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Antimicrobials and

Astringents
Mechanisms of action:
• Can be divided into 3 general categories:
• Oxidation
• Halogenation
• protein precipitation
• These are the primary reactions that occur between the agent and the microbial protein can
result in:
• death of microbe
• inhibit growth
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-
• 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
• 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 O2 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 MnO2
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)ŸH2O
• 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 hypochlorous 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 in alcohol (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 (I3-)
• 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: oligo-dynamic action = active in small quantities; found in distilled
water that has been in contact with metallic silver = bactericidal to
suspensions heavy in viable organisms
• Lethal 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 (argyria)
• 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, various
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
mixture 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 conjunctivas
• 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 mixing 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
Asringents

• Protein precipitants with limited penetrating power


• Coagulate protein primarily on the cell surface
• Uses:
• Styptic
• Stop bleeding by coagulation and constrictions of small capillaries
• Antiperspirant
• Constriction of pores = decrease secretion of perspiration
• Restriction of blood supply by reducing inflammation
• Remove unwanted tissue
• Requires higher concentration
• Corrosive
Alum
• Aka: Tawas; ammonium alum, potassium alum
• Large, colorless crystals, crystalline fragments or as white powder
• Odorless and has sweetish, strongly astringent taste
• Freely soluble in water, slowly soluble in glycerin
Alum
• Uses
• Source of aluminum ion
• Topical astringent
• High concentration = Irritant and caustic
• Footbaths
• Toughening the skin and avoid formation of blisters
• Active ingredient in styptic pencils
• Preparation of biologic product due to its protein precipitant property
• e.g diphtheria and tetanus toxoids
Aluminum chloride
• White or yellowish white deliquescent, crystalline powder
• Odorless, sweet, very astringent taste
• Very soluble in water, freely soluble in alcohol and soluble in glycerin
Aluminum chloride
• Hydrolysis of the salt and forming acidic solution = Irritating property
• Adjustment of pH to neutral
• Decrease irritating property
• Decrease concentration of aluminum ion
• Decrease astringent property
Aluminum chloride
• Uses:
• Local external astringent
• Mild antiseptic
• Usually used in aq. Solution in 10-25%
• Initially used as antiperspirant but found to be irritating to sensitive
tissue and also damaged clothing
• Formation of HCl by hydrolysis
• it was replaced by aluminum hydrochloride Al(OH)Cl2
Other Aluminum-Containing Astringents
• Aluminum sulfate
• Aka: cake alum, pickle alum, pearl alum, papermaker’s alum
• Aluminum acetate solution
• Aka: Burrow’s solution
• Zinc Chloride
• Aka: Butter of Zinc
• Use: astringent and dentin desensitizer; escharotic
• Zinc sulfate
• Aka: White vitriol
• Use: ophthalmic solution but requires addition of buffer

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