188: Antifungals Flashcards
What is the mechanism of action of allylamines in antifungal therapy?
Allylamines suppress ergosterol synthesis by inhibiting the action of the squalene epoxidase enzyme, leading to a deficiency of ergosterol which results in a fungistatic effect. Additionally, the buildup of squalene contributes to its fungicidal activity.
What are the clinical indications for naftifine?
Naftifine is indicated for the treatment of interdigital tinea pedis, tinea cruris, tinea corporis, tinea versicolor, and Candida infections.
What are the common side effects associated with terbinafine?
Common side effects of terbinafine include dryness, pruritus, local irritation, and erythema for topical applications. For oral administration, unique side effects may include altered taste, which can last up to 6 weeks, and hepatotoxicity leading to organ failure.
How does the pharmacokinetics of terbinafine differ from that of naftifine?
Terbinafine has a long half-life of 17 hours and is rapidly distributed to hair follicles, nails, and skin, with minimal plasma concentrations. In contrast, naftifine’s systemic absorption is low (3%-6%) and therapeutic drug levels can persist in the stratum corneum for up to 5 days after a single application.
What formulations are available for terbinafine and how is it administered?
Terbinafine is available in cream, powder, solution, spray, and gel (1%). For oral administration, it is typically given as a single daily application for 2 to 4 weeks, with formulations including 250-mg tablets and oral granules.
What is the mechanism of action of terbinafine?
Terbinafine suppresses the squalene epoxidase enzyme, blocking the formation of ergosterol. This leads to a deficiency of ergosterol (fungistatic effect) and a buildup of squalene (fungicidal activity), making it effective against dermatophytes.
How does terbinafine’s efficacy compare to griseofulvin for tinea capitis?
Terbinafine is less effective than griseofulvin in eradicating ectothrix tinea capitis.
How long do therapeutic drug levels of naftifine persist in the stratum corneum after a single application?
Therapeutic drug levels of naftifine persist in the stratum corneum for up to 5 days following a single application.
What is the recommended dosage and duration of terbinafine for tinea pedis?
For tinea pedis, terbinafine is prescribed at 250 mg once daily for 2 to 4 weeks.
What is the recommended dosage and duration of naftifine for tinea pedis?
For tinea pedis, naftifine 1% gel or cream is applied once daily for 2 to 4 weeks.
What is the recommended dosage and duration of terbinafine for tinea cruris?
For tinea cruris, terbinafine is prescribed at 250 mg once daily for 2 to 4 weeks.
What is the recommended dosage and duration of naftifine for tinea cruris?
For tinea cruris, naftifine 1% gel or cream is applied once daily for 2 to 4 weeks.
How does terbinafine’s pharmacokinetics contribute to its efficacy?
Terbinafine’s lipophilic properties allow it to rapidly distribute and accumulate in hair follicles, nails, and skin, with minimal plasma concentrations, contributing to its efficacy.
What is the mechanism of action of Butenafine in antifungal treatment?
Butenafine inhibits the synthesis of ergosterol, enhancing membrane permeability and leakage of important cellular components, resulting in mycotic cell death.
What are the clinical uses of Butenafine?
Butenafine is used for the treatment of dermatophyte infections, with efficacy superior to that of allylamines. It can also be used in cases of pityriasis versicolor (PV) and candidiasis.
What are the common side effects associated with Butenafine?
Common side effects of Butenafine include itching, burning, erythema, and contact dermatitis.
What is the role of azoles in antifungal therapy?
Azoles inhibit the lanosterol demethylase enzyme (14α-demethylase), blocking the conversion of lanosterol into ergosterol, which is essential for fungal cell membrane integrity.
How do the concentrations of azoles affect their antifungal activity?
Azoles exhibit fungistatic activity at normal concentrations and fungicidal activity at high concentrations.
What are the clinical implications of using antifungals in patients with advanced renal or liver diseases?
In patients with advanced renal or liver diseases, the use of antifungals may require careful monitoring due to the potential for increased toxicity and adverse effects.
How does Butenafine’s efficacy compare to allylamines for dermatophyte infections?
