Clobetasol¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ The precise mechanism of the antiinflammatory activity of topical steroids in the treatment of steroid-responsive dermatoses, in general, is uncertain. However, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2. Neomycin¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Aminoglycosides like neomycin "irreversibly" bind to specific 30S-subunit proteins and 16S rRNA. Specifically neomycin binds to four nucleotides of 16S rRNA and a single amino acid of protein S12. This interferes with decoding site in the vicinity of nucleotide 1400 in 16S rRNA of 30S subunit. This region interacts with the wobble base in the anticodon of tRNA. This leads to interference with the initiation complex, misreading of mRNA so incorrect amino acids are inserted into the polypeptide leading to nonfunctional or toxic peptides and the breakup of polysomes into nonfunctional monosomes. Nystatin¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Nystatin interacts with 14-¥á demethylase, a cytochrome P-450 enzyme necessary for the conversion of lanosterol to ergosterol. This results in inhibition of ergosterol synthesis and increased fungal cellular permeability.
Pharmacology
Clobetasol¿¡ ´ëÇÑ Pharmacology Á¤º¸ Like other topical corticosteroids, clobetasol has anti-inflammatory, antipruritic, and vasoconstrictive properties. It is a very high potency topical corticosteroid that should not be used with occlusive dressings. It is recommended that treatment should be limited to 2 consecutive weeks and therapy should be discontinued when adequate results have been achieved. Neomycin¿¡ ´ëÇÑ Pharmacology Á¤º¸ Neomycin is an aminoglycoside antibiotic. Aminoglycosides work by binding to the bacterial 30S ribosomal subunit, causing misreading of t-RNA, leaving the bacterium unable to synthesize proteins vital to its growth. Aminoglycosides are useful primarily in infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some mycobacteria, including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. Infections caused by Gram-positive bacteria can also be treated with aminoglycosides, but other types of antibiotics are more potent and less damaging to the host. In the past the aminoglycosides have been used in conjunction with penicillin-related antibiotics in streptococcal infections for their synergistic effects, particularly in endocarditis. Aminoglycosides are mostly ineffective against anaerobic bacteria, fungi and viruses. Nystatin¿¡ ´ëÇÑ Pharmacology Á¤º¸ Nystatin is an antibiotic which is both fungistatic and fungicidal in vitro against a wide variety of yeasts and yeast-like fungi, including Candida albicans, C. parapsilosis, C. tropicalis, C. guilliermondi, C. pseudotropicalis, C. krusei, Torulopsis glabrata, Tricophyton rubrum, T. mentagrophytes. Nystatin acts by binding to sterols in the cell membrane of susceptible species resulting in a change in membrane permeability and the subsequent leakage of intracellular components. On repeated subculturing with increasing levels of nystatin, Candida albicans does not develop resistance to nystatin. Generally, resistance to nystatin does not develop during therapy. However, other species of Candida (C. tropicalis, C. guilliermondi, C. krusei, and C. stellatoides) become quite resistant on treatment with nystatin and simultaneously become cross resistant to amphotericin as well. This resistance is lost when the antibiotic is removed. Nystatin exhibits no appreciable activity against bacteria, protozoa, or viruses.
Clobetasol¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ Not Available Neomycin¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ Protein binding studies have shown that the degree of aminoglycoside protein binding is low and, depending upon the methods used for testing, may be between 0% and 30%.
