Antimicrobials and Astringents

Mechanisms of action:

 Can be divided into 3 general categories: oxidation, halogenation and protein precipitation:
represent the primary reactions that occur between the agent and the microbial protein can result
in the death of microbe or inhibit growth
 Site of action of inorganic compounds are non-specific
1. Oxidation

 Capable of functioning as antimicrobial agents through oxidative mechanism

 H2O2, metal peroxides, permanganates, halogens, certain oxohalogen anions
 Effective oxidative action: reducing groups present in most proteins (ex. Sulfhydryl –SH)
 Formation of the disulfate bridge will alter the protein’s function
 Overall change or destruction of function is responsible for the ultimate destruction of the microorganism
 Chemical result of oxidizing the protein is reduction of the antimicrobial agent
2. Halogenation

 Reaction occurring with antiseptic of the hypohalite type and hypochlorite, OCl -
 These types of compounds can serve as reagents in the chlorination of primary and secondary amides =
similar reaction can take place under appropriate conditions with the peptide linkage between the amino acid
groups comprising the protein molecule
 Substitution of chlorine atom for the hydrogen produces change in the forces (hydrogen bonding)
responsible for the proper conformation of the protein molecule; In oxidation: changes in confirmation
results in destruction of function
3. Protein Precipitation

 Involves the interaction of proteins with metallic ions having large charge/radius ratio or strong electrostatic fields
 Property is available in transition metal cations (Grp. I-B, Grp. II-B); Aluminum is also effective due to its charge
and small ionic radius
 Various polar groups on the protein act as the ligands
 Complexation of the metal results in the radical change in the properties of the protein or protein precipitant
 Interaction of metal ions with protein is non-specific, in specific concentration: will react with host as well as
microbial protein
 Protein precipitant properties of metal cations can be altered according to the concentration at the site of action
 By increasing concentrations, antimicrobial, astringent, irritant and corrosive properties are available
Astringent

 Application of very dilute solution of a metal cation to tissue primarily provides a local or surface protein
precipitant action
 Being a surface phenomenon, it doesn’t destruct tissue
 “shrinkage” or “firming” of tissues
Control of Antimicrobial/Astringent Action

 Largely non-specific in their actions and proteins

 Action is determined by the concentration
 Soluble compounds maybe controlled by making appropriate concentrations and by placing them in a
vehicle which will slow their release to the site
 For some compounds, this can be accomplished by placing then in solutions with glycerin
 Complexation with a ligand (Povidone-Iodine) also provides a controllesd release, minimizing toxicity and
activity at host cells
 Insolubility of the compounds makes the formulation of preparation somewhat easier from the standpoint of
controlling activity
Hydrogen Peroxide Solution USP 31
H2O2; 32.02

 Aka hydrogen Peroxide, Agua Oxigenada

 In each 100mL, n.l.t. 2.5g, n.m.t. 3.5g
 Clear, colorless liquid, maybe odorless or may have an odor resembling that of the ozone
 Acid to litmus, produces a froth in the mouth when tasted
 Pure: colorless, syrupy liquid with astringent properties
 When heated to 100˚C, pure hydrogen peroxide decomposes explosively to form water and oxygen
 Deteriorates upon standing and rapidly decomposes when in contact with many oxidizing/reducing
substances
Hydrogen Peroxide Solution USP 31
H2O2; 32.02

 To make it more stable: should be kept in a cool place protected from light and dust; preservatives such as
acetanilide is added; may be stabilized with any organic and inorganic acids
 Weak acid in aqueous solutions
 Complexing or chelating agents will chelate trace amounts of abundant metals, making them unable to
catalyze decomposition
 Adsorbents will remove impurities
Hydrogen Peroxide Solution USP 31
H2O2; 32.02

 Uses
 Mild oxidizing antiseptic
 Catalase: catalyzes the decomposition of Hydrogen peroxide to water and oxygen (evolution of O 2 gas = bubbling,
effervescence)
 Oxygen acts as oxidizing agents on bacteria
 Major difficulty: rapidity of oxygen release under the influence of catalase
 Antiseptic action does not penetrate below the surface to which it is applied
Hydrogen Peroxide Solution USP 31
H2O2; 32.02

