Pharmaceutical And Medicinal Organic Chemistry Student Activity Sheet#5 PDF

Course Code: PHA 051 (PHARMACEUTICAL AND MEDICINAL ORGANIC CHEMISTRY) STUDENT ACTIVITY SHEET#5 Name: ____________________________________________________________...

Course Code: PHA 051 (PHARMACEUTICAL AND MEDICINAL ORGANIC CHEMISTRY) STUDENT ACTIVITY SHEET#5 Name: _________________________________________________________________ Class number: _______ Section: ____________ Schedule: ________________________________________ Date: ________________ Lesson title: Local Anti-infectives and Preservatives Materials: Lesson Objectives: SAS and Pen At the end of the lesson, you should be able to: 1. Identify the structure of local anti-infectives and preservatives and References: determine the functional groups responsible for its biologic activity John M. Beale Jr., John H. Block. 2. Describe the mechanism of action and the therapeutic uses of the Wilson and Gisvold Textbook of local anti-infectives and preservatives. Organic Medicinal and 1. Pharmaceutical Chemistry, 12th edition. Productivity tip: You can’t work at high intensity for long periods of time: you’ll need to take a break for a few minutes to refresh and recharge. Always get up from your desk on your breaks: a change of scenery and chance to stretch your limbs, if only for a couple of minutes, is vital to help you reset. A. LESSON PREVIEW/REVIEW 1) Introduction (5 mins) The history of work on the prevention of bacterial infection can be traced back to the 19th century when Joseph Lister (in 1867) introduced antiseptic principles for use in surgery and post-traumatic injury. He used phenol (carbolic acid) as a wash for the hands, as a spray on an incision site, and on bandages applied to wounds. Lister’s principles caused a dramatic decrease in the incidence of post-surgical infections. Around 1881 and continuing to 1900, microbiologist Paul Ehrlich, a disciple of Robert Koch, began work with a set of antibacterial dyes and antiparasitic organic arsenicals. His goal was to develop compounds that retained antimicrobial activity at the expense of toxicity to the human host; he called the agents that he sought “magic bullets.” At the time that Ehrlich began his experiments, there were only a few compounds that could be used in treating infectious diseases, and none was very useful in the treatment of severe Gram-positive and Gram-negative infections. Ehrlich discovered that the dyes and arsenicals could stain target cells selectively and that the antimicrobial properties of the dyes paralleled the staining activity. This discovery was the first demonstration of selective toxicity, the property of certain chemicals to kill one type of organism while not harming another. Selective toxicity is the main tenet of modern antimicrobial chemotherapy, and Ehrlich’s seminal discovery paved the way for the development of the sulfonamides and penicillins and the elucidation of the mechanisms of their selective toxicity. Prior to Ehrlich’s studies, the local antimicrobial properties of phenol and iodine were well known, but the only useful systemic agents were the herbal remedies cinchona for malaria and ipecac for amebic dysentery. Ehrlich’s discovery of compound 606, the effective anti-syphilitic drug Salvarsan/ Arsphenamine, was a breakthrough in the treatment of a serious, previously untreatable disease. This document is the property of PHINMA EDUCATION  Course Code: PHA 051 (PHARMACEUTICAL AND MEDICINAL ORGANIC CHEMISTRY) STUDENT ACTIVITY SHEET#5 Name: _________________________________________________________________ Class number: _______ Section: ____________ Schedule: ________________________________________ Date: ________________ Until the 1920s, most successful anti-infective agents were based on the group-IIB element mercury and the group-VA elements arsenic and antimony. Atoxyl (sodium arsanilate and arsphenamine) was used for sleeping sickness. Certain dyes, such as gentian violet and methylene blue, were also found to be somewhat effective, as were a few chemical congeners of the quinine molecule. Some of these agents represented significant achievements in antiinfective therapy, but they also possessed some important limitations. Heavy metal toxicity after treatment with mercury, arsenic, and antimony severely limited the usefulness of agents containing these elements. Modules 5-7 addresses an extremely broad base of anti-infective agents, including the local compounds (alcohols, phenols, oxidizing agents, halogen-containing compounds, cationic surfactants, dyes, and mercurials), preservatives, antifungal agents, synthetic antibacterial drugs, anti-tubercular and antiprotozoal agents, and anthelmintics. This document is the property of PHINMA EDUCATION  Course Code: PHA 051 (PHARMACEUTICAL AND MEDICINAL ORGANIC CHEMISTRY) STUDENT ACTIVITY SHEET#5 Name: _________________________________________________________________ Class number: _______ Section: ____________ Schedule: ________________________________________ Date: ________________ 2) Activity 1: What I Know Chart, part 1 (3 mins) What do you Know about the topic of the day? Answer the questions given and write your answers on the first column. Leave the third column blank for now. What I Know Questions: What I Learned (Activity 4) 1. Differentiate antiseptic from disinfectant. 2. What is the most important means of preventing transmission of infectious agents from person to person? 