A protease inhibitors, 2. NS5B nucleoside polymerase inhibitors, 3. NS5B non-nucleoside polymerase inhibitors, 4. NS5A inhibitors.</li> </ol> Signup and view all the answers

Considering the case study, what is the most appropriate treatment for CMV retinitis in the patient?

<p>Ganciclovir.</p> Signup and view all the answers

What is the primary goal of hepatitis C antiviral drugs?

<p>The primary goal is viral eradication.</p> Signup and view all the answers

What were the mainstays of chronic hepatitis C treatment before the introduction of DAAs?

<p>Peg-interferon alpha-2a, Peg-interferon alpha-2b, and Ribavirin.</p> Signup and view all the answers

What is the mechanism of action (MOA) of Enfuvirtide in the treatment of HIV?

<p>Enfuvirtide binds to the gp41 viral protein, preventing conformational changes necessary for viral fusion with host cells.</p> Signup and view all the answers

What is the black box warning associated with Maraviroc?

<p>Maraviroc has a black box warning for hepatotoxicity.</p> Signup and view all the answers

Which combination therapy contains the integrase inhibitor Elvitegravir?

<p>The combination therapy Elvitegravir/cobicistat/Emtricitabine/Tenofovir disoproxil fumarate is known as Stribild.</p> Signup and view all the answers

What role does integrase play in HIV replication?

<p>Integrase facilitates the transfer of viral DNA into the host cell's genome, a critical step for HIV replication.</p> Signup and view all the answers

How are influenza A virus strains classified?

<p>Influenza A strains are classified by core proteins (A, B, C) and subtypes based on surface proteins H (hemagglutinin) and N (neuraminidase).</p> Signup and view all the answers

What is the effect of adamantines on influenza A viruses?

<p>Adamantines inhibit un-coating during the early stage of influenza A virus replication.</p> Signup and view all the answers

Which HIV medications are classified as nucleoside reverse transcriptase inhibitors (NRTIs)?

<p>Abacavir, Lamivudine, Emtricitabine, and Tenofovir are classified as NRTIs.</p> Signup and view all the answers

What disease do Influenza B viruses primarily infect?

<p>Influenza B viruses usually infect only humans.</p> Signup and view all the answers

