unit 5- Antiinfectives.ppt

Anti-infective agents Unit-5 PCHE 0301 Fall 2023-24 Learning objectives After the completion of the unit students shall be able to: • Define and classify anti-infective agents. • Explain the ideal properties of antiseptic and disinfectant • Understand mechanism of action of anti-infectives. • Sele...

Anti-infective agents Unit-5 PCHE 0301 Fall 2023-24 Learning objectives After the completion of the unit students shall be able to: • Define and classify anti-infective agents. • Explain the ideal properties of antiseptic and disinfectant • Understand mechanism of action of anti-infectives. • Select appropriate anti-infective agent as per the requirement Overview of Lecture-1 • • • • • Historical perspective of anti-infective therapy Antiseptic and their ideal properties Disinfectant and their ideal characteristics Classification of antiseptic and disinfectants Mechanism of action of anti-infective agents Anti-infective agents • Infections are caused by parasitic organisms like virus, bacteria, fungus, ameba, worms etc. • • Prevention and treatment of infection are the prime concern in health care system. • Most of the infections are communicable and therefore prophylaxis is also given emphasis in public health care. Anti-infective Agents • Joseph Lister (1867) introduced the antiseptic principles for use in surgery and post traumatic injury (used phenol/carbolic acid). • Paul Ehrlich worked on antibacterial dyes and antiparasitic organic arsenicals as “magic bullets” for treating infections. Modern chemotherapy • Selective toxicity of chemicals to kill one type of organism while not harming another, led to the modern antimicrobial chemotherapy. • Germicides: Anti-infective agents that are used locally to kill pathogens . • Antiseptics: Agents which kill or prevent growth of microorganisms when applied on living tissue. – They have either cidal or static effect. Ideal antiseptic shall be; • Disinfectants: Agents that prevent transmission or infection by the destruction of pathogenic microorganism when applied on inanimate objects. • Ideal disinfectant shall have Standards for removing microorganisms Antiseptic and disinfectants Classification of Antiseptics and Disinfectants B. Inorganic substances 1. Halogens: • Iodine • Povidon-Iodine (Betadinum) • Iodophorm • Lugol’s solution • Chlorhexidine bigluconate • Halazone 2. Oxidizing agents: • Hydrogen peroxide • Potassium permanganate 3. Acids and alkalis: • Solution of ammonia 4. Metallic salts: • • • • Silver nitrate Copper sulfate Zinc sulfate Zinc oxide 5. Cationic surfactants 6. Mercury compounds Sites of action of anti-infective agents Mechanism of action of anti-infective agents • Interfere with Cell wall: e.g. Phenol, formaldehyde and hypochlorite ( bleaching powder) Cytoplasmic membrane: e.g. chlorhexidine, hexachlorophene Protein metabolism: Coagulation: e.g. chlorhexidine, hexachlorophene, alcohol NH2 group: e.g. formaldehyde, glutaraldehyde • • • • • COOH group: e.g. cationic surfactant • SH group: e.g. ethylene oxide, iodine, hydrogen peroxide, • Nucleic acid: acridine Overview of Lecture-2 • • • • • Alcohols and related compounds Aldehydes Phenols and their derivatives Oxidizing agents Halogen containing compounds Alcohols and related compounds • Ethyl alcohol and isopropyl alcohol are used as antiseptic and disinfectants. – Alcohols have the ability to denature important proteins and carbohydrates in microorganisms. • Alcohol is metabolized in human body by alcohol dehydrogenase to acetaldehyde and then to acetic acid. Types of Alcohol • Denatured alcohol – is rendered unfit for use in intoxicating beverages by adding other substances like methanol, benzene or naphtha. • 70% alcohol – has antiseptic, preservative, mild local anesthetic and rubefacient properties. • Isopropyl Alcohol: – Colorless, volatile liquid and slightly bitter taste. – 50-95% solution is bactericidal. – Must not be ingested. • Ethylene oxide: C2H4O – Colorless flammable gas, liquefies at 120C. – Uses: To sterilize temperature sensitive medical equipment (surgical sutures –catgut) and drugs. – Mechanism of germicidal action: Alkylation of functional groups of nucleic acid and proteins. – It is extremely toxic and carcinogenic. Avoid exposure to