Methodical instructions
for students of dental department
lesson № 14 (practical classes – 6 hours)
Theme:
1. ANTISEPTICS AND DESINFECTANTS (Chloraminum b, Chlorhexidini bygluconas, Solutio iodi spirituosae, Solutio lugoli, Ioddicerinum, , Solutio hydrogenii peroxydi diluta, Kalii permanganas, Solutio ammonii caustici, Hydrargyri oxydum flavum, Argenti nitras, Pix liquida betulae, Phenolum, Tricresolum, Resorcinum, Linimentum balsamicum wishnevsky, Ichthyolum, Furacillinum, Furaplastum, Viride nitens, Methylenum coeruleum, Aetharidini lactas, Hexamyletteraminum, Aethonium, Dekamethoxinum, Chlorhexidinum, Chlorphilipt, Novoimaninum).
2. SULFONAMIDES AND OTHER ANTIMICROBIAL DRUGS. (Phthalazolum, Aethazolum, Sulfacylum-natrium, Sulfadimethoxinum, Sulfapyridazinum, Sulfalenum, Biseptolum (bactrinum), Salazosulfopiridinum, Salazopiridazinum, Acidum nalidixicum, Nitroxolinum, Ofloxacinum, Cyprofloxacinum, Furasolidonm, Furaginum)
3. ANTIMYCOBACTERIAL AGENTS. (Isoniazidum, Steptomicini sulfas, Rifampicinum, Kanamycini sulfas, Cycloserinum, Amycacinum, Ethionamidum, Protionamidum, Natrii paraaminosalicylas, Ethambutolum pirazimidinum, Cyprofloxacinum, Ophloxacinum)
Aim: To memorise the pharmacokinetic and pharmacodynamics effects of antiseptics and disinfectants, sulfanilamide, and different antibacterial agents
Professional motivation
The antiseptics and disinfectants differ fundamentally from, systemically active chemotherapeutic agents in that they possess little O2 no selective toxicity. Most of these substances are toxic not only for microbial parasites but for most cells as well. There for, they may be used to reduce the microbial population in the inanimate environment, beet they can usually be applied only topically, not systemically, to humans. The antibacterial action of antiseptics and disinfectants is largely dependent on concentration temperature, and time. Very low concentration may stimulate bacterial growth, higher concentration may be inhibitory, and still higher concentrations may be bactericidal for certain organisms.
Many antiseptics and disinfectants are now used in medical and surgical practice.
The modern antimicrobial chemotherapeutic era began in the early 1930’s when Prontosil, a chemical developed by the German dye industry, was to combat Streptococcal infection in mice after metabolism to paraaminobenzene sulfonamide (sulfanilamide) and antibacterial compounds. The sulfonamides were once a mainstay in the treatment of infections disease, but their importance has diminished as bacterial resistance has increased and more effective agents have been developed. Nevertheless, because of their established effectiveness, low cost and the relative lack of the new compounds, sulfonamides are among the drugs which are used in healing of some disease, for example, tuberculosis.
In the latest years the arsenal of antituberculosis preparations has been enriched with the row of new highly effective preparations. At the current moment despite of the success in the healing and prophylaxis of tuberculosis, according the data of, in the world there are more then 7 million people suffering from active form of tuberculosis. The main reason of decreased effectively of healing is the increased resistance of Mycobacterium due to irregular and wrong use of antituberculosis preparations. For the overcoming of resistance the antimycobacterial drugs, preparations are prescribed in combination with other agents for example, at the beginning of the healing it is recommended to use 3 medicines.
1. Students’ practical activities
900-1200 in case of 6-hours practical classes
Theme № 1.Antseptics and desinfectants
I Write out the prescriptions in the protocol copybook, note their pharmacological group and clinical usage for the following drugs: flores calendula, folium plantago mayor, furacilinum, phenolum, pix liquida betulae, ichthiolum, hydrargyri dichloridum, hydrargyri oxydi flavi, argenti nitras, cupri sulfas, chloraminum b, solutio iodi spirituosa, spiritus aethylicus 70%, 90%, 95%, solutio formaldehydum, zinci sulfas, unitiolum, natrii sulfas, solutio ammonii caustici, viride nitens, aetacridini lactas, solutio hydrogenii peroxydi diluta, kalii permanganas, zinci oxydi, decametoxinum, aethonium.
II choose the correct answer and write down in protocols:
A. Chloramine is used for: 1.washing the stomach morphine poisoning; 2. surgical instrument sterilisation; 3. as a eyedrops; 4. room desifection; 5. cleanser of wounds, 6. all of the following are antiseptics o2 disifecrtors except:
1. Chloramine
2. Kalii permanganes
3. Magnij sulfas
4. Cupri sulfas
5. Zunci sulfas.
Real – life situation to be solved. The patient has been brought to emergency room with acute morphine poisoning. What substance may be used for stomach cleaning? Why?
Theme № 2-3. Sulfonamides and other antimicrobial drugs.antimycobacterial agents.
