Antifungals For Dermatologic Use
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Antifungals For Dermatologic Use
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. Routes of administration Ocular Indicated when the fungal infection is located in the eye. There is currently only one ocular antifungal available: natamycin. However, various other antifungal agents could be compounded in this formulation. Intrathecal Used occasionally when there's an infection of the central nervous system and other systemic options cannot reach the concentration required in that region for therapeutic benefit. Example(s): amphotericin B. Vaginal This may be used to treat some fungal infect ...
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Clotrimazole
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. Common side effects when taken by mouth include nausea and itchiness. When applied to the skin, common side effects include redness and a burning sensation. In pregnancy, use on the skin or in the vagina is believed to be safe. There is no evidence of harm when used by mouth during pregnancy but this has been less well studied. When used by mouth, greater care should be taken in those with liver problems. It is in the azole class of medications and works by disrupting the fungal cell membrane. Clotrimazole was discovered in 1969. It is on the WHO Model List of Essential Medicines, World Health Organization's List of Essential Medicines. It is available as a ...
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Cholesterol
Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils. Cholesterol is biosynthesis, biosynthesized by all animal Cell (biology)#Eukaryotic cells, cells and is an essential structural and cholesterol signaling, signaling component of animal cell membranes. In vertebrates, hepatocyte, hepatic cells typically produce the greatest amounts. In the brain, astrocytes produce cholesterol and transport it to neurons. It is absent among prokaryotes (bacteria and archaea), although there are some exceptions, such as ''Mycoplasma'', which require cholesterol for growth. Cholesterol also serves as a Precursor (chemistry), precursor for the biosynthesis of steroid hormones, bile acid and vitamin D. Elevated levels of cholesterol in the blood, especially when bound to low-density lipoprotein (LDL, often referred to as "bad cholesterol"), may increase the risk of ...
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Ergosterol
Ergosterol (ergosta-5,7,22-trien-3β-ol) is a mycosterol found in cell membranes of fungi and protozoa, serving many of the same functions that cholesterol serves in animal cells. Because many fungi and protozoa cannot survive without ergosterol, the enzymes that synthesize it have become important targets for drug discovery. In human nutrition, ergosterol is a provitamin form of vitamin D2; exposure to ultraviolet (UV) light causes a chemical reaction that produces vitamin D2. Role in fungi Ergosterol (ergosta-5,7,22-trien-3β-ol) is a sterol found in fungi, and named after ergot, the common name of members of the fungal genus '' Claviceps'' from which ergosterol was first isolated. Ergosterol is a component of yeast and other fungal cell membranes, serving many of the same functions that cholesterol serves in animal cells. Its specificity in higher fungi is thought to be related to the climatic instabilities (highly varying humidity and moisture conditions) encountered by ...
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Cell Membrane
The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extracellular space). The cell membrane consists of a lipid bilayer, made up of two layers of phospholipids with cholesterols (a lipid component) interspersed between them, maintaining appropriate membrane fluidity at various temperatures. The membrane also contains membrane proteins, including integral proteins that span the membrane and serve as membrane transporters, and peripheral proteins that loosely attach to the outer (peripheral) side of the cell membrane, acting as enzymes to facilitate interaction with the cell's environment. Glycolipids embedded in the outer lipid layer serve a similar purpose. The cell membrane controls the movement of substances in and out of a cell, being selectively permeable to ions and organic mole ...
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Sterol
A sterol is any organic compound with a Skeletal formula, skeleton closely related to Cholestanol, cholestan-3-ol. The simplest sterol is gonan-3-ol, which has a formula of , and is derived from that of gonane by replacement of a hydrogen atom on C3 position by a hydroxyl group. It is therefore an alcohol (chemistry), alcohol of gonane. More generally, any compounds that contain the gonane structure, additional functional groups, and/or modified ring systems derived from gonane are called steroids. Therefore, sterols are a subgroup of the steroids. They occur naturally in most Eukaryote, eukaryotes, including plants, animals, and fungi, and can also be produced by some bacteria (however likely with different functions). The most familiar type of animal sterol is cholesterol, which is vital to the structure of the cell membrane, and functions as a precursor to fat-soluble vitamins and steroid hormones. While technically alcohols, sterols are classified by biochemists as lipids (f ...
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Polyene Antimycotic
Polyene antimycotics, sometimes referred to as polyene antibiotics, are a class of antimicrobial polyene compounds that target fungi. These polyene antimycotics are typically obtained from certain species of ''Streptomyces'' bacteria. Previously, polyenes were thought to bind to ergosterol in the fungal cell membrane, weakening it and causing leakage of K+ and Na+ ions, which could contribute to fungal cell death. However, more detailed studies of polyene molecular properties have challenged this model suggesting that polyenes instead bind and extract ergosterol directly from the cellular membrane thus disrupting the many cellular functions ergosterols perform. Amphotericin B, nystatin, and natamycin are examples of polyene antimycotics. They are a subgroup of macrolides. Structures Their chemical structures feature a large ring of atoms (in essence, a cyclic ester ring) containing multiple conjugated carbon-carbon double bonds (hence ''polyene'') on one side of the ring and mul ...
