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Questions and Answers
What is a key precaution to consider when administering Amphotericin B?
What is a key precaution to consider when administering Amphotericin B?
Which of the following is an Azole antifungal medication?
Which of the following is an Azole antifungal medication?
In which situation is Fluconazole typically used therapeutically?
In which situation is Fluconazole typically used therapeutically?
Which type of infections are categorized as superficial mycoses?
Which type of infections are categorized as superficial mycoses?
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Which antifungal medication is particularly toxic and requires careful monitoring of renal function?
Which antifungal medication is particularly toxic and requires careful monitoring of renal function?
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What is the primary mechanism of action of Polyene antifungal agents like Amphotericin B?
What is the primary mechanism of action of Polyene antifungal agents like Amphotericin B?
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What is the result of resistance to polyenes in fungi?
What is the result of resistance to polyenes in fungi?
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What is the recommended administration route for Amphotericin B?
What is the recommended administration route for Amphotericin B?
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Which of the following is a disadvantage of azole antifungals?
Which of the following is a disadvantage of azole antifungals?
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What is a therapeutic use of Fluconazole?
What is a therapeutic use of Fluconazole?
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Which statement about Ketoconazole is accurate?
Which statement about Ketoconazole is accurate?
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What condition is NOT classified as a superficial mycosis?
What condition is NOT classified as a superficial mycosis?
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Which side effect is NOT associated with Fluconazole?
Which side effect is NOT associated with Fluconazole?
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Which fungal infection is commonly treated with topical agents such as Tolnaftate?
Which fungal infection is commonly treated with topical agents such as Tolnaftate?
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What can be a consequence of hypokalemia from Amphotericin B administration?
What can be a consequence of hypokalemia from Amphotericin B administration?
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Study Notes
Amphotericin B
- Poorly absorbed from the gastrointestinal tract, rendering oral administration ineffective.
- Administered intravenously, over 2-6 hours, daily or every other day for several months (3-4 months).
- Infusion reactions, such as fever, chills, rigors, nausea, and headache, are common, typically beginning 1-3 hours after infusion.
- Lipid-based infusion reduces the intensity of infusion reactions.
- Acetaminophen and diphenhydramine can be given to alleviate symptoms.
- Hypokalemia, a side effect resulting from kidney damage, may require potassium supplements.
- Amphotericin B can cause bone marrow suppression.
Azoles
- Broad-spectrum synthetic antifungal compounds used to treat systemic mycoses.
- Generally less toxic than Amphotericin B.
- Can be administered orally.
- Inhibits cytochrome P450 drug-metabolizing enzymes which can lead to increased levels of other drugs.
Itraconazole (Sporanox)
- Broader spectrum than most azoles.
- Well absorbed from the gastrointestinal tract when taken with meals.
- Highly bound to plasma proteins (>99%).
- Long half-life, approximately 20 hours after a single dose.
- Mostly metabolized in the liver.
- Adverse reactions include cardiosuppression, hepatotoxicity, hypokalemia, and hypertension.
Fluconazole (Diflucan)
- Well absorbed from the gastrointestinal tract, distributing throughout the body, including the central nervous system.
- Effective in treating cryptococcal meningitis, blastomycosis, and histoplasmosis in immunocompromised patients.
- Long half-life, ranging from 20 - 50 hours in adults and 17 hours in children.
- Primarily excreted unchanged in the kidney.
- Used to treat mucosal (oropharyngeal/esophageal) candidiasis.
- Employed for weekly prophylaxis against mucosal candidiasis in patients with HIV/AIDS.
Fluconazole Adverse Effects
- Gastrointestinal disturbances: nausea, vomiting, gastric pain.
- Headaches.
- Rashes.
- Seizures.
- Anaphylaxis.
- Dermatitis.
- High doses during the first trimester of pregnancy can cause birth defects.
Ketoconazole (Nizoral)
- First oral antifungal approved for chronic systemic mycoses.
- Well absorbed from the gastrointestinal tract if stomach contents are acidic.
- Generally well tolerated but absorption can be significantly reduced by antacids and H2 antihistamines.
Ketoconazole Toxicity
- Less toxic alternative to Amphotericin B.
- Severe hepatotoxicity occurs in approximately 0.01% of individuals.
- Markedly inhibits the synthesis of testosterone and estradiol, leading to gynecomastia, menstrual irregularities, and alterations in adrenal steroid synthesis.
Superficial Mycoses
-
Fungal infections affecting the skin, nails, or mucous membranes.
-
Examples include:
- Tinea pedis (ringworm of the foot, "athlete's foot").
- Tinea corporis (ringworm of the body).
- Tinea cruris (ringworm of the groin, "jock itch").
- Tinea capitis (ringworm of the scalp).
- Vulvovaginal candidiasis.
- Oral Candidiasis (thrush).
- Onychomycosis (fungal infection of nails).
-
Treated with topical and/or oral drugs.
Tolnaftate
- Thiocarbamate commonly used as a topical antifungal agent.
- Effective against superficial skin and nail infections, such as tinea pedis, tinea cruris, etc.
- Generally ineffective against yeast infections.
Systemic Mycoses
- Involve various internal organs and are difficult to treat.
- Often require toxic medications.
Opportunistic Mycoses
- Primarily occur in debilitated or immunocompromised patients, including those with AIDS, leukemia, or lymphoma.
- Caused by various pathogens, including:
- Candida.
- Aspergillus.
- Cryptococcus.
- Phycomycetes.
Endemic Mycoses
- Caused by various pathogens distributed unevenly around the world, and can affect any host.
- Examples include:
- Blastomycosis.
- Histoplasmosis.
- Coccidiomycosis ("Valley Fever").
- Sporotrichosis.
Antifungal Drugs
-
Two major classes:
- Polyene antibiotics (Amphotericin B, Nystatin).
- Azoles (Fluconazole, Itraconazole, Ketoconazole, Clotrimazole).
-
Other classes include:
- Echinocandins.
- Pyrimidine analogs.
Polyene Antifungal Agents
-
Amphotericin B:
- Used to treat deep systemic mycoses.
- Before the availability of Amphotericin B, most systemic fungal infections were fatal.
-
Nystatin:
- Useful in treating superficial mycoses caused by candidiasis, affecting the skin, mouth, esophagus, and vagina.
Polyene Antifungal Agents Mechanism of Action
- Binds to ergosterol, a component of the fungal cell membrane.
- Binding forms channels in the cell membrane, increasing its permeability.
- This leakage of intracellular cations, such as Na+, K+, and H+ ions, disrupts cellular function.
- Resistance to polyenes is associated with the replacement of ergosterol by other sterols in the fungal plasma membrane.
Caution with Amphotericin B
- Broad-spectrum antifungal agent, considered the drug of choice for systemic mycoses.
- Highly toxic; fungistatic or fungicidal depending on pH, concentration, and fungus.
- Effective against some protozoa, such as Leishmania.
- Infusion reactions and renal damage occur in all patients to varying degrees.
- The extent of kidney damage is related to the total dose, and can be minimized by infusing additional normal saline.
- Avoid using Amphotericin B with other nephrotoxic drugs.
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Description
This quiz covers the pharmacological details of Amphotericin B and azole antifungals. It includes information on their administration routes, side effects, and interactions. Test your knowledge on these crucial antifungal medications used to treat systemic mycoses.
