CHAPTER 6: ANTI-INFECTIVE AGENTS
Anti-infective
- Agents used to counteract or prevent infection
Joseph Lister
 (1867) introduces antiseptic principles for use in
surgery and posttraumatic injury
 Phenol (carbolic acid)
Paul Ehrlich
 “magic bullets”
 Selective toxicity
 Main tenet of modern
chemotherapy
 Compound 606
 Antisyphilitic drug Salvarsan
Hand washing
- Most important means of preventing transmission
of infectious agents
Antisepsis
Decontamination
Disinfection
antimicrobial
Most successful anti-infective agents
 Mercury, arsenic, antimony
 Sodium arsanilate and arsphenamine
 Used for sleeping sickness
 Dyes (gentian violet, methylene blue)
 Chemical congeners of the quinine molecule
 Sulfonamides and sulfones
 Hexachlorophene
Germicides – anti-infective agents that are used locally
(-cidal) – kill
(-static) – prevent the growth
Ideal antiseptic
 Exert a rapid and sustained lethal action against
microorganisms
 Have a low surface tension
 Retain activity in the presence of body fluids
 Non-irritating to tissues
 Non-allergenic
 Lack systemic toxicity when applied to skin or
mucous membranes
 Should not interfere with healing
Disinfectant
- Prevents transmission of infection by the
destruction of pathogenic microorganisms when
applied to inanimate objects
Ideal disinfectant
 Rapidly lethal action
 Soaps
 Not activated by living tissue
 Noncorrosive
 Aesthetically pleasing (nonstaining and odorless)
Sanitization
Sterilization
Pasteurization
Application of an agent to living tissue
for the purpose of preventing infection.
Destruction or marked reduction in the
number or activity of microorganism.
Chemical or physical treatment that
destroys most vegetative microbes or
viruses, but no spores, in or on
inanimate surfaces.
Reduction of microbial load on an
inanimate surface to a level considered
acceptable for public health purposes.
A process intended to kill or remove all
types of microorganisms, including
spores, and usually including viruses
with an acceptably low probability of
survival.
A process that kills nonsporulating
microorganisms by hot water or steam
o
o
at 65 C-100 C.
Evaluation of the effectiveness of sterilants
 Resistance of microbe
 Microbial load
 Mixture of microbial population
 Organic material present
 Concentration
 Stability
 Time and temperature
 pH
 hydration
 binding to surfaces
 Environmental Protection Agency (EPA)
 regulates disinfectants and sterilants
 Food and Drug Administration (FDA)
 regulates antiseptics
Common contaminants:
 Pseudomonas aeruginosa
 Serratia marcescens
ALCOHOLS AND RELATED COMPOUNDS
 Antibacterial potencies of primary alcohols (tested
against S. aureus) increase with MW up to C8
 Branching decreases antibacterial potency
 Primary > secondary > tertiary
CCS
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Ethyl alcohol, hydrated oxide of ethyl, spirit of wine
 Proof of 160 or more
X whiskey, brandy, rum, or gin
Uses
 Antiseptic
 Preservative
 mild counterirritant
 solvent
 mild local anesthetic
 mild sedative
 carminative
Preparations: spirits (ethanol as the solvent),
tinctures (hydroalcoholic mixtures), fluidextracts
(alcohol as cosolvent)
Ethanol
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Ethyl alcohol, wine spirit, hydrated oxide of ethyl
Clear, colorless, volatile liquid with a burning taste;
pleasant odor
Flammable, miscible with water
Soluble in organic
Commercial ethanol
 95% ethanol
 Forms an azeotrope with water that distils at
78.2oC
Fermentation from grain and carbohydrates
Prepared by sulfuric-acid-catalyzed hydration of
ethylene
Injected near nerves and ganglia to alleviate pain
Low narcotic potency
Mild sedative
Weak vasodilator
carminative
Denaturated alcohol
 Unfit for intoxicating beverages
Completely denaturated alcohol
 Contains wood alcohol (methanol) and benzene
 Unsuitable for internal or external use
Specially denaturated alcohol
 Treated with one or more substances
 Examples:
tincture
of
iodine,
methanol,
mouthwashes and aftershave lotions, methanol in
alcohol for plant extracts
Rubbing alcohol
 Use: astringent, rubefacient, mild local anesthetic
Acetaldehyde
 N, V, flushing
 Antidote: disulfiram
 Blocks aldehyde dehydrogenase
Dehydrated ethanol
 Absolute ethanol
 Not less than 99% w/w of C2H5OH
 Prepared by azeotropic distillation of an ethanolbenzene mixture
Isopropyl alcohol
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2-propanol
Substitute for ethanol
Disinfectant
Prepared by sulphuric-acid-catalyzed hydration of
propylene
Bactericidal in the concentration range of 50% to
95%
40% concentration = 60% ethanol
Azeotropic isopropyl alcohol
 Gauze pads, toiletries
Used commercially instead of n-propyl alcohol,
because it is less expensive
Slightly more active than ethyl alcohol against
vegetative bacterial growth, but both alcohols are
largely ineffective against spores
Ethylene oxide
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Liquefies at 12oC
Sterilize temperature-sensitive equipment
pharmaceuticals
Explosive in air??  add carbon dioxide
Carboxide - 10% E.O. + 90% CO2
MOA: alkylating agent
and
ALDEHYDES
Formaldehyde
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IUPAC name: methanol
Formalin NLT 37% w/v of formaldehyde with
methanol (retards polymerization)
Oxidation  PARAFORMALDEHYDE
Polymerization  FORMIC ACID (methanoic acid)
CCS
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Irritating to mucous membrane, contact dermatitis,
carcinogenic
Glutaraldehyde
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Cidex, a 5C dialdehyde
Used as sterilant for equipment and instrument
Stabilized in alkaline solution
Preparation: glutaraldehyde and buffer
Activated: 2% glutaraldehyde buffered at pH 7.5 to
8.0
Nonbuffered: acidic
PHENOLS AND THEIR DERIVATIVES
 Remains the standard to which the activity of most
germicidal substances is compared
 Phenolic coefficient
 Ratio of a dilution of a given test disinfectant to
the dilution of phenol that is required to kill a
strain of Salmonella typhi
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Antipruritic in phenolated calamine lotion (0.1%-1%
concentrations)
 Almost obsolete
Liquified phenol
 Phenol with 10% water
 Can be measured and transferred easily
p-Chlorophenol
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Combination with camphor in liquid petrolatum as
an external antiseptic and anti-irritant
p-Chloro-m-xylenol
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Metastep, 2% shampoo
Tx of tinