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Questions and Answers
What is the recommended oral dosage of acyclovir for the acute treatment of herpes zoster?
Which pharmacokinetic aspect of oseltamivir is influenced by age?
How does food consumption affect the pharmacokinetics of oseltamivir?
What is a factor influencing the pharmacokinetics of oseltamivir?
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In which scenario is therapeutic drug monitoring (TDM) for antiretroviral therapy (ART) considered useful?
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What is the calculated steady state cyclosporine trough concentration that the initial oral dose aims to achieve?
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How much cyclosporine should be administered every 12 hours to maintain the target steady state after adjusting from an initial dose of 400 mg every 12 hours?
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What is the elimination half-life of Acyclovir?
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What is the main route of excretion for Acyclovir?
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What factor promotes the effectiveness of Acyclovir against herpes viruses?
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Which of the following medications is used as an anti-influenza virus drug?
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What is the clearance value calculated for cyclosporine in the initial dosage estimate?
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Which drug class does not include antivirals specifically for SARS-CoV-2 infection?
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What is the primary goal of therapy with cyclosporin in transplant patients?
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Which factor is NOT mentioned as influencing the pharmacokinetics of cyclosporin?
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What is the general average oral bioavailability of cyclosporin?
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Which formulation of cyclosporin has a closer correlation between trough level concentration and AUC?
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What is the half-life (t1/2) of cyclosporin in adults generally stated to be?
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In patients with liver failure, what change occurs to the clearance of cyclosporin?
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Which of the following describes the metabolism of cyclosporin?
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What is the average volume of distribution (Vd) for cyclosporin?
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What is the primary reason for the lack of supportive studies in NRTIs concerning plasma concentrations?
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What conclusion can be drawn about the relationship between plasma concentrations and the potential toxicities of NNRTIs?
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Why are plasma concentrations of PIs considered significant in monitoring treatment efficacy?
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What is the target concentration for Darunavir?
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Which of the following drugs is associated with the highest target concentration among the listed PIs?
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What does the term 'poor BA' in relation to PIs primarily refer to?
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Why is plasma concentration monitoring crucial for PIs?
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What adverse effect is commonly associated with PIs due to their pharmacological properties?
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What is the primary purpose of measuring C2 blood concentration at 2 hours after cyclosporine dosing?
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Which of the following is NOT a monitoring parameter for renal transplant rejection?
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What is a common side effect of cyclosporine that could affect patient management?
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How is the determination of the initial cyclosporine dose for oral therapy calculated?
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Which of the following reflects the concept of dose adjustment for cyclosporine?
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What indicates the presence of graft-versus-host disease that should be monitored?
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What adverse reaction is less frequently associated with cyclosporine therapy?
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Which parameter is crucial for monitoring during a heart transplant evaluation?
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Study Notes
Introduction to Immunosuppressants & Antivirals
- Immunosuppressants inhibit immune activity, including cyclosporin, tacrolimus, azathioprine, and corticosteroids.
- Indications include preventing graft rejection in solid organ transplants, preventing graft-versus-host disease in bone marrow transplants, and treating autoimmune diseases like psoriasis and rheumatoid arthritis.
- Drug monitoring is essential for cyclosporin and tacrolimus due to narrow therapeutic indices and variability in blood concentrations.
Cyclosporin Overview
- Potent non-myelotoxic immunosuppressant with significant nephrotoxicity.
- Used primarily to prevent or treat graft rejection in bone marrow, kidney, liver, and heart transplants.
- Desired concentrations vary based on transplant type, time post-transplantation, and specific protocols.
- Therapy aims to prevent rejection while minimizing side effects.
Sandimmune® vs Neoral®
- Sandimmune®: Oily solution with erratic absorption, leading to poor correlation between trough levels and AUC.
- Neoral®: Reformulated microemulsion for better correlation between trough concentrations and AUC.
Pharmacokinetic Parameters of Cyclosporin
- Follows linear pharmacokinetics, where steady-state concentration changes proportionately with the dose.
- Average oral bioavailability is about 30%, influenced by meal fat content.
- Volume of distribution (Vd) averages 4-5 L/kg.
- Metabolized hepatically (>99%) mainly via the CYP3A4 system; <1% excreted unchanged in urine.
- Average half-life (t1/2) is 6-12 hours, varying with volume of distribution and clearance.
Factors Influencing Pharmacokinetics
- Age: Children have higher clearance rates and shorter half-life.
- Liver Function: Liver failure results in reduced clearance and prolonged half-life.
- Absorption Profiling: Targeting blood cyclosporin concentration within 4 hours post-dosing improves outcomes.
- C2 blood concentration at 2 hours post-dose correlates well with AUC0-4.
Monitoring Parameters
- Monitor for graft-versus-host disease symptoms such as rash, diarrhea, and abdominal pain.
- For solid organ transplants, watch for specific signs of rejection associated with each organ type.
- Common adverse effects include hypertension, nephrotoxicity, and hyperlipidemia, alongside less frequent issues such as hepatotoxicity and hyperglycemia.
- Adjust cyclosporin dose based on C0 and C2 blood concentrations.
Determination and Adjustment of Initial Dose
- For oral therapy, use CSS = [F(D/τ)]/Cl or D = (CSS * Cl * τ)/F for calculating initial doses.
- For intravenous therapy, CSS = (D/τ)/Cl.
- Cyclosporin is adjusted linearly based on previous doses and required concentrations.
Case Studies in Dosage Calculation
- Case 1: A 70 kg male renal transplant patient requires an initial dose of approx. 200 mg every 12 hours.
- Case 2: A renal transplant recipient on 400 mg every 12 hours adjusts to a new dose of 600 mg/day based on steady-state concentration changes.
Antiviral Therapy Overview
- Vaccines can prevent viral diseases; antiviral drugs are used to stop infections quickly.
- Limited market presence compared to antibiotics, primarily targeting influenza, HIV, HBV, and HCV.
Clinical Use of Antivirals
- Key antiviral agents classified as anti-herpes, anti-retroviral, and anti-influenza.
- Acyclovir is effective against herpes viruses with oral bioavailability of 10-20%.
- Oseltamivir is an ethyl ester prodrug with 80% bioavailability for its active metabolite.
Acyclovir Specifics
- Effective against HSV-1, HSV-2, VZV, EBV, and CMV.
- Renal excretion (62-90% unchanged).
- Dosing example for herpes zoster: 800 mg every 4 hours for 7-10 days.
Oseltamivir Specifics
- Converted to oseltamivir carboxylate, with 90% urinary excretion.
- Peak levels occur 3-4 hours post-dose.
- Metabolism is hepatic with minimal interaction with P450 enzymes.
Therapeutic Drug Monitoring (TDM) Implications
- TDM is not routinely recommended but could be beneficial in select circumstances.
- Ensures optimal therapy in patients with altered pharmacokinetics due to age, organ function, or treatment history.
- Target concentrations vary by drug class, with NNRTIs and PIs showing strong correlations between drug levels and efficacy.
Summary of Antiretroviral Therapy (ART)
- NRTI TDM is uncertain due to intracellular metabolism concerns.
- NNRTI and PI TDM is feasible and often correlated with treatment outcomes.
- Specific target levels are established for each class based on observed clinical responses.
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Description
This quiz covers the fundamental concepts of immunosuppressants and antivirals, highlighting their mechanisms, applications, and important drugs like cyclosporin and tacrolimus. Understand the indications for use in organ transplants and autoimmune diseases, as well as the significance of drug monitoring. Test your knowledge on the differences between Sandimmune® and Neoral® and their clinical implications.