3. What happens to the antimicrobial activity of alcohols as the carbon chain becomes more branched? B.MAIN LESSON 1) Activity 2: Content Notes (50 mins) Anti-infective agents that are used locally are called germicides and within this classification, there are two primary subtypes (Antiseptics and Disinfectants) Antiseptics are compounds that kill (-cidal) or prevent the growth of (-static) microorganisms when applied to living tissue. This caveat of use on living tissue points to the properties that the useful antiseptic must have. The ideal antiseptic must have low-enough toxicity that it can be used directly on skin or wounds; it will exert a rapid and sustained lethal action against microorganisms (the spectrum may be narrow or broad depending on the use). The agent should have a low surface tension so that it will spread into the wound; it should retain activity in the presence of body fluids (including pus), be nonirritating to tissues, be nonallergenic, lack systemic toxicity when applied to skin or mucous membranes, This document is the property of PHINMA EDUCATION  Course Code: PHA 051 (PHARMACEUTICAL AND MEDICINAL ORGANIC CHEMISTRY) STUDENT ACTIVITY SHEET#5 Name: _________________________________________________________________ Class number: _______ Section: ____________ Schedule: ________________________________________ Date: ________________ and not interfere with healing. No antiseptic available today meets all of these criteria. A few antibiotics, such as bacitracin, polymyxin, silver sulfadiazine, and neomycin, are poorly absorbed through the skin and mucous membranes and are used topically for the treatment of local infections; they have been found very effective against infections such as these. In general, however, the topical use of antibiotics has been restricted by concern about the development of resistant microbial strains and possible allergic reactions. These problems can reduce the usefulness of these antibiotics for more serious infections. A disinfectant is an agent that prevents transmission of infection by the destruction of pathogenic microorganisms when applied to inanimate objects. The ideal disinfectant exerts a rapidly lethal action against all potentially pathogenic microorganisms and spores, has good penetrating properties into organic matter, shares compatibility with organic compounds (particularly soaps), is not inactivated by living tissue, is noncorrosive, and is aesthetically pleasing (nonstaining and odorless). The most important means of preventing transmission of infectious agents from person to person or from regions of high microbial load, such as the mouth, nose, or gut, to potential sites of infection is simply washing the hands. In fact, one of the breakthroughs in surgical technique in the 1800s was the finding that the incidence of post-surgical infection decreased dramatically if surgeons washed their hands before operating. Regular hand washing is properly done without disinfection to minimize drying, irritation, and sensitization of the skin. Simple soap and warm water remove bacteria efficiently. Skin disinfectants along with soap and water are usually used as preoperative surgical scrubs and sterilants for surgical incisions. A. ALCOHOLS AND RELATED COMPOUNDS  Alcohols and aldehydes have been used as antiseptics and disinfectants for many years. Two of the most commonly used antiseptics and disinfectants are ethyl and isopropyl alcohol.  The antibacterial potencies of the primary alcohols (against test cultures of Staphylococcus aureus) increase with molecular weight until the 8-carbon atom octanol is reached.  As the primary alcohol chain length increases, van der Waals interactions increase, and the ability to penetrate microbial membranes increases.  As water solubility decreases, the apparent antimicrobial potency diminishes with molecular weight.  Branching of the alcohol chain decreases antibacterial potency; weaker van der Waals forces brought about by branching do not penetrate bacterial cell membranes as efficiently.  The isomeric alcohols’ potencies decrease in the order primary > secondary > tertiary.  Isopropyl alcohol is slightly more active than ethyl alcohol against vegetative bacterial growth, but both alcohols are largely ineffective against spores.  The activity of alcohols against microorganisms is the result of their ability to denature important proteins and carbohydrates. 1. Alcohol Ethanol (ethyl alcohol, wine spirit) is a clear, colorless, volatile liquid with a burning taste and a characteristic pleasant odor. It is flammable, miscible with water in all proportions, and soluble in most organic solvents. This document is the property of PHINMA EDUCATION  Course Code: PHA 051 (PHARMACEUTICAL AND MEDICINAL ORGANIC CHEMISTRY) STUDENT ACTIVITY SHEET#5 Name: _________________________________________________________________ Class number: _______ Section: ____________ Schedule: ________________________________________ Date: ________________ Commercial ethanol contains approximately 95% ethanol by volume. This concentration forms an azeotrope with water that distills at 78.2°C. Alcohol has been known for centuries as a product of fermentation from grain and many other carbohydrates. Ethanol can also be prepared synthetically by the sulfuric-acid–catalyzed hydration of ethylene. “The term alcohol means that substance known as ethyl alcohol, hydrated oxide of ethyl, or spirit of wine, from whatever source or whatever process produced, having a proof of 160 or more and not including the substances commonly known as whiskey, brandy, rum, or gin.”  Denatured alcohol is ethanol that has been rendered unfit for use in intoxicating beverages by the addition of other substances.  Completely denatured alcohol contains added wood alcohol (methanol) and benzene and is unsuitable for either internal or external use.  Specially denatured alcohol is ethanol treated with one or more substances so that its use may be permitted for a specialized purpose (ex. iodine in alcohol for tincture of iodine, methanol, and other substances in mouthwashes and aftershave lotions, and methanol in alcohol for preparing plant extracts.  The primary medicinal use of alcohol is external, as an antiseptic, preservative, mild counterirritant, or solvent. Rubbing alcohol is used as an astringent, rubefacient, and a mild local anesthetic. The anesthetic effect is results from the evaporative refrigerant action of alcohol when applied to the skin. Ethanol has even been injected near nerves and ganglia to alleviate pain. It has a low narcotic potency and has been used internally in diluted form as a mild sedative, a weak vasodilator, and a carminative.  