Antiseptics, Disinfectants

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1. Antiseptics, Disinfectants and other locally acting drugs Dr. Karun Kumar Senior Lecturer Dept. of Pharmacology

2. Antiseptics  A gents used on living surfaces (skin, mouth) Disinfectants  Agents used for inanimate objects (instruments, water supply) Germicide  Covers both Sterilization  C omplete killing of all forms of microorganisms Disinfection  Re duction in the number of viable pathogenic microbes to a level that they do not pose a risk to individuals with normal host defence .

3. A good antiseptic/disinfectant should be: Chemically stable. Cheap. Nonstaining with agreeable colour and odour . Cidal and not merely static, destroying spores as well. Active against all pathogens—bacteria, fungi, viruses, protozoa. Require brief time of exposure. Active even in the presence of blood, pus, exudates and excreta.

4. An antiseptic in addition should be: Rapid in action and exert sustained protection. Nonirritating to tissues, should not delay healing. Nonabsorbable , produce minimum toxicity if absorbed. Nonsensitizing (no allergy). Compatible with soaps and other detergents.

5. Spectrum of activity Selective  H exachlorophene, chlorhexidine , quaternary ammonium antiseptics, gentian violet and acriflavin are more active on gram-positive than gram-negative bacteria Silver nitrate is highly active against gonococci Benzoyl peroxide is highly active against P. acnes

6. Mechanisms of action Oxidation of bacterial protoplasm Denaturation of bacterial proteins including enzymes Detergent like action increasing permeability of bacterial membrane

7. Factors modifying the activity of germicides Temperature and pH Period of contact with the microorganism. Nature of microbe involved. Size of inoculum. Presence of blood, pus or other organic matter

8. Potency of a germicide  E xpressed by its phenol coefficient or Rideal Walker coefficient (Ratio of the minimum concentration of test drug required to kill a 24 hour culture of B. typhosa in 7.5 minute at 37.5°C to that of phenol under similar conditions) Therapeutic index of an antiseptic  C omparing the concentration at which it acts on microorganisms with that which produces local irritation, tissue damage or interference with healing.

9. Classification Phenol derivatives  Phenol, Cresol, Hexylresorcinol, Chloroxylenol , Hexachlorophene Oxidizing agents  Pot. permangnate , Hydrogen peroxide, Benzoyl peroxide Halogens  Iodine, Iodophores , Chlorine, Chlorophores Biguanide  Chlorhexidine Quaternary ammonium (Cationic)  Cetrimide , Benzalkonium chloride, Dequalinium chloride

10. 6. Soaps  of Sod. and Pot. 7. Alcohols  Ethanol, Isopropanol. 8. Aldehydes  Formaldehyde, Glutaraldehyde . 9. Acids  Boric acid, Acetic acid. 10. Metallic salts  Silver nitrate, Silver sulfadiazine, Mild silver protein, Zinc sulfate , Calamine, Zinc oxide. 11. Dyes  Gentian violet, Acriflavine , Proflavine . 12. Furan derivative  Nitrofurazone

11. Phenol derivatives Phenol Cresol Hexylresorcinol Chloroxylenol Hexachlorophene Triclosan

12. Phenol (Carbolic acid) Antiseptic (static at 0.2%, cidal at >1%, poor action on bacterial spores) Protoplasmic poison, injuring microbes and tissue cells alike— at higher concentrations causes skin burns and is a caustic Acts by disrupting bacterial membranes and denaturing bacterial proteins

13. Organic matter diminishes its action slightly while alkalies and soaps do so profoundly (carbolic soaps are not more germicidal than soap itself) Used to disinfect urine, faeces , pus, sputum of patients and is sometimes included in antipruritic preparations because of its mild local anaesthetic action

14. Cresol It is methyl-phenol; more active (3–10 times) and less damaging to tissues. Used for disinfection of utensils, excreta and for washing hands

15. Hexylresorcinol It is a more potent derivative of the phenolic compound resorcinol that is odourless and nonstaining Used as mouthwash, lozenge and as antifungal

