Respiratory Fungal Infections
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Questions and Answers

What is the primary goal of the WHO fungal priority pathogens list?

  • To guide research toward pathogens posing a public health threat (correct)
  • To eliminate all fungal infections worldwide
  • To categorize fungal infections by their transmission rates
  • To establish new antifungal regulations in law

Which aspect is NOT included in the learning objectives regarding respiratory fungal infections?

  • Economic impacts of fungal infections (correct)
  • General aspects of respiratory fungal infections
  • Therapeutic drug monitoring
  • Aspects of antifungal therapy

What does the WHO aim to achieve concerning antifungal development pipelines?

  • To rigorously evaluate existing antifungal drugs only
  • To simplify the process of antifungal prescription
  • To track trends and identify research gaps in antifungal development (correct)
  • To ban the use of certain antifungal medications

What is a key action the WHO priority pathogens list promotes?

<p>Investments in research and development of new therapeutics (A)</p> Signup and view all the answers

Which statement correctly summarizes the need for the WHO fungal priority pathogens list?

<p>Emerging resistance and treatability issues highlight gaps in knowledge about these pathogens. (A)</p> Signup and view all the answers

What is one of the objectives for informing policymakers through the WHO fungal priority pathogens list?

<p>To implement measures that effectively address invasive fungal diseases and antifungal resistance (B)</p> Signup and view all the answers

Which of the following is a general aspect of antifungal therapy?

<p>Therapeutic drug monitoring enhances treatment efficacy (D)</p> Signup and view all the answers

What effect does inflammation have on drug clearance in patients with liver dysfunction?

<p>It decreases drug clearance. (C)</p> Signup and view all the answers

How does increased inflammation affect voriconazole concentrations?

<p>Voriconazole concentrations increase when inflammation rises. (D)</p> Signup and view all the answers

What is the mechanism of action for posaconazole?

<p>Inhibits ergosterol cell wall synthesis. (B)</p> Signup and view all the answers

What clinical implication arises from non-linear pharmacokinetics at high concentrations?

<p>Reduced drug metabolism. (B)</p> Signup and view all the answers

How are the loading and maintenance doses of posaconazole administered for invasive infections via IV and tablet routes?

<p>400mg twice daily for loading and 300mg once daily for maintenance. (B)</p> Signup and view all the answers

What is the primary method by which mold spores cause pulmonary infections?

<p>By inhalation of spores (B)</p> Signup and view all the answers

Which of the following is a characteristic of yeast fungi?

<p>Consist of single oval cells (D)</p> Signup and view all the answers

What type of infection is primarily associated with Candida?

<p>Non-respiratory infection (B)</p> Signup and view all the answers

In which area of the human body is Candida commonly found?

<p>Mouth and gut (A)</p> Signup and view all the answers

What is the effect of neutropenia on fungal infections?

<p>Leads to a higher risk of fungal infections (C)</p> Signup and view all the answers

Which fungus is known to predominantly cause respiratory infections?

<p>Aspergillus (B)</p> Signup and view all the answers

What allows for the growth of mold in humid environments?

<p>Presence of organic matter (D)</p> Signup and view all the answers

What mechanism contributes to immunosuppression during fungal infections?

<p>Decreased production of normal neutrophils (C)</p> Signup and view all the answers

Which fungal infection is specifically associated with reduced immune function?

<p>Pneumocystis (B)</p> Signup and view all the answers

What drug class does voriconazole belong to?

<p>Triazole (C)</p> Signup and view all the answers

Which condition is voriconazole primarily used to treat?

<p>Candida and Aspergillus infections (C)</p> Signup and view all the answers

Which of the following statements about voriconazole is incorrect?

<p>It is primarily used as a first-line treatment for viral infections. (A)</p> Signup and view all the answers

What are the recommended maintenance and loading doses of voriconazole in mg?

<p>400mg loading dose, 200mg maintenance dose (C)</p> Signup and view all the answers

Which adverse effect can occur at high concentrations of voriconazole?

<p>Visual hallucination (A)</p> Signup and view all the answers

Which CYP450 enzymes are involved with voriconazole?

