Clotrimazole¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Clotrimazole interacts with yeast 14-¥á demethylase, a cytochrome P-450 enzyme that converts lanosterol to ergosterol, an essential component of the membrane. In this way, clotrimazole inhibits ergosterol synthesis, resulting in increased cellular permeability. Clotrimazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms and the uptake of purine, impair triglyceride and/or phospholipid biosynthesis, and inhibit the movement of calcium and potassium ions across the cell membrane by blocking the ion transport pathway known as the Gardos channel. Hydrocortisone¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Hydrocortisone binds to the cytosolic glucocorticoid receptor. After binding the receptor the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing the increase in expression of specific target genes. The anti-inflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. Specifically glucocorticoids induce lipocortin-1 (annexin-1) synthesis, which then binds to cell membranes preventing the phospholipase A2 from coming into contact with its substrate arachidonic acid. This leads to diminished eicosanoid production. The cyclooxygenase (both COX-1 and COX-2) expression is also suppressed, potentiating the effect. In another words, the two main products in inflammation Prostaglandins and Leukotrienes are inhibited by the action of Glucocorticoids. Glucocorticoids also stimulate the lipocortin-1 escaping to the extracellular space, where it binds to the leukocyte membrane receptors and inhibits various inflammatory events: epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst and the release of various inflammatory mediators (lysosomal enzymes, cytokines, tissue plasminogen activator, chemokines etc.) from neutrophils, macrophages and mastocytes. Additionally the immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding.
Pharmacology
Clotrimazole¿¡ ´ëÇÑ Pharmacology Á¤º¸ Clotrimazole, an imidazole derivative with a broad spectrum of antimycotic activity, inhibits biosynthesis of the sterol ergostol, an important component of fungal cell membranes. Its action leads to increased membrane permeability and apparent disruption of enzyme systems bound to the membrane. Betamethasone and clotrimazole are used together to treat cutaneous tinea infections. In studies in fungal cultures, the minimum fungicidal concentration of clotrimazole caused leakage of intracellular phosphorous compounds into the ambient medium with concomitant breakdown of cellular nucleic acids, and accelerated potassium etflux. Both of these events began rapidly and extensively after addition of the drug to the cultures. The primary action of clotrimazole is against dividing and growing organisms. Hydrocortisone¿¡ ´ëÇÑ Pharmacology Á¤º¸ Hydrocortisone is the most important human glucocorticoid. It is essential for life and regulates or supports a variety of important cardiovascular, metabolic, immunologic and homeostatic functions. Topical hydrocortisone is used for its anti-inflammatory or immunosuppressive properties to treat inflammation due to corticosteroid-responsive dermatoses. Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger a variety of important cardiovascular, metabolic, immunologic and homeostatic effects. Glucocorticoids are distinguished from mineralocorticoids and sex steroids by having different receptors, target cells, and effects. Technically, the term corticosteroid refers to both glucocorticoids and mineralocorticoids, but is often used as a synonym for glucocorticoid. Glucocorticoids suppress cell-mediated immunity. They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and TNF-alpha, the most important of which is the IL-2. Reduced cytokine production limits T cell proliferation. Glucocorticoids also suppress humoral immunity, causing B cells to express lower amounts of IL-2 and IL-2 receptors. This diminishes both B cell clonal expansion and antibody synthesis. The diminished amounts of IL-2 also leads to fewer T lymphocyte cells being activated.
Clotrimazole¿¡ ´ëÇÑ Absorption Á¤º¸ Poorly and erratically absorbed orally, minimal vaginal or topical absorption. Hydrocortisone¿¡ ´ëÇÑ Absorption Á¤º¸ Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin increase percutaneous absorption.