Alcohol is metabolized in the human body by a series of oxidations: Ethanal/ Acetaldehyde Ethanol Ethanoic acid  Acetaldehyde causes nausea, vomiting, and vasodilatory flushing. This fact has been used in aversion therapy with the drug disulfiram, which blocks aldehyde dehydrogenase, allowing acetaldehyde to accumulate. This document is the property of PHINMA EDUCATION  Course Code: PHA 051 (PHARMACEUTICAL AND MEDICINAL ORGANIC CHEMISTRY) STUDENT ACTIVITY SHEET#5 Name: _________________________________________________________________ Class number: _______ Section: ____________ Schedule: ________________________________________ Date: ________________  Alcohol is used in the practice of pharmacy for the preparation of spirits, tinctures, and fluid extracts. Spirits are preparations containing ethanol as the sole solvent, whereas tinctures are hydro- alcoholic mixtures. Many fluid extracts contain alcohol as a co-solvent. 2. Dehydrated Ethanol  Dehydrated ethanol, or absolute ethanol, contains not less than 99% w/w of C2H5OH. It is prepared commercially by azeotropic distillation of an ethanol–benzene mixture, with provisions made for efficient removal of water.  This form of ethanol is used primarily as a chemical reagent or solvent but has been injected for the local relief of pain in carcinomas and neuralgias.  Absolute alcohol cannot be ingested because there is always some benzene remaining from the azeotropic distillation that cannot be removed. 3. Isopropyl Alcohol  Isopropanol (2-propanol) is a colorless, volatile liquid with a characteristic odor and a slightly bitter taste. It is considered a suitable substitute for ethanol in most cases but must not be ingested.  Isopropyl alcohol is prepared commercially by the sulfuric-acid–catalyzed hydration of propylene: Propylene Isopropyl Alcohol  Isopropyl alcohol is used primarily as a disinfectant for the skin and for surgical instruments. The alcohol is rapidly bactericidal in the concentration range of 50% to 95%. 4. Ethylene Oxide  Ethylene oxide, C2H4O, is a colorless, flammable gas that liquefies at 12°C. It has been used to sterilize temperaturesensitive medical equipment and certain pharmaceuticals that cannot be heat sterilized in an autoclave. Ethylene oxide  Ethylene oxide diffuses readily through porous materials and very effectively destroys all forms of microorganisms at ambient temperatures  Ethylene oxide forms explosive mixtures in air at concentrations ranging from 3% to 80% by volume.  The explosion hazard is eliminated when the gas is mixed with sufficient concentrations of carbon dioxide. Carboxide is a commercial sterilant containing 10% ethylene oxide and 90% carbon dioxide by volume that can be handled and released in air without danger of explosion.  Sterilization is accomplished in a sealed, autoclave-like chamber or in gasimpermeable bags. This document is the property of PHINMA EDUCATION  Course Code: PHA 051 (PHARMACEUTICAL AND MEDICINAL ORGANIC CHEMISTRY) STUDENT ACTIVITY SHEET#5 Name: _________________________________________________________________ Class number: _______ Section: ____________ Schedule: ________________________________________ Date: ________________  The mechanism of the germicidal action of ethylene oxide probably involves the alkylation of functional groups in nucleic acids and proteins by nucleophilic opening of the oxide ring. Ethylene oxide is a nonselective alkylating agent, and for that reason is extremely toxic and potentially carcinogenic.  Exposure to skin and mucous membranes should be avoided, and inhalation of the gas should be prevented by use of an appropriate respiratory mask during handling and sterilization procedures. 5. Aldehydes  Formaldehyde solution  Formalin is a colorless aqueous solution that officially contains not less than 37% w/v of formaldehyde (HCHO), with methanol added to retard polymerization  Formaldehyde readily undergoes oxidation and polymerization, leading to formic acid and Formaldehyde paraformaldehyde respectively, so the preparation should be stored in tightly closed, light-resistant containers.  Formalin must be stored at temperatures above 15°C to prevent cloudiness, which develops at lower temperatures.  The germicidal action of formaldehyde is slow but powerful.  The mechanism of action is believed to involve direct, nonspecific alkylation of nucleophilic functional groups (amino, hydroxyl, and sulfhydryl) in proteins and nucleic acids to form carbinol derivatives. The action of formaldehyde is not confined to microorganisms. The compound is irritating to mucous membranes and causes hardening of the skin.  Oral ingestion of the solution leads to severe gastrointestinal distress. Contact dermatitis is common with formalin, and pure formaldehyde is suspected to be a carcinogen.  Glutaraldehyde Disinfectant Solution  Glutaraldehyde (Cidex, a 5-carbon dialdehyde) is used as a dilute solution for sterilization of equipment and instruments that cannot be Glutaraldehyde autoclaved. B. PHENOLS AND THEIR DERIVATIVES  Phenol, USP, remains the standard to which the activity of most germicidal substances is compared. The phenol coefficient is defined as the ratio of a dilution of a given test disinfectant to the dilution of phenol This document is the property of PHINMA EDUCATION  Course Code: PHA 051 (PHARMACEUTICAL AND MEDICINAL ORGANIC CHEMISTRY) STUDENT ACTIVITY SHEET#5 Name: _________________________________________________________________ Class number: _______ Section: ____________ Schedule: ________________________________________ Date: ________________ that is required to kill (to the same extent) a strain of Salmonella typhi under carefully controlled time and temperature conditions.  Several phenols are actually more bactericidal than phenol itself. Substitution with alkyl, aryl, and halogen (especially in the para position) groups increases bactericidal activity. Straight-chain alkyl groups enhance bactericidal activity more than branched groups. Alkylated phenols and resorcinols are less toxic than the parent compounds while retaining bactericidal properties.  