 Uses
 Official solution: 3%, 10 volume solution; 6% (20mL) for hair and fabric bleach
 Undiluted for its antiseptic and cleansing effect on wounds
 Used as a gargle or mouthwash for bacterial infections of the throat and mouth
 Half-strengths: vaginal douche
 Tends to lose its antiseptic property when diluted to less than half-strength
Potassium Permanganate USP 31
KmnO4 158.04

 Aka Mineral Chamaleon

 Odorless, dark purple crystalline compound
 Crystals are almost opaque in transmitted light and of blue metallic luster in reflected light
 Concentrated solutions: deep violet-red color; highly diluted solutions: pink
 Solutions have a sweetish astringent taste
 Strong oxidizing agent both in dry state and solution
Potassium Permanganate USP 31
KmnO4 158.04

 “Caution: Observe great care in handling potassium permanganate, as dangerous explosions may occur if
brought in contact with organic or other readily oxidizable substances, either in solution or dry state”
 Dry state + charcoal = explosive mixtures
 Dry state + glycerin = fire
 Will also oxidize alcohol
Potassium Permanganate USP 31
KmnO4 158.04

 Acid solutions react to reduce the permanganate ion, MnO4- to the mangous ion (Mn2+) with the evolution of
oxygen
2KMnO4 + 3H2SO4 -> K2SO4 + 2MnSO4 + 3H2O + 5 (O)
 Neutral or alkaline solutions produce a similar reaction with the characteristic brown precipitate of MnO 2
2KMnO4 + H2O -> 2MnO2 + 2KOH + 3 (O)
 For therapeutic importance since potassium permanganate is usually applied to the skin as a neutral aqueous solution
Potassium Permanganate USP 31
KmnO4 158.04

 Antimicrobial action is dependent upon its oxidation of protein or other bio-organic substances in neutral
media
 Manganese dioxide formed as the permanganate is reduced, leaves a brown stain on the skin and tissues
 Activity is not selected
 Activity on microorganisms is decided diminished in the presence of extraneous organic substances
Potassium Permanganate USP 31
KmnO4 158.04

 Uses
 Not used for both antibacterial and antifungal actions
 Short duration of action, low penetrating power and slightly staining of the skin = preparation has been declined
 Solutions are primarily used for skin infections (dermatitis) caused by bacteria and fungi, for plant poisoning and
animal toxins
 Wet dressings prepared from a 1:10,000 solution for vesicular stage of eczema, athlete’s foot (Tine pedis) and fungal
infections (Groin: Tine curries)
 More effective when applied directly, dressing material might inactivate the permanganate
Chlorine-Containing

 Germicidal through the formation of HOCl

Sodium Hypochlorite Solution USP 31 NaOCl
72

 Aka Dakin’s Solution, Chlorinated Soda Solution

 Contains n.l.t. 4%, n.m.t. 6& by weight of NaOCl
 Clear pale greenish yellow liquid, having an odor of chlorine
 Solution is affected by light
 Alkaline pH coloring red litmus to blue, chlorine will later bleach the color
 Common household bleach: 4.5%-5.0% solution of NaOCl
 Disinfectant
 “Caution: this solution is not suitable for application to wounds”
 Alkalinity and oxidizing action is too strong for use on tissue; dissolves blood clot and delay healing
Sodium Hypochlorite Solution USP 31 NaOCl
72

 Diluted form: Labarraque’s Solution; consists of sodium hypochlorite solution diluted with equal volume of
water (approx. 2.5% NaOCl); disinfectant for inanimate objects
 Loses active chlorine and product upon exposure to air
 Deterioration also takes place on keeping, heat and light
 Decomposed even by dilute and weak acid
 Primary component of Clorox
 Uses
 Laundry bleach
 Germicidal agent
Diluted Sodium Hypochlorite Solution

