Pharm 484: Chemotherapy and Antiviral Agents
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Questions and Answers

Where do DNA viruses usually enter to direct the generation of new viruses?

  • Host cell cytoplasm
  • Host cell nucleus (correct)
  • Host cell ribosomes
  • Host cell membrane

    • Which of the following RNA viruses involves the host cell nucleus during replication?

  • Measles virus
  • Polio virus
  • Influenza virus (correct)
  • Rabies virus

    • What is the primary function of enzymes synthesized during DNA virus replication?

  • To inhibit host cell enzymes
  • To break down host cell proteins
  • To synthesize more viral DNA (correct)
  • To destroy host cell nucleus

    • Which of the following is a type of DNA virus?

    <p>Adenovirus</p> Signup and view all the answers

    How do RNA viruses replicate in the host cell?

    <p>Using enzymes in the virion</p> Signup and view all the answers

    Which of the following is NOT a type of RNA virus?

    <p>Hepatitis B virus</p> Signup and view all the answers

    What happens to the viral DNA after it enters the host cell nucleus during DNA virus replication?

    <p>It is transcribed into mRNA by host cell RNA polymerase</p> Signup and view all the answers

    What is the final step of DNA virus replication?

    <p>Release of complete virions by budding or cell lysis</p> Signup and view all the answers

    What is the mechanism of action of Amantadine?

    <p>Blocks the ion channel of the viral membrane protein, M2</p> Signup and view all the answers

    How is Amantadine excreted?

    <p>Secreted unchanged in urine</p> Signup and view all the answers

    What is the side effect of Amantadine?

    <p>Dizziness and insomnia</p> Signup and view all the answers

    What is the name of the anti-influenza agent that is a prodrug and RNA polymerase inhibitor?

    <p>Remdesivir</p> Signup and view all the answers

    How is Remdesivir administered?

    <p>Administered slowly over 2 hours</p> Signup and view all the answers

    What is the loading dose of Remdesivir?

    <p>200mg</p> Signup and view all the answers

    What is the name of the virus that causes COVID-19?

    <p>SARS-CoV-2</p> Signup and view all the answers

    How is COVID-19 transmitted?

    <p>Through respiratory droplets and contact with contaminated surfaces</p> Signup and view all the answers

    What is the primary objective of the course Pharm 484?

    <p>To provide knowledge of agents used in viral infections</p> Signup and view all the answers

    What is the focus of the 'Recap - virology' section?

    <p>Life cycle, pathogenesis, and types of viruses</p> Signup and view all the answers

    What is the term for viruses that are small infective agents or obligate intracellular parasites?

    <p>Viruses</p> Signup and view all the answers

    What is the mechanism of action of Miraviroc?

    <p>Inhibiting fusion of viral and host cellular membranes</p> Signup and view all the answers

    What is the purpose of HAART treatment?

    <p>To treat HIV infection</p> Signup and view all the answers

    What is a side effect of Miraviroc?

    <p>Cough</p> Signup and view all the answers

    What is the term for the inhibitors that target the reverse transcription stage of the HIV life cycle?

    <p>Nucleotide Reverse Transcriptase inhibitors (NRTIs)</p> Signup and view all the answers

    What is the purpose of immunization and vaccination?

    <p>To prevent viral infections</p> Signup and view all the answers

    What is the result of NRTIs action on HIV DNA chain production?

    <p>Premature termination</p> Signup and view all the answers

    What is the term for the agents that inhibit the entry of HIV into the host cell?

    <p>Entry and fusion inhibitors</p> Signup and view all the answers

    What is the purpose of phosphorylation of NRTIs?

    <p>To give the 5'-trisphosphate</p> Signup and view all the answers

    Why are phosphorylated emtricitabine, lamivudine, and tenofovir considered safe?

    <p>They have low affinity for DNA polymerase</p> Signup and view all the answers

    What is the focus of the 'Antiretroviral drug Interactions' section?

    <p>Interactions between antiretroviral drugs</p> Signup and view all the answers

    What is the consequence of giving NRTIs as single drugs alone?

    <p>Rapid development of resistance</p> Signup and view all the answers

    Why are NRTIs not involved in clinically significant pharmacokinetic drug interactions?

    <p>They are not substrates for hepatic cytochrome P450 enzymes</p> Signup and view all the answers

    What is the target of NRTIs action?

    <p>Reverse transcriptase enzyme</p> Signup and view all the answers

    What percentage of the plasma level of the drug is found in the CSF?

    <p>45%</p> Signup and view all the answers

    What is the purpose of administering the drug to the parturient mother and the neonate?

    <p>To prevent mother-to-baby transmission of HIV</p> Signup and view all the answers

    What is the name of the skin condition that may develop in some cases?

    <p>Stevens-Johnson syndrome</p> Signup and view all the answers

    How do Protease Inhibitors (PIs) work?

    <p>By inhibiting maturation of virion</p> Signup and view all the answers

    Which of the following PIs has the highest CSF levels?

    <p>Indinavir</p> Signup and view all the answers

    What is a common side effect of Protease Inhibitors?

    <p>Metabolic abnormalities</p> Signup and view all the answers

    How are PIs administered?

