Clinical data | |
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Trade names | Gris-peg, Grifulvin V, others |
AHFS/Drugs.com | Monograph |
MedlinePlus | a682295 |
Pregnancy category |
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Routes of administration | By mouth |
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Pharmacokinetic data | |
Bioavailability | Highly variable (25 to 70%) |
Metabolism | Liver (demethylation and glucuronidation) |
Elimination half-life | 9–21 hours |
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CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.004.335 |
Chemical and physical data | |
Formula | C17H17ClO6 |
Molar mass | 352.77 g·mol−1 |
3D model (JSmol) | |
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Griseofulvin is an antifungal medication used to treat a number of types of dermatophytoses (ringworm). [1] This includes fungal infections of the nails and scalp, as well as the skin when antifungal creams have not worked. [2] It is taken by mouth. [1]
Common side effects include allergic reactions, nausea, diarrhea, headache, trouble sleeping, and feeling tired. [1] It is not recommended in people with liver failure or porphyria. [1] Use during or in the months before pregnancy may result in harm to the baby. [1] [2] Griseofulvin works by interfering with fungal mitosis. [1]
Griseofulvin was discovered in 1939 from the soil fungus Penicillium griseofulvum . [3] [4] [5] It is on the World Health Organization's List of Essential Medicines. [6]
Griseofulvin is used orally only for dermatophytosis. It is ineffective topically. It is reserved for cases in which topical treatment with creams is ineffective. [7]
Terbinafine given for 2 to 4 weeks is at least as effective as griseofulvin given for 6 to 8 weeks for treatment of Trichophyton scalp infections. However, griseofulvin is more effective than terbinafine for treatment of Microsporum scalp infections. [8] [9]
The drug binds to tubulin, interfering with microtubule function, thus inhibiting mitosis. It binds to keratin in keratin precursor cells and makes them resistant to fungal infections. The drug reaches its site of action only when hair or skin is replaced by the keratin-griseofulvin complex. Griseofulvin then enters the dermatophyte through energy-dependent transport processes and binds to fungal microtubules. This alters the processing for mitosis and also underlying information for deposition of fungal cell walls.[ citation needed ]
It is produced industrially by fermenting the fungus Penicillium griseofulvum . [10] [11] [12]
The first step in the biosynthesis of griseofulvin by P. griseofulvin is the synthesis of the 14-carbon poly-β-keto chain by a type I iterative polyketide synthase (PKS) via iterative addition of 6 malonyl-CoA to an acyl-CoA starter unit. The 14-carbon poly-β-keto chain undergoes cyclization/aromatization, using cyclase/aromatase, respectively, through a Claisen and aldol condensation to form the benzophenone intermediate. The benzophenone intermediate is then methylated via S-adenosyl methionine (SAM) twice to yield griseophenone C. The griseophenone C is then halogenated at the activated site ortho to the phenol group on the left aromatic ring to form griseophenone B. The halogenated species then undergoes a single phenolic oxidation in both rings forming the two oxygen diradical species. The right oxygen radical shifts alpha to the carbonyl via resonance allowing for a stereospecific radical coupling by the oxygen radical on the left ring forming a tetrahydrofuranone species. [13] The newly formed grisan skeleton with a spiro center is then O-methylated by SAM to generate dehydrogriseofulvin. Ultimately, a stereoselective reduction of the olefin on dehydrogriseofulvin by NADPH affords griseofulvin. [14] [15]
Griseofulvin is found to alter the bile metabolism of mice by Yokoo et al. 1979. The same team went on to find a similar effect on mice by a chemically unrelated substance, 3,5-diethoxycarbonyl-1,4-dihydrocollidine, in Yokoo et al. 1982 and Tsunoo et al. 1987. [16]
An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as cryptococcal meningitis, and others. Such drugs are usually obtained by a doctor's prescription, but a few are available over the counter (OTC). The evolution of antifungal resistance is a growing threat to health globally.