<p>CYP2C9, 2C19, 3A4 (A)</p> Signup and view all the answers

What does a 'poor metabolizer' designation indicate in the context of CYP2C19?

<p>Inefficient drug metabolism (D)</p> Signup and view all the answers

What happens to the half-life of voriconazole when liver function is impaired?

<p>It is prolonged (B)</p> Signup and view all the answers

What is a common drug-drug interaction concern with voriconazole?

<p>Inhibition of CYP3A4 (A)</p> Signup and view all the answers

Which of the following is not a known adverse effect of voriconazole?

<p>Nervous system disorders (D)</p> Signup and view all the answers

Which antifungal drug does not require renal function adjustments?

<p>Caspofungin (D)</p> Signup and view all the answers

What is the primary mechanism of action for fluconazole?

<p>Inhibition of ergosterol synthesis (D)</p> Signup and view all the answers

Which of the following antifungal drugs has the broadest spectrum of activity?

<p>Amphotericin B (B)</p> Signup and view all the answers

Which dosing strategy is recommended for an invasive Candida disease treatment with fluconazole?

<p>Loading dose of 800mg or IV 12mg/kg once daily (D)</p> Signup and view all the answers

Which antifungal drug is primarily used for the treatment of oral thrush?

<p>Fluconazole (A)</p> Signup and view all the answers

Which drug-drug interactions are associated with fluconazole?

<p>Inhibits CYP3A4, 2C19 and 2C9 (A)</p> Signup and view all the answers

What adjustment should be made for fluconazole in patients with a creatinine clearance of 25 mL/min?

<p>Administer 50% of the daily dose (D)</p> Signup and view all the answers

Which antifungal drug listed does not require monitoring for hepatic function?

<p>Anidulafungin (C)</p> Signup and view all the answers

Which of the following antifungals is administered intravenously only?

<p>Caspofungin (B)</p> Signup and view all the answers

In antifungal stepdown therapy, when should a switch to oral therapy be made?

<p>When clinical signs of improvement are observed (B)</p> Signup and view all the answers

What is the purpose of the WHO fungal priority pathogens list (FPPL) in relation to public health?

<p>To guide research towards the most threatening fungal pathogens. (B)</p> Signup and view all the answers

How does the WHO FPPL aim to enhance the understanding of antifungal resistance?

<p>By generating knowledge to improve the global response to fungal infections. (A)</p> Signup and view all the answers

Which of the following is NOT a goal of the WHO regarding fungal infections?

<p>To eliminate all fungal pathogens worldwide. (D)</p> Signup and view all the answers

In the context of the WHO FPPL, what does R&D stand for?

<p>Research and Development (B)</p> Signup and view all the answers

Which of the following describes a priority objective of the WHO FPPL?

<p>To facilitate international coordination for improving patient outcomes. (A)</p> Signup and view all the answers

What is a central aspect of the therapeutic approach emphasized in the content?

<p>Ongoing therapeutic drug monitoring. (A)</p> Signup and view all the answers

What challenge does the WHO FPPL aim to address regarding antifungal treatments?

<p>Emerging resistance and treatability issues. (C)</p> Signup and view all the answers

What is the first-line treatment for a severe pulmonary Cryptococcus infection?

<p>Liposomal amphotericin B 10 mg/kg plus Flucytosine 25 mg/kg (B)</p> Signup and view all the answers

What is a common consequence of using broad-spectrum antibiotics in relation to fungal infections?

<p>Increased colonization with Candida (C)</p> Signup and view all the answers

Which of the following is NOT true regarding the prophylactic treatment for Pneumocystis infections?

<p>It's the same for both mild and severe infections (A)</p> Signup and view all the answers

Which statement accurately describes a component of maintenance therapy for Cryptococcus infections?

<p>Fluconazole 200 mg daily for 12 months (D)</p> Signup and view all the answers

What is the loading dose for Anidulafungin in invasive Candida infections?

<p>200 mg IV followed by 100 mg once daily (A)</p> Signup and view all the answers

What factor is associated with impaired immune response contributing to fungal infections?

<p>Intravenous catheter use (D)</p> Signup and view all the answers

Which alternative treatment can be used for Pneumocystis infections if Trimethoprim-sulfamethoxazole is not tolerated?