I Write out the prescriptions in the protocol copybook, note their pharmacological group and clinical usage for the following drugs: sulfadimezinum, sulfacilum-natrium, sulfadimethoxinum, sulfadiperazinym, phthalazolum, biseptolum ( bactrim ), acidum nalidixicum, enteroseptolum, furasolidonum, isoniazidum, streptomicini sulfas, rifampicinum, pasa, ethambutolum.
II Choose the correct answer/statement
A. Which of the following agents used in the treatment of pulmonary tuberculosis has a toxicity of producing a lupus-like syndrome?
A. Isoniazid
B. Ethambutol
C. Streptomycin
D. PASA
B. Sulfonamides:
1. Are competitive antagonists of PABA, and thereby decrease bacterial utilisation of paraaminobensoic acid in the synthesis of folicacid.
1. Are bacteriostatic.
2. Are batericidal.
3. Can be antagonised by PABA
4. Are synergistic with trimethoprim, which inhibits dihydrofolate reductase.
C. Isoniasid is the most widely used agent in the treatment of tuberculosis. True statements regarding this agent include which of the following?
1. It is used in conjunction with other agents in the treatment of tuberculosis
2. Its metabolism is partly undre genetic control
3. It is ineffective against many atypical mycobacteria
4. It can be administered as a prophylactic agent to children or young adullts, who have converted from a tuberculin-negative to tuberculin-positive skin test
5. It is well absorbed from the gastrointestinal tract and diffuses readily into all body tissues and body fluids, including cerebrospinal fluid
1. Real-life situation to be solved
After several injection of antimycobacteria agent the color of urine, sweat, tears became orange; rash and jaundice, gastrointestinal disturbances were determined. What drug was used?
III Choose the correct statement:
1. What is the indication for Isoniasidum?
A. Pulmonary tuberculosis
B. Leptospirosis
C. Infection of the urinary tract
D. Acute pneumonia
E. Viruses infection
2. What are the side effects of sulfonamides?
1) crystalluria;
2) eosinophilia, agranulocytosis, aplastic anemia;
3) Stevens-Johnson syndrome (fever, malaise, erythma multiforme);
4) dry mouth;
5) ototoxicity.
3. Real-life situation to be solved:
After the long period of using of drug for tuberculosis treatment of the patient
Such signs were observed as the orange color of urine, sweat, jaundice and nausea. What drug can cause these side effects?
IV Answer the following questions:
1. What sulfonamides are used for systemic infection healing?
2. What is the mechanism of sulfonamides action?
3. Why can novocainum and acidum folicum weaken sulfonamide’s activity?
4. Why is cristalization of acetylderivates of sulfonamides in renal tubes occurs?
5. What is the localization of infection for prescribing of acidum nalidixicum, enteroseptolum?
6. What are the indications for furazolidonum?
7. What are the reasons for isoniazidum adverse reactions?
8. Why is combination of 2-3 antimycobacterial agents prescribed?
2. Student’s Independent Study Program
Antituberculosis agents
History: Although the recent AIDS’ epidemic has refocused attention on tuberculosis, in fact, tuberculosis has plagued mankind for over 3000 years. The most effective antituberculosis drug isoniazid (INH), was not discovered until the late 1940s and approved in 1952. Prior to this, streptomycin and aminosalicylic acid were the only agents available for the treatment of tuberculosis. To this day, isoniazid remains one of the most effect antimycobacterial agents.Despite the effectiveness of isoniazid against mycobacteria, resistance to isoniazid develops readily if used as a single agent. For this reason, tuberculosis is always treated with combinations of drugs with isoniazid included. There is currently controversy regarding the use of fixed-dose combinations such as Rifamate (isoniazid with rifampin) and Rifater (isoniazid, pyrazinamide, and rifampin). While fixed-dose combination products address the issue of drug resistance, the evaluation and management of adverse reactions is made more difficult.
Antituberculosis agents can be divided into 2 groups based on efficiacy and severity of toxicity. The primary agents, followed by their date of approval, include: streptomycin (1944), isoniazid (1952), pyrazinamide (1955), ethambutol (1967), and rifampin (1971). Second-line agents which are used in cases of drug resistance or patient intolerance to the first-line agents include: aminosalicylic acid (1949), cycloserine (1956), kanamycin (1958), capreomycin (1971), and amikacin (1976). Because of the AIDS epidemic, tuberculosis has gained new attention. The American Thoracic Society and the Centers for Disease Control and Prevention recommend that HIV-infected patients with drug-susceptible tuberculosis receive 2 months of therapy with isoniazid, rifampin, pyrazinamide, and ethambutol, followed by an additional 7 months of isoniazid and rifampin. This regimen was recently tested in Los Angeles county and was found effective in 84 HIV-infected patients. Subsequently, a study of HIV-positive and HIV-negative patients in Zaire demonstrated that 2 months of therapy with isoniazid, rifampin, pyrazinamide, and ethambutol followed by 4 months of isoniazid and rifampin achieved similar results in both groups at 6 months but HIV-positive patients tended to relapse more often than HIV-negative patients.
Despite the number of agents available for the treatment of tuberculosis, multidrug-resistant tuberculosis is now becoming a significant concern. Study of patients first diagnosed in the late 1970s and early 1980s indicate that previous therapy with a drug for more than a month was associated with diminished responsiveness to that drug regardless of in vitro tests which indicated susceptibility. It is currently recommended that 3 drugs be used when the chance of drug resistance is small and in areas where the rate of drug resistance is 4%, a fourth drug, ethambutol, should be added. Mechanism of Action: Each antituberculosis drug works by a distinct mechanism (see each respective monograph for a detailed explanation of mechanism). This variety in mechanism is advantageous since Mycobacterium tuberculosis is an obligate aerobe and its metabolic and replication rates vary with the surrounding oxygen supply. Within a cavity tubercle bacilli are actively multiplying; isoniazid, rifampin, and streptomycin are effective here. Within macrophages or closed caseous lesions, however, growth is slower; pyrazinamide is most active, followed by rifampin and isoniazid. Distinguishing Features/Adverse Reactions: The antituberculosis agents are a diverse group of drugs; the only similarity among the antituberculosis agents is that they are used to treat Mycobacterium tuberculosis. Not only does each agent exhibit a unique mechanism of action, adverse reactions are diverse and numerous. Isoniazid: is a primary therapeutic agent for all types of tuberculosis; is hepatotoxic and can cause peripheral neuritis; is administered orally or parenterally. rifampin: is a primary therapeutic agent for all types of tuberculosis; is hepatotoxic and can cause hemolytic anemia; is a potent inducer of hepatic enzymes and can cause many drug interactions; is administered orally.
•ethambutol: is an important therapeutic agent commonly used for treatment of resistant strains; can cause hyperuricemia and a dose-related optic neuritis; is administered orally.
•streptomycin: is an effective therapeutic agent, however, use is limited by intramuscular administration which is painful; is ototoxic.
•ethionamide: is a secondary therapeutic agent; GI intolerance is a significant adverse reaction; is administered orally.
•aminosalicylic acid: is a secondary therapeutic agent; GI intolerance is a significant adverse reaction; is administered orally.
•cycloserine: is a secondary therapeutic agent; causes adverse CNS effects; is administered orally.
•kanamycin: is a secondary therapeutic agent; is ototoxic; must be administered by injection.
•amikacin: is a secondary therapeutic agent; is ototoxic; must be administered by injection.
The antiseptics and disinfectants differ fundamentally from systemically active chemotherapeutic agents in that they possess little or no selective toxicity. Most of these substances are toxic not only for microbial parasites but for host cells as well. Therefore, they may be used to reduce the microbial population in the inanimate environment, but they can usually be applied only topically, not systemically, to humans.
The terms disinfectants, antiseptics, or germicides have been used interchangeably by some, and the definitions overlap greatly in the literature. The term disinfectant often denotes a substance that kills microorganisms in the inanimate environment. The term antiseptic often is applied to substances that inhibit bacterial growth both in vitro and in vivo when applied to the surface of living tissue under suitable conditions of contact.
The antibacterial action of antiseptics and disinfectants is largely dependent on concentration, temperature, and time. Very low concentrations may stimulate bacterial growth, higher concentrations may be inhibitory, and still higher concentrations may be bactericidal for certain organisms.
Evaluation of the antiseptics and disinfectants is difficult. Methods of testing are controversial and results are subject to different interpretations. There is a need for effective, nontoxic compounds to neutralize disinfectants in vitro. Ideally, disinfectants should be lethal for microorganisms in high dilution, non injury tissues or inanimate substances, inexpensive, stable, odorless, and rapid-acting even in the presence of foreign proteins, exudates, or fibers. No preparatioow available combines these characteristics to a high degree.
Many antiseptics and disinfectants were at one time used in medical and surgical practice. Most have now been displaced by chemotherapeutic substances. The 2 remaining areas of use are urinary antiseptics and topical antiseptics. Most topical antiseptics do not aid wound healing but, on the contrary, often impair healing. In general, cleansing of abrasions and superficial wounds by washing with soap and water is far more effective and less damaging than the application of topical antiseptics. Substances applied topically to skin or mucous membranes are absorbed irregularly and often unpredictably. Occlusive dressings with plastic films often greatly enhance absorption. Penetration of drugs through skin epithelium is also greatly influenced by relative humidity and temperature.
A few chemical classes of disinfectants and antiseptics are briefly characterized in the following paragraphs.
Alcohols
Aliphatic alcohols are antimicrobial in varying degree by precipitating protein. Ethanol (ethyl alcohol) in 70% concentration is bactericidal in 1-2 minutes at 30 °c but less effective at lower and higher concentrations. Ethyl alcohol, 70%, and isopropyl alcohol, 70-90%, are at present the most satisfactory general disinfectants for skin surfaces. They may be useful for sterilizing instruments but have no effect on spores, and better agents are available for this purpose. Aerosols of 70% alcohol with l-inn size droplets may be practical and effective disinfectants for mechanical respirators.
Propylene glycol and other glycol have been used as vapors to disinfect air. Precise control of humidity is necessary for good antimicrobial action. Glycol vapors are rarely employed at present.
Aldehydes
Formaldehyde in a concentration of 1 -10% effectively kills microorganisms and their spores in 1-6 hours. It acts by combining with and precipitating protein. It is too irritating for use on tissues, but it is widely employed as a disinfectant for instruments. Formaldehyde solution contains 37% formaldehyde by weight, with methyl alcohol added to prevent polymerization.
Glutaraldehyde as a 2% alkaline solution in 70% isopropanol (ph 7.5-8.5) serves as a liquid disinfectant for some optical and other instruments and for some prosthetic materials. It kills viable microorganisms in 10 minutes and spores in 3-10 hours. Contact with tissue must be avoided.
Methenamine taken orally can release formaldehyde into acid urine. It is employed as a urinary antiseptic.
Acids
Several inorganic acids have been used for cauterization of tissue. Although they are effective antimicrobial agents, the tissue destruction they cause precludes their use. Boric acid, 5% in water, or as powder, can be applied to a variety of skin lesions as an antimicrobial agent. However, the toxicity of absorbed boric acid is high, particularly for small children, and its use is not advisable. Among the organic acids, benzoic acid, 0.1%, is employed as a food preservative. Esters of benzoic acid (parabens) are used as antimicrobial preservatives of certain other drugs. Acetic acid, 1%, can be used in surgical dressings as a topical antimicrobial agent; 0.25% acetic acid is a useful antibacterial agent for irrigation of the lower urinary tract. This can also be used with an indwelling catheter and a closed system for urinary drainage. It is particularly active against aerobic gram-negative bacteria, eg, pseudomonas sp. Salicylic and undecylenic and other fatty acids can serve as fungicides on skin. They are employed particularly in dermatophytosis involving intertriginous areas, eg, “athlete’s foot.”
Mandelic acid is excreted unchanged in the urine after oral intake; 12 g daily taken orally can lower the ph of urine to 5.0, sufficient to be antibacterial.
Halogens & halogen-containing compounds
A. Iodine: Elemental iodine is an effective germicide. Its mode of action is not definitely known. A 1:20,000 solution of iodine kills bacteria in 1 minute and spores in 15 minutes, and its tissue toxicity is relatively low. Iodine tincture contains 2% iodine and 2.4% sodium iodide in alcohol. It is the most effective disinfectant available for intact skin and should be used to disinfect skin when obtaining blood cultures by venipuncture. Its principal disadvantage is the occasional dermatitis that can occur in hypersensitive individuals. This can be avoided by promptly removing the tincture of iodine with alcohol.
Iodine can be complexed with polyvinylpyr-rolidone to yield povidone-iodine usp. This is a water-soluble complex that liberates free iodine in solution (eg, 1% free iodine in 10% solution). It is widely employed as a skin disinfectant, particularly for preoperative skin preparation. It is an effective local antibacterial substance, killing not only vegetative forms but also clostridial spores. Hypersensitivity reactions are infrequent. Povidone-iodine (betadine, isodine) is available in many forms: solution, ointment, aerosol, surgical scrub, shampoo, skin cleanser, vaginal gel, vaginal douche, and individual cotton swabs. Povidone-iodine solutions can become contaminated with pseudomonas sp. and other aerobic gram-negative bacteria. Rarely, the addition of iodine in solution is used for the emergency treatment of contaminated water in small quantities.
B. Chlorine: Chlorine exerts its antimicrobial action in the form of undissociated hypochlorous acid (hoc1), which is formed when chlorine is dissolved in water at neutral or acid ph. chlorine concentrations of 0.25 ppm are effectively bactericidal for many microorganisms except mycobacteria, which are 500 times more resistant. Organic matter greatly reduces the antimicrobial activity of chlorine. The amount of chlorine bound by organic matter in an environment (eg, water) and thus not available for antimicrobial activity is called the ‘‘chlorine demand.” The chlorine demand of relatively pure water is low, so that the addition of 0.5 ppm chlorine is sufficient for disinfection. The chlorine demand of grossly polluted water may be very high, so that 20 ppm or more of chlorine may have to be added for effective bactericidal action.
Chlorine is used mainly for the disinfection of inanimate objects and particularly for the purification of water. Chlorinated lime forms hypochlorite solution when dissolved. It is a cheap (but unstable) form of chlorine used mainly for disinfection of excreta in the field. Halazone usp is a chloramine employed in tablet form for the sterilization of drinking water. The addition of 4-8 mg halazone per liter will sterilize water in 15-60 minutes unless a large quantity of organic material is present. It may not inactivate cysts of entamoeba histolytica.
Sodium hypochlorite solution usp, 0.5% naoci (diluted sodium hypochlorite [modified dakin’s] solution), contains about 0.1 g of available chlorine per 100 ml and can be used as an irrigating fluid for the cleansing and disinfecting of contaminated wounds. Household bleaches containing chlorine can serve as disinfectants for inanimate objects.
Oxidizing agents
Some antiseptics exert an antimicrobial action because they are oxidizing agents. Most are of no practical importance, and only hydrogen peroxide, sodium perborate, and potassium permanganate are occasionally used.
Hydrogen peroxide solution contains 3% h202 in water. Contact with tissues releases molecular oxygen and there is a brief period of antimicrobial action. There is no penetration of tissues, and the main applications of hydrogen peroxide are as a mouthwash and for the cleansing of wounds. Hydrogen peroxide can probably be used to disinfect smooth contact lenses that are subsequently applied to the eye. Hydrous ben-zoyl peroxide usp can be bactericidal to microorganisms. When applied to the skin as a lotion, it is also keratolytic, antiseborrheic, and irritant. It has been used in treating acne and seborrhea, but it bleaches clothing and may produce contact dermatitis.
Potassium permanganate consists of purple crystals that dissolve in water to give deep purple solutions that stain tissues and clothing brown. A 1:10,000 dilution of potassium permanganate kills many microorganisms in one hour. Higher concentrations are irritating to tissues. The principal use of potassium permanganate solution is in the treatment of weeping skin lesions.
Heavy metals
A. Mercury: mercuric ion precipitates protein and inhibits sulfhydryl enzymes. Microorganisms in-activated by mercury can be reactivated by thiols (sulfhydryl compounds). Mercurial antiseptics inhibit thesulfhydryl enzymes of tissue cells as well as those of bacteria. Therefore, most mercury preparations are highly toxic if ingested. Mercury bichloride nf (1:100) can be used as a disinfectant for instruments or unabraded skin.
Ammoniated mercury ointment usp contains 5% of the active insoluble compound (hgnfcl). It is a skin disinfectant in impetigo.
Some organic mercury compounds are less toxic than the inorganic salts and somewhat more antibacte-rial. nitromersol usp, thimerosal usp (merthiolate), and phenylmercuric acetate or nitrate are marketed in many different liquid and solid forms as bacteriostatic antiseptics. Zhey are also used as “preservatives” in various biologic products to reduce the chance of accidental contamination. Merbromin (mercurochrome) is used as a 2% solution that is a feeble antiseptic but stains tissue a brilliant red color. The psychologic effect of this stain has lent support to the (otherwise almost negligible) antiseptic properties of this material.
B. Silver: silver ion precipitates protein and also interferes with essential metabolic activities of micro-bial cells. Inorganic silver salts in solution are strongly bactericidal. Silver nitrate, 1:1000, destroys most microorganisms rapidly upon contact. Silver nitrate ophthalmic solution usp contains 1% of the salt, to be instilled into the eyes of newboms to prevent gonococ-cal ophthalmia. It is effective for this purpose but may cause chemical conjunctivitis by being quite acid;
Therefore, antibiotic ointment has been used instead at times. Other inorganic silver salts are rarely used for their antimicrobial properties because they are strongly irritating to tissues. In bums, compresses of 0.5% silver nitrate can reduce infection of the bum wound, aid rapid eschar formation, and reduce mortality. If silver nitrate is reduced to nitrite by bacteria in the bum, methemoglobinemia may result. Silver sul-fadiazine 1% cream slowly releases sulfadiazine and also silver (see chapter 47) and effectively suppresses microbial flora in bums. It may have some advantages and causes less pain than mafenide acetate (sulfamy-lon) in the treatment of bums, but it has occasionally produced leukopenia.
Colloidal preparations of silver are less injurious to superficial tissues and have significant bacteriostatic properties. Mild silver protein contains about 20% silver and can be applied as an antiseptic to mucous membranes. Prolonged use of any silver preparation may result in argyria.
Other metals
Other metal salts (eg, zinc sulfate, copper sulfate) have significant antimicrobial properties but are rarely employed in medicine for this purpose.
Soaps
Soaps are anionic surface-active agents, usually sodium or potassium salts of various fatty acids. They vary in composition depending on the specific fats or oils and on the particular alkali from which they are made. Since naoh and koh are strong bases, whereas most fatty acids are weak acids, most so aps when dissolved in water are strongly alkaline (ph 8.0-10.0). Thus, they may irritate skin, which has a ph of 5.5-6.5. Special soaps (eg, neutrogena) use triethanolamine as a base and, when dissolved, are near ph 7.0. While most common soaps are well tolerated, excessive use will dry normal skin. Admixed synthetic fragrances may cause irritation or photosensitization of skin.
Most common soaps remove dirt as well as surface secretions, desquamated epithelium, and bacteria contained in them. The physical action of thorough handwashing with plain soaps is quite effective in removing transient bacteria and other contaminating microorganisms from skin surfaces. For additional an-tibacterial action, certain disinfectant chemicals (hexachlorophene, phenols, carbanilides, etc) have been added to certain soaps. These chemicals may be both beneficial and potentially harmful and are discussed below.
Phenols & related compounds
Phenol denatures protein. It was the first antiseptic employed, as a spray, during surgical procedures by lister in 1867. Concentrations of at least 1-2% are required for antimicrobial activity, whereas a 5% concentration is strongly irritating to tissues. Therefore, phenol is used mainly for the disinfection of inanimate objects and excreta. Substituted phenols are more effective (and more expensive) as environmental disinfectants. Among them are many proprietary preparations containing cresol and other alkyl-substituted phenols. Exaggerated claims for the antibacterial and antiviral properties for some such preparations (eg, lysol) and their possible health benefits have been made.
Other phenol derivatives such as resorcinol, thymol, and hexylresorcinol have enjoyed some popularity in the past as antiseptics. several chlorinated phenols are much more active antimicrobial agents.
Hexachlorophene is a white crystalline powder that is insoluble in water but soluble in organic solvents, dilutes alkalies, and soaps and is an effective bacteriostatic agent. Hexachlorophene liquid soap usp and many proprietary preparations are used widely in surgical scrub routines and as deodorant soaps. Single applications of such preparations are no more effective than plain soaps, but daily use results in a deposit of hexachlorophene on the skin that exerts a prolonged bacteriostatic action. Thus, the number of resident skin bacteria is lower on the surgeon’s hands if hexachlorophene soap is used daily and if other soaps, which promptly remove the residual hexachlorophene film, are not employed.
Soaps or detergents containing 3% hexachlorophene are effective in delaying or preventing colonization of the newborn’s skin with pathogenic staphylococci in hospital nurseries. However, repeated bathing of newborn (and particularly premature infants) with such preparations may permit sufficient absorption of hexachlorophene to result in toxic effects to the nervous system, especially a spongiform degeneration of the white matter in the brain. For this reason, the “routine prophylactic use” of 3% hexachlorophene preparations was discouraged. Stopping the use of hexachlorophene-containing preparations for bathing of newborn has been accompanied by a resurgence of staphylococcal infections iursery populations.
Hexachlorophene
Other antiseptics have been added to soaps and detergents, e.g., carbanilides or salicylanilides. trichlorocarbanilide now takes the place ofhexachlorophenes in several “antiseptic soaps.” regular use of such antiseptic soaps may reduce body odor by preventing bacterial decomposition of organic material in apocrine sweat. All antiseptic soaps may induce allergic reactions or photosensitization.
Chlorhexidine is a bisdiguanide antiseptic that disrupts the cytoplasmic membrane, especially of gram-positive organisms. It is employed as a skin cleanser and as a constituent of disinfectant soaps. A 4% solution of chlorhexidine gluconate can be used to cleanse wounds. When incorporated into soaps it is used as an antiseptic handwashing preparation, especially in hospitals, and for surgical scrub and preparation of skin sites for operative procedures. Repeated application ofchlorhexidine-containing soap results in persistence of the chemical on the skin to give a cumulative antibacterial effect. Chlorhexidine is somewhat less effective against pseudomonas and serratia strains than against coliform and gram-positive organisms.
Lindane (kwell, scabene), previously called gamma benzene hexachloride, is employed as a 1% lotion, shampoo, or cream to treat scabies, mites, or lice. Usually it is used just twice: it is applied after the skin or hairy areas have been washed with soap and water, and the treatment is repeated one week later. Up to 10% of the chemical may be absorbed from application to the skin, and it may produce toxic effects (skin rashes, blood dyscrasias, or convulsions), especially if ingested accidentally by infants. To prevent reinfestation with mites and lice it is necessary to treat all contacts and wash all clothes of the afflicted individual.
The use of lindaneas an insecticide in agriculture has been associated with poisoning after inhalation of substantial amounts of spray or mist. Lindane is also suspected of causing nerve damage, birth defects, and aplastic anemia on rare occasion and of being a possible carcinogen.
Cationic surface-active agents
Surface-active compounds are widely used as wetting agents and detergents in industry and in the home. They act by altering the energy relationship at interfaces. Cationic surface-active agents are bactericidal, probably by altering the permeability characteristics of the cell membrane. Cationic agents are antagonized by anionic surface-active agents and thus are incompatible with soaps. Cationic agents are also strongly adsorbed onto porous or fibrous materials, e.g., rubber or cotton, and are effectively removed by them from solutions.
A variety of cationic surface-active agents are employed as antiseptics for the disinfection of instruments, mucous membranes, and skin, eg, benzalkonium chloride (zephiran) and cetylpyridinium chloride. Aqueous solutions of 1:1000-1:10,000 exhibit good antimicrobial activity but have some disadvantages. These quaternary ammonium disinfectants are antagonized by soaps, and soaps should not be used on surfaces where the antibacterial activity of quaternary ammonium disinfectants is desired. They are adsorbed onto cotton and thereby removed from solution. When applied to skin, they form a film under which microorganisms can survive. Because of these properties, these substances have given rise to outbreaks of serious infections due to pseudomonas and other gram-negative bacteria. They cannot be employed safely as skin disinfectants and can only rarely be used as disinfectants of instruments.