16. Chloroxylenol Commercial 4.8% solution (DETTOL) is prepared in 9% terpinol and 13% alcohol; used for surgical antisepsis . A 0.8% skin cream and soap, 1.4 % lubricating obstetric cream (for vaginal examination, use on forceps, etc.), and a mouthwash ( DETTOLIN 1% with menthol 0.45%) are also available. These preparations lose activity if diluted with water and kept for a time

17. Triclosan Bactericidal (denaturation of membrane bound enzymes) Hydroalc . Soln. is a mixture of phenolic volatile oils thymol , menthol, eucalyptol along with benzoic acid is a popular mouthwash LISTERINE Widely used for bad breath, dental plaque & gingivitis

18. Hexachlorophene Chlorinated phenol acts by inhibiting bacterial enzymes and (in high conc.) causing bact. Lysis Odourless , nonirritating and does not stain Activity is ↓ by organic matter but not by soap Commonly incorporated in soap and other cleansing antiseptics for surgical scrub , patient’s skin, etc., but is narrow spectrum; kills gram-positive but not gram-negative bacteria or spores

19. Degerming action is slow but persistent due to deposition on the skin as a fine film that is not removed by rinsing with water Incorporated in toilet products, it is a good deodorant

20. Oxidizing agents Pot . Permangnate Hydrogen peroxide Benzoyl peroxide

21. Potassium permanganate Occurs as purple crystals, highly water soluble, liberates oxygen which oxidizes bacterial protoplasm. The available oxygen and germicidal capacity is used up if much organic matter is present—the solution gets decolourised A 1:4000 to 1:10,000 solution ( Condy’s lotion) is used for gargling, douching, irrigating cavities, urethra and wounds.

22. The action is rather slow and higher concentrations cause burns and blistering—popularity therefore has declined. It has also been used to disinfect water (wells, ponds) and for stomach wash in alkaloidal poisoning (except atropine and cocaine which are not efficiently oxidized). It promotes rusting and is not good for surgical instruments.

23. Hydrogen peroxide It liberates nascent oxygen which oxidizes necrotic matter and bacteria A 3.0% solution produces 10 volumes of oxygen, much of which escapes in the molecular form Catalase present in tissues speeds decomposition resulting in foaming—helps in loosening and removing slough, ear wax, etc. Hydrogen peroxide has poor penetrability and a weak, transient antiseptic action

24. Hydrogen peroxide mouthwash has been employed in acute necrotizing gingivitis (anaerobic bacteria) Also used in periodontal disease A 20-30% solution in water or ether has been used as a bleaching agent on teeth Frequent use can produce oral ulcers

25. Benzoyl peroxide Specifically active against P. acnes and used on acne vulgaris

26. Halogens Iodine Iodophores Chlorine Chlorophores

27. Iodine Rapidly acting, broad-spectrum (bacteria, fungi, viruses) microbicidal agent Acts by iodinating and oxidizing microbial protoplasm. A 1 : 20,000 solution kills most vegetative forms within 1 min. Even bacterial spores are killed with higher concentrations/longer contact. Organic matter retards but does not abolish its germicidal action. Solid iodine is corrosive, stronger solutions (> 5%) cause burning and blistering of skin.

28. Tincture iodine (2% in alcohol) stings on abrasions. It is used on cuts, for degerming skin before surgery, and to treat ring worm, etc. Mandel’s paint (1.25% iodine dissolved with the help of Pot. iodide forming soluble I¯-ions) is applied on sore throat. A nonstaining iodine ointment (IODEX 4%) is popular as antiseptic and counterirritant. Some individuals are sensitive to iodine—rashes and systemic manifestations occur in them.

29. Iodophores Soluble complexes of iodine with large molecular organic compounds that serve as carriers—release free iodine slowly. The most popular— Povidone iodine: is nonirritating , nontoxic, nonstaining and exerts prolonged germicidal action. Treated areas can be bandaged or occluded without risk of blistering.

