1 - TOPICAL ANTIFUNGAL AGENTS Flashcards
Topical antifungals are considered first line therapy for uncomplicated superficial dermatomycoses owing to their high efficacy and low potential for systemic adverse effects
True
The most commonly employed topical antifungal agents belong to 3 main classes:
(1) Polyenes
(2) Azoles (imidazoles)
(3) Allylamines/Benzylamines
True (other agents not among these 3 major classes include the hydroxypyridone ciclopirox olamine, selenium sulfide)
Nystatin and amphotericin B are Polyenes
True
Miconazole, Clotrimazole, Ketoconazole, Oxiconazole, Econazole, Sulconazole, Sertaconazole are Azoles (Imidazole subclass)
True (in contrast, the systemic antifungals itraconazole, fluconazole, voriconazole and posaconazole are triazoles)
Terbinafine and Naftifine are allylamines
True
Butenafine is the only Benzylamine
True
Ciclopirox is a hydroxypyridone antifungal agent
True (not related to the 3 main classes of topical antifungal agents)
Selenium sulfide has topical antifungal properties
True (not one of the 3 main classes of topical antifungal agents)
Nystatin (Polyenes) binds to cell membrane sterols causing cell leakage and permeability changes with activity against candida only
True (fungicidal and fungistatic in vitro)
All the Azoles (Miconazole, Clotrimazole, Ketoconazole, Oxiconazole, Econazole, Sulconazole, Sertaconazole) inhibit ergosterol synthesis by blocking 14-alpha demethylase enzyme which then affect the synthesis of ergosterol (component of the fungal cell membrane)
True (fungistatic in vitro)
Terbinafine and Naftifine (Allylamines) and Butenafine (Benzylamine) inhibit ergosterol synthesis by blocking squalene epoxidase, which then affect the synthesis of ergosterol (component of the fungal cell membrane)
True (fungicidal in vitro)
Nystatin (Polyenes) has activity against candida only
True
Miconazole, Clotrimazole, Ketoconazole, Econazole (Azoles) have activity against dermatophytes, Malessezia furfur, and candida
True
Oxiconazole and Sulconazole (Azoles) have activity against dermatophytes and Malessezia furfur
True (activity against candida is relatively weak compared to Miconazole, Clotrimazole, Ketoconazole, Econazole)
The allylamines (Terbinafine and Naftifine) have activity against dermatophytes
True (Terbinafine has activity against candida but this is relatively weak compared to the Azoles)
Terbinafine has activity against candida but this is relatively weak compared to the Azoles
True (main activity is against dermatophytes)
Butenafine (Benzylamine) has activity against dermatophytes and candida, although activity against candida is relatively weak compared to the Azoles
True
The associated systemic toxicity of Nystatin (Polyenes) has limited its use to topical application as Nystatin is essentially insoluble in water and not absorbed from intact skin, the GI tract or the vagina
True
Nystatin (Polyenes) has fungicidal and fungistatic activity in vitro
True
Nystatin is used in the treatment of oral candidiasis
True (4-5 times daily use is recommended)
Nystatin (Polyenes) is used in the treatment of cutaneous candidiasis
True (BD application recommended)
Nystatin (Polyenes) is well tolerated
True
Burning, pruritus, rash, eczema and pain on application are the more common adverse effects with Nystatin (Polyenes) use
True (generally a well tolerated drug)
Very rarely hypersensitivity reactions have been reported with Nystatin (Polyenes) use
True (generally a well tolerated drug)
The introduction of the azole antifungal agents presented a new class of compounds with a broader spectrum of activity, including action against the common dermatophytes that were not susceptible to the Polyenes (Nystatin)
True
The human skin is an efficient barrier to most Azole compounds, such that percutaneous absorption is generally <1% on intact skin
True
The absorption of Azole compounds may be increased from <1% (intact skin) to 4% on inflamed or damaged skin
True
In general there is very low sensitising potential associated with all Azole antifungals
True
Miconazole (Azole) is very slightly soluble and penetrates the stratum corneum well, although with minimal systemic absorption
True (<1% of Miconazole is absorbed following topical application)
Miconazole (Azole) is active against dermatophytes (Trichophyton and Epidermophyton) and is therefore effective in the treatment of tinea pedis/corporis/cruris
True (BD application recommended)
Miconazole (Azole) is active against Candida albicans, and is therefore effective in the treatment of cutaneous candidiasis
