Methodical instructions

for students of pharmacy department

LESSON № 23 (practical classes – 6 hours)

 

Theme:

SULFONAMIDES AND OTHER ANTIMICROBIAL DRUGS. (Phthalazolum, Aethazolum, Sulfacylum-natrium, Sulfadimethoxinum, Sulfapyridazinum, Sulfalenum, Biseptolum (Bactrinum), Salazosulfopiridinum, Salazopiridazinum, Acidum nalidixicum, Nitroxolinum, Ofloxacinum, Cyprofloxacinum,, Furasolidonm, Furaginum)

 

Aim: To memorise the pharmacokinetic and pharmacodynamics effects of antibiotics, antiseptics and disinfectants, sulfanilamide, and different antibacterial agents.

 

Professional motivation

 

Antibiotics are the most important chemotherapeutical medicinal preparations. Thanks to theme it became possible to cure the pulmonal form of plague people, sharply decrease death rate in case of such disease as typhus, meningitis, tuberculosis, etc. There are more than six thousand antibiotic preparation described, but in practice only 50-60 of them are widely used.

      Excessive use of this highly-active group of chemotherapeutical preparations and underestimating of its potential danger, irrational and non-effective use called the row of undesirable results of antibiotic therapy-increasing of antibiotic resistance and polyresitance of microbes and their selection, damaging of separate organs and systems, development of non-specific sensitisation, increasing of frequency of endogen mixed with super-infections. Above mentioned facts led us to the decision of more careful use of antibiotic preparations strict observing rational therapy principles.

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.

 

1. Students’ practical activities

 9.00-12.00 in case of 6-hours practical classes

 

Theme № 1. SULFONAMIDES AND OTHER ANTIMICROBIAL DRUGS.

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.

II. Choose the correct answer/statement

A.   Sulfonamides:

1.          Are competitive antagonists of paba, and thereby decrease bacterial utilisation of paraaminobensoic acid in the synthesis of folicacid.

2.         Are bacteriostatic.

3.         . Are batericidal.

4.          Can be antagonised by paba

5.          Are synergistic with trimethoprim, which inhibits dihydrofolate reductase.

 

B.   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.

 

III. Answer the following questions:

1.     Why neomycin sulphates can be injected only parenterally?

2.     What side effects are observed after using tetracycline?

3.     What antibiotics are not prescribed together?

4.     What sulfonamides are used for systemic infection healing?

5.     What is the mechanism of sulfonamides action?

6.     Why caovocainum and acidum folicum weaken sulfonamide’s activity?

7.     Why is cristalization of acetylderivates of sulfonamides in renal tubes occurs?

8.     What is the localization of infection for prescribing of acidum nalidixicum, enteroseptolum?

9.     What are the indications for furazolidonum?

IV Get acquainted with thematic medicine collection

 

III. 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?

 