<p>Dapsone with clindamycin (A)</p> Signup and view all the answers

What is the recommended dose of Fluconazole for severe cryptococcal infections if Flucytosine is unavailable?

<p>1200 mg once daily (A)</p> Signup and view all the answers

Which of the following statements correctly identifies the role of glucocorticoids in fungal infections?

<p>Impair immune response when used in high doses (A)</p> Signup and view all the answers

What is a characteristic feature of mold fungi?

<p>Multicellular filaments called hyphae (C)</p> Signup and view all the answers

What is a primary characteristic of the treatment protocol for mild Pneumocystis infections?

<p>Fluconazole 400-800 mg once daily for several months (B)</p> Signup and view all the answers

Which fungus is commonly associated with pulmonary infections?

<p>Aspergillus (C)</p> Signup and view all the answers

In which bodily environment is the yeast Candida typically found?

<p>In moist areas like the mouth and gut (C)</p> Signup and view all the answers

What is a primary risk factor for increased susceptibility to fungal infections in patients with acute leukemia?

<p>Decrease in neutrophil production (D)</p> Signup and view all the answers

Neutropenia specifically affects vulnerability to fungal infections how?

<p>By reducing the body's general immune response (D)</p> Signup and view all the answers

What is the main type of infection typically associated with Pneumocystis?

<p>Respiratory infections (B)</p> Signup and view all the answers

Which fungus is often linked to infections that can become established in the brain after inhalation?

<p>Cryptococcus (A)</p> Signup and view all the answers

Which environmental condition is most favorable for the growth of mold?

<p>Warm and humid conditions (A)</p> Signup and view all the answers

What is the major reproductive method of yeast fungi?

<p>Budding and spore formation (C)</p> Signup and view all the answers

How does mild liver dysfunction predominantly affect drug metabolism?

<p>Reduces metabolism and increases drug half-life (C)</p> Signup and view all the answers

What is the relationship between C-reactive protein levels and voriconazole concentrations?

<p>Increased C-reactive protein results in higher voriconazole concentrations at the same dose (C)</p> Signup and view all the answers

Which factor contributes to the reduction of metabolic ratio at elevated C-reactive protein levels?

<p>Higher severity of inflammation (B)</p> Signup and view all the answers

In what way does posaconazole differ from voriconazole in terms of C-reactive protein influence on plasma concentration?

<p>Posaconazole is not affected by systemic inflammation while voriconazole is (B)</p> Signup and view all the answers

Which of the following statements about drug-drug interactions concerning posaconazole is correct?

<p>It can have interactions through multiple pathways, including P-glycoprotein (D)</p> Signup and view all the answers

What is the primary mechanism of action of voriconazole?

<p>Inhibits ergosterol synthesis (A)</p> Signup and view all the answers

Which combination of metabolic designations corresponds to an extensive metabolizer of CYP2C19?

<p>2C19*1 (D)</p> Signup and view all the answers

What is a possible consequence of prolonged half-life of voriconazole in patients with impaired liver function?

<p>Increased risk of hepatotoxicity (C)</p> Signup and view all the answers

Which of the following is NOT a documented adverse effect of voriconazole?

<p>Nephrotoxicity (A)</p> Signup and view all the answers

Which of the following describes the drug-drug interaction profile of voriconazole?

<p>Inhibits CYP3A4 and is a substrate of CYP2C19 (B)</p> Signup and view all the answers

What is the recommended loading dose of voriconazole for initial treatment?

<p>400mg (B)</p> Signup and view all the answers

What condition can voriconazole be used to treat specifically?

<p>Invasive Aspergillus infections (D)</p> Signup and view all the answers

At high concentrations of voriconazole, which adverse effect is more likely to occur?

<p>Hallucinations (B)</p> Signup and view all the answers

How frequently should the maintenance dose of voriconazole be administered?

<p>Twice daily (A)</p> Signup and view all the answers

Which precedent of CYP450 teaching is applicable to voriconazole's interaction with drug metabolism?

<p>2C19 can lead to variable drug responses (B)</p> Signup and view all the answers

Flashcards

Respiratory fungal infections

Infections of the lungs and respiratory system caused by fungi.

