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Pharmacology-1 PHL 211 2nd Term 12th Lecture By Abdelkader Ashour, Ph.D. Phone: 4677212 Email: [email protected] Disinfectants & Antiseptics, Overview Disinfectants A disinfectant is a strong chemical agent that inhibits or kills microorganisms Disinfection: Chemical or physical treatment that destroys most vegetative microbes or viruses, but not spores, in or on inanimate surfaces The process of disinfection prevents infection by reducing the number of potentially infective organisms either by killing, removing or diluting them Disinfection can be accomplished by application of chemical agents (e.g., formaldehyde) or use of physical agents such as ionizing irradiation, dry or moist heat, or superheated steam (autoclave, 120 °C) to kill microorganisms Antiseptics An antiseptic is a disinfecting agents (e.g., 70% ethanol) with sufficiently low toxicity for host cells that it can be used directly on skin, mucous membranes or wounds Antisepsis: Application of an agent to living tissue for the purpose of preventing infection Users of antiseptics and disinfectants need to consider their short-term and long-term toxicity since these agents may have general biocidal activity and may accumulate in the environment or in the body of the patient or caregiver using the agent Disinfectants and antiseptics may also become contaminated by resistant microorganisms—e.g., spores, Pseudomonas aeruginosa—and actually transmit infection Most topical antiseptics interfere with wound healing to some degree. Simple cleansing with soap and water is less damaging than antiseptics to wounds Disinfectants & Antiseptics, Individual Agents Alcohols The two alcohols most frequently used for antisepsis and disinfection are ethanol and isopropyl alcohol (isopropanol) They are rapidly active, killing vegetative bacteria, M. tuberculosis and many fungi, and inactivating lipophilic viruses The optimum bactericidal concentration is 60–90% by volume in water They act by denaturation of proteins Their skin-drying effect can be partially alleviated by addition of emollients to the formulation Chlorhexidine It is a cationic surfactant. Water-soluble chlorhexidine digluconate is used in water-based formulations as an antiseptic It is active against vegetative bacteria and mycobacteria and has moderate activity against fungi and viruses It strongly adsorbs to bacterial membranes, causing leakage of small molecules and precipitation of cytoplasmic proteins It is slower in its action than alcohols, but because of its persistence it has residual activity when used repeatedly, producing bactericidal action equivalent to alcohols It has a very low skin-sensitizing or irritating capacity. Oral toxicity is low because chlorhexidine is poorly absorbed from the alimentary tract Chlorhexidine must not be used during surgery on the middle ear because it causes sensorineural deafness. Similar neural toxicity may be encountered during neurosurgery Disinfectants & Antiseptics, Individual Agents Iodine Iodine in a 1:20,000 solution is bactericidal in 1 minute and kills spores in 15 minutes. Tincture of iodine USP contains 2% iodine and 2.4% sodium iodide in alcohol It is the most active antiseptic for intact skin. It is not commonly used because of serious hypersensitivity reactions that may occur and because of its staining of clothing and dressings Iodophors Complexes of iodine with a surface-active agent such as polyvinyl pyrrolidone (PVP; povidone-iodine). Iodophors retain the activity of iodine. They kill vegetative bacteria, mycobacteria, fungi, and lipid-containing viruses. They may be sporicidal upon prolonged exposure Iodophors can be used as antiseptics or disinfectants, the latter containing more free iodine (which is low, but it is released as the solution is diluted). An iodophor solution must be diluted according to the manufacturer's directions in order to obtain full activity Iodophors are less irritating and less likely to produce skin hypersensitivity than tincture of iodine They act as rapidly as chlorhexidine and have a broader spectrum of action, including sporicidal action, but they lack the persistent action of chlorhexidine Dentifrices Definition: Preparations used for cleaning teeth. From Latin dentifricium, from denti- + fricare to rub A dentifrices is an integral component of daily home care to enhance oral hygiene Dentifrices effectively double the efficiency of mechanical plaque removal and therefore help to prevent oral diseases such as caries and gingival inflammation They usually contain an abrasive (the most important component) such as alumina and silica, detergent, binder and flavouring agent. May also contain medicaments and certain preventives These ingredients prevent caries (e.g., fluorides), treat hypersensitive exposed dentin (e.g., fluorides, strontium