Butenafine inhibits ergosterol synthesis, enhancing membrane permeability and causing mycotic cell death. It has superior efficacy compared to allylamines for dermatophyte infections.
What is the recommended dosage and duration of Butenafine for tinea pedis?
For tinea pedis, butenafine 1% cream is applied once daily for 2 to 4 weeks.
What is the mechanism of action of Clotrimazole?
Clotrimazole disrupts mycotic phospholipids, leading to leakage of intracellular iron, degradation of nucleic acids, and suppression of cell respiration.
What are the common formulations of Ketoconazole?
Ketoconazole is available in 5% shampoo, 2% cream, and 200-mg tablets.
What is the clinical significance of Miconazole’s absorption characteristics?
Miconazole efficiently penetrates the stratum corneum with less than 1% absorbed into systemic circulation, making it effective for localized infections like tinea cruris, corporis, and pedis.
What are the side effects associated with oral Ketoconazole?
Side effects include liver toxicity, anaphylactic reactions, nausea, vomiting, diarrhea, abdominal pain, headache, sleeping disturbances, dizziness, pancytopenia, impotence, gynecomastia, and decreased libido.
How does Luliconazole differ from other imidazoles in terms of its structure and efficacy?
Luliconazole has a modified structure that makes it less liable to keratin binding and more available for penetration into deeper nail layers, providing superior potency over lanoconazole.
What is the primary use of Sertaconazole in the US?
In the US, Sertaconazole is limited to the treatment of tinea pedis.
What is the recommended application frequency and duration of ketoconazole shampoo for seborrheic dermatitis?
For seborrheic dermatitis, ketoconazole shampoo is applied twice a week for 4 weeks.
What is the mechanism of action of miconazole?
Miconazole blocks the mycotic peroxidase enzyme, leading to the accumulation of toxic peroxide and subsequent fungal cell death.
What is the mechanism of action of sertaconazole?
Sertaconazole binds to nonsterol lipids in the mycotic cell wall, increasing permeability and causing cell death. It forms a drug depot that persists in the stratum corneum for up to 48 hours after the last dose.
What structural modification enhances luliconazole’s penetration into deeper nail layers?
Luliconazole’s structure includes a second meta-replaced chlorine on its benzene ring, enhancing its penetration into deeper nail layers.
What is the recommended dosage and duration of sertaconazole for tinea cruris?
For tinea cruris, sertaconazole 2% cream is applied once daily for 2 to 4 weeks.
What is the recommended dosage and duration of miconazole for tinea corporis?
For tinea corporis, miconazole 2% cream is applied twice daily for 2 to 4 weeks.
What is the recommended dosage and duration of sertaconazole for tinea pedis?
For tinea pedis, sertaconazole 2% cream is applied once daily for 2 to 4 weeks.
What is the recommended dosage and duration of luliconazole for tinea corporis?
For tinea corporis, luliconazole 1% cream is applied once daily for 2 weeks.
What is the mechanism of action of Efinaconazole in treating onychomycosis?
Efinaconazole reduces ergosterol synthesis in a dose-dependent manner by inhibiting lanosterol 14-alpha-demethylase, preventing the transformation of lanosterol into ergosterol. It is less bound to keratin compared to other treatments, allowing more drug penetration into the nail plate.
What are the clinical applications of Fluconazole?
Fluconazole is used for the treatment of esophageal, vaginal, and oropharyngeal candidiasis, cryptococcal meningitis, and off-label for onychomycosis and tinea infections. It is also used for chronic mucocutaneous candidiasis when itraconazole and terbinafine are contraindicated.
What are the common side effects associated with Fluconazole?
Common side effects of Fluconazole include headache, myalgia, dizziness, nausea, dyspepsia, diarrhea, and abdominal pain. Rarely, it can cause cardiac abnormalities, exfoliative cutaneous reactions, and anaphylactic reactions.
How does the bioavailability of Fluconazole compare to other antifungals?
Fluconazole has excellent oral bioavailability, attaining nearly 90%, and its absorption is linear, predictable, and independent of gastric acidity, food intake, or disease activity, which is advantageous compared to other antifungals.