EO. Aldehydes • Formaldehyde solution: – Aqueous solution containing 37% w/v of formaldehyde with small amount of methanol added (to retard polymerization to paraformaldehyde). – Stored in airtight- light resistant container at above 150C to prevent cloudiness. – Germicide action is slow but powerful. – Nonspecific alkylation of nucleophilic functional groups of proteins and nucleic acid to form carbinol derivatives. – It is irritant and causes dermatitis. HO H H H O O O Gluteraldehyde Gluteraldehyde Hemiacetal Glutaraldehyde: •Uses: to disinfectant & to sterilize equipment and instruments that can not be autoclaved. •It is commercially available as 2% solution buffered at pH 7.5-8.0. stabilized in Alkaline solution. • Non buffered solution of glutaraldehyde is acidic and is stable but lack sporicidal activity. Phenols and their derivatives • Germicidal activity of disinfectant is expressed in Phenol coefficient. • The phenol coefficient is defined as the Ratio of a dilution of a given test disinfectant to the dilution of phenol that is required to kill a strain of Salmonella typhi under carefully controlled time and temperature conditions. • Phenols denature bacterial proteins in low concentration while lyses of bacterial cell membranes at higher concentration • SAR: • Phenol (carbolic acid) • Caustic to skin………diluted to avoid tissue destruction and dermatitis. • 0.1 to 1% concentration phenol ….. antipruritic and antiseptic. • 4% Phenol in glycerin ………to cauterize small wounds. • Not used now a days. OH Phenol Phenol derivatives • Liquified phenol is phenol containing 10% water. • p-chlorophenol: is used in combination with camphor in liquid paraffin as external antiseptic and anti-irritant. • p-chloro-m-xylenol: is nonirritating antiseptic with broad spectrum antibacterial and antifungal properties. It is used topical in tinea infections like athlete’s foot p-Chloro m-xylenol • Cresol: Its phenol coefficient is 2.5. It is disinfectant. • Chlorocresol: 4-Chloro-3methylphenol, In low concentration as preservative. (PC=4) OH p-chloro-m-cresol CH3 Cl • Thymol: (Isopropyl m-cresol) from thyme oil. • mild fungicidal and is used in dusting powder or alcoholic solution for treating tinea (ringworm) infections. • Eugenol: clove, local anesthetic, antiseptic, toothache, mouthwash OH Thymol Eugenol from clove oil Hexylresorcinol HO • Soluble in Alcohol • It is effective antiseptic and local anesthetic. • It is used as lozenges in laryngitis. • It’s Phenol coefficient is 98 OH Hexachlorophene (2,2’-methylenebis(3,4,6-tichlorophenol) • Soluble in alcohol. • Adsorbed onto the skin and enters the sebaceous glands. Prolong effect • In 2-3% concentration is available as soap, creams, lotions, shampoo for antiseptic uses. BAN - OTC, cosmetics • The systemic toxicity has been reported. Cl Cl Cl Cl Cl Cl OH OH Oxidizing agents • Mostly inorganic agents, react with tissues and generate oxygen or oxygen radicals. • Effective against anaerobic bacteria, can be used to clean contaminated wounds. • Drawback: poor penetrability into infected tissues and organic matter. • Exps; – H2O2, – Metal peroxide, – KMnO4, denature proteins in microorganisms thru direct oxidation rxn Carbamide peroxide- topical sol • Stable complex of hydrogen peroxide. Urea and • 12.6% solution in anhydrous glycerin for mouth ulcer and in dental care. H2NCONH2.H2O2 O H2N HO OH NH2 Hydrous Benzoyl peroxide • 5-10% solution is keratogenic & keratolytic, • Used to treat acne. • It induces proliferation of epithelial cells leading to sloughing and repair. Halogen containing compounds Iodophors: Active complexes of Iodine. • Elemental iodine is germicidal. Iodine inactivates protein by iodination of aromatic residue and oxidation of sulfhydryl groups. • Tincture Iodine:2% iodine in 50% alcohol. • Strong iodine solution (Lugol’s): 5% iodine in H2O with KI • Iodine solution: 2% I2 in water with sodium iodide Povidone iodine (Betadine, PVP-iodine) Complexes with surfactants, help in retaining the germicidal properties of I2 while reducing its volatility and removing its irritant properties. A charge transfer complex of iodine with nonionic surfactant polymer polyvinyl-pyrrolidone (PVP). • Complex is extremely water soluble. • It is nontoxic, nonvolatile and non-staining