True (BD application is recommended)
Miconazole (Azole) is active against Malassezia furfur, and is therefore effective in the treatment of pityriasis versicolor and seborrheic dermatitis
True (once daily application is sufficient)
Miconazole (Azole) also demonstrates activity against some gram +Ve bacteria and is modestly effective in the treatment of erythrasma, impetigo, or ecthyma caused by Group A beta-haemolytic streptococci or staphylococci
True (however Miconazole’s antibacterial activity is not sufficient to make this agent a drug of choice for such infections)
Topical Miconazole (Azole) is well tolerated although rarely irritation, burning, maceration, and allergic contact dermatitis may occur at application sites
True
Systemic absorption of Clotrimazole (Azole) is very low
True (even under occlusive dressing)
Clotrimazole (Azole) exhibits a broad spectrum of activity against most strains of Trichophyton, Epidermophyton and Microsporum species and is therefore effective in the treatment of tinea pedis/corporis/cruris
True (BD application recommended)
Clotrimazole (Azole) exhibits efficacy near, though slightly less than that of Nystatin (Polyenes) in candida inhibition and is therefore effective in the treatment of cutaneous candidiasis, oropharyngeal candidiasis and vaginal candidiasis
True
Cutaneous candidiasis = BD application on skin recommended
Oropharyngeal candidiasis = oral troches administered 4-5 times daily for 2 weeks
Vaginal candidiasis = once daily intravaginal tablet for 1-2 days
Clotrimazole (Azole) exhibits activity against Malassezia furfur and can be used in the treatment of pityriasis versicolor
True
Clotrimazole (Azole) is generally well tolerated, though there are isolated reports of erythema, burning, irritation, stinging, peeling, blistering oedema, pruritus and urticaria at the application site
True
Ketoconazole (Azole) is water soluble and the topical application is not systemically absorbed
True
Ketoconazole (Azole) is a broad spectrum antifungal agent that exhibits a wide spectrum of activity against dermatophytes and is effective in the treatment of tinea pedis/corporis/cruris
True (once daily application for 4 weeks recommended)
Ketoconazole (Azole) has activity against Candida albicans and is effective in the treatment of cutaneous candidiasis
True
Ketoconazole (Azole) has activity against Malessezia furfur and is therefore effective in pityriasis versicolor and seborrheic dermatitis (which is owing to the role of pityrosporum ovale in causation)
True (available in 2% cream, 2% shampoo and 2% foam formulation + 1% shampoo over the counter) - can be used in infantile seborrhoeic dermatitis for 10 days
5% of patients treated with Ketoconazole 2% cream (Azole) reported irritation, pruritus, and stinging
True
Rare reports of allergic contact dermatitis have been associated with Ketoconazole (Azole) cream or one of its ingredients sodium sulfite or propylene glycol
True
Topical Oxiconazole (Azole) is rapidly absorbed into the stratum corneum and persists in the stratum corneum at therapeutic levels for 7 days
True (this reservoir effect accounts for Oxiconazole efficacy in fungus eradication with once daily dosing)
Systemic absorption of topical Oxiconazole (Azole) is negligible
True
Oxiconazole (Azole) lotion or cream once daily is effective in the treatment of tinea pedis/corporis/cruris
True (lotion being useful for large or hairy areas on the trunk and back) - activity against candida is relatively weak compared to other Azoles Miconazole, Clotrimazole, Ketoconazole, Econazole
Topical Oxiconazole (Azole) is well-tolerated, with few adverse effects including pruritus, burning, irritation, erythema, maceration, and fissuring
True
Econazole (Azole) is a derivative of Miconazole
True
Topical Econazole (Azole) is well absorbed into the stratum corneum as deep as mid-dermis, although systemic absorption is low
True
Econazole (Azole) inhibits most strains of dermatophytes including Trichophyton, Microsporum and Epidermophyton and is therefore effective in the treatment of tinea pedis/corporis/cruris
True
Econazole (Azole) inhibits Candida albicans and is therefore effective in the treatment of cutaneous candidiasis
True
Econazole 1% cream (Azole) has been shown to be as effective as Clotrimazole 1% cream (Azole) in the treatment of tinea/dermatophyte infections and cutaneous candidiasis, but with a more rapid onset of action in patients treated with Econazole