    <p>Orally</p> Signup and view all the answers

    What happens when PIs inhibit the cytochrome P450 enzymes?

    <p>Metabolic abnormalities occur</p> Signup and view all the answers

    Study Notes

    Course Objectives and Outcomes

    • Provide knowledge of agents used in viral infections
    • Discuss agents used in viral infections
    • Classify antiviral agents
    • Demonstrate knowledge of the spectrum of antiviral agents
    • Explain the mechanism of action of antiviral agents

    Viral Infections

    • Viruses are small infective agents/obligate intracellular parasites consisting of RNA or DNA enclosed in a capsid
    • DNA viruses usually enter the host cell nucleus and direct the generation of new viruses
    • RNA viruses direct the generation of new viruses, usually without involving the host cell nucleus

    RNA Viruses

    • Examples:
      • Orthomyxoviruses (influenza)
      • Paramyxoviruses (measles, mumps)
      • Rubella virus (German measles)
      • Rhabdoviruses (rabies)
      • Picornaviruses (colds, meningitis, poliomyelitis, hepatitis A)
      • Arenaviruses (meningitis, Lassa fever)
      • Hepadnaviruses (serum hepatitis)
      • Arboviruses (arthropod-borne encephalitis and various fevers, e.g. yellow fever)
      • Flaviviruses (West Nile meningoencephalitis, yellow fever, hepatitis C)
      • Coronaviruses (colds, severe acute respiratory syndrome [SARS])

    DNA Viruses

    • Examples:
      • Poxviruses (smallpox)
      • Herpesviruses (chickenpox, shingles, oral and genital herpes)
      • Adenoviruses (conjunctivitis, sore throat)
      • Hepadnaviruses (hepatitis B virus [HBV])
      • Papillomaviruses (warts)

    DNA Virus Replication

    • Entry of viral DNA into host cell nucleus
    • Transcription of viral DNA into mRNA by host cell RNA polymerase
    • Translation of mRNA into virus-specific proteins
    • Assembly of complete virions and release by budding or cell lysis

    RNA Virus Replication

    • Replication relies on enzymes in the virion which synthesize its mRNA or the viral RNA serves as its own mRNA
    • Similar to Amantadine in its effects/activity

    Amantadine and Rimantadine

    • Mechanism of action:
      • Block the M2 proton ion channel of the virus particle
      • Inhibit uncoating of viral RNA within infected host cells
    • Pharmacokinetics:
      • Amantadine: secreted unchanged in urine
      • Rimantadine: undergoes extensive metabolism
    • Resistance:
      • From mutation in neuraminidase and haemaglutinin
    • Side effects:
      • GI
      • CNS (insomnia, lightheadedness, seizure, hallucination)
      • Dizziness
      • Insomnia
      • Slurred speech

    Anti-Influenza Agents

    • Examples:
      • Oseltamivir
      • Zanamivir
      • Amantadine
      • Rimantadine
      • Adapromine
      • Umefenovir

    Coronavirus

    • COVID-19 caused by the novel SARS-CoV-2
    • Respiratory illness, transmission between people through respiratory droplets and contact with contaminated surfaces
    • Symptoms: unknown
    • Remdesivir:
      • A prodrug, an RNA polymerase inhibitor
      • Disrupts the production of viral RNA, preventing multiplication of the virus
      • Loading dose of 200mg and a maintenance dose of 100mg daily for 5-10 days
      • Administer slowly over 2 hours

    Miraviroc

    • A CCR5 receptor blocker
    • Also a substrate for CYP3A4 enzyme
    • Dosage adjustments may be needed in the presence of drugs that induce or inhibit this enzyme
    • Adverse effects:
      • Cough
      • Diarrhea
      • Muscle and joint pain
      • Increases in hepatic transaminases

    Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

    • Mechanism of action:
      • Cause phosphorylation of reverse transcriptase enzyme and act as a false substrate
      • Lead to premature termination of the production of the HIV DNA chain
      • Resistance rapidly develops if given as single drugs alone (monotherapy)
    • Examples:
      • Emtricitabine
      • Lamivudine
      • Tenofovir

    Protease Inhibitors (PIs)

    • Examples:
      • Saquinavir (SQV)
      • Nelfinavir (NFV)
      • Indinavir (IDV)
      • Ritonavir (RTV)
      • Atazanavir
      • Darunavir
      • Fosamprenavir
      • Amprenavir (AMP)
    • Mechanism of action:
      • Inhibit maturation of virion by interrupting the protein processing by binding to active site of HIV-1 protease enzyme
      • Prevent virus maturation of newly produced virions so that they remain non-infectious
    • Administration:
      • Oral administration
      • All inhibit the cytochrome P450 enzymes (indinavir and saquinavir to a lesser extent than ritonavir)
      • Saquinavir undergoes first-pass metabolism
      • CSF levels are negligible with saquinavir and highest with indinavir (76% of the plasma concentration)
      • Nelfinavir and ritonavir are best taken with food
      • Saquinavir within 2 hours of a meal
    • Side effects:
      • Metabolic abnormalities - insulin resistance, high blood sugar and hyperlipidaemia

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    Description

    This course covers the chemotherapy agents used to treat viral infections, including their classification, spectrum, and mechanism of action.

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