30. It is used on boils, furunculosis , burns, otitis externa , ulcers, tinea , monilial / trichomonal / nonspecific vaginitis and for surgical scrubbing, disinfection of endoscopes and instruments. In dentistry, 1% povidone iodine oral rinse is employed for gingivitis

31. Chlorine A highly reactive element and a rapidly acting potent germicide 0.1–0.25 ppm kills most pathogens (but not M. tuberculosis ) in 30 sec Degerming action is soon exhausted , and it lacks substantivity Used to disinfect urban water supplies

32. Organic matter binds chlorine, so that excess has to be added to obtain free chlorine concentration of 0.2–0.4 ppm This is known as the ‘ chlorine demand ’ of water Chlorine is more active in acidic or neutral medium

33. Chlorophores Compounds that slowly release hypochlorous acid ( HOCl ) Ease of handling  U sed in pref. to gaseous chlorine. Chlorinated lime (bleaching powder)  O btained by the action of chlorine on lime Mixture of calcium chloride and calcium hypochlorite Used as disinfectant for drinking water, swimming pools and sanitizer for privies, etc. Bleaching action is utilized for removing stains from teeth & for their cosmetic whitening

34. 2. Sodium hypochlorite solution  Contains 4–6% sodium hypochlorite. Powerful disinfectant used in dairies for milk cans, other equipment and for infant feeding bottles. It is used in root canal therapy in dentistry. Irrigation of root canal with 2% Sodium hypochlorite solution loosens & dissolves dead tooth pulp in addition to exerting rapid antisepsis

35. Chlorhexidine ( Biguanide ) A powerful, nonirritating, cationic antiseptic that disrupts bacterial cell membrane. S econdary action  D enaturation of microbial proteins. More active against gram-positive bacteria. Present in SAVLON Extensively used for surgical scrub, neonatal bath, mouthwash, obstetrics and as general skin antiseptic

36. Most widely employed antiseptic in dentistry. As 0.12–0.2% oral rinse or 0.5–1% toothpaste, it is highly active in preventing/treating gingivitis and plaques Good results have been obtained in acute necrotizing gingivitis Rinsing before the procedure, prev. inf. foll . periodontal & other forms of oral surgery

37. Twice daily chlorhexidine oral rinse markedly reduces oral infections in immunocompromised patients, including AIDS. However, it may leave an unpleasant after taste, and repeated application causes brownish discolouration of teeth and oral ulceration

38. Quaternary ammonium (Cationic ) antiseptics Cetrimide Cetylpyridinium chloride Benzalkonium chloride

39. Detergents; cidal to bacteria, fungi & viruses . However , many gram-negative bacteria ( esp. Pseudomonas), M. tuberculosis and bacterial spores are relatively resistant. Alter permeability of cell membranes and denature bact. proteins Soaps, being anionic, neutralize their action, while alcohol potentiates

40. Spread through oil and grease, have cleansing and emulgent properties Nonirritating and mildly keratolytic Germicidal action is rather slow and bacteria may thrive under a film formed by them on the skin.

41. Pus, debris and porous material like cotton, polyethylene reduce their activity. Occasionally sensitization occurs Widely used as sanitizers, antiseptic and disinfectant for surgical instruments, gloves, etc , but should not be considered sterilizing.

42. Cetrimide A soapy powder with a faint fishy odour . Used as 1–3% solution, it has good cleansing action, efficiently removing dirt, grease, tar and congealed blood from road side accident wounds . Alone or in combination with chlorhexidine , it is one of the most popular hospital antiseptic and disinfectant for surgical instruments , utensils , baths, etc.

43. Cetylpyridinium chloride Similar to Cetrimide Incl. in mouth washes & lozenges to ↓ plaque formn . Leaves a bad taste & can cause oral ulceration

44. Benzalkonium chloride It is highly soluble in water and alcohol. A 1:1000 solution is used for sterile storage of instruments and 1 in 5000 to 1 in 10,000 for douches , irrigation, etc.

45. Soaps Anionic detergents; weak antiseptics, affect only gram-positive bacteria. Their usefulness primarily resides in their cleansing action. Washing with soap and warm water is one of the most effective methods of preventing transmission of infection by removing/diluting pathogenic bacteria. Soaps can be medicated by other antiseptics.

