Questions and Answers
What is the effectiveness of prophylaxis in preventing influenza?
What is the unique mechanism of action of Baloxavir Marboxil (Xofluza)?
What is the oral bioavailability of acyclovir?
What is the benefit of valacyclovir over acyclovir?
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What is the benefit of famciclovir over acyclovir?
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What is the benefit of treating genital herpes with nucleoside analogues?
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What is the benefit of treating shingles with nucleoside analogues?
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What is the benefit of the vaccine Zostavax?
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What is the primary characteristic that makes ganciclovir more effective against CMV than acyclovir?
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What is the primary use of cidofovir?
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Which of the following drugs is available in an ophthalmic gel formulation?
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What is the primary indication for trifluridine?
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Which of the following adverse reactions is associated with foscarnet?
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What is the advantage of combining foscarnet with ganciclovir?
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What is the primary route of administration for foscarnet?
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Which of the following is NOT a characteristic of trifluridine?
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Which enzyme is involved in the replication of HIV genetic material into host DNA?
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What is the primary goal of highly active antiretroviral therapy (HAART)?
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Which of the following is NOT a step in the pathophysiology of HIV?
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What is the primary mechanism of action of non-nucleoside reverse transcriptase inhibitors (NNRTIs)?
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Which drug class does Atripla belong to?
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What is the result of HIV protease cleaving polyproteins?
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What is the primary advantage of recent HAART regimens?
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Which of the following is NOT a drug class used to treat HIV?
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Which of the following is NOT a type of Reverse Transcriptase inhibitor?
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What is the mechanism of action of NRTIs?
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Which of the following NRTIs is classified as a nucleotide RTI?
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What is the usual combination of drugs in the initial treatment of HIV?
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What is the common adverse effect of all NRTIs?
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Which of the following is NOT a combination drug containing AZT?
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What is the benefit of AZT treatment in pregnant women with HIV?
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What is the advantage of Atripla over other NRTI combinations?
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What is the primary function of integrase inhibitors in the treatment of HIV?
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Which of the following medications is not a combination of ritonavir and another PI?
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What is the characteristic of enfuvirtide that makes it less convenient for patients?
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What is a benefit of maraviroc and other fusion and entry inhibitors?
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What is the term for the process inhibited by integrase inhibitors?
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What is the benefit of using raltegravir in initial treatment regimens?
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What is a common side effect of enfuvirtide?
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What is the characteristic of enfuvirtide that makes it a valuable treatment option?
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Study Notes
Influenza Treatment
- Oseltamivir may still provide benefit in reducing respiratory failure and death in pregnant women if started 3-4 days after onset.
- Prophylaxis is 70-90% effective in preventing influenza and is a useful adjunct to vaccines, but the CDC recommends against it due to the risk of resistance.
- Prophylaxis is only recommended for populations at risk of complications and to control institutional outbreaks.
Baloxavir Marboxil (Xofluza)
- Single-dose PO treatment for influenza A and B.
- First-in-class medication with a unique MOA that targets ribonuclease activity affecting transcription of viral RNA.
- Approved in the US in 2018 and potentially has fewer side effects compared to oseltamivir.
Herpesvirus Infections
- Cytomegalovirus (CMV) infections are usually asymptomatic in immunocompetent individuals, but can cause retinitis, esophagitis, and colitis in immunocompromised patients.
Nucleoside Analogues
- Acyclovir (Zovirax) is effective in treating serious herpesvirus infections, including encephalitis and infections in immunocompromised patients.
- Topical acyclovir can be used to treat genital herpes and mild mucocutaneous infections, but is less effective than oral treatment.
- Valacyclovir (Valtrex) is a prodrug that gets rapidly converted to acyclovir and has more complete absorption (55%) compared to acyclovir (22%).
- Famciclovir (Famvir) has the greatest bioavailability (80%) and gets rapidly hydrolyzed to penciclovir after absorption.
Other Drugs
- Foscarney (Foscavir) is used to treat CMV retinitis in AIDS patients and acyclovir-resistant HSV infections and shingles.
Treating Genital Herpes
- Oral treatment with acyclovir, valacyclovir, or famciclovir prevents replication of HSV, reduces pain and symptoms of acute infection, and shortens the time to healing of lesions and reduces viral shedding.
- Does not eliminate the virus, and recurrent episodes are common.
Treating Shingles
- Oral treatment with acyclovir, valacyclovir, or famciclovir shortens the duration of acute illness and pain and lowers the incidence of postherpetic pain.
- Famciclovir and valacyclovir are more effective than acyclovir, and newer drugs have less frequent administration and higher serum levels.
- A vaccine is now available (Zostavac) that reduces the incidence and severity of herpes zoster infections in older adults.
Treating CMV
- Nucleoside analogues are used to prevent and treat CMV disease, including retinitis, esophagitis, and colitis.
- Ganciclovir is 100 times more active against CMV than acyclovir.
HIV Infection
- Combined use of 2 or more drugs from different classes has been shown to markedly reduce viral load and improve survival.
- Multidrug treatment called highly active antiretroviral therapy (HAART) has been developed.
HAART
- Initially, complicated regimens required multiple doses of several drugs every day, but recent emphasis is on developing drug regimens that require only a few doses each day or even a single pill (like atripla).
- Guidelines continue to evolve as new regimens are developed and testing improves.
Pathophysiology of HIV
- HIV enters CD4 cells, and viral RNA is produced, which gets converted to double-stranded DNA via reverse transcriptase.
- Viral DNA enters the host cell nucleus and gets incorporated into the host genome via HIV integrase.
- Eventually, the viral DNA gets transcribed/translated to produce polyproteins that get packed into immature virions.
Drug Classes
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- Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)
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- Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
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- Protease inhibitors (PIs)
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- Fusion and entry inhibitors
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- Integrase strand transfer inhibitors
Reverse Transcriptase Inhibitors
- NRTIs are converted to active triphosphate metabolites by host cell kinases, which compete with corresponding endogenous nucleoside triphosphate for incorporation into DNA, causing chain termination.
Nucleoside vs Nucleotide
- Tenofovir disoproxil fumarate (TDF) is classified as a nucleotide RTI, which gets hydrolyzed in the body to form tenofovir.
Nucleoside Transcriptase Inhibitors (NRTIs)
- First class of drugs developed for treating HIV+ individuals.
- Included in almost all regimens.
- Serve as antimetabolites for different purine and pyrimidine bases of DNA.
- Often more effective when combined with other NRTIs.
Fusion and Entry Inhibitors
- Enfuvirtide (Fuzeon) is a large peptide that binds to HIV glycoprotein 41 and blocks the fusion process.
- Maraviroc (Selzentry) is a newer drug that inhibits fusion and entry of HIV.
- Active against HIV strains resistant to RTIs and PIs.
Integrase Inhibitors
- Raltegravir (Isentress) is the first integrase strand inhibitor approved to treat HIV.
- Works by preventing DNA strand transfer.
- Potent in vitro activity against wild-type and MDR HIV strains.
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Description
This quiz covers the treatment and prophylaxis of influenza, including antiviral medications and their effectiveness in preventing respiratory failure and death.