 Solution of chlorine compounds of sodium containing in each 100mL, n.l.t. 450mg, n.m.t. 500mg (0.5%) of
NaOCl
 Colorless or light yellow liquid, slight odor suggesting chlorine
 Prepared by diluting sodium hypochlorite solution with 5x the quantity of water and adjusting the pH with
5% solution of sodium bicarbonate = pH of 8.3 or less
 Due to reduced concentration and pH, resulting solution is used only for local application to tissues as an
antibacterial
 Dilution of household bleach does not normally meet the USP standards as an antiseptic because of the lack
of pH adjustment
Diluted Sodium Hypochlorite Solution

 Uses
 Antiseptic on pus-forming wounds
 Irritation solution for infections inside certain body openings
 Effective as an antiseptic and at removing necrotic tissue
 Disadvantage: dissolving certain types of sutures and dissolving blood clots and prolonging clotting time = secondary
hemorrhage
 Foot bath in prevention of various fungal infections
Other Chlorine-Containing Compounds

 Chlorinated Lime – Bleaching powder, chlorine of lime

 Chemically calcium chloride hypochlorite [CaOCl(Cl) ŸH 2O
 Product obtained by passing chlorite gas over slaked lime
 Has a distinct odor of chlorine
 Decomposes in the air to release hypochlorous acid
 Disinfectant in swimming pools and “sterile” rooms and as a bleaching agent
Other Chlorine-Containing Compounds

 Chloramines
 Organic amines with one or two chlorine atoms bonded to the nitrogen
 Slowly hydrolyze to release hypochlolous acid when dissolved in water
 Products are used as disinfectants and in the purification of drinking water (Chloramine-T and Halazone)
 Antimicrobial action is that when chlorine gas is dissolved in neutral or acidic water, hypochlorous acid is formed
 Cl2 + H2O -> HCl _ HOCl

 Basis of using chlorine as disinfectants

 Antimicrobial action is due to the presence of HOCl
Iodine USP 31 I 125.90

 Aka Iodinum, Jodum

 Heavy, grayish, black plates or granules, having a metallic luster and a characteristic penetrating odor
 Very slightly soluble in water (1 in 2950), soluble inalcohol (1 in 12.5) and in solutions of iodine, freely
soluble n carbon disulfate and chloroform
 Solubility in solutions of iodide (ex. Sodium iodide) is due to the formation of the triiodide (I 3-)
 Most notable chemical property in aqueous solution is that of a mild oxidizing agent; less reactive than
chlorine
 Oxidizing action is mediated through the formation of hypoiodous acid (HIO)
 I2 + H2O -> HI + HIO
 HIO -> HI + (O)
Iodine USP 31 I 125.90

 Free iodine is about six times more effective that hypoiodous acid, HIO
 Iodine will oxidize iron to form ferrous iodide = metal spatulas should be protected against pitting by using
weighing papers
 Toxicity of preparations containing free iodide is frequently mentioned and somewhat overstated
 Very active element and is therefore easily inactivated by organic materials in the GI tract; very little free iodine is
absorbed
 Most toxicity due to ingestion is a result of corrosive action of the element in the GI tract, producing abdominal
pains, gastroenteritis and bloody diarrhea
 Treatment involves gastric lavage with a soluble starch solution or administration of a 5% sodium thiosulfate
solution
 Starch solution forms a complex with the iodine, thus aiding in its removal from starch (blue vomit)
Iodine USP 31 I 125.90

 Iodine Solution and Iodine Tincture: most frequently used preparations for antimicrobial purposes
 In each 100mL, n.l.t. 1.8g and n.m.t. 2.2g of Iodine; n.l.t. 2.1g, n.m.t. 2.6g sodium iodide (NaI)
 Differ only in the nature of the solvent: Iodine Solution is aqueous having been prepared with purified water, Iodine
Tincture contains approx.. 50% alcohol as the final solvent
 Transparent, reddish brown color, characteristic odor of iodine (Iodine Tincture has an alcohol odor)
 Active antimicrobial agent common to both is iodine
Iodine USP 31 I 125.90

 Uses
 Most effective topical antiseptic agents available
 Antiseptics to skin prior to surgery
 Iodine Tincture may be more suitable for surgery since alcohol seems to improve penetration of the iodine due to a “wetting”
or spreading effect
 Can be diluted with water to provide effective solutions or reduced concentration for wounds
 Alcohol in tincture is very irritating to open wounds = reason for stinging
 Effective against bacterial and fungal infections of the skin
 Tincture: disinfect drinking water; 3drops/quart will destroy amoebae and bacteria in 15 minutes
 Both are available in official concentration (2%) and can be diluted to 0.5% to 1% for application to wounds and 0.1% for
irrigation
Povidone-Iodine USP 31