What is the recommended dosage of Fluconazole for treating onychomycosis in adults?
The recommended dosage of Fluconazole for treating onychomycosis in adults is a weekly dose of 150 to 450 mg for 3 months for fingernails and 6 months for toenails.
How does Efinaconazole’s mechanism of action differ from amorolfine?
Efinaconazole inhibits lanosterol 14-alpha-demethylase, preventing the transformation of lanosterol into ergosterol. Amorolfine interrupts ergosterol synthesis at the 14-reduction and 7-8 isomerization steps, leading to ergosterol depletion and accumulation of 24-methylene ignosterol.
What is the recommended dosage and duration of fluconazole for toenail onychomycosis in adults?
For toenail onychomycosis in adults, fluconazole is prescribed at a weekly dose of 150 to 450 mg for 6 months.
What is the recommended application schedule and duration of efinaconazole?
Efinaconazole 10% solution is applied as a single daily application for 48 weeks.
How does fluconazole’s pharmacokinetics make it suitable for onychomycosis?
Fluconazole has excellent oral bioavailability (90%), a long half-life (25-30 hours), and wide tissue distribution, including nails, making it suitable for onychomycosis.
What is the recommended dosage and duration of fluconazole for fingernail onychomycosis in adults?
For fingernail onychomycosis in adults, fluconazole is prescribed at a weekly dose of 150 to 450 mg for 3 months.
What is the mechanism of action of Itraconazole?
Itraconazole works by inhibiting 14-α-demethylase, which suppresses the conversion of lanosterol to ergosterol. This action disrupts the fungal cell membrane integrity.
What are the clinical uses of Itraconazole?
Itraconazole is primarily used for the treatment of Candida and nondermatophyte onychomycosis. It is also effective for various dermatophytoses, including tinea corporis, tinea capitis, tinea pedis, tinea cruris, tinea manuum, and PV.
What are the dosing recommendations for Itraconazole in children?
For children, the recommended dose of Itraconazole is 5 mg/kg/day for both continuous or pulse regimens. For tinea infections and PV, the dose is 100 mg twice daily for 5 days.
What are the side effects associated with Itraconazole?
Side effects of Itraconazole may include GI disorders, particularly an unpleasant taste, edema, hypertension, hyperkalemia, and a negative inotropic effect that can predispose to complete heart failure. Rarely, it can cause hepatitis, jaundice, Stevens-Johnson syndrome, peripheral neuropathy, and adrenal suppression.
What is the primary use of Nystatin?
Nystatin is primarily used for the treatment of cutaneous, oropharyngeal, and vaginal candidiasis. It is not effective against dermatophytes or Malassezia spp.
What are the formulations available for Nystatin?
Nystatin is available in various formulations including cream, ointment, liquid, suspension, powder, and lozenge.
What are the common side effects of Nystatin?
Common side effects of Nystatin include allergic contact dermatitis, erythema, itching, and edema when used topically. Additionally, nausea, vomiting, and diarrhea have been reported with large doses.
What is the recommended dosage and duration of itraconazole for tinea versicolor?
For tinea versicolor, itraconazole is prescribed at 100 mg twice daily for 5 days.
What is the recommended dosage and duration of itraconazole for tinea corporis?
For tinea corporis, itraconazole is prescribed at 100 mg twice daily for 5 days.
What are the key antifungal activities of Ciclopirox?
Ciclopirox exhibits broad-spectrum fungicidal and fungistatic, antibacterial, and anti-inflammatory activities. It inhibits the transmembrane uptake of RNA, DNA, and protein precursors.
What is the recommended dosage and duration for itraconazole in treating tinea corporis?
For tinea corporis, itraconazole is prescribed at 100 mg twice daily for 5 days.
What are the key antifungal activities of Ciclopirox?
Ciclopirox exhibits broad-spectrum fungicidal and fungistatic, antibacterial, and anti-inflammatory activities. It inhibits the transmembrane uptake of RNA, DNA, and protein precursors, suppresses aerobic glycolysis in yeast cells, and decreases the adherence of Candida albicans to vaginal and buccal epithelial cells.