2. Student’s Independent Study Program

Aminoglycosides History: The first aminoglycoside antibiotic, streptomycin, was isolated in 1944 and shortly thereafter was observed to be effective in the treatment of tuberculosis. In 1949, neomycin was isolated, followed by kanamycin in 1957. In 1959, another less known aminoglycoside, paromomycin, was developed. Today, these four aminoglycoside antibiotics are seldom used due to the availability of gentamicin (1963), tobramycin (1975), and amikacin (1976). Gentamicin is most widely used since it is available as a generic formulation and, as such, is much less expensive than either tobramycin or amikacin. Also responsible for the decline in the use of streptomycin and neomycin is the risk of severe ototoxicity, although the newer agents also possess this potential. Currently, neomycin is used only orally in the treatment of hepatic encephalopathy because toxicity is too great with parenteral administration or topical irrigation. Administration in higher doses at longer dosing intervals may simultaneously increase efficacy and decrease toxicity. Mechanism of Action: Despite many years of investigation, it is not clear how aminoglycosides cause bacterial cell death. It is known that aminoglycosides bind irreversibly to one of two aminoglycoside-binding sites on the 30 S ribosomal subunit, subsequently inhibiting bacterial protein synthesis. This inhibition, however, does not adequately explain the bactericidal effect of aminoglycosides because other non-aminoglycoside antibiotics that also inhibit protein synthesis are only bacteriostatic. One aspect essential to aminoglycoside lethality is the need to achieve intracellular concentrations in excess of extracellular ones. Anaerobic bacteria are not susceptible to aminoglycosides due, at least in part, to a lack of an active transport mechanism for aminoglycoside uptake. Aminoglycosides exhibit “concentration-dependent killing” and a “post-antibiotic effect” (PAE). “Concentration-dependent killing” describes the principle that bactericidal effects increase as the antibiotic concentration increases. “PAE” represents a sustained inhibitory effect on bacterial growth persisting for several hours after aminoglycoside concentrations are no longer detectable. Both of these phenomena can be exploited with dosage regimens that employ higher doses administered at longer intervals. Distinguishing Features/Adverse Reactions: Aminoglycosides are similar in actions and adverse reactions. Two well-known adverse reactions are ototoxicity and nephrotoxicity. It is believed that certain aminoglycosides, such as neomycin and streptomycin, are more ototoxic than the others, although there has never been a clear association between aminoglycoside serum concentrations and the development of ototoxicity. While it is believed that neomycin ototoxicity is predominantly cochlear and streptomycin causes vestibular toxicity, all aminoglycosides have the potential for causing either type. Ototoxicity is believed to develop after prolonged use and may not be reversible. Nephrotoxicity is another well-described adverse reaction to aminoglycoside therapy. Aminoglycosides are taken up by pinocytosis in cells lining the proximal nephron where the drug is concentrated within lysosomes. With no mechanism for intracellular elimination of the aminoglycoside-lysosome complex, the cell swells and bursts. There appears to be a stronger association between aminoglycoside serum concentrations and the occurrence of nephrotoxicity than with ototoxicity. Elevated trough concentrations for a sustained period of time appear to aggravate aminoglycoside nephrotoxicity. Tubular cellular uptake of drug was greater during a continuous 24-hour infusion of minoglycoside compared with the same dose infused over 30 minutes. In addition, efficacy does not appear to be compromised by administering the aminoglycoside in larger doses at extended intervals. Because the clinical differences among aminoglycoside antibiotics are subtle, it is likely that cost will remain a significant factor in selecting one agent over another.

Macrolides   History: Erythromycin, the first and still most widely used macrolide antibiotic, has been used clinically as an antibiotic since 1952. Until recently, erythromycin and an infrequently used macrolide, troleandomycin, were the only members of this group. In 1991, azithromycin and clarithromycin were made available and in 1995 dirithromycin reached the market. These new agents appear to possess distinct advantages over erythromycin, albeit at a greater cost. Roxithromycin is a macrolide still under investigation. Mechanism of Action: Macrolide antibiotics bind to the 50 S ribosomal subunit, inhibiting bacterial protein synthesis. Erythromycin is effective against a wide range of microorganisms, and, like other antibiotics that inhibit protein synthesis, erythromycin is mainly bacteriostatic. Activity of erythromycin against gram-positive organisms generally is greater than against gram-negative organisms due to its superior penetration into gram-positive organisms. Azithromycin appears to have less gram-positive activity but greater gram-negative activity than erythromycin.A well-known adverse reaction to erythromycin has been converted into a new use. For many years it has been known that erythromycin can cause GI intolerance. Recently, it has been proposed that erythromycin acts as a motilin agonist by binding to motilin receptors in the GI tract, and erythromycin was shown to be more effective than placebo in the treatment of diabetic gastroparesis. Both azithromycin and clarithromycin appear to cause fewer GI side effects than erythromycin and thus may not be appropriate for this indication.