46. Ethanol It is an effective antiseptic and cleansing agent at 40–90% concentration. The rapidity of action increases with concentration upto 70% and decreases above 90%. Acts by precipitating bacterial proteins. A cotton swab soaked in 70% ethanol rubbed on the skin kills 90 % bacteria in 2 min.; has been used before hypodermic injection and on minor cuts.

47. Irritant; not be applied to mucous membranes or to delicate skin (scrotum), ulcers, etc. On open wounds it produces a burning sensation, injures the surface and forms a coagulum under which bacteria could grow. It is a poor disinfectant for instruments—does not kill spores and promotes rusting Usefulness is limited in dentistry Eff. conc. cannot be applied on gums, oral mucosa

48. Conc. present in mouth rinses (5-10%) has no antiseptic efficacy Low conc. enh . the antiseptic activity of iodine and chlorhexidine when used as solvent for these Used to sanitize working surfaces in dentistry but a poor disnf . for instruments – does not kill spores & promotes rusting Isopropanol  Less volatile; can be used in place of ethanol

49. Formaldehyde Pungent gas—sometimes used for fumigation. A 37% aqueous solution called Formalin is diluted to 4% and used for hardening and preserving dead tissues. It denatures proteins and is a general protoplasmic poison , but acts slowly. A broad-spectrum germicide, but use as antiseptic is restricted by its irritating nature and pungent odor

50. Though the desens . acn . is weak, low conc. are incl. in some desens . toothpastes It is occasionally employed to disinfect instruments and excreta. Also used to precipitate toxoids from toxins Ppl handling formalin can develop eczematoid reactions

51. Glutaraldehyde Less volatile, less pungent, less irritating and better sterilizing agent than formalin. Broad-spectrum activity against bacteria, fungi and viruses, but needs to be activated by alkalinization of the solution. Organic matter does not inactivate it A 2% solution is used to disinfect surg. instruments and endoscopes, but prolonged contact is needed

52. Should not be used to disinf . working surfaces because repeated inh . of its vapours can induce asthma Repeated application on skin can cause sensitization. The alkalinized solution has a short shelf life (2 weeks) unless stablilizing agents are added.

53. Boric acid Bacteriostatic and a very weak antiseptic. Nonirritating; used for irrigating eyes , mouthwash , douche, etc. Boroglycerine paint ( 30%) is used for stomatitis and glossitis . A 10% ointment (BOROCIDE) is available for cuts and abrasion.

54. I ncluded in prickly heat powders and ear drops. Systemic absorption causes vomiting, abdominal pain, diarrhoea , visual disturbances and kidney damage

55. Silver nitrate Rapidly kills microbes, action persisting for long periods because of slow release of Ag + ions from silver proteinate formed by interaction with tissue proteins. Tissues get stained black due to deposition of reduced silver. Uses  H ypertrophied tonsillitis & aphthous ulcers Highly active against gonococci—1 % solution is used for ophthalmia neonatorum .

56. O phthalmia neonatorum

57. Silver sulfadiazine Highly active against Pseudomonas and has been used on burns.

58. Zinc salts Astringent and mild antiseptics. Zinc sulfate  U sed for eyewash and in eye/ear drops. Applied to skin, it decreases perspiration . Calamine and zinc oxide  M ildly antiseptic ; dermal protectives and adsorbants .

59. Gentian violet (crystal violet) Active against staphylococci, other grampositive bacteria and fungi, but gram-negative organisms and mycobacteria are insensitive. Aqueous or alcoholic solution (0.5–1%) is used on furunculosis , bedsores, chronic ulcers, infected eczema , thrush, Vincent’s angina, ringworm, etc. It has become unpopular due to deep staining

60. THRUSH

61. Acriflavine and Proflavine Active against gram-positive bacteria and gonococci. Efficacy is not reduced by organic matter and is enhanced in alkaline medium. Solutions lose efficacy on exposure to light—store in amber bottles. Nonirritant and do not retard healing—particularly suitable for chronic ulcers and wounds. Bandage impregnated with acriflavine-vaseline is used for burn dressing

62. The triple dye lotion contains gentian violet 0.25 % + brilliant green 0.25% + acriflavine 0.1 % ( TRIPLE DY), has been used for burns and for dressing umbilical stump in neonates.