Clotrimazole¿¡ ´ëÇÑ Biotransformation Á¤º¸ Hepatic (metabolized to inactive metabolites) Hydrocortisone¿¡ ´ëÇÑ Biotransformation Á¤º¸ Primarily hepatic via CYP3A4
Toxicity
Clotrimazole¿¡ ´ëÇÑ Toxicity Á¤º¸ Symptoms of overdose include erythema, stinging, blistering, peeling, edema, pruritus, urticaria, burning, and general irritation of the skin, and cramps. Hydrocortisone¿¡ ´ëÇÑ Toxicity Á¤º¸ Side effects include inhibition of bone formation, suppression of calcium absorption and delayed wound healing
Drug Interactions
Clotrimazole¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Not Available Hydrocortisone¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Ambenonium The corticosteroid decreases the effect of anticholinesterasesEdrophonium The corticosteroid decreases the effect of anticholinesterasesNeostigmine The corticosteroid decreases the effect of anticholinesterasesPyridostigmine The corticosteroid decreases the effect of anticholinesterasesAspirin The corticosteroid decreases the effect of salicylatesBismuth Subsalicylate The corticosteroid decreases the effect of salicylatesSalicylate-magnesium The corticosteroid decreases the effect of salicylatesSalicylate-sodium The corticosteroid decreases the effect of salicylatesSalsalate The corticosteroid decreases the effect of salicylatesTrisalicylate-choline The corticosteroid decreases the effect of salicylatesWarfarin The corticosteroid alters the anticoagulant effectAcenocoumarol The corticosteroid alters the anticoagulant effectDicumarol The corticosteroid alters the anticoagulant effectAnisindione The corticosteroid alters the anticoagulant effectCholestyramine Cholestyramine decreases the effect of hydrocortisoneColestipol Cholestyramine decreases the effect of hydrocortisoneAmobarbital The barbiturate decreases the effect of the corticosteroidAprobarbital The barbiturate decreases the effect of the corticosteroidButabarbital The barbiturate decreases the effect of the corticosteroidButalbital The barbiturate decreases the effect of the corticosteroidButethal The barbiturate decreases the effect of the corticosteroidDihydroquinidine barbiturate The barbiturate decreases the effect of the corticosteroidHeptabarbital The barbiturate decreases the effect of the corticosteroidHexobarbital The barbiturate decreases the effect of the corticosteroidMethohexital The barbiturate decreases the effect of the corticosteroidMethylphenobarbital The barbiturate decreases the effect of the corticosteroidPentobarbital The barbiturate decreases the effect of the corticosteroidPhenobarbital The barbiturate decreases the effect of the corticosteroidPrimidone The barbiturate decreases the effect of the corticosteroidQuinidine barbiturate The barbiturate decreases the effect of the corticosteroidSecobarbital The barbiturate decreases the effect of the corticosteroidTalbutal The barbiturate decreases the effect of the corticosteroidRifampin The enzyme inducer decreases the effect of the corticosteroidPhenytoin The enzyme inducer decreases the effect of the corticosteroidMephenytoin The enzyme inducer decreases the effect of the corticosteroidFosphenytoin The enzyme inducer decreases the effect of the corticosteroidEthotoin The enzyme inducer decreases the effect of the corticosteroidMidodrine Increased arterial pressure
Clotrimazole¿¡ ´ëÇÑ Food Interaction Á¤º¸ Not Available Hydrocortisone¿¡ ´ëÇÑ Food Interaction Á¤º¸ Take with food to reduce irritation. Calcium, phosphorous, potassium, Vitamin A, C, D and zinc needs increased with long term use.
Clotrimazole¿¡ ´ëÇÑ Description Á¤º¸ An imidazole derivative with a broad spectrum of antimycotic activity. It inhibits biosynthesis of the sterol ergostol, an important component of fungal cell membranes. Its action leads to increased membrane permeability and apparent disruption of enzyme systems bound to the membrane. [PubChem] Hydrocortisone¿¡ ´ëÇÑ Description Á¤º¸ The main glucocorticoid secreted by the adrenal cortex. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions. [PubChem]