Study Notes

Pharmacology 3: Anti-Viral Drugs

  • Viruses are characterized as either exceptionally complex non-living chemical aggregations or exceptionally simple living microbes.
  • Viruses are obligate intracellular parasites, meaning their replication relies on the synthetic processes of the host cell.
  • Effective antiviral agents either block viral entry/exit or are active inside the host cell.
  • Non-selective viral replication inhibitors can be toxic to host cells.
  • Treatment periods vary depending on the virus:
    • Monotherapy (e.g., acyclovir for herpes simplex virus) for short periods.
    • Dual therapy (e.g., interferon alfa/ribavirin for HCV) for prolonged durations.
    • Multiple drug therapy (e.g., for HIV) for indefinite periods.
  • Virus structure includes: an envelope, capsid, nucleic acid (DNA or RNA).
  • Viral replication involves stages like adsorption, penetration, uncoating, synthesis, assembly, and release.
  • Retrovirus Replication involves stages like uncoating, endocytosis, integration (nucleas), DNA transcription, mRNA production, budding, assembly, and releasing new virions.
  • Specific antiviral drugs and their uses:
    • Acyclovir is a guanosine analog for herpes simplex virus (HSV-1 & 2) and Varicella-Zoster virus (VZV).
    • Valacyclovir & Famciclovir are pro-drugs of acyclovir.
    • Ganciclovir is a nucleoside analogue for cytomegalovirus (CMV).
    • Foscarnet is a pyrophosphate analog for inhibiting DNA polymerase for CMV.
    • Cidofovir is a nucleotide analogue for CMV, with similar mechanism to ganciclovir.
    • Interferon-α is a cytokine that increases the formation of antiviral proteins.
  • Pharmacokinetics of acyclovir:
    • Poorly absorbed orally. Bioavailability 15-20%.
    • Unaffected by food.
    • Cmax 1.5-2 hours post-dosing.
    • Five times daily dosage orally for HSV treatment.
  • Acyclovir and valacyclovir/famciclovir are better absorbed orally and can be administered less frequently.
  • IV acyclovir is for severe HSV infections like encephalitis.
  • Acyclovir is primarily excreted via glomerular filtration and tubular secretion. Half-life is 3 hours in normal renal function patients.
  • Topically applied acyclovir produces high local concentrations in herpetic sores, with undetectable systemic concentrations. CSF values are 50% of serum values.
  • Drug crosses the blood-brain barrier and metabolites appear in urine.
  • Clinical administration routes: oral, IV, and topical.
  • Resistance to antiviral drugs such as acyclovir can occur.
  • Agents such as foscarnet, cidofovir, and trifluridine do not require activation by thymidine kinase, thus having improved activity against acyclovir resistant strains.
  • Treatment of herpes simplex virus, oral herpes, genital herpes, HSV, encephalitis, VZV shingles.
  • Adverse effects of acyclovir include nephrotoxicity.
  • Crystallization of acyclovir is preventable by hydration.
  • Other CNS effects (seizures, tremors) and common side effects (nausea, diarrhea, rash) are also possible, Thrombotic thrombocytopenic purpura has been documented in HIV patients receiving valacyclovir.
  • Ganciclovir and valganciclovir are effective against CMV infections.
  • Clinically important uses for antiviral drugs include preventing or treating severe or difficult-to-treat herpes simplex virus infections and cytomegalovirus Infections.
  • CMV infection results in end-organ disease (retinitis, colitis, esophagitis, CNS disease, pneumonitis).
  • Cidofovir is effective in treating CMV retinitis, colitis, esophagitis, and acyclovir-resistant HSV & VZV infections.
  • Foscarnet has a crucial role in treating CMV retinitis and colitis and other infections that have developed resistance to acyclovir.
  • Adverse effects include renal impairment, nephrotoxicity, hypo-/hypercalcemia, hypo-/hyperphosphatemia, hypokalemia, hypomagnesemia, genital ulcerations possibly due to high ionized drug levels in urine, anorexia, nausea, vomiting, anemia, elevation of liver enzymes, fatigue, CNS toxicity (headache, hallucinations, seizures), toxicity risk additive with concurrent HIV drugs.
  • Important notes on drug interactions and administration: need to monitor kidney function, and the use of combinations.
  • Specific drugs like ganciclovir, valganciclovir, cidofovir, and foscarnet are used in treatment-naïve and prophylaxis, as well as salvage regimens and are important in HIV and CMV infections.
  • Antiretroviral combination therapy with a minimum of three agents reduces the likelihood of resistance emergence and increases the effectiveness of treatment for HIV.
  • Classes of anti-retroviral agents include NRTIs, NNRTIs, protease inhibitors, entry/fusion inhibitors, integrase inhibitors, and drug combinations.
  • Anti-influenza drugs includes amantadine, rimantadine; and others such as oseltamivir and zanamivir which are neuraminidase inhibitors.
  • The neuraminidase inhibitors in clinical use are oseltamivir, zanamivir, peramivir.
  • Oseltamivir and zanamivir are used orally & inhaled respectively to treat influenza A and B infections and can reduce the duration of symptoms if used within 24 hours of onset.
  • Antiviral drugs for hepatitis B infection primarily suppress the virus rather than curing it.
  • Effective agents include interferon alpha-2a, lamivudine, adefovir dipivoxil, entecavir, telbivudine, tenofovir, & ribavirin
  • HCV treatment is centered on achieving viral eradication for the infection with current regimens.
  • Four types of direct-acting antiviral agents (DAAs) are used, including NS3/4A protease inhibitors, NS5B nucleoside polymerase inhibitors, NS5B non-nucleoside polymerase inhibitors and NS5A inhibitors.

Case Study and Questions

  • A 43-year-old male HIV patient presents with blurry vision, eye pain in both eyes with CD4 count of 43.
  • The most likely cause is CMV retinitis. The appropriate treatment is ganciclovir.

Pregnancy Classification for Antiviral Drugs

  • A table with categories (C) and (B) for pregnancy classification of selected antiviral drugs.

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Description

This quiz explores the mechanisms of antiviral agents, including their action against viruses, the significance of viral components, and treatment strategies for conditions like herpes and HCV. Test your knowledge on antiviral drugs, including NRTIs and their implications in therapy.

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