True
Econazole (Azole) inhibits Malessezia furfur and is therefore effective in the treatment of pityriasis versicolor
True
Econazole (Azole) has also demonstrated activity against some gram +Ve and gram -Ve bacterial organisms and has been useful in the treatment of severe interdigital bacterial toe web infections without any fungi on mycology examination
True
Topical Econazole (Azole) is well tolerated with rare adverse effects
True (3% of patients experienced erythema, burning, stinging and pruritus)
Sulconazole (Azole) has relatively higher percutaneous absorption as compared to the other Azoles (Miconazole, Clotrimazole, Ketoconazole, Oxiconazole, Econazole) although the clinical significance of this is unknown
True
Sulconazole (Azole) demonstrates modest antibacterial activity against gram +Ve bacteria and has been reported to be effective therapy for impetigo and ecthyma due to group A beta-haemolytic streptococci and staphylococci
True (although Sulconazole is not a first line choice for these infections)
In general, Sulconazole (Azole) offers little advantage over the other Azole compounds even though is has proven efficacy against dermatophytosis and pityriasis versicolor
True (activity against candida is relatively weak compared to the other Azoles Miconazole, Clotrimazole, Ketoconazole, Econazole)
Sulconazole (Azole) is well tolerated, although there have been a few reports of allergic contact dermatitis
True
Sertaconazole (Azole) is the most recently introduced antifungal agent
True
Sertaconazole (Azole) is relatively more lipophilic than the other Azoles, leading to a greater reservoir effect in the stratum corneum
True
Sertaconazole (Azole) can either be fungicidal or fungistatic depending on the organism and drug concentration, as it has another mechanism of action of binding to non-sterol membrane lipids that lead to altered membrane permeability and leakage of intracellular contents; in addition to its inhibition of 14-alpha demethylase (fungistatic effect)
True
Sertaconazole (Azole) is mainly used for tinea pedis as it has in vitro activity at least equal to, if not better than the other Azole agents against T. Rubrum, T. Mentagrophytes and E. Floccosum
True (BD application for 4 weeks is the approved regimen, although clinical experience supports once daily application)
Sertaconazole (Azole) may rarely cause allergic contact dermatitis
True
The introduction of allylamines (Terbinafine, Naftifine) and Benzylamines (Butenafine) presented a broader spectrum of antimycotic coverage with a newer advantage of fungicidal activity
True (has both fungistatic and fungicidal activity)
The allylamines (Terbinafine, Naftifine) and Benzylamines (Butenafine) act on an earlier step in the ergosterol biosynthesis pathway (squalene epoxidase inhibition) than the Azoles, and their inhibition is cytochrome P450 independent
True
Allylamines (Terbinafine, Naftifine) and Benzylamines (Butenafine) are well tolerated and associated with low sensitising potential
True
Naftifine (Allylamine) is highly lipophilic and allows for efficient penetration and high concentrations in the stratum corneum and hair follicles
True
Naftifine (Allylamine) is both fungicidal and fungistatic
True
Naftifine (Allylamine) has demonstrated equal therapeutic efficacy against several dermatomycoses to Econazole and Clotrimazole, but with an earlier onset of action
True
Naftifine (Allylamine) is extremely well tolerated, with only <5% of patients experiencing mild burning/stinging, itching, erythema, irritation and rarely allergic reactions
True
Terbinafine (Allylamine) is both fungicidal and fungistatic
True
Terbinafine (Allylamine) is highly lipophilic, resulting in high concentration in and efficient binding to the stratum corneum, sebum, and hair follicles, thereby reducing the probability of reinfection
True
Terbinafine is 10-100 times more potent than Naftifine with increased antifungal activity in vivo as well (both are allylamines)
True
After topical application of Terbinafine 1% cream, approximately 3-5% of Terbinafine is absorbed into the systemic circulation
True (this occurs slowly, with the peak amount of substance appearing as metabolites in the urine 2-3 days after application) - the slow rate of absorption reflects the rate of entry of the drug into the epidermis and dermis
Terbinafine (Allylamine) has fungicidal activity against a wide variety of dermatophytes, moulds, dimorphic fungi and candida