Antifungal therapy

Treatment for fungal infections using medications.

Therapeutic drug monitoring

Tracking medication levels in the body to ensure effective treatment.

WHO fungal priority pathogens list

A list of fungi that pose significant public health risks, identified by the WHO.

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Public health threat

A significant risk of harm or disease to people in a community.

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Research & Development (R&D)

The process of creating and improving new products or processes.

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Antifungal Resistance

The ability of fungi to survive treatment with antifungal drugs

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Mold

A furry growth on organic matter, consisting of multicellular filaments (hyphae).

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Yeast

A fungus consisting of single oval cells that reproduce by budding. Often found on human skin and in moist areas like the mouth and gut.

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Hyphae

Multicellular filaments that form the structure of mold.

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Spores

Reproductive units of fungi that can be inhaled and cause infection.

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Respiratory Infection (fungal)

Fungal infection affecting the lungs or respiratory system.

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Cryptococcus

A specific type of fungus that can cause infection.

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Candida

A type of yeast that can cause infection.

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Pneumocystis

A type of fungus that can cause infection.

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Aspergillus

A type of mold that can cause infection.

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Fluconazole loading dose

800 mg orally or 12 mg/kg intravenously once daily

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Fluconazole maintenance dose

400 mg orally or 6 mg/kg intravenously once daily

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Fluconazole use

Treatment of oral thrush, invasive Candida

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Fluconazole drug class

Triazole

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Fluconazole mechanism

Inhibits ergosterol synthesis for cell wall formation

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Antifungal stewardship

Using antifungal drugs carefully and effectively

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Step-down therapy

Changing from IV to oral antifungal as possible

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CrCl >50 mL/min

Fluconazole dose: once daily

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CrCl 11-20 mL/min

Fluconazole dose: 25% of normal once daily

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Drug-drug interactions (Fluconazole)

Inhibits CYP3A4, 2C19, and 2C9 enzymes

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Inflammation impact on drug clearance

Inflammation, often indicated by elevated C-reactive protein (CRP), can significantly reduce the rate at which drugs are eliminated from the body, leading to elevated drug concentrations.

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Voriconazole mechanism

Inhibits ergosterol synthesis, crucial for fungal cell wall formation.

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Liver dysfunction & drug metabolism

Mild liver problems can alter how the body processes drugs, potentially leading to slower metabolism and longer plasma half-lives (t½), potentially causing toxic levels.

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Non-linear PK and high drug concentrations

Drug metabolism can be non-linear, meaning the rate of metabolism changes with drug concentration. At higher concentrations, metabolism may slow down.

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Voriconazole use

Treats Candida and Aspergillus infections, esp. invasive diseases.

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Voriconazole and inflammation

Higher inflammation (as measured by C-reactive protein) correlates with higher voriconazole blood levels at the same dosage.

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Voriconazole dosage (loading)

400 mg oral or 6 mg/kg IV, twice daily.

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Voriconazole dosage (maintenance)

200 mg oral or 4 mg/kg IV, twice daily.

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Posaconazole and CRP levels

Unlike voriconazole, posaconazole's plasma concentration isn't influenced by C-reactive protein (CRP) levels.

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CYP450 enzyme types

2C19 (ultra rapid, extensive, poor metabolizer), 2C9, 3A4.

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Voriconazole-CYP interaction

Voriconazole affects and is affected by CYP450 enzymes (2C9, 2C19, 3A4).

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Voriconazole adverse effects

Hepatotoxicity, visual issues (high doses), skin rash (photosensitivity).

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Prolonged Voriconazole half-life

Liver issues can lead to a longer time for the drug to be cleared from the body.

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2C19*17

Ultra-rapid metabolizer of voriconazole.

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2C191, 2C192/*3

Extensive and poor voriconazole metabolizer types, respectively.

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WHO fungal priority pathogens

List of fungi prioritized for research, development, and public health action due to their threat, limited knowledge or treatment issues.

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Antifungal R&D

Research and development of new and improved antifungal treatments and diagnostics.

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Fungal Priority

Fungal pathogens prioritized for research and treatment based on public health impact and knowledge gaps.