form of iodine that is not irritating to the skin or to wounds. • Ointment, surgical scrubs, sponges, aerosol, foams, mouthwashes, etc. Povidone Iodine It is used as an aqueous solution for presurgical disinfection of the incision site. Overview of Lecture-3 • • • • Cationic surfactants Dyes Mercury compounds Preservatives Cationic surfactants • Quaternary ammonium compounds • Water soluble surfactants exerting bactericidal action and are effective against fungi and protozoa. • Used as antiseptic, preservative and disinfectant. • Nontoxic, stable, non-staining and non-corrosive. • Exps: Benzalkonium chloride, Cetylpyridinium chloride Inactivated by soap and anionic agents Slower than iodine Benzalkonium chloride • Alkylbenzyldimethylammonium chloride. • It is detergent, an emulsifier and a wetting agent. • Solution 1:750 to 1:20,000 is antiseptic CH3 + N CH3 R = C8H17 R Cetylpyridinium chloride • 1-Hexadecylpyridinium chloride • White water soluble surfactant. 1:100-1;1000 is used as antisepticthroat lozenges, mouthwash + N Cl - https://www.ibtimes.sg/mouthwash-kills-coron avirus-within-few-seconds-laboratory-tests-53 417 CH3 Chlorhexidine gluconate • Broad spectrum antibacterial biguanide. • Not effective against acid-fast bacteria, spores or virus. • Topical antiseptic, preoperative disinfection & mouthwash 1,6 di(4`chlorophenyldiguanidino)hexane gluconate as Dyes • Triphenylmethane dyes –cationic dyes are active against Gram positive bacteria & fungus • Gentian violet • Basic fuchsine • Methylene blue Methylene Blue • • • • 3,7-bis(dimethylamino)-phenathiazonium chloride Dark green crystals Weak antiseptic –treatment of cystitis and urethritis. Colors urine and stool blue green. Phenothiazine N H3C N CH3 S N CH3 CH3 Mercury compounds (mercurials) • Hg incorporated into ointment bases for treatment of localized infections and syphilis. • HgCl2, , Hg2Cl2(calomel)- antiseptic • HgO- to treat inflammation resulting from infection of eye. • Drawback: low water solubility reduces their interaction with tissues, irritating, cause hypersensitivity. • Their use is not recommended. Thiomerosal • Non-staining and nonirritant topical bacteriostatic agent. S Hg O OH CH3 Preservatives • Added to Prevent microbial contamination in food, drugs and cosmetics and to maintain sterility in parenteral and ophthalmic prep. • Ideal preservative shall be – effective in low concentration against most of the organisms, – nontoxic, – compatible with other constituent and – Stable for shelf life of the preparation. • • • • p-Hydroxybenzoic acid (Parabens) derivatives Methylparaben Ethylparaben Propylparaben Butylparaben COOH OH •Esters of Parabens have antifungal properties. •Low toxicity because hydrolyzed to PHBA rapidly in vivo, which is conjguated and excreted. •Useful preservatives for liquid preparations. •Activity increases with molecular weight, but methyl ester is most effective against molds and Propyl ester against yeasts, therefore preferred for drugs in oil or lipophilic bases. Methyl paraben • Methylparaben is methyl p- hydroxy-benzoate. • water soluble non-polar preservative • Propyl paraben is also used in combination as preservative COOCH 3 OH Chlorobutanol • 1,1,1-trichloro-2-methyl-2-propanol • Bacteriostatic in injection, eye drops and ointment. • Solution at pH around 5 is reasonably stable HO H3C CH3 CCl 3 Benzyl alcohol (Phenyl carbinol, phenylmethanol) • It is present in volatile oils, resins like Peru balsm, tolu balsm, benzoin etc. • 1-4% in IM.injection (vials) as preservative. • In Ointments & lotions as antiseptic. CH 2OH Phenylethyl alcohol • Present in orange oil and rose oil. • Preservative in cosmetics and confectionary items CH 2CH 2OH 2-phenylethanol Benzoic acid • Antifungal, preservative in lotions, ointment, mouthwashes • Sodium benzoate is water soluble & used to preserve acid liquid preparations O OH Sorbic acid • 2,4-hexadienoic acid, Potassium salt is also used. • Water immiscible, effective antifungal preservative. • Elixirs, syrups, lotion, ointment H3C O OH Learning outcomes • Able to suggest the mechanism of action from the structure of antiseptics • Able to predict the physicochemical properties of the antiseptics ] • Able to suggest better choice of antiseptics for various application