Distinguishing Features: Until azithromycin and clarithromycin were released, erythromycin was the only macrolide in widespread clinical use. Erythromycin itself is available in a variety of salts and dosage forms, making it difficult to compare erythromycin products. Erythromycin lactobionate is administered parenterally, while ethylsuccinate, estolate, stearate, and erythromycin base are administered orally. Erythromycin base is acid-labile, so various salts are available in an attempt to increase oral bioavailability. The oral bioavailability of both azithromycin and clarithromycin are superior to that of erythromycin. Roxithromycin, an investigational agent, appears to be the most bioavailable of all the macrolides.Despite their significant cost compared with erythromycin, azithromycin and clarithromycin have earned a solid place in therapy. Both azithromycin and clarithromycin possess greater intrinsic activity against H. influenzae than does erythromycin, although other effective antibiotics are less costly. Azithromycin and clarithromycin are concentrated within macrophages, making them useful against organisms that are taken up by macrophages such Mycobacterium avium intracellulare. In December 1993, clarithromycin was approved for treatment of AIDS-related Mycobacterium avium complex (MAC). The significant tissue penetration of both agents and the prolonged elimination half-life for azithromycin (11-14 hours) allows once-daily dosing for azithromycin and twice-daily dosing for clarithromycin. In addition, clarithromycin is metabolized to a compound with bioactivity similar to that of the parent. Because of significant tissue concentrations and prolonged elimination, azithromycin has been shown effective as a single-dose treatment for chlamydial infection. Finally, both agents appear to cause fewer gastrointestinal adverse reactions and fewer drug interactions than erythromycin.   Adverse Reactions: Erythromycin is well known to cause adverse GI effects. Adverse GI effects are reported for roughly 21% of patients receiving erythromycin, about 10% of patients receiving clarithromycin, and less than 5% for azithromycin. Elevated hepatic enzymes and cholestatic jaundice have been reported during treatment with various salts of erythromycin, but, in general, this occurs infrequently. A less well-known but nonetheless significant adverse reaction to erythromycin, especially after intravenous administration, is ototoxicity, manifest as tinnitus and/or deafness. Intravenous administration of erythromycin is also painful and can cause phlebitis.

The antiseptics

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. They 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 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 soaps 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 out breaks 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 formerly 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.

 

Theme № 1. Sulfonamides and other antimicrobial drugs

 

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.

 

3. Discussion of basic questions

 12.30 – 14.00 in case of 6 – hour’s practical classes

 

4. The example of the control task

A. Rifampicine is used mainly in the tratment of :

1.     Cholera

2.     Typhoid fever

3.     Tuberculosis

4.     Rickettsial diseases

5.     Pseudomonas infections

B. Patients having a history of a severe, immediate reaction to penicillin:

1.     may be given a cephalosporin without concern

2.     have a definite risk of reaction to any cephalosporin

3.     have a low risk of having a reaction to a broad spectrum antipseudomonal penicillin

4.     have a high risk of hypersensitivity to a broad spectrum antipseudomonal penicillin

C. Tetracyclines:

1.     are bacteriostatic in vitro

2.     are bacteriocidal in vitro

3.     are effective against rickettsial

4.     interfere primary with cell wall synthesis

 

D. What antiseptics has oxidant properties:

1.     Kalii permanganas

2.     Viride nitens

3.     Furacilinum

4.     Iodinolum

5.     Aethonium

E. 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

F. Which of the following is halogen – containing compound antiseptic:

1.     Chloramine

2.     Kalii permanganas

3.     Argenti nitras

4.     Cupri sulfas.

5.     Zinci sulfas.

Real – life situations to be solved:

1.       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?

2.       A known diabetic patient presents with cough, haemoptysis, and a single shaking chill. His temperature 38,5o c, and a chest x-ray demonstrates lobar pneumonia.gram staining reveals gram-positive diplococc. What would the most sensible antibiotic.

 

5. Students must know:

Student work (14¹⁵-15⁰⁰ hour) are checked by solving situational tasks for each topic, answers in test evaluations and constructive questions (the instructor has tests & situational tasks).

 

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.

 

6. 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.

 

7. Correct answers for the control task

A – 3, B- 2, 4, C – 1,3, D – 1; E – 1, 3, 4; F –1.

 

Real – life situations to be solved

1. It may be hydrogenii peroxide, kalii parmanganas, viride nitens, aethacridini lactas, iodinolum.

2. Penicillin

 

8. 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 3^d course students

7.            http://intranet.tdmu.edu.ua/ukr/kafedra/index.php?kafid=pharm&lengid=eng

 

Methodical instructions were prepared by Volska A.S.

Discussed and adopted at chair-sitting of Pharmacology department

with Clinical pharmacology

04 january 2013, minute № 7

Readopted at chair-sitting of Pharmacology department

with Clinical pharmacology

 27.08.2013, minute № 1