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Respiratory Fungal Infections

Fungal infections affecting the lungs and airways.

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Antifungal Therapy

Treatment for fungal infections with drugs.

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Therapeutic Drug Monitoring

Tracking drug levels in the body to ensure the correct dose for treatment.

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Mold

A furry growth on organic matter, consisting of multicellular filaments (hyphae).

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Yeast

A fungus consisting of single oval cells that reproduce by budding. Commonly found on human skin and in moist areas like the mouth and gut.

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Hyphae

Multicellular filaments that form the structure of mold.

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Spores

Reproductive units of fungi that can be inhaled and cause infection.

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Respiratory Fungal Infection

Fungal infection affecting the lungs or respiratory system.

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Risk Factors (Fungal)

Conditions that increase the chance of getting a fungal infection, such as acute leukemia or neutropenia.

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Cryptococcus

A specific type of fungus that can cause infection.

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Impaired immune response

Weakened ability of the body's immune system to fight infections.

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Glucocorticoids (>0.3mg/kg/day)

High doses of glucocorticoids weaken the immune system.

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Mucositis

Inflammation of the mucous membranes causing impaired barrier function.

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Central venous catheters

IV lines that can be a point of entry for infections, often fungal.

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Broad-spectrum antibiotic use

Using antibiotics targeting many types of bacteria which can increase fungal colonization.

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Genetic factors

Genetic predispositions can impact the effectiveness of the immune response in fighting fungal infections.

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Cryptococcus infections - Severe pulmonary

Induction therapy (2 weeks) with Liposomal amphotericin B, Flucytosine, and Fluconazole, followed by consolidation and maintenance therapies.

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Pneumocystis infection - Prophylaxis

Trimethoprim-sulfamethoxazole is used to prevent Pneumocystis infection.

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Pneumocystis infection - Treatment

Trimethoprim-sulfamethoxazole is the standard treatment for Pneumocystis.

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Candida treatment

Fluconazole is a frequent treatment for Candida infections, especially those that aren't life-threatening, using oral or intravenous methods.

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Inflammation impact on drug clearance

Inflammation (often measured by C-reactive protein - CRP) can reduce how quickly the body gets rid of drugs, causing higher drug concentrations.

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Liver dysfunction & drug metabolism

Mild liver problems can change how the body processes drugs, potentially leading to slower metabolism and longer drug stays in the blood (longer half-life).

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Non-linear PK and high drug concentrations

Some drugs' metabolism changes with their concentration in the blood. Higher concentrations may slow down the body's ability to break down the drug.

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Voriconazole & Inflammation

Higher inflammation (higher C-reactive protein) correlates with higher voriconazole blood levels at the same dosage.

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Posaconazole & CRP influence

Unlike voriconazole, posaconazole's blood levels aren't affected by C-reactive protein levels (CRP).

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Voriconazole class

A triazole antifungal medication

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Voriconazole mechanism

Blocks ergosterol production, needed for fungal cell walls.

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Voriconazole use

Treats Candida and Aspergillus infections, especially invasive ones.

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Voriconazole loading dose (oral)

400 mg, twice daily

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Voriconazole loading dose (IV)

6mg/kg twice daily

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Voriconazole maintenance dose (oral)

200 mg, twice daily

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Voriconazole maintenance dose (IV)

4mg/kg twice daily

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Voriconazole CYP interactions

Voriconazole both inhibits and is a substrate for CYP3A4, 2C9, and 2C19.

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Voriconazole adverse effects

Hepatotoxicity (liver damage), visual issues, and rash from photosensitivity are possible.

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Prolonged Voriconazole half-life

Liver problems can cause the drug to stay in the body longer.

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Study Notes

WHO Fungal Priority Pathogens List

  • The primary goal is to guide research, development, and interventions for fungal infections.

Objectives Regarding Respiratory Fungal Infections

  • Not included: Learning objectives don't cover antifungal resistance mechanisms.

WHO Aim for Antifungal Development Pipelines

  • Aims to stimulate the development of new antifungals with improved efficacy and safety.

WHO Priority Pathogens List Promotion

  • Promotes collaborative action and resource allocation for fungal infections.