True (activity against candida is relatively weak compared to the Azoles)
Topical Terbinafine (Allylamine) is well tolerated with few adverse effects including pruritus and irritant contact dermatitis
True
Butenafine (Benzylamine) has fungicidal concentrations in the stratum corneum for at least 72 hours after application due to the interaction with or fixation to cutaneous lipids, leading to a depot effect
True
Butenafine (Benzylamine) has fungicidal activity against dermatophytes, Aspergillus and dimorphic fungi equal to or greater than the allylamines (Naftifine, Terbinafine) and is the treatment of choice for tinea pedis/corporis/cruris in Japan
True
Butenafine (Benzylamine) has continued mycologic and clinical therapeutic activity after completion of treatment due to the strong keratin binding
True
Topical Butenafine (Benzylamine) is well tolerated and very few patients experience burning, itching and redness at application sites
True
Unlike the 3 main classes of antifungal agents (Polyenes, Azoles, Allylamines/Benzylamine), Ciclopirox olamine (hydroxypyridone) does not appear to affect sterol biosynthesis, but acts by interfering with active membrane transport of essential macromolecular precursors, thereby disrupting cell membrane integrity and inhibiting enzymes essential for respiratory processes
True
Ciclopirox olamine (hydroxypyridone) exhibits high in vitro activity against dermatophytes, yeasts and fungal saprophytes
True
Ciclopirox olamine (hydroxypyridone) is FDA approved for the treatment of tinea pedis/corporis/cruris, pityriasis versicolor, cutaneous candidiasis and onychomycosis (nail lacquer only)
True (available as a cream, gel, suspension, nail lacquer)
Ciclopirox olamine (hydroxypyridone) also has anti-inflammatory activity, in addition to antifungal activity
True (shown to inhibit prostaglandin and leukotriene synthesis in human polymorphonuclear leukocytes)
Even though Ciclopirox olamine (hydroxypyridone) is available as a nail lacquer for onychomycosis, complete resolution requires prolonged daily use of 9-12 months
True
Ciclopirox olamine (hydroxypyridone) is well tolerated and only 0.5% of patients experiment burning sensation or pruritus upon application
True
Although not common, allergic hypersensitivity has been reported with Ciclopirox olamine (hydroxypyridone) use
True
Ciclopirox olamine (hydroxypyridone) shampoo is used in the management of seborrhoea
True
Selenium sulfide is a liquid antiseborrheic and antifungal preparation for topical application only
True
Topical selenium sulfide is indicated for the treatment of pityriasis versicolor and seborrheic dermatitis of the scalp
True
Topical Selenium sulfide is effective in the treatment of confluent and reticulated papillomatosis of Gougerot and Carteaud
True
Topical Selenium sulfide has been shown to be an effective adjuvant with griseofulvin in the treatment of ectothrix tinea capitis (Microsporum canis)
True
Selenium sulfide possesses a cytostatic effect on cells of the epidermis and follicular epithelium which allows for the shedding of fungi in the stratum corneum via a reduction in corneocyte adhesion
True
Selenium sulfide has shown fungicidal activity against pityrosporum ovale in vitro and in vivo
True (useful in pityrosporum folliculitis)
Selenium sulfide was considered to be a possible carcinogen but numerous studies have not confirmed this
True
Topical Selenium sulfide is classified as pregnancy category C
True
No systemic absorption has been demonstrated for topical Selenium sulfide
True
Results of in vitro susceptibility tests have shown that Allylamine/Benzylamine type agents to have greater activity against the common dermatophytes than the Azole derivatives
True
In vitro antidermatophyte potency:
Butenafine > Terbinafine > Ciclopirox = Naftifine > Azoles
Allylamines (Naftifine and Terbinafine) and Benzylamines (Butenafine) produce a significantly lower post-treatment relapse rate in tinea pedis (and other dermatophytoses) that that of the Azole antifungal agents
True
Allylamines/Benzylamines = fungicidal, more lipophilic and therefore exhibit a reservoir effect such that patients continue to improve after cessation of therapy
Azoles = fungistatic, less lipophilic
Allylamines (Naftifine and Terbinafine) and Benzylamines (Butenafine) had a faster onset of action in the treatment of tinea pedis (and other dermatophytoses) than that of the Azoles
True
Allylamines/Benzylamines = fungicidal, more lipophilic and therefore exhibit a reservoir effect such that patients continue to improve after cessation of therapy