Half-life
Clobetasol¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ Not Available Neomycin¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 2 to 3 hours Nystatin¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ Not Available
Absorption
Clobetasol¿¡ ´ëÇÑ Absorption Á¤º¸ Topical corticosteroids can be absorbed from intact healthy skin. The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle and the integrity of the epidermal barrier. Occlusion, inflammation and/or other disease processes in the skin may also increase percutaneous absorption. Neomycin¿¡ ´ëÇÑ Absorption Á¤º¸ Poorly absorbed from the normal gastrointestinal tract. Although only approximately 3% of neomycin is absorbed through intact intestinal mucosa, significant amounts may be absorbed through ulcerated or denuded mucosa or if inflammation is present. Nystatin¿¡ ´ëÇÑ Absorption Á¤º¸ Nystatin is not absorbed from intact skin or mucous membrane
Biotransformation
Clobetasol¿¡ ´ëÇÑ Biotransformation Á¤º¸ Metabolized, primarily in the liver, and then excreted by the kidneys. Neomycin¿¡ ´ëÇÑ Biotransformation Á¤º¸ Neomycin undergoes negligible biotransformation after parenteral administration.
Toxicity
Clobetasol¿¡ ´ëÇÑ Toxicity Á¤º¸ Oral LD50 in rat and mouse is >3000 mg/kg. Topically applied clobetasol can be absorbed in sufficient amounts to produce systemic effects. Symptoms of overdose include thinning of skin and suppression of adrenal cortex (decreased ability to respond to stress). Neomycin¿¡ ´ëÇÑ Toxicity Á¤º¸ LD50 = 200 mg/kg (rat). Because of low absorption, it is unlikely that acute overdosage would occur with oral neomycin. However, prolonged administration could result in sufficient systemic drug levels to produce neurotoxicity, ototoxicity and/or nephrotoxicity. Nystatin¿¡ ´ëÇÑ Toxicity Á¤º¸ Not Available
Drug Interactions
Clobetasol¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Not Available Neomycin¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Not Available Nystatin¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Not Available
Clobetasol¿¡ ´ëÇÑ Food Interaction Á¤º¸ Not Available Neomycin¿¡ ´ëÇÑ Food Interaction Á¤º¸ Not Available Nystatin¿¡ ´ëÇÑ Food Interaction Á¤º¸ Take without regard to meals.
Clobetasol¿¡ ´ëÇÑ Description Á¤º¸ A derivative of prednisolone with high glucocorticoid activity and low mineralocorticoid activity. Absorbed through the skin faster than fluocinonide, it is used topically in treatment of psoriasis but may cause marked adrenocortical suppression. [PubChem] Neomycin¿¡ ´ëÇÑ Description Á¤º¸ A component of neomycin that is produced by Streptomyces fradiae. On hydrolysis it yields neamine and neobiosamine B. (From Merck Index, 11th ed) Nystatin¿¡ ´ëÇÑ Description Á¤º¸ Nystatin is a polyene antifungal drug to which many molds and yeasts are sensitive, including Candida spp. Nystatin has some toxicity associated with it when given intravenously, but it is not absorbed across intact skin or mucous membranes. It is considered a relatively safe drug for treating oral or gastrointestinal fungal infections.
The database contains the following fields: The generic name of each chemical For module A10 (liver enzyme composite module): Overall activity category for each compound (A for active, M for marginally active, or I for inactive) based on the number of active and marginally active scores for each compound at the five individual endpoints (see research article for full description of method) Number of endpoints at which each compound is marginally active (M) Number of endpoints at which each compound is active (A) For modules A11 to A15 (alkaline phosphatase increased, SGOT increased, SGPT increased, LDH increased, and GGT increased, respectively): Overall activity category for each compound (A for active, M for marginally active, or I for inactive) based on the RI and ADR values (see the research article for full description of method) Number of ADR reports for each compound, given as <4 or ¡Ã4 Reporting Index value for each compound, except where no shipping units were available (NSU) Group 1 comprises of compounds for which ADR data were available for the first five years of marketing, so when no ADR reports were listed during this period the compounds were evaluated as inactive. Group 2 comprises of compounds for which a 'steady state' period of ADR data were available (1992-1996). In cases where no ADR reports were filed during this period, the compounds were scored as 'NA' (data not available) since they may have had one or more ADR reports during their first five years of marketing which should not be negated by a lack of ADR reports during the steady-state period. CLOBETASOL [GGT Increase] [Composite Activity] (Score)I (Marginal) 0 (Active) 0