Nitrofurans
Nitrofurazone (furacin) is used as a topical antimicrobial agent on superficial wounds or skin lesions and as a surgical dressing. The preparations contain about 0.2% of the active drug and do not interfere with wound healing. However, about 2% of patients may become sensitized and may develop reactions, eg, allergic pneumonitis. nitrofurantoin (furadantin) is a urinary antiseptic.
Miscellaneous antiseptics
Lysostaphin, a peptide enzyme, prepared for topical application, can eliminate staphylococci from the nostrils of carriers, but it is not marketed.
Many synthetic organic dyes have antimicrobial properties. Gentian violet usp is bacteriostatic and inhibits yeast growth, but it is aesthetically unappealing. acridine dyes have been used as topical antiseptics in 1:2000 concentration. Methylene blue was for merly used as a urinary antiseptic. pyridium, an azo dye, was used as a urinary antiseptic although it acts primarily as an analgesic in the bladder. Local anesthetics (eg, procaine, lidocaine) have some inhibitory effect on the growth of bacteria and fungi. Thus, they may interfere with culture of an etiologic agent in specimens from tissues or surfaces exposed to these agents.
Sulfur, in various preparations, is employed as a fungicide and parasiticide for topical use. Many fatty acids, especially propionic and undecylenic acids, are important topical antifungal drugs. Undecylenic acid nf, 5%, and zinc undecylenate nf, 20%, are among the least irritating and most fungistatic drugs available for treatment of dermatophytosis.
Sterilization procedures
It is the purpose of sterilization to make materials free from viable microorganisms, spores, and viruses. This is accomplished commonly by the application of heat under controlled conditions.
Incineration, using controlled burning, is used to dispose of infectious materials. Dry heat (160-170 °c for more than 1 hour) is employed to sterilize dry glassware, ceramics, and other materials. Moist heat or autoclaving (121 °c for 15 minutes or more at 15 ib/in2) is used for many instruments, dressings, linens, and bacteriologic media. All of these procedures must be carefully controlled with respect to time, temperature, size of materials, air circulation, displacement of cold air by steam, permeability of packaging materials, and other features that determine the efficacy of the application of heat.
Many materials that must be sterilized do not tolerate high heat, eg, plastics, optical devices, pump oxygenators, and extracorporeal circulation devices.
These materials are “gas sterilized” by exposure to ethylene oxide, because irradiation is not readily controllable. Ethylene oxide can destroy the viability of microorganisms, probably by the alkylation of sulfhydryl groups of proteins.
Since ethylene oxide is a highly flammable gas, it is usually employed in combination with either 90% c02 or fluorinated hydrocarbons. With such a mixture at a temperature of about 40 °c and a relative humidity of 40%, about 4 hours are required for sterilization. Ethylene oxide rapidly penetrates many types of materials exposed to it in a vacuum, and sterilization is accomplished in 4 hours; it then must be removed because it leaves toxic residues, eg, ethylene glycol and ethylene chlorohydrin. for proper ethylene oxide sterilization, materials must be wrapped in cloth, paper, or polyethylene; exposed to the gas for a proper period under controlled temperature; and then evacuated to remove gas and toxic residues and aerated for a prescribed time (often 12-120 hours) before being used.in most sterilization procedures, indicators of adequate time and temperature exposure and of sterility (“spore strips”) must be employed. Careful records are essential and must be kept for years. Chemical indicators for ethylene oxide exposure must be employed.
Theme № 1.Antseptics and desinfectants
1. Concept about aseptic, antiseptic and disinfection. Factors, determinate antimicrobal activity of medicines.
2. Main mechanism of antiseptic action on micro-organisms.
3. Nitrofurans: antimicrobal spectrum, usage.
4. Local and antimicrobal activities of heavy metals, their usage in practice.
5. Resorbtive activity of heavy metal salts. Emergency of poison.
6. Antimicrobal action of iodine and chlorine. The usage in medical practice.
7. Antimicrobal action of oxidising agents: of their usage.
8. Antiseptic of aliphatic structure: mechanism of action, usage of ethyl alcohol and formaldehyde.
9. Antiseptic activities of acid and alkalinise mechanism of action and usage of Amonii Caustic.
10. Peculiarities of action and usage of Painters (Viride nitens, Aethacridini lactas).
11. Antiseptic of detergents group (Decametoxinum, Aethonium).
12. Antiseptic of a vegetative origin.
Theme № 2-3. Sulfonamides and other antimicrobial drugs. Antimycobacterial agents.
1. Mechanism and antibacterial spectrum of sulfonamides.
2. Pharmacokinetics of sulfonamides.
3. Period of action and dosage of sulfonamides.
4. Clinical classification and indications of usage of sulfonamide agents.
5. Combine usage of sulfonamides and antibacterial agents of other chemical structure.
6. Adverse reactions and complications of sulfonamides therapy, their prevention and healing.
7. Naftiridinum derivates (acidum nalidixicum), their charecteristic and uses.
8. 8-oxychinolinum derivates (enteroseptolum), their charecteristic and uses.