Athlete's foot, known medically as tinea pedis, is a common skin infection of the feet caused by a fungus. Signs and symptoms often include itching, scaling, cracking and redness. In rare cases the skin may blister. Athlete's foot fungus may infect any part of the foot, but most often grows between the toes. The next most common area is the bottom of the foot. The same fungus may also affect the nails or the hands. It is a member of the group of diseases known as tinea.
Tolnaftate (INN) is a synthetic thiocarbamate used as an anti-fungal agent that may be sold without medical prescription in most jurisdictions. It is supplied as a cream, powder, spray, liquid, and liquid aerosol. Tolnaftate is used to treat fungal conditions such as jock itch, athlete's foot and ringworm.
Terbinafine, sold under the brand name Lamisil among others, is an antifungal medication used to treat pityriasis versicolor, fungal nail infections, and ringworm including jock itch and athlete's foot. It is either taken by mouth or applied to the skin as a cream or ointment. The cream and ointment are not effective for nail infections.
Dermatophyte is a common label for a group of fungus of Arthrodermataceae that commonly causes skin disease in animals and humans. Traditionally, these anamorphic mold genera are: Microsporum, Epidermophyton and Trichophyton. There are about 40 species in these three genera. Species capable of reproducing sexually belong in the teleomorphic genus Arthroderma, of the Ascomycota. As of 2019 a total of nine genera are identified and new phylogenetic taxonomy has been proposed.
Tinea corporis is a fungal infection of the body, similar to other forms of tinea. Specifically, it is a type of dermatophytosis that appears on the arms and legs, especially on glabrous skin; however, it may occur on any superficial part of the body.
Tinea capitis is a cutaneous fungal infection (dermatophytosis) of the scalp. The disease is primarily caused by dermatophytes in the genera Trichophyton and Microsporum that invade the hair shaft. The clinical presentation is typically single or multiple patches of hair loss, sometimes with a 'black dot' pattern, that may be accompanied by inflammation, scaling, pustules, and itching. Uncommon in adults, tinea capitis is predominantly seen in pre-pubertal children, more often boys than girls.
Dermatophytosis, also known as ringworm, is a fungal infection of the skin (Dermatomycosis). Typically it results in a red, itchy, scaly, circular rash. Hair loss may occur in the area affected. Symptoms begin four to fourteen days after exposure. Multiple areas can be affected at a given time.
Kerion or kerion celsi is an acute inflammatory process which is the result of the host's response to a fungal ringworm infection of the hair follicles of the scalp that can be accompanied by secondary bacterial infection(s). It usually appears as raised, spongy lesions, and typically occurs in children. This honeycomb is a painful inflammatory reaction with deep suppurative lesions on the scalp. Follicles may be seen discharging pus. There may be sinus formation and rarely mycetoma-like grains are produced. It is usually caused by dermatophytes such as Trichophyton verrucosum, T. mentagrophytes, and Microsporum canis. Treatment with oral griseofulvin common.
Trichophyton rubrum is a dermatophytic fungus in the phylum Ascomycota. It is an exclusively clonal, anthropophilic saprotroph that colonizes the upper layers of dead skin, and is the most common cause of athlete's foot, fungal infection of nail, jock itch, and ringworm worldwide. Trichophyton rubrum was first described by Malmsten in 1845 and is currently considered to be a complex of species that comprises multiple, geographically patterned morphotypes, several of which have been formally described as distinct taxa, including T. raubitschekii, T. gourvilii, T. megninii and T. soudanense.
Clotrimazole, sold under the brand name Lotrimin, among others, is an antifungal medication. It is used to treat vaginal yeast infections, oral thrush, diaper rash, tinea versicolor, and types of ringworm including athlete's foot and jock itch. It can be taken by mouth or applied as a cream to the skin or in the vagina.