salts), possess disinfecting properties (e.g., triclosan) and serve to whiten stained teeth (H2O2; carbamide) They may exist in the form of liquid, paste or powder The most essential dentifrice recommended by dentists is toothpaste which is used in conjunction with a toothbrush to help remove food debris and dental plaque Dentifrice is the French word for toothpaste Fluorides, Overview Fluoride increases resistance to dental caries and therefore is referred to as a cariostatic agent; fluoride also desensitizes dentin Fluoride is used to reduce the incidence of dental caries and to slow or reverse the progression of existing dental lesions. Exposure to small amounts of oral and topical fluoride on a daily basis will reduce the risk for dental caries in all age groups Combined use of fluoridated dentifrices and fluoridated water has been found to provide greater protection against dental caries than either source alone Sodium fluoride (NaF) oral solutions and oral tablets are used as dietary supplements for the prevention of dental caries in children in areas where the concentration of fluoride ion in drinking water is less than optimal Dosage is based on the concentration of fluoride in the drinking water and the child's age Topical Fluorides: NaF, acidulated phosphate fluoride (NaF and phosphoric acid), and stannous fluoride are applied directly to the surfaces of teeth in the form of solutions, foams, creams, or gels for the prevention of dental caries Topical application of fluoride can be used as an alternative to oral administration to provide supplemental fluoride to children who live in areas with inadequate concentrations of fluoride ion in drinking water Fluorides, MOA & Indications MOA: Fluoride ions are incorporated into and stabilize the apatite crystal of teeth and bone Deposition of fluoride in tooth enamel increases resistance to acid dissolution and formation of dental caries Fluoride also promotes remineralization of decalcified enamel and inhibits the cariogenic microbial process in dental plaque Fluoride enhances precipitation of calcium phosphates in the dental tissues Fluoride is incorporated into teeth by occupying sites otherwise occupied by hydroxyl and/or carbonate anions in the apatite structure of the tooth enamel. This reaction results in the formation of fluorapatite which is less soluble in an acid medium than is hydroxyapatite and therefore increases resistance of tooth enamel to acid Orally administered fluoride apparently exerts its anticaries effect preeruptively while teeth are developing and posteruptively, and both mechanisms are thought to be necessary to attain maximum protection against caries Indications: Prevention of dental caries and slowing or reversing the progression of existing dental lesions Desensitizing Dentin. NaF and acidulated phosphate fluoride are used topically to desensitize exposed root surfaces of teeth Bone Diseases. NaF is used orally to increase bone density and relieve bone pain in the treatment of various metabolic and neoplastic bone diseases Fluorides, Precautions & Adverse effects The recommended dosage of oral and topical fluoride preparations should not be exceeded, and dosage should be adjusted in proportion to the amount of fluoride ion present in drinking water (….. dental fluorosis, next) Prolonged daily ingestion of excessive amounts of fluoride during the period of tooth development results in varying degrees of dental fluorosis. Dental fluorosis, or mottled enamel, is characterized by markings of hypocalcification or hypocalcification and hypoplasia, and the extent of fluorotic changes is dose dependent Dental fluorosis is the most sensitive index of chronic fluoride poisoning Sensitivity Reactions. Allergic rash and other idiosyncratic reactions have been reported with oral and topical NaF preparations. Urticaria, exfoliative dermatitis, atopic dermatitis, stomatitis, and GI and respiratory allergic reactions have occurred rarely following the use of dentifrices or multivitamin preparations containing fluoride Acute Toxicity. Symptoms of acute fluoride overdosage include hypersalivation, a salty or soapy taste, epigastric pain, nausea, vomiting, burning or crampy abdominal pain, diarrhea, dehydration, thirst, localized or generalized urticaria, muscle weakness and tremors. Death may result from cardiac failure, respiratory arrest, or shock and usually occurs within 2-4 hours following ingestion; if a victim survives the first 24 hours, the prognosis is good Treatment. Prevent further systemic absorption of fluoride by administration of emetics to induce vomiting or by the use of gastric lavage fluids containing calcium. Milk, calcium salts, or aluminum- and/or magnesium-containing antacids should be given orally. Hemodialysis may be beneficial in patients with severe intoxication or in those with impaired renal function