 Complex of iodine with povidone (polymer also known as polyvinylpyrrolidone or PVP)

 Contains n.l.t. 9& n.m.t. 12% of available iodine
 Yellowish brown amorphous powder and has a slight characteristic odor
 Aqueous solution is acid to litmus
 Insoluble in organic solvents
 Member of a class of compounds referred to as iodophors
 Iodophors: complexes of iodine, with carrier organic molecules serving as solubilizing agent; these complexes
slowly liberate iodine in solution
 Development of iodophore: effort to prepare less irritating iodine products without losing antimicrobial
effectiveness
Povidone-Iodine USP 31

 Uses
 Same uses as iodine solution and tincture
 Not to be as effective as aqueous or alcoholic solutions of elemental iodine
 Major advantage: lack of tissue irritation = useful for application to sensitive areas and mucous membranes
 Solutions are recommended for surgical scrubs and preoperative antisepsis of the skin
 Used in gargles and mouthwashes for the treatment of infections in the oral activity (Vincent’s angina)
 Aerosol: 0.5%; solutions: 1%; surgical scrub: (0.75%); vaginal douche (1%)
Silver Nitrate USP 31
AgNO3; 169.87

 Aka Azotas Argentious, Cristales Lunares

 Colorless or white crystals which become gray or grayish black on exposure to light in the presence of
organic matter
 Sparingly soluble in alcohol
 When a protein is treated with a solution containing a soluble silver salt, a heavy ppt is formed involving a
complex interaction between the silver ions and proteins; this type of reaction is the basis for the direct
antimicrobial action of silver compounds
 The protein precipitant action of silver is not selective and will precipitate both bacterial and human protein
 Antibacterial, astringent, irritant, corrosive (depending upon the concentration applied)
Silver Nitrate USP 31
AgNO3; 169.87

 When applied to tissues: 0.1% Ag+; activity is rapidly bactericidal; action is somewhat localized due to
precipitation with tissue proteins and chloride ions in the tissue fluids; bactericidal effect continues after the
initial application due to slow production of silver ions from the silver proteinate and silver chloride… this
sustained action at the tissue level has given rise to colloidal products of silver proteinate and halides as
antimicrobial
 Silver: olilgo-dynamic action = active in small quantities; found in distilled water that has been in contact
with metallic silver = bactericidal to suspentions heavy in viable organisms
 Leathal action required a few hours, but water treated in this way, eg distilled through silver condenser, will
remain sterile for a long period of time
Silver Nitrate USP 31
AgNO3; 169.87

 Extended use of silver preparations = darkening of the skin due to the deposition of free silver below the
epidermis (arygria)
 Uses
 Antimicrobial in solutions ranging in concentration from 0.01% to 10%
 Higher/10%: astringent and irritant properties to the tissue
Silver Nitrate Ophthalmic Solution USP 31

 1% solution for instillation into the eyes of newborn babies

 Silver salts: effective against gonococcal organisms
 Two drops of this solution are placed in each eye as a prophylactic measure against infections produced by
these organisms (Ophthalmia Neonatorum)
 Shown to be more effective than antibiotics such as penicillin
 USP allows buffering of the Ophthalmic Solutions with sodium acetate and the ph should be between 4.5 and
6
Silver Nitrate Ophthalmic Solution USP 31

 Available in wax capsules containing about 0.3mL, should be discarded after use
 Most recent important use: application of 0.5% aqueous solution in the form of wet dressing on burned areas
of patients suffering from third degree burns, because silver ion seemed to be particularly effective at
reducing infection due to Staphylococcus aureus, varius species of Proteus and Pseudomonas aeruginosa
 Side effects: electrolyte imbalance due to the precipitation of chloride
Toughened Silver Nitrate USP 31