Piedraia hortae is a superficial fungus that exists in the soils of tropical and subtropical environments and affects both sexes of all ages. The fungus grows very slowly, forming dark hyphae, which contain chlamydoconidia cells and black colonies when grown on agar. Piedraia hortae is a dermatophyte and causes a superficial fungal infection known as black piedra, which causes the formation of black nodules on the hair shaft and leads to progressive weakening of the hair. The infection usually infects hairs on the scalp and beard, but other varieties tend to grow on pubic hairs. The infection is usually treated with cutting or shaving of the hair and followed by the application of anti-fungal and topical agents. The fungus is used for cosmetic purposes to darken hair in some societies as a symbol of attractiveness.
Microsporum audouinii is an anthropophilic fungus in the genus Microsporum. It is a type of dermatophyte that colonizes keratinized tissues causing infection. The fungus is characterized by its spindle-shaped macroconidia, clavate microconidia as well as its pitted or spiny external walls.
Trichophyton tonsurans is a fungus in the family Arthrodermataceae that causes ringworm infection of the scalp. It was first recognized by David Gruby in 1844. Isolates are characterized as the "–" or negative mating type of the Arthroderma vanbreuseghemii complex. This species is thought to be conspecific with T. equinum, although the latter represents the "+" mating strain of the same biological species Despite their biological conspecificity, clones of the two mating types appear to have undergone evolutionary divergence with isolates of the T. tonsurans-type consistently associated with Tinea capitis whereas the T. equinum-type, as its name implies, is associated with horses as a regular host. Phylogenetic relationships were established in isolates from Northern Brazil, through fingerprinting polymorphic RAPD and M13 markers. There seems to be lower genomic variability in the T. tonsurans species due to allopatric divergence. Any phenotypic density is likely due to environmental factors, not genetic characteristics of the fungus.
Pityriasis amiantacea is an eczematous condition of the scalp in which thick tenaciously adherent scale infiltrates and surrounds the base of a group of scalp hairs. It does not result in scarring or alopecia.
Non scarring hair loss, also known as noncicatricial alopecia is the loss of hair without any scarring being present. There is typically little inflammation and irritation, but hair loss is significant. This is in contrast to scarring hair loss during which hair follicles are replaced with scar tissue as a result of inflammation. Hair loss may be spread throughout the scalp (diffuse) or at certain spots (focal). The loss may be sudden or gradual with accompanying stress.
Majocchi's granuloma is a skin condition characterized by deep, pustular plaques, and is a form of tinea corporis. It is a localized form of fungal folliculitis. Lesions often have a pink and scaly central component with pustules or folliculocentric papules at the periphery. The name comes from Domenico Majocchi, who discovered the disorder in 1883. Majocchi was a professor of dermatology at the University of Parma and later the University of Bologna. The most common dermatophyte is called Trichophyton rubrum.
Microsporum gypseum is a soil-associated dermatophyte that occasionally is known to colonise and infect the upper dead layers of the skin of mammals. The name refers to an asexual "form-taxon" that has been associated with four related biological species of fungi: the pathogenic taxa Arthroderma incurvatum, A. gypsea, A. fulva and the non-pathogenic saprotroph A. corniculata. More recent studies have restricted M. gypseum to two teleomorphic species A. gypseum and A. incurvatum. The conidial states of A. fulva and A. corniculata have been assigned to M. fulvum and M. boullardii. Because the anamorphic states of these fungi are so similar, they can be identified reliably only by mating. Two mating strains have been discovered, "+" and "–". The classification of this species has been based on the characteristically rough-walled, blunt, club-shaped, multicelled macroconidia. Synonyms include Achorion gypseum, Microsporum flavescens, M. scorteum, and M. xanthodes. There has been past nomenclatural confusion in the usage of the generic names Microsporum and Microsporon.
Topical antifungaldrugs are used to treat fungal infections on the skin, scalp, nails, vagina or inside the mouth. These medications come as creams, gels, lotions, ointments, powders, shampoos, tinctures and sprays. Most antifungal drugs induce fungal cell death by destroying the cell wall of the fungus. These drugs inhibit the production of ergosterol, which is a fundamental component of the fungal cell membrane and wall.