Need for WHO Fungal Priority Pathogens List

  • The increasing burden of fungal infections, lack of effective treatments, and limited research necessitates this list.

Informing Policymakers through WHO Fungal Priority Pathogens List

  • To increase awareness of fungal infections and promote prioritization of research and resource allocation.

General Aspects of Antifungal Therapy

  • Antifungal therapy often requires prolonged treatment durations.

Inflammation and Drug Clearance in Liver Dysfunction

  • Inflammation increases drug clearance in patients with liver dysfunction.

Effect of Increased Inflammation on Voriconazole Concentrations

  • Increased inflammation leads to lower voriconazole concentrations.

Mechanism of Action for Posaconazole

  • Inhibits fungal cell wall synthesis.

Clinical Implication of Non-Linear Pharmacokinetics at High Concentrations

  • High concentrations may result in disproportionately larger increases in drug exposure.

Loading and Maintenance Doses of Posaconazole for Invasive Infections

  • IV route: 400mg loading dose followed by 200mg maintenance dose daily
  • Tablet route: 200mg loading dose followed by 100mg maintenance dose twice daily

Mold Spores and Pulmonary Infections

  • Mold spores enter the lungs through inhalation.

Characteristics of Yeast Fungi

  • Unicellular organisms with oval or spherical shapes.

Candida Infection Association

  • Primarily associated with mucosal infections.

Location of Candida in the Human Body

  • Commonly found in the mouth, gut, and vagina.

Effect of Neutropenia on Fungal Infections

  • Neutropenia increases the susceptibility to fungal infections.

Respiratory Infections Caused by Specific Fungus

  • Aspergillus fumigatus is the most common cause of respiratory infections.

Mold Growth in Humid Environments

  • Mold thrives in humid environments with moisture and organic matter.

Immunosuppression Mechanism during Fungal Infections

  • Fungal infections can suppress the immune system through various mechanisms.

Fungal Infection Specifically Associated with Reduced Immune Function

  • Cryptococcus neoformans infections are more common in individuals with compromised immune systems.

Drug Class of Voriconazole

  • Triazole antifungal

Primary Use of Voriconazole

  • Treatment of invasive aspergillosis and candidaemia.

Incorrect Statement about Voriconazole

  • It is not a substrate for CYP3A4.
  • In actuality, voriconazole is a substrate for CYP3A4.
  • Loading dose: 200mg twice daily
  • Maintenance dose: 200mg once daily

Adverse Effect of High Voriconazole Concentrations

  • Visual disturbances

CYP450 Enzymes Involved with Voriconazole

  • CYP2C19 and CYP3A4

Meaning of 'Poor Metabolizer' in Relation to CYP2C19

  • Individuals with this designation metabolize voriconazole more slowly.

Effect of Impaired Liver Function on Voriconazole Half-Life

  • The half-life of voriconazole increases.

Drug-Drug Interaction Concern with Voriconazole

  • Voriconazole can interact with other medications metabolized by CYP3A4.

Adverse Effect Not Associated with Voriconazole

  • Nephrotoxicity
  • Voriconazole does not have nephrotoxicity as an associated adverse effect.

Antifungal Drug Not Requiring Renal Function Adjustments

  • Fluconazole

Primary Mechanism of Action for Fluconazole

  • Inhibits fungal cytochrome P450 enzyme

Antifungal Drug with Broadest Spectrum of Activity

  • Posaconazole

Dosing Strategy for Invasive Candida Disease Treatment with Fluconazole

  • High-dose loading followed by maintenance therapy.

Antifungal Drug for Oral Thrush Treatment

  • Fluconazole

Drug-Drug Interactions Associated with Fluconazole

  • Fluconazole can interact with medications metabolized by CYP3A4.

Fluconazole Adjustment for Creatinine Clearance of 25 mL/min

  • Reduce the dose by 50%.

Antifungal Drug Not Requiring Hepatic Function Monitoring

  • Fluconazole

Intravenous Antifungal

  • Caspofungin

Switching to Oral Therapy in Antifungal Stepdown Therapy

  • When clinical improvement is observed and the patient is stable.

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