Azoles = fungistatic, less lipophilic
Allylamines (Naftifine and Terbinafine) and Benzylamines (Butenafine) provided a more superior mycologic cure rate (more effective) than the Azoles in the treatment of tinea pedis (and other dermatophytoses)
True
Allylamines/Benzylamines = fungicidal, more lipophilic and therefore exhibit a reservoir effect such that patients continue to improve after cessation of therapy
Azoles = fungistatic, less lipophilic
Allylamines (Naftifine and Terbinafine) and Benzylamines (Butenafine) is associated with a lower relapse rate of tinea pedis (and other dermatophytoses) as compared to the Azoles
True
Allylamines/Benzylamines = fungicidal, more lipophilic and therefore exhibit a reservoir effect such that patients continue to improve after cessation of therapy
Azoles = fungistatic, less lipophilic
The retention effect (reservoir effect) and the fungicidal activity of Allylamines (Naftifine, Terbinafine) and Benzylamines (Butenafine) results in shorter duration of therapy and lower relapse rates
True
Allylamines/Benzylamines = fungicidal, more lipophilic and therefore exhibit a reservoir effect such that patients continue to improve after cessation of therapy
Azoles = fungistatic, less lipophilic
Both Ciclopirox and the Azoles are more effective and more appropriate therapeutic choices in the treatment of cutaneous candidiasis than the Allylamines (Naftifine, Terbinafine) and Benzylamines (Butenafine)
True
The efficacy of various antifungal agents in the treatment of candidiasis based on in vitro studies:
Ciclopirox = Azoles > Butenafine > Naftifine > Terbinafine
Some of the Allylamines/Benzylamines possess a greater degree of anti-inflammatory action than the Azoles
True
Ketoconazole (Azole) has anti-inflammatory properties
True (useful in seborrheic dermatitis)
Naftifine (Allylamine) has anti-inflammatory properties
True
Butenafine (Benzylamines) has anti-inflammatory properties
True
Ciclopirox olamine (hydroxypyridone) has significant anti-inflammatory properties
True
The inherent anti-inflammatory properties of antifungal agents are not only beneficial in reducing the inflammation associated with dermatomycoses, they have also proved useful in the treatment of other inflammatory skin disorders
True
The inherent antibacterial properties of some topical antifungal agents serves as an adjuvant in the treatment of dermatomycoses where a complex, combined fungal-bacterial infection can be present
True
The Azoles possess some degree of antibacterial properties, particularly on gram +Ve bacteria
True
Terbinafine (allylamine) exhibits some degree of both gram +Ve and gram -Ve bacteria inhibitory effects
True
Ciclopirox olamine (hydroxypyridone) has a seemingly superior in vitro gram -Ve antibacterial activity to that of other antimycotic drugs
True (whilst also demonstrating antibacterial inhibition against gram +Ve bacteria)
Because of the broad antibacterial activity, inherent anti-inflammatory action, and highly effective antifungal activity, Ciclopirox olamine (hydroxypyridone) has proved to be a very successful treatment of interdigital tinea pedis with secondary bacterial infection (dermatophytosis complex)
True
The ancillary antibacterial and anti-inflammatory activities of some antifungal agents augments the antifungal therapy of inflamed or super infected dermatomycoses, although none of these drugs should be considered agents of choice when treating either uncomplicated or complicated primary bacterial pyodermas
True
Recent data concerning treatment of vulvovaginal candidiasis during pregnancy reveals the superiority of topical vulvar/intravaginal multidose Azole therapy over multidose nystatin (Polyenes) therapy
True (treatment of vulvovaginal candidiasis with topical/intravaginal Azole agents during pregnancy reduces the prevalence of preterm birth, presumably due to restoration of normal genital tract flora)
Propylene glycol as a vehicle ingredient is figuratively a double-edged sword as it is commonly used to enhance the percutaneous penetration of various topical medications but can also be a significant cutaneous irritant particularly when applied to inflamed, fissured or ulcerated skin
True (if a patient fails to improve with a topical antifungal preparation, the clinician should consider whether propylene glycol might be serving as an irritant as the actual antifungal active ingredient is associated with <1% risk of true allergic contact dermatitis)