What is the clinical significance of combining Ciclopirox with oral terbinafine for onychomycosis treatment?
Combining Ciclopirox with oral terbinafine increases the cure rate for onychomycosis to 88.2%, compared to 64.7% achieved by terbinafine alone.
How is Amorolfine metabolized and eliminated from the body?
Amorolfine is generally eliminated in urine and stool at a very slow rate, indicating a prolonged presence in the body after application.
What is the recommended application frequency for Amorolfine nail lacquer in treating onychomycosis?
Amorolfine nail lacquer should be applied weekly until the regeneration of the nail, which typically takes approximately 6 to 12 months for finger and toenail onychomycosis.
What are the potential side effects associated with the use of Ciclopirox?
The potential side effects of Ciclopirox include mild erythema and itching of the skin adjacent to the application site, as well as infrequent nail alterations.
What additional benefits does ciclopirox provide beyond its antifungal activity?
Ciclopirox exhibits antibacterial and anti-inflammatory activities. It reduces the synthesis and release of proinflammatory prostaglandin E2.
How does the application schedule of Amorolfine nail lacquer differ from efinaconazole?
Amorolfine nail lacquer is applied weekly until nail regeneration (approximately 6 months for fingernails and 12 months for toenails), while efinaconazole is applied daily for 48 weeks.
What is the recommended application schedule for ciclopirox nail lacquer?
Ciclopirox nail lacquer should be applied daily and removed with alcohol once a week before reapplication.
How does the mechanism of action of Amorolfine differ from tavaborole?
Amorolfine interrupts ergosterol synthesis at the 14-reduction and 7-8 isomerization steps, while tavaborole inhibits aminoacyl transfer RNA synthetase (AARS), selectively inhibiting mycotic protein synthesis.
What is the recommended application schedule and duration for amorolfine in treating onychomycosis?
For onychomycosis, amorolfine nail lacquer is applied weekly until nail regeneration (approximately 6 months for fingernails and 12 months for toenails).
How does the efficacy of ciclopirox improve when combined with oral terbinafine?
Combination therapy of ciclopirox with oral terbinafine increases the cure rate to 88.2% compared to 64.7% achieved by terbinafine alone.
What is the mechanism of action of Tavaborole as an antifungal drug?
Tavaborole inhibits a new target, aminoacyl transfer RNA synthetase (AARS), which has an affinity a thousand times that of mammalian cells, thereby selectively inhibiting mycotic protein synthesis.
What are the clinical uses of Griseofulvin?
Griseofulvin is the first line of treatment for tinea capitis caused by Microsporum species due to its higher efficacy compared to terbinafine and similar efficiency at a lower cost compared to itraconazole and fluconazole.
What are the common side effects associated with Griseofulvin?
Common side effects of Griseofulvin include hypersensitivity reactions (urticaria, serum sickness), photosensitivity (photo-toxic and photo-allergic reactions), neurologic problems (peripheral neuritis, memory loss, confusion, insomnia). Rare but serious effects include hepatotoxicity, leukopenia, thrombocytopenia, and anemia.
How is Tavaborole administered for the treatment of onychomycosis?
Tavaborole is administered as a 5% topical solution, applied once daily for 48 weeks for the treatment of onychomycosis.
What factors affect the absorption of Griseofulvin?
The absorption of Griseofulvin is affected by coating with polyethylene glycol, coadministration with fatty meals, and most absorption occurs in the duodenum, leading to a low bioavailability profile.
What is the recommended dosage and duration of griseofulvin for tinea capitis in children?
For tinea capitis in children, the dosage of griseofulvin depends on body weight: ultramicrosize 10-15 mg/kg, oral suspension 15-25 mg/kg, or microsize 20-25 mg/kg, continued for 1 to 2 months.
What is the unique mechanism of action of tavaborole, and why is it selective for fungal cells?
Tavaborole inhibits aminoacyl transfer RNA synthetase (AARS), selectively inhibiting mycotic protein synthesis due to its thousand-fold higher affinity for fungal cells compared to mammalian cells.
What is the recommended dosage and duration for griseofulvin in treating tinea cruris?
