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Questions and Answers
Where do DNA viruses usually enter to direct the generation of new viruses?
Which of the following RNA viruses involves the host cell nucleus during replication?
What is the primary function of enzymes synthesized during DNA virus replication?
Which of the following is a type of DNA virus?
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How do RNA viruses replicate in the host cell?
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Which of the following is NOT a type of RNA virus?
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What happens to the viral DNA after it enters the host cell nucleus during DNA virus replication?
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What is the final step of DNA virus replication?
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What is the mechanism of action of Amantadine?
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How is Amantadine excreted?
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What is the side effect of Amantadine?
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What is the name of the anti-influenza agent that is a prodrug and RNA polymerase inhibitor?
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How is Remdesivir administered?
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What is the loading dose of Remdesivir?
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What is the name of the virus that causes COVID-19?
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How is COVID-19 transmitted?
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What is the primary objective of the course Pharm 484?
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What is the focus of the 'Recap - virology' section?
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What is the term for viruses that are small infective agents or obligate intracellular parasites?
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What is the mechanism of action of Miraviroc?
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What is the purpose of HAART treatment?
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What is a side effect of Miraviroc?
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What is the term for the inhibitors that target the reverse transcription stage of the HIV life cycle?
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What is the purpose of immunization and vaccination?
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What is the result of NRTIs action on HIV DNA chain production?
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What is the term for the agents that inhibit the entry of HIV into the host cell?
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What is the purpose of phosphorylation of NRTIs?
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Why are phosphorylated emtricitabine, lamivudine, and tenofovir considered safe?
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What is the focus of the 'Antiretroviral drug Interactions' section?
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What is the consequence of giving NRTIs as single drugs alone?
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Why are NRTIs not involved in clinically significant pharmacokinetic drug interactions?
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What is the target of NRTIs action?
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What percentage of the plasma level of the drug is found in the CSF?
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What is the purpose of administering the drug to the parturient mother and the neonate?
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What is the name of the skin condition that may develop in some cases?
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How do Protease Inhibitors (PIs) work?
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Which of the following PIs has the highest CSF levels?
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What is a common side effect of Protease Inhibitors?
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How are PIs administered?
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What happens when PIs inhibit the cytochrome P450 enzymes?
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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.