Phenols denature bacterial proteins at low concentrations, whereas lysis of bacterial cell membranes occurs at higher concentrations 1. Phenol (carbolic acid)  is a colorless to pale-pink crystalline material with a characteristic “medicinal odor.” It is soluble to the extent of 1 part to 15 parts water, very soluble in alcohol, and soluble in methanol and salol (phenyl salicylate)  Phenol exhibits germicidal activity (general protoplasmic poison), is caustic to skin, exerts local anesthetic effects, and must be diluted to avoid tissue Phenol destruction and dermatitis.  Sir Joseph Lister introduced phenol as a surgical antiseptic in 1867, and it is still used occasionally as an antipruritic in phenolated calamine lotion (0.1%–1% concentrations).  A 4% solution of phenol in glycerin has been used to cauterize small wounds.  Phenol is almost obsolete as an antiseptic and disinfectant. 2. Liquified Phenol  Liquified phenol is simply phenol containing 10% water.  The liquid form is convenient for adding phenol to various pharmaceutical p- chlorophenol preparations because it can be measured and transferred easily.  The water content, however, precludes its use in fixed oils or liquid petrolatum, because the solution is not miscible with lipophilic ointment bases. 3. p-Chlorophenol  p-Chlorophenol is used in combination with camphor in liquid petrolatum as an external antiseptic and anti-irritant. 4. p-Chloro-m-xylenol p-Chloro-m-xylenol  p-Chloro-m-xylenol (PC-MX; Metasep) is a nonirritating antiseptic agent with broad-spectrum antibacterial and anti fungal properties.  It is marketed in a 2% concentration as a shampoo.  It has also been used topically for the treatment of tinea (ringworm) infections such as athlete’s foot (tinea pedis) and jock itch (tinea cruris). 5. Hexachlorophene  2,2’-methylenebis (3,4,6-trichlorophenol); 2,2’-dihydroxy-3,5,6,3’,5’, 6’ hexachlorodiphenylmethane (Gamophen, Surgicon, pHisoHex) is a white to Hexachlorophene This document is the property of PHINMA EDUCATION  Course Code: PHA 051 (PHARMACEUTICAL AND MEDICINAL ORGANIC CHEMISTRY) STUDENT ACTIVITY SHEET#5 Name: _________________________________________________________________ Class number: _______ Section: ____________ Schedule: ________________________________________ Date: ________________ light-tan crystalline powder that is insoluble in water but is soluble in alcohol and most other organic solvents.  A biphenol such as hexachlorophene will, in general, possess greater potency than a monophenol. In addition, as expected, the increased degree of chlorination of hexachlorophene increases its antiseptic potency further.  Hexachlorophene is easily adsorbed onto the skin and enters the sebaceous glands. Because of this, topical application elicits a prolonged antiseptic effect, even in low concentrations.  Hexachlorophene is used in concentrations of 2% to 3% in soaps, detergent creams, lotions, and shampoos for various antiseptic uses.  It is, in general, effective against Gram-positive bacteria, but many Gram-negative bacteria are resistant.  The systemic toxicity of hexachlorophene in animals after oral and parenteral administration had been known for some time, but in the late 1960s and early 1970s, reports of neurotoxicity in infants bathed in hexachlorophene and in burn patients cleansed with the agent prompted the FDA to ban its use in over- the-counter (OTC) antiseptic and cosmetic preparations.  Hexachlorophene is still available by prescription. 6. Cresol  is actually a mixture of three isomeric methylphenols:  The mixture occurs as a yellow to brownish yellow liquid that has a characteristic odor of creosote.  Cresol is obtained from coal tar or petroleum by Cresol alkaline extraction into aqueous medium, acidification, and fractional distillation.  The mixture is an inexpensive antiseptic and disinfectant  The drawback to its use as an antiseptic is its unpleasant odor. 6. Chlorocresol  4-Chloro-3-methylphenol occurs as colorless crystals.  Chlorocresol is only slightly soluble in water. At the low concentration that Chlorocresol can be achieved in aqueous media, the compound is only useful as a preservative. 7. Thymol  Isopropyl m-cresol is extracted from oil of Thymus vulgaris (thyme, of the mint family) by partitioning into alkaline aqueous medium followed by acidification. The crystals obtained from the mother liquor are large and colorless, with a thyme like odor. Thymol This document is the property of PHINMA EDUCATION  Course Code: PHA 051 (PHARMACEUTICAL AND MEDICINAL ORGANIC CHEMISTRY) STUDENT ACTIVITY SHEET#5 Name: _________________________________________________________________ Class number: _______ Section: ____________ Schedule: ________________________________________ Date: ________________  Thymol is only slightly soluble in water, but it is extremely soluble in alcohols and other organic solvents.  Thymol has mild fungicidal properties and is used in alcohol solutions and in dusting powders for the treatment of tinea (ringworm) infections. 8. Eugenol  4-Allyl-2-methoxyphenol is obtained primarily from clove oil  It is a pale-yellow liquid with a strong aroma of cloves and a pungent taste.  Eugenol is only slightly soluble in water but is miscible with alcohol and other organic solvents.  Eugenol possesses both local anesthetic and antiseptic activity and can be directly applied on a piece of cotton to relieve toothaches.  Eugenol is also used in mouthwashes because of its antiseptic property Eugenol and pleasant taste. 9. Resorcinol  m-Dihydroxybenzene (resorcin), or resorcinol, is prepared synthetically  it is used in 1% to 3% solutions and in ointments and pastes in concentrations of 10% to 20% for the treatment of skin conditions such as ringworm, eczema, psoriasis, and seborrheic dermatitis.  In addition to its antiseptic action, resorcinol is a keratolytic agent. This property causes the stratum corneum of the skin to slough, opening the Resorcinol barrier to penetration for antifungal agents. 10. Hexylresorcinol  4-Hexylresorcinol, or “hexylresorcinol,”  When applied to the tongue it produces a sensation of numbness.  Hexylresorcinol is an effective antiseptic, possessing both bactericidal and fungicidal properties.  Hexylresorcinol is formulated into throat lozenges because of its local Hexylresorcinol anesthetic and antiseptic properties C. OXIDIZING AGENTS  In general, oxidizing agents that are of any value as germicidal agents depend on their ability to liberate oxygen in the tissues. Many of these agents are inorganic compounds, including hydrogen peroxide, several metal peroxides, and sodium perborate.  All of these react in the tissues to generate oxygen and oxygen radicals. Other oxidizing agents, such as KMnO4, denature proteins in microorganisms through a direct oxidation reaction.  Oxidizing agents are especially effective against anaerobic bacteria and can be used in cleansing contaminated wounds. The bubbles that form during the liberation of oxygen help to dislodge debris.  The effectiveness of the oxidizing agents is somewhat limited by their generally poor penetrability into infected tissues and organic matter. Additionally, the action of the oxidizers is typically transient. This document is the property of PHINMA EDUCATION  Course Code: PHA 051 (PHARMACEUTICAL AND MEDICINAL ORGANIC CHEMISTRY) STUDENT ACTIVITY SHEET#5 Name: _________________________________________________________________ Class number: _______ Section: ____________ Schedule: ________________________________________ Date: ________________ 1. Carbamide Peroxide Topical Solution  Carbamide peroxide (Gly-Oxide) is a stable complex of urea and hydrogen peroxide. It has the molecular formula H2NCONH2 H2O2. The commercial preparation is a solution of 12.6% carbamide peroxide in anhydrous glycerin.  When mixed with water, hydrogen peroxide is liberated.  Carbamide peroxide is used as both an antiseptic and disinfectant. The preparation is especially effective in the treatment of oral ulcerations or in dental care. The oxygen bubbles that are liberated remove debris. 2. Hydrous Benzoyl Peroxide  Hydrous benzoyl peroxide (Oxy-5, Oxy-10, Vanoxide) is a white granular powder. In its pure powder form, it is explosive. The compound is formulated with 30% water to make it safer to handle  Compounded at 5% and 10% concentrations, benzoyl peroxide is both keratolytic and keratogenic. It is used in the treatment of acne. Benzoyl peroxide induces proliferation of epithelial cells, Hydrous Benzoyl Peroxide leading to sloughing and repair. D. HALOGEN- CONTAINING COMPOUNDS 1. Iodophors  Elemental iodine (I2) is probably the oldest germicide still in use today.  Iodine tincture (2% iodine in 50% alcohol with sodium iodide), strong iodine solution (Lugol’s solution, 5% iodine in water with potassium iodide), and iodine solution (2% iodine in water with sodium iodide) are currently official preparations in the USP. The iodide salt is admixed to increase the solubility of the iodine and to reduce its volatility  Iodine is one of the most effective and useful of the germicides. It probably acts to inactivate proteins by iodination of aromatic residues (phenylalanyl and tyrosyl) and oxidation (sulfhydryl groups). Mixing with several nonionic and cationic surfactants can solubilize iodine. Complexes form that retain the germicidal properties of the iodine while reducing its volatility and removing its irritant properties.  In some of the more active, nonionic surfactant complexes, it is estimated that approximately 80% of the dissolved iodine remains available in bacteriologically active form. These active complexes, called iodophors, are both bactericidal and fungicidal.  Povidone–iodine (Betadine, Isodine, polymer polyvinylpyrrolidone [PVP]–iodine) is a charge-transfer complex of iodine with the nonionic surfactant PVP. Povidone- Iodine This document is the property of PHINMA EDUCATION  Course Code: PHA 051 (PHARMACEUTICAL AND MEDICINAL ORGANIC CHEMISTRY) STUDENT ACTIVITY SHEET#5 Name: _________________________________________________________________ Class number: _______ Section: ____________ Schedule: ________________________________________ Date: ________________  The complex is extremely water soluble and releases iodine very slowly. Hence, the preparation provides a nontoxic, nonvolatile, and nonstaining form of iodine that is not irritating to the skin or to wounds.  Approximately 10% of the iodine in the complex is bioavailable. Povidone–iodine is used as an aqueous solution for pre-surgical disinfection of the incision site.  It can also be used to treat infected wounds and damage to the skin, and it is effective for local bacterial and fungal infections. Several other forms of PVP–iodine are available, including aerosols, foams, ointments, surgical scrubs, antiseptic gauze pads, sponges, mouthwashes, and a preparation that disinfects whirlpool baths and hot tubs. 2. Chlorine- containing compounds  Chlorine and chlorine-releasing compounds have been used in the disinfection of water supplies for more than a century. The discovery that hypochlorous acid (HClO) is the active germicidal species that is formed when chlorine is dissolved in water led to the development and use of the first inorganic hypochlorite salts such as NaOCl and Ca(OCl)2  Later, organic N-chloro compounds were developed as disinfectants. These compounds release hypochlorous acid when dissolved in water, especially in the presence of acid. Two equally plausible mechanisms have been proposed for the germicidal action of hypochlorous acid: the chlorination of amide nitrogen atoms and the oxidation of sulfhydryl groups in proteins. Organic compounds that form stable N- chloro derivatives include amides, imides, and amidines. N-Chloro compounds slowly release HOCl in water. The antiseptic effect of these agents is optimal at around pH 7.  Halazone  p-Dichlorosulfamoylbenzoic acid  The sodium salt of halazone is used to disinfect drinking water.  Chloroazodin  N,N-Dichlorodicarbonamidine (Azochloramid) is a bright yellow crystalline solid with a faint odor of chlorine.  The compound is soluble enough in water to be used in very dilute solution to disinfect wounds, as packing for dental caries, Halazone and for lavage and irrigation. A glyceryltriacetate solution is used as a wound dressing. The antiseptic action of chloroazodin is long lasting because of its extremely slow reaction with water. Chloroazodin This document is the property of PHINMA EDUCATION  Course Code: PHA 051 (PHARMACEUTICAL AND MEDICINAL ORGANIC CHEMISTRY) STUDENT ACTIVITY SHEET#5 Name: _________________________________________________________________ Class number: _______ Section: ____________ Schedule: ________________________________________ Date: ________________ E. CATIONIC SURFACTANTS  All of the cationic surfactants are quaternary ammonium compounds  For that reason, they are always ionized in water and exhibit surface- active properties.  The compounds, with a polar head group and nonpolar hydrocarbon chain, form micelles by concentrating at the interface of immiscible solvents.  The surface activity of these compounds, exemplified by lauryl triethylammonium sulfate, results from two structural moieties: (a) a cationic head group, which has a high affinity for water and (b) A long hydrocarbon tail, which has an affinity for lipids and nonpolar solvents  At the right concentration (the critical micelle concentration), the molecules concentrate at the interface between immiscible solvents, such as water and lipid, and water-in-oil or oil-in-water emulsions may be formed with the ammonium head group in the water layer and the non-polar hydrocarbon chain associated with the oil phase.  The cationic surfactants exert a bactericidal action against a broad spectrum of Gram-positive and Gram- negative bacteria. They are also active against several pathogenic species of fungi and protozoa. All spores resist these agents.  The mechanism of action probably involves dissolution of the surfactant into the microbial cell membrane, destabilization, and subsequent lysis. The surfactants may also interfere with enzymes associated with the cell membrane  In addition to their broad-spectrum antimicrobial activity, they are useful as germicides.  They are highly water soluble, relatively nontoxic, stable in solution, nonstaining, and noncorrosive. The surface activity causes a keratolytic action in the stratum corneum and, hence, provides good tissue penetration. This document is the property of PHINMA EDUCATION  Course Code: PHA 051 (PHARMACEUTICAL AND MEDICINAL ORGANIC CHEMISTRY) STUDENT ACTIVITY SHEET#5 Name: _________________________________________________________________ Class number: _______ Section: ____________ Schedule: ________________________________________ Date: ________________  Soaps and other anionic detergents inactivate them. All traces of soap must be removed from skin and other surfaces before they are applied. Tissue debris, blood, serum, and pus reduce the effectiveness of the surfactants. Cationic surfactants are also adsorbed on glass, talc, and kaolin to reduce or prevent their action.  The bactericidal action of cationic surfactants is slower than that of iodine. Solutions of cationic surfactants intended for disinfecting surgical instruments, gloves, etc. should never be reused because they can harbor infectious microorganisms, especially Pseudomonas and Enterobacter spp. 1. Benzalkonium Chloride  is a detergent, an emulsifier, and a wetting agent.  It is used as an antiseptic for skin and mucous membranes, for irrigation and for storage of surgical instruments 2. Methylbenzethonium Chloride  used specifically for the treatment of diaper rash in infants, caused by the yeast Candida albicans, which produces ammonia. The agent is also used as a general antiseptic. 3. Benzethonium Chloride  The actions and uses of this agent are similar to those of benzalkonium chloride. 4. Cetylpyridinium Chloride  Used as a general antiseptic for intact skin, for minor lacerations, and for irrigation of mucous membranes  Also available in the form of throat lozenges and a mouthwash 5. Chlorhexidine Gluconate  is the most effective of a series of antibacterial biguanides originally developed in Great Britain  for topical uses such as preoperative skin disinfection, wound irrigation, Cetylpyridinium chloride mouthwashes, and general sanitization Chlorhexidine gluconate This document is the property of PHINMA EDUCATION  Course Code: PHA 051 (PHARMACEUTICAL AND MEDICINAL ORGANIC CHEMISTRY) STUDENT ACTIVITY SHEET#5 Name: _________________________________________________________________ Class number: _______ Section: ____________ Schedule: ________________________________________ Date: ________________ F. DYES  Cationic dyes are active against Gram-positive bacteria and many fungi; Gram-negative bacteria are generally resistant. The difference in susceptibility is probably related to the cellular characteristics that underlie the Gram stain. 1. Gentian Violet  variously known as hexamethyl-p-rosaniline chloride, crystal violet, methyl violet, and methylrosaniline chloride.  is available in vaginal suppositories for the treatment of yeast infections. It is also used as a 1% to 3% solution for the treatment of ringworm and yeast infections.  Gentian violet has also been used orally as an anthelmintic for strongyloidiasis (threadworm) and oxyuriasis. 2. Basic Fuchsin  is a component of carbol–fuchsin solution (Castellani’s paint), which is used topically in the treatment of fungal infections, notably ringworm and athlete’s foot. 3. Methylene blue  3,7-bis(dimethylamino)-phenazathionium chloride (Urised)  has weak antiseptic properties that make it useful for the treatment of cystitis and urethritis.  The action of methylene blue is considered to be bacteriostatic.  The compound colors the urine and stool blue green. G. MERCURY COMPOUNDS  The comparatively few organomercurials still in use are employed as antiseptics, preservatives, or diuretics.  Organomercurials can be grouped into two general classes: (a) compounds with at least one carbon– mercury bond that does not ionize readily and (b) compounds with mercury bonded to heteroatoms (e.g., oxygen, nitrogen, sulfur) that ionize partially or completely.  In addition to its effect on ionization, the organic moiety may increase the lipid solubility of an organomercurial compound, thereby facilitating its penetration into microorganisms and host tissues.  The antibacterial action of mercury compounds is believed to result from their reaction with sulfhydryl (-SH) groups in enzymes and other proteins to form covalent compounds of the type R-S-Hg-R’. This action is reversible by treatment with thiol-containing compounds such as cysteine and dimercaprol (BAL); hence, organomercurials, reacting reversibly, are largely bacteriostatic.  The antibacterial activity of organomercurial antiseptics is greatly reduced in serum because of the presence of proteins that inactivate mercury compounds.  Organomercurial antiseptics are not very effective against spores.  The disadvantages of mercurials for antiseptic and disinfectant uses far outweigh any possible advantages that they might have. Hence, other more effective and less potentially toxic agents are preferable. 1. Nitromersol  nonirritating to mucous membranes and is nonstaining.  at one time, it was a very popular antiseptic for skin and ocular infections. This document is the property of PHINMA EDUCATION  Course Code: PHA 051 (PHARMACEUTICAL AND MEDICINAL ORGANIC CHEMISTRY) STUDENT ACTIVITY SHEET#5 Name: _________________________________________________________________ Class number: _______ Section: ____________ Schedule: ________________________________________ Date: ________________  Nitromersol has largely been replaced by superior agents 2. Thimerosal  [(o-Carboxyphenyl)-thio]ethylmercury sodium salt(Merthiolate)  nonstaining and nonirritating to tissues.  Thimerosal is a weakly bacteriostatic antiseptic that is applied topically in ointments or aqueous solutions. Nitromersol Thimerosal H. PRESERVATIVES  Preservatives are added to various dosage forms and cosmetic preparations to prevent microbial contamination.  In parenteral and ophthalmic preparations, preservatives are used to maintain sterility in the event of accidental contamination during use.  An ideal preservative would be effective at low concentrations against all possible microorganisms, be nontoxic and compatible with other constituents of the preparation, and be stable for the shelf life of the preparation. The ideal preservative does not exist, but there is quite a bit of experience with some of them. In some cases, combinations of preservative agents are used to approximate a mixture of ideal features 1. p-Hydroxybenzoic Acid Derivatives  Esters of p-hydroxybenzoic acid (parabens) have distinct antifungal properties. Their toxicity to the human host is typically low because they undergo rapid hydrolysis in vivo to p-hydroxybenzoic acid, which is quickly conjugated and excreted.  This property makes the parabens useful as preservatives for liquid dosage forms. The preservative activity generally increases with molecular Methylparaben weight, but the methyl ester is most effective against molds, whereas the propyl ester is most effective against yeasts. The more lipid-soluble propyl ester is the preferred preservative for drugs in oil or lipophilic bases.  Methylparaben  Methyl p-hydroxybenzoate, or methylparaben Propylparaben  used as a safeguard against mold growth. This document is the property of PHINMA EDUCATION  Course Code: PHA 051 (PHARMACEUTICAL AND MEDICINAL ORGANIC CHEMISTRY) STUDENT ACTIVITY SHEET#5 Name: _________________________________________________________________ Class number: _______ Section: ____________ Schedule: ________________________________________ Date: ________________  Propylparaben  Propyl p-hydroxybenzoate, or propylparaben  It is used as a preservative, primarily to retard yeast growth.  Butylparaben  n-Butyl p-hydroxybenzoate (butylparaben) Butylparaben  Ethylparaben  Ethyl p-hydroxybenzoate (ethylparaben) Ethylparaben 4-hydroxybenzoic acid/ p-hydroxybenzoic acid OTHER PRESERVATIVES 2. Chlorobutanol  1,1,1-Trichloro-2-methyl-2-propanol  Chlorobutanol is used as a bacteriostatic agent in pharmaceuticals for injection, ophthalmic use, and intranasal administration. 3. Benzyl Alcohol (phenylcarbinol, phenylmethanol) Chlorobutanol  is commonly used as a preservative in vials of injectable drugs in concentrations of 1% to 4% in water or saline solution.  Benzyl alcohol has the added advantage of having a local anesthetic action.  It is commonly used in ointments and lotions as an antiseptic in the treatment of various pruritic skin conditions. 4. Phenylethyl Alcohol (2-phenylethanol, orange oil, rose oil, C6H5CH2CH2OH)  It occurs naturally in rose oil and pineneedle oil. It is used primarily in perfumery. 5. Benzoic acid  used externally as an antiseptic in lotions, ointments, and mouthwashes.  It is more effective as a preservative in foods and pharmaceutical products at low pH (less than the pKa). Benzoic acid  When used as a preservative in emulsions, its effectiveness depends on both pH and distribution into the two phases. 6. Sodium benzoate  used as a preservative in acidic liquid preparations in which benzoic acid is released. Sorbic acid This document is the property of PHINMA EDUCATION  Course Code: PHA 051 (PHARMACEUTICAL AND MEDICINAL ORGANIC CHEMISTRY) STUDENT ACTIVITY SHEET#5 Name: _________________________________________________________________ Class number: _______ Section: ____________ Schedule: ________________________________________ Date: ________________ 7. Sodium propionate  It is an effective anti-fungal agent that is used as a preservative. Sodium propionate is most effective at low pH. 8. Sorbic acid  2,4-Hexadienoic acid is an effective antifungal preservative.  Sorbic acid is used to preserve syrups, elixirs, ointments, and lotions containing components such as sugars that support mold growth. 9. Potassium Sorbate Phenylmercuric nitrate  used in the same way as sorbic acid when greater water solubility is required. 10. Phenylmercuric Nitrate  Phenylmercuric nitrate is a mixture of phenylmercuric nitrate and phenylmercuric hydroxide  Used to preserve injectable drugs against bacterial contamination.  A disadvantage to organomercurials is that their bacteriostatic efficacy is reduced in the presence of serum. Phenylmercuric acetate 11. Phenylmercuric Acetate (Acetoxyphenylmercury)  Used as a preservative 2) Activity 3: Skill-building Activities (with answer key) (14 mins answer + 2 mins checking) I. Match the ff. Anti- infectives to their corresponding structure. Write your answers on the space before each number. A. E. I. B. F. J. This document is the property of PHINMA EDUCATION  Course Code: PHA 051 (PHARMACEUTICAL AND MEDICINAL ORGANIC CHEMISTRY) STUDENT ACTIVITY SHEET#5 Name: _________________________________________________________________ Class number: _______ Section: ____________ Schedule: ________________________________________ Date: ________________ C. G. K. D. H. L. _____1. Methylene blue _____2. Isopropyl alcohol _____3. Resorcinol _____4. Benzoic acid _____5. Glutaraldehyde _____6. Thimerosal _____7. Eugenol _____8. Hydrous Benzoyl Peroxide _____9. Sorbic acid _____10. Arsphenamine _____11. Propylparaben _____12. Ethylene oxide II. Modified True or False. Write TRUE if the statement is correct, and if FALSE change the underlined word or group of words to make the whole statement true. Check your answers against the Key to Corrections found at the end of this SAS. Write your score on your paper. _______________1. P-chlorophenol is phenol containing 10% water. _______________2. 4-allyl-2-methoxyphenol is Resorcinol. _______________3. Benzoyl peroxide induces proliferation of epithelial cells, leading to sloughing and repair. _______________4. Oxidizing agents are especially effective against aerobic bacteria and can be used in cleansing contaminated wounds. _______________5. All of the cationic surfactants are quaternary ammonium compounds. 3) Activity 4: What I Know Chart, part 2 (3 mins) This serves as a review and summary of what you have learned from the session. Monitor how your knowledge has changed by reviewing the questions in the What I Know Chart from Activity 1 and write your answers to the questions based on what you now know in the third column of the chart. This document is the property of PHINMA EDUCATION  Course Code: PHA 051 (PHARMACEUTICAL AND MEDICINAL ORGANIC CHEMISTRY) STUDENT ACTIVITY SHEET#5 Name: _________________________________________________________________ Class number: _______ Section: ____________ Schedule: ________________________________________ Date: ________________ 4) Activity 5: Check for Understanding (10 mins) I. Multiple choice. Write the capital letter of your answer before the number. 1. Remains the standard to which the activity of most germicidal substances is compared A. Ethanol C. Benzoic acid B. Phenol D. Formalin 2. Which of the ff. organic dyes has been used orally as an anthelmintic for strongyloidiasis and oxyuriasis? A. Gentian violet C. Methylene blue B. Basic fuchsin D. Methyl red 3. Which of the ff. Is added to formalin to retard polymerization of formaldehyde? A. Sodium chloride C. Methanol B. Benzene D. Water 4. Which of the ff. Is used in the treatment of acne? A. Benzalkonium chloride C. Benzoyl peroxide B. Carbamide peroxide D. Sodium propionate 5. A process that kills nonsporulating microorganisms by hot water or steam at 65℃-100℃? A. Antisepsis C. Sterilization B. Decontamination D. Pasteurization 6. Refers to ethanol treated with one or more substances so that its use may be permitted for a specialized purpose. A. Absolute alcohol C. Completely denatured alcohol B. Denatured alcohol D. Specially denatured alcohol 7. It has been used to sterilize temperature- sensitive medical equipment and certain pharmaceuticals that cannot be heat sterilized in an autoclave. A. Glutaraldehyde Disinfectant solution C. Formalin B. Ethylene oxide D. Isopropyl alcohol 8. Refers to application of an agent to living tissue for the purpose of preventing infection. A. Disinfection C. Sanitization B. Antisepsis D. Sterilization 9. Which of the ff. Preservatives is used as a bacteriostatic agent in pharmaceuticals for injection, ophthalmic use, and intranasal administration? A. Chlorobutanol C. Benzoic acid B. Benzyl Alcohol D. Phenylmercuric nitrate 10. 4-chloro-3-methylphenol A. Chlorocresol C. Eugenol B. Thymol D. Resorcinol This document is the property of PHINMA EDUCATION  Course Code: PHA 051 (PHARMACEUTICAL AND MEDICINAL ORGANIC CHEMISTRY) STUDENT ACTIVITY SHEET#5 Name: _________________________________________________________________ Class number: _______ Section: ____________ Schedule: ________________________________________ Date: ________________ C. LESSON WRAP-UP 1) Activity 6: Thinking about Learning (5 mins) A. Work Tracker You are done with this session! Let’s track your progress. Shade the session number you just completed. P1 P2 P3 1 2 3 4 5 6 7 8 9 10 B. Think about your Learning  Which part of the topic was easy for you?  Which part of the topic was difficult to understand?  How did you study and comprehend hard topics of this module? This document is the property of PHINMA EDUCATION  Course Code: PHA 051 (PHARMACEUTICAL AND MEDICINAL ORGANIC CHEMISTRY) STUDENT ACTIVITY SHEET#5 Name: _________________________________________________________________ Class number: _______ Section: ____________ Schedule: ________________________________________ Date: ________________ FREQUENTLY ASKED QUESTION What is/are the advantage/s of combining iodine with surfactant polyvinylpyrrolidione? Polyvinylpyrrolidone is a water-soluble, physiologically acceptable polymer which has the ability to tie up iodine. The PVP-iodine resulting from this combination retains the germicidal and chemical nature of the iodine yet it is more water-soluble than iodine alone; it provides a more stable form of iodine in solution than iodine alone or some of the more common iodine preparations such as iodine tincture and Lugol's solution. The iodine present in PVP-iodine is not as irritating to tissue and mucosa as other iodine preparations of the same strength, and the toxicity of the iodine is reduced. KEY TO CORRECTIONS ACTIVITY 3: SKILL BUILDING ACTIVITIES I. MATCHING TYPE II. MODIFIED TRUE OR FALSE 1. D 1. LIQUIFIED PHENOL 2. K 2. EUGENOL 3. H 3. TRUE 4. E 4. ANAEROBIC 5. J 5. TRUE 6. F 7. L 8. A 9. B 10. C 11. I 12. G This document is the property of PHINMA EDUCATION