Podcast
Questions and Answers
Why is foscarnet typically reserved as a last-line treatment option for herpesvirus infections?
Why is foscarnet typically reserved as a last-line treatment option for herpesvirus infections?
- It carries a high risk of nephrotoxicity and severe electrolyte disturbances. (correct)
- It has a narrow spectrum of activity, limited only to HSV-1 infections.
- It commonly causes myelosuppression, leading to severe anemia and increased infection risk.
- It requires multiple phosphorylation steps for activation, which can be inefficient in some patients.
Which statement accurately differentiates acyclovir from foscarnet in the treatment of herpes simplex virus (HSV) infections?
Which statement accurately differentiates acyclovir from foscarnet in the treatment of herpes simplex virus (HSV) infections?
- Acyclovir is effective against a broader spectrum of viruses, including CMV, whereas foscarnet is limited to HSV.
- Acyclovir is a prodrug that requires initial activation by cellular kinases, while foscarnet directly inhibits viral DNA polymerase.
- Acyclovir is administered intravenously to bypass the need for kinase activation, unlike foscarnet which is orally bioavailable.
- Acyclovir requires activation by viral thymidine kinase, while foscarnet directly inhibits viral DNA polymerase without prior activation. (correct)
A patient with a history of renal impairment is prescribed acyclovir for herpes zoster. Which precaution is most critical to prevent adverse effects?
A patient with a history of renal impairment is prescribed acyclovir for herpes zoster. Which precaution is most critical to prevent adverse effects?
- Monitoring liver function tests regularly to detect any hepatotoxic effects.
- Supplementing the treatment with high doses of vitamin D to prevent hypocalcemia.
- Administering the drug with an aminoglycoside antibiotic to enhance its antiviral effect.
- Ensuring slow infusion rates and maintaining adequate hydration to minimize the risk of crystalline nephropathy. (correct)
Which of the following best describes the mechanism by which cytomegalovirus antiviral treatments like ganciclovir function?
Which of the following best describes the mechanism by which cytomegalovirus antiviral treatments like ganciclovir function?
Why is valganciclovir often preferred over intravenous ganciclovir for long-term treatment of cytomegalovirus (CMV) infections?
Why is valganciclovir often preferred over intravenous ganciclovir for long-term treatment of cytomegalovirus (CMV) infections?
A patient on ganciclovir for CMV retinitis develops neutropenia. Which medication should be avoided due to an increased risk of myelosuppression?
A patient on ganciclovir for CMV retinitis develops neutropenia. Which medication should be avoided due to an increased risk of myelosuppression?
A patient with acyclovir-resistant HSV is being considered for foscarnet therapy. Which pre-existing condition would raise the greatest concern regarding the use of foscarnet?
A patient with acyclovir-resistant HSV is being considered for foscarnet therapy. Which pre-existing condition would raise the greatest concern regarding the use of foscarnet?
Which antiviral agent for herpesviruses is least likely to induce resistance due to its mechanism of action?
Which antiviral agent for herpesviruses is least likely to induce resistance due to its mechanism of action?
A patient receiving cidofovir for a resistant herpesvirus infection should be closely monitored for which combination of side effects?
A patient receiving cidofovir for a resistant herpesvirus infection should be closely monitored for which combination of side effects?
Which therapeutic strategy is designed to circumvent acyclovir resistance in herpes simplex virus (HSV) infections?
Which therapeutic strategy is designed to circumvent acyclovir resistance in herpes simplex virus (HSV) infections?
Flashcards
Acyclovir Activation
Acyclovir Activation
Anti-herpes agents need three phosphorylation steps for activation. Acyclovir's effectiveness depends on the virus's ability to induce thymidine kinase.
Acyclovir Mechanism
Acyclovir Mechanism
Acyclovir, Valacyclovir, and Famciclovir treat herpes simplex and varicella-zoster by inhibiting viral DNA polymerase, stopping viral DNA replication.
Acyclovir Side Effects
Acyclovir Side Effects
Acyclovir and Valacyclovir side effects include seizures and obstructive crystalline nephropathy, especially with renal impairment. Prevent nephropathy with slow infusion and hydration.
Foscarnet Action
Foscarnet Action
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Foscarnet Toxicity
Foscarnet Toxicity
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Cidofovir Mechanism
Cidofovir Mechanism
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Ganciclovir and Valganciclovir
Ganciclovir and Valganciclovir
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Ganciclovir side effects
Ganciclovir side effects
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Study Notes
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There is no vaccine available for herpes infection
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Pharmacological management focuses on treating the underlying condition
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For CMV-caused herpes, ganciclovir can be used
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Anti-herpes agents need three phosphorylation steps to activate
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First converted to the monophosphate derivative by the virus-specified thymidine kinase, then di-, then tri-
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Acyclovir's effectiveness against herpesviruses is directly related to the virus's ability to induce thymidine kinase
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Anti-herpes antivirals work by blocking either nucleoside to monophosphate conversion, or monophosphate to diphosphate conversion
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Herpes simplex and varicella-zoster virus are treated by inhibiting viral DNA polymerase, thus preventing viral DNA replication
Anti-Herpes Drugs
- Acyclovir
- Valacyclovir (prodrug of acyclovir)
- Famciclovir (Prodrug of penciclovir)
- Penciclovir (topical only for cold sores)
- Spectrum of activity includes: HSV-1, HSV-2, varicella zoster virus
- Contraindications: Renal failure, which may cause seizures
- Side effects of acyclovir and valacyclovir: seizures, especially with renal impairment and obstructive crystalline nephropathy
- To avoid crystalline nephropathy: infuse slowly and keep the patient well-hydrated
Cytomegalovirus Treatment
- Uses antivirals that are viral DNA/RNA polymerase inhibitors and HIV reverse transcriptase inhibitors
- Cytomegalovirus binds to the pyrophosphate-binding site of enzyme and does not require kinase activation
Foscarnet
- Used for resistant cases of cytomegalovirus
- Does not require kinase activation, making resistance rare
- Has severe toxicity including extreme nephrotoxicity and electrolyte disturbances
- Reserved for last-line treatment
- Spectrum of activity: CMV and HSV (resistant)
- Side effects: nephrotoxicity, electrolyte disturbance (hypo- or hypercalcemia, hypo- or hyperphosphatemia, hypokalemia, hypomagnesemia) can all cause seizures
- Drug interactions: increased risk of nephrotoxicity when used with amphotericin B, aminoglycosides, loop diuretics, tacrolimus, cyclosporine, or cisplatin
- Uses: CMV retinitis in patients who fail ganciclovir, and acyclovir-resistant HSV
Inhibitors
- Cytomegalovirus is treated through antivirals that inhibit replication of viral DNA since it is a nucleotide analogue that does not need to be activated by thymidine kinase, including cidofovir.
- Spectrum of activity: CMV and HSV (resistant)
- Side effects: nephrotoxicity, neutropenia, and metabolic acidosis
- Monitor blood markers of blood urea nitrogen (BUN) and serum creatinine (SCr)
Ganciclovir and Valganciclovir
- Ganciclovir is typically the first drug used to treat cytomegalovirus
- Valganciclovir is the prodrug of ganciclovir, and can be given orally
- For resistant cases: Foscarnet and Cidofovir are used (drugs with significant side effects)
- Spectrum of activity: CMV and HSV (resistant)
- Side effects: myelosuppression, nephrotoxicity, and seizures
- Increases risk of myelosuppression when used with other immunosuppressive drugs
- Increased risk of nephrotoxicity when used with amphotericin B, aminoglycosides, loop diuretics, tacrolimus, cyclosporine, or cisplatin
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