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Amphiphilic
In chemistry, an amphiphile (), or amphipath, is a chemical compound possessing both hydrophilic (''water-loving'', polar) and lipophilic (''fat-loving'', nonpolar) properties. Such a compound is called amphiphilic or amphipathic. Amphiphilic compounds include surfactants and detergents. The phospholipid amphiphiles are the major structural component of cell membranes. Amphiphiles are the basis for a number of areas of research in chemistry and biochemistry, notably that of lipid polymorphism. Organic compounds containing hydrophilic groups at both ends of the molecule are called bolaamphiphilic. The micelles they form in the aggregate are prolate. Structure The lipophilic group is typically a large hydrocarbon moiety, such as a long chain of the form CH3(CH2)n, with n > 4. The hydrophilic group falls into one of the following categories: # charged groups #* anionic. Examples, with the lipophilic part of the molecule represented by ''R'', are: #** carboxylates: RCO2− #* ...
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Conjugated System
In physical organic chemistry, a conjugated system is a system of connected p-orbitals with delocalized electrons in a molecule, which in general lowers the overall energy of the molecule and increases Chemical stability, stability. It is Resonance (chemistry), conventionally represented as having alternating single and multiple covalent bond, bonds. Lone pairs, radical (chemistry), radicals or carbenium ions may be part of the system, which may be Cyclic molecule, cyclic, acyclic, Linear molecular geometry, linear or mixed. The term "conjugated" was coined in 1899 by the German chemist Johannes Thiele (chemist), Johannes Thiele. Conjugation is the orbital overlap, overlap of one p-orbital with another across an adjacent Sigma bond, σ bond (in transition metals, d-orbitals can be involved). A conjugated system has a region of overlapping p-orbitals, bridging the interjacent locations that simple diagrams illustrate as not having a π bond. They allow a delocalization of pi el ...
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Polyene
In organic chemistry, polyenes are polyunsaturated organic compounds that contain multiple carbon–carbon double bonds (). Some sources consider dienes to be polyenes, whereas others require polyenes to contain at least three carbon–carbon double bonds. Conjugated polyenes contain a conjugated system of alternating single and double carbon–carbon bonds, with characteristic optical properties. The following polyenes are used as antimycotics for humans: amphotericin B, nystatin, candicidin, pimaricin, methyl partricin, and trichomycin. Optical properties Some polyenes are brightly colored, an otherwise rare property for a hydrocarbon. Normally alkenes absorb in the ultraviolet region of a spectrum, but the absorption energy state of polyenes with numerous conjugated double bonds can be lowered such that they enter the visible region of the spectrum, resulting in compounds which are coloured (because they contain a chromophore). Thus many natural dyes contain linear ...
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Coccidioidomycosis
Coccidioidomycosis (, ) is a mammalian mycosis, fungal disease caused by ''Coccidioides immitis'' or ''Coccidioides posadasii''. It is commonly known as cocci, Valley fever, California fever, desert rheumatism, or San Joaquin Valley fever. Coccidioidomycosis is endemic (epidemiology), endemic in certain parts of the United States in Arizona, California, Nevada, New Mexico, Texas, Utah, and northern Mexico. Description ''C. immitis'' is a Polymorphism (biology), dimorphic saprophytic fungus that grows as a mycelium in the soil and produces a spherule form in the Host (biology), host organism. It resides in the soil in certain parts of the southwestern United States, most notably in California and Arizona. It is also commonly found in northern Mexico, and parts of Central America, Central and South America. ''C. immitis'' is dormant during long dry spells, then develops as a mold with long filaments that break off into airborne spores when it rains. The spores, known as arthroc ...
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Ketoconazole
Ketoconazole, sold under the brand name Nizoral, among others, is an antiandrogen, antifungal drug, antifungal, and antiglucocorticoid medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin infections such as tinea, cutaneous candidiasis, pityriasis versicolor, dandruff, and seborrhoeic dermatitis, seborrheic dermatitis. Taken oral administration, by mouth it is a less preferred option and recommended for only severe infections when other agents cannot be used. Other uses include treatment of hirsutism, excessive male-patterned hair growth in women and Cushing's syndrome. Common side effects when transdermal administration, applied to the skin include redness. Common side effects when taken by mouth include nausea, headache, and liver problems. Liver problems may result in death or the need for a liver transplantation. Other severe side effects when taken orally include QT prolongation, adrenocortical insufficiency, and anaphyl ...
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