9. Nitroforanum derivates as chemiotherapeutic agents.
10. Antituberculosal preparations classification, spectrum and mechanism of activity.
11. Pharmacodynamics, pharmacokinetics and peculiarities of audimycobacterial agents uses.
12. Adverse reactions of antimycobacterial drugs.
13. Principles of tuberculosis chemotherapy
3. Discussion of basic questions
1230 – 1400 in case of 6 – hour’s practical classes
4. Example of control task.
A. What antiseptics is oxidants:
1. Kalii permanganas
2. Viride nitens
3. Furacilinum
4. Iodinolum
5. Aethonium
B. Kalii permanganas is used to :
1. cleanse of purulent wound
2. deinfection of room
3. cleanse of burn
4. as uroligic antiseptic
5. for sterilisation of surgical instruments
C. Which of the following is halogen – containing compound antiseptic:
1. Chloramine
2. Kalii permanganas
3. Argenti nitras
4. Cupri sulfas.
5. Zinci sulfas.
1. Real – life situation to be solved:
The patient has been brought to the hospital from place of work. There are no serious injuries, only superficial ones. What antiseptics may be used for cleanser of wounds?
5. Initial level of knowledge and skills are checked by solving situational tasks for each topic, answers in test evaluations and constructive questions. (the instructor has tests & situational tasks) (1415-1500).
6. Students must know:
1. Concept about aseptic, antiseptic and disinfection. Factors, determinate antimicrobal activity of medicines.
2. Main mechanism of antiseptic action on micro-organisms.
3. Nitrofurans: antimicrobal spectrum, usage.
4. Local and antimicrobal activities of heavy metals, their usage in practice.
5. Resorbtive activity of heavy metal salts. Emergency of poison.
6. Antimicrobal action of iodine and chlorine. The usage in medical practice.
7. Antimicrobal action of oxidising agents: of their usage.
8. Antiseptic of aliphatic structure: mechanism of action, usage of ethyl alcohol and formaldehyde.
9. Antiseptic activities of acid and alkalinise mechanism of action and usage of Amonii Caustic.
10. Peculiarities of action and usage of Painters (Viride nitens, Aethacridini lactas).
11. Antiseptic of detergents group (Decametoxinum, Aethonium).
12. Antiseptic of a vegetative origin.
13. Mechanism and antibacterial spectrum of sulfonamides.
14. Pharmacokinetics of sulfonamides.
15. Period of action and dosage of sulfonamides.
16. Clinical classification and indications of usage of sulfonamide agents.
17. Combine usage of sulfonamides and antibacterial agents of other chemical structure.
18. Adverse reactions and complications of sulfonamides therapy, their prevention and healing.
19. Naftiridinum derivates (acidum nalidixicum), their charecteristic and uses.
20. 8-oxychinolinum derivates (enteroseptolum), their charecteristic and uses.
21. Nitroforanum derivates as chemiotherapeutic agents.
22. Antituberculosal preparations classification, spectrum and mechanism of activity.
23. 11. Pharmacodynamics, pharmacokinetics and peculiarities of audimycobacterial agents uses.
24. Adverse reactions of antimycobacterial drugs.
25. Principles of tuberculosis chemotherapy
7. Students should be able to: choose the drug in correspondent medicinal form for injection, write out the prescription for solution for injection, for drugs in liquid medicinal forms, make a choice of different above-mentioned drugs in real-life situations, know the measures to prevent their adverse effects, write out the prescriptions for these drugs in different pharmaceutical forms.
8. Correct answers for the control task.
A – 1; B – 1, 3, 4; C –1.
It may be Hydrogenii peroxide, kalii parmanganas, viride nitens, aethacridini lactas, iodinolum.
9. References:
1. Pharmacology at your palms: reference book / Drogovoz S.M., Kutsenko T.A. – Kharkiv: NPhaU, 2008. – 80 p.
2. Pharmacology secrets / edited by Patricia K. Anthony. – Hanley Belfus, INC/ – Philadelphia, 2002. – 305 p.
3. Rang and Dale’s Pharmacology / H.P. Rang, M.M. Dale, J.M. Ritter, R.J. Flower // Churchill Livingstone, 2007. – 829 p.
4. Tripathi K.D. Essentials of medical pharmacology 6 th Edition. – Jaypee Brothers Medical Publishers (P) LTD New Delhi, 2008. – 875 p.
5. Stefanov O., Kucher V. Pharmacology with general prescription. – Kiev, 2004. – 150 p.
6. Multimedia lectures from pharmacology for 3d course students
7. http://intranet.tdmu.edu.ua/ukr/kafedra/index.php?kafid=pharm&lengid=eng
Methodical instructions were prepared by Oleshchuk O.M.
Discussed and adopted at chair-sitting of Pharmacology department
with Clinical pharmacology
04.01.2013, minute № 7
Readopted at chair-sitting of Pharmacology department
with Clinical pharmacology
27.08.2013, minute №1