63. Nitrofurazone ( Nitrofural ) Cidal to both gram-positive and negative, aerobic and anaerobic bacteria , even in high dilutions, but activity is reduced in the presence of serum. Acts by inhibiting enzymes necessary for carbohydrate metabolism in bacteria. Highly efficacious in burns and for skin grafting. Local toxicity is negligible—but sensitization occurs frequently.

64. Use & sel. Of A/D in dentistry Purposes Pref. agents Cleaning & disinf . of working surfaces, instrument trays, oper . light handles Alc., Ammon. antispetics Cold steriliz . Of certain instruments & storage of steriliz . equipment Glutarald ., Ammon. antispetics Decontamination of the dentist’s & assistant’s hands Soaps, alc , Chloroxylenol , Ammon. antispetics Prev. & t/t of dental plaque & periodontal disease Chlorhexidine , Ammon. Antispetics , Triclosan

65. Purposes Pref. agents T/t of ANUG, aphthous ulcers & other inf. oral conditions Povidone iodine, Chlorhexidine , H 2 O 2 , Boric acid, silver nitrate RCT Sod. hypochlorite Preop . prep. of oral mucosa by ↓ bact. load so as to minimise local as well as distant inf. Povidone iodine, Chlorhexidine As an ingredient of certain dentrifices Chlorhexidine , Triclosan , Amm . antiseptic

66. Locally acting drugs Variety of drugs topically applied to the skin or mucous memb .  Produce therap. eff. localized to the site of application Act by virtue of their physical / mechanical / chemical / biological attributes

67. Demulcents Inert subst. which sooth inflamed/denuded mucosa or skin by preventing contact with air/irritants in surr HMW subst. applied as thick colloidal / viscid soln. in water Glycyrrhiza Glycerine Methylcellulose Gum acacia Propylene glycol

68. Glycyrrhiza  Sweet tasting root of liquorice used to sooth throat & as flavouring / sweetening agent Glycerine  Clear, sweet, viscous liquid used as vehicle for gum/throat paints & as emollient on dry/cracked lips Undil . glycerine is dehyd . & prod. a warm sens. in mouth. Also, has mild antispetic prop.

69. Emollients Bland oily substances which sooth & soften skin Form an occlusive film over the skin prev. evapor . Used as vehicle for topically applied medicaments & as ointment bases Olive oil Sesame oil Liquid paraffin Hard & soft paraffin Bees wax

70. Adsorbants & protectives Adsorbants  Finely powdered, inert & insoluble solids capable of binding to their surface (adsorbing) noxious & irritant substances Also called protectives because they afford physical protection to the skin or mucosa Other protect. form a continuous, adherent & flexible occlusive coating on the skin Demulcents & emollients also serve as protectives

71. Mg stearate, Zn stearate, talc, calamine, ZnO , starch, aloe vera gel, dimethicone & sucralfate are used as protectives Sucralfate is an Aluminium salt of sulfated sucrose used as PU protective Topical gel of Sucralfate applied on aphthous ulcers, burns, bedsores, excoriated skin, diabetic ulcers

72. Astringents Subst. that ppt. proteins but do not penetrate cells (affect the superficial layer only) Toughen the surface making it mech. stronger & decrease exudation Tannic acid Zn chloride ZnSO 4 AlCl 3 Ferric chloride

73. Incl. in several mouthwashes & dental gels to afford symptomatic relief & promote healing of oral lesions as well as to ↓ dentine sensit . & gum bleeding Alc. unsuitable for use in mouth (burning sens. ); rubbed on skin to prev. bedsores Other uses Bleeding piles Antiperspirant / deodorant

74. Caustics Corrosive chem. causing local tissue destr . & sloughing Conc. solns . of AgNO 3 , ZnCl 2 , Phenol, Trichloroacetic acid & Podophyllum resin are used to remove moles, warts, papillomas & necrotic material (To be applied carefully on the lesions only)

75. Use is limited in dentistry Occasional applic . on aphthous ulcers AgNO3 painted on exposed necks of teeth can reduce dentine sensitivity (not favoured due to black staining) Carefully applied trichloroacetic acid can reduce pain of pericoronitis