 Aka Lunar Caustic, Silver Nitrate Pencils

 Made by adding to silver nitrate 4% of its weight of HCl, melting the micture at a low temp. as possible and
casting in silver molds
 Presence of about 5% silver chloride toughens the silver nitrate = lessens the friability of the pencils
 Used as escharotic and germicide for small septic wounds and ulcers
Ammoniated Mercury USP 31
Hg(NH2)Cl 252

 Aka White Precipitate

 White, pulverizable pieces or as white, amorphous powder, odorless, stable in air, darkens on exposure to
light
 Readily dissolves in HCl, HNO3, HAc
 Prolonged contact with water = formulation of a yellow basic compound which necessitates the use of oils in
lotions
Ammoniated Mercury USP 31
Hg(NH2)Cl 252

 Antiseptic action of mercury on microorganisms and body tissues is due to the mercuric ion, which will react
with many polar group on the amino acids of proteins but has a particular affinity for sulfhydryl (-SH)
groups
 Inhibition of bacterial sulfhydryl containing enzymes by the metal ions = inhibition in metal growth and
function
 Uses
 Local anti-infective
 Topically: 5% ointment to skin
 3% ophthalmic ointment to conjuctivas
 Not given internally because of its toxicity
Sublimed Sulfur USP 31

 Aka Flowers of Sulfur, Azufre

 Fine, yellow, crystalline (rhombic) powder, faint color and taste
 One gram dissolves slowly and usually incompletely in about 2mL of carbon disulfide
 Obtained by condensing the sulfur vapors produced by heating any form of sulfur
Precipitated Sulfur USP 31

 Aka Milk of Sulfur

 Prepared by micing sulfur with metal hydroxides to form mixtures of metal sulfides and thiosulfates; sulfur
can be precipitated by addition of acid such as HCl
 Very fine, pale yellow, amorphous or rhombic powder without odor or taste
 Solubility in carbon disulfide is the same with sublimed sulfur
Precipitated Sulfur USP 31

 Uses
 Both forms: scabicides
 Used in Sulfur Ointment USP at a concentration between 9.5% to 10.5%
 Treatment of scabies, kills the mite sarcoptes scabiei
 Sulfur: dermatological agent in the treatment of seborrhea (abnormal secretion of sebum… oily/scaly appearance to
the skin), acne, psoriasis, etc
 Keratolytic agent
 Activity of sulfur is one of loosening and softening horny elements and the scaly formation of sebum and removing
them from site = symptomatic treatment for many dermatological problems
Sulfurated Potash

 Aka Liver of Sulfur

 Mixture composed chiefly of potassium polysulfides and potassium thiosulfate
 N.l.t. 12% of sulfur n combination as sulfide
 Irregular, liver brown pieces when freshly made, changing to a greenish yellow color
 Odor of hydrogen sulfide and bitter, acrid and alkaline taste
Sulfurated Potash

 Uses
 Official as a pharmaceutical aid as a source of sulfide
 Used in the preparation of White lotion
 As a parasiticide (scabicide)
 Treatment of acne and psoriasis
Selenium Sulfide

 N.l.t. 52%, n.m.t. 55.5% of selenium

 Bright orange powder, no more than a faint odor
 Insoluble in water and organic solvents
 White selenium: toxic in large quantities; appears to be an important nutrient in trace amounts
 Selenium is not well absorbed through the skin = topical application to limited areas of unbroken, unirritated
skin will not usually result in selenium toxicity
Selenium Sulfide

 Uses
 Used in shampoos in concentration 1% to 2.5% as an anti-seborrheic
 Normal method is applying topically on the scalp and letting it stay there for 5 minutes before washing it out
 Hands should be thoroughly washed and fingernails meticulously cleanses after due to the danger of introduction into
the eyes
Antimony Potassium Tartrate USP 31
(SbO)KC4H5O6Ÿ 1/2H2O

 Aka Tartar Emetic

 Formaly used as an emetic and expectorant (Brown Mixture)
 Official category and only rational use is as treatment of schistosomiasis
 Drug of choice in infections produced by Schistosma japonicum
 Stibophen: effective against Schistosoma haematobium and Schistosoma mansoni but less effective against
Schistosoma japonica
 May be given orally but intravenous doses are more effective