For tinea cruris, griseofulvin is prescribed at half the daily dose used for tinea pedis, continued for 4 to 8 weeks.
What is the recommended application schedule and duration for tavaborole?
Tavaborole is applied as a 5% topical solution once daily for 48 weeks.
How does the mechanism of action of tavaborole differ from efinaconazole?
Tavaborole inhibits aminoacyl transfer RNA synthetase (AARS), selectively inhibiting mycotic protein synthesis, while efinaconazole inhibits lanosterol 14-alpha-demethylase, preventing ergosterol synthesis.
What are the advantages of combination therapy for the treatment of onychomycosis?
Combination therapy of a topical agent with a systemic antifungal provides several advantages: higher rates of fungal killing, prevention of drug resistance, and expansion of spectrum activity.
What are some new carrier systems investigated to improve the bioavailability of topical antifungals?
New carriers include micelles, solid lipid nanoparticles, nanostructured lipid carriers, drug microemulsions, and vesicular carrier systems such as liposomes, niosomes, transferosomes, ethosomes, and penetration enhancer vesicles.
What should be considered when prescribing systemic antifungals?
Attention should be paid to drug-drug interactions when prescribing systemic antifungals.
What is the mechanism of action of allylamines and benzylamines in antifungal therapy?
Allylamines and benzylamines inhibit the enzyme squalene epoxidase, which is crucial for the synthesis of squalene precursors, ultimately affecting the production of lanosterol, a key component in fungal cell membrane synthesis.
How do azoles function in antifungal treatment?
Azoles inhibit the enzyme 14 alpha demethylase, which is involved in the conversion of lanosterol to ergosterol. This disruption in ergosterol synthesis compromises the integrity of the fungal cell membrane.
What is the role of polyenes in antifungal therapy?
Polyenes, such as Amphotericin B, bind to ergosterol in the fungal cell membrane, creating pores that lead to cell leakage and ultimately cell death.
What is the mechanism of action of Griseofulvin in antifungal therapy?
Griseofulvin disrupts microtubule formation, which is essential for fungal cell division, thereby inhibiting fungal growth.
What is the action of Tavaborole in antifungal treatment?
Tavaborole inhibits fungal protein synthesis by targeting the RNA and DNA processes within the fungal cell, affecting its ability to produce necessary proteins for survival.
What are the usual formulations for Nystatin and its indications?
Nystatin is available in cream, powder, and ointment formulations. It is indicated for mucosal and cutaneous candidiasis.
What is the dosing regimen for Clotrimazole and its indications?
Clotrimazole is available in cream, solution, and lotion formulations. It is indicated for Tinea corporis/cruris/pedis and is dosed twice daily for 2-4 weeks.
What are the indications for Terbinafine and its usual formulations?
Terbinafine is available in cream, powder, solution, spray, and gel formulations. It is indicated for dermatophytoses and tinea versicolor.
What is the pregnancy category for Econazole and its dosing regimen?
Econazole is classified as category C for pregnancy and is dosed once daily (twice for candidiasis) for 2 weeks.
What are the usual formulations and indications for the drug Butenafine?
Butenafine is available in cream, spray, and powder formulations. It is indicated for dermatophytoses and tinea versicolor.
What are the usual formulations and indications for Terbinafine in the treatment of fungal infections?
Usual Formulations: Tablets (250 mg), Oral granules. Indications: Tinea unguium, Tinea capitis, Tinea pedis, curis, corporis, Seborrheic dermatitis.
What is the dosing regime for Fluconazole in adults and pediatric patients for esophageal candidiasis?
Adult Dosing Regime: 150 mg for 2-3 weeks after clinical improvement. Pediatric Dosing Regime: 6 mg/kg/d until clinical improvement, then 3 mg/kg/d for 2 weeks.
What are the indications for Itraconazole and its formulations?
Usual Formulations: Capsules (100 mg), Cyclodextrin oral solution. Indications: Oropharyngeal candidiasis, Onychomycosis, Tinea pedis, corporis, barbae, Tinea versicolor.
What is the pregnancy category for Terbinafine and Fluconazole?
Terbinafine: Pregnancy Category B. Fluconazole: Pregnancy Category C.
What are the usual formulations and indications for the antifungal drug Griseofulvin?
Griseofulvin is available in tablet form (Microsize 250, 500 mg) and ultramicrosize (125, 165, 250 mg). It is indicated for various fungal infections and has specific dosing regimens for adults and pediatrics.
What is the dosing regimen for the antifungal drug T. capitis in adults and pediatrics?
For adults, T. capitis is dosed at 200 mg for 28 weeks. In pediatrics, the dosing is 5 mg/kg for 4-8 weeks, with variations based on age and weight.
What is the pregnancy category for the antifungal drug Micafungin?
Micafungin is classified as category C for pregnancy, indicating that risk cannot be ruled out and should be used only if the potential benefit justifies the potential risk to the fetus.
What are the indications for the pediatric dosing of T. pedis?
The pediatric dosing for T. pedis is 20 mg/kg for 4-8 weeks, which is used for treating fungal infections in children.
What are the common side effects associated with Terbinafine?
Common side effects include altered taste, loss of smell, tongue discoloration, hepatotoxicity, hematologic disorders, gastrointestinal upset, psoriasis, and lupus erythematosus.
What precautions should be taken when administering Fluconazole?
Precautions include monitoring hepatic and renal impairment, co-administration with statins (increased risk of myopathy), and caution in patients with arrhythmias.
What monitoring is recommended for patients taking Itraconazole?
Recommended monitoring includes baseline liver function tests (LFTs), regular LFTs, and monitoring for signs of heart failure.
What are the side effects of Griseofulvin?
Side effects include hepatotoxicity, pancytopenia, photosensitivity, gastrointestinal upset, and neurologic problems.
What monitoring is necessary for patients on Griseofulvin?
Necessary monitoring includes baseline LFTs, liver enzymes after 8 weeks of continuous use, and regular LFTs thereafter.
What is the mechanism of interaction between Terbinafine and Warfarin?
Terbinafine is a CYP2D6 isoenzyme inhibitor, which can lead to decreased anticoagulant activity and increased risk of thrombosis when used with Warfarin.
What are the resulting effects of Fluconazole when used with Phenytoin?
Fluconazole can induce the metabolism of Phenytoin, leading to clinically evident Phenytoin toxicity and hypoglycemia.
How does Itraconazole affect the metabolism of drugs that are CYP3A4 substrates?
Itraconazole is a CYP3A4 inhibitor, which decreases the metabolism of drugs that are substrates of CYP3A4, potentially increasing their therapeutic and side effects.
What recommendation is given when combining Terbinafine with Rifampin?
The recommendation is to avoid combination, or to decrease the dose of Terbinafine due to the induction of its metabolism by Rifampin.
What should be monitored when using Itraconazole with other drugs?
Monitor the level of coadministered drugs for their effects, including the level of myopathy and myoglobinuria in case of statins, and consider Terbinafine as an alternative.
What is the mechanism of interaction between Griseofulvin and Warfarin, phenobarbital, and estrogens?
Griseofulvin acts as an enzymatic inducer, which increases the metabolism of Warfarin, phenobarbital, and estrogens.
What are the resulting effects of Griseofulvin interacting with phenobarbital?
The interaction with phenobarbital results in decreased oral absorption and induces the metabolism of Griseofulvin, leading to failure in Griseofulvin therapy.
What is the recommendation when using Griseofulvin with concurrent drugs like Warfarin and phenobarbital?
The recommendation is to perform a dose adjustment of the concurrent medications.
What is Griseofulvin’s role as an enzymatic inducer?
Griseofulvin increases the metabolism of Warfarin, phenobarbital, and estrogens.
What are the effects of Griseofulvin interacting with phenobarbital?
The interaction results in decreased oral absorption and induces the metabolism of Griseofulvin, leading to failure in Griseofulvin therapy.
What is the recommendation when using Griseofulvin with concurrent drugs like Warfarin and phenobarbital?
The recommendation is to perform a dose adjustment of the concurrent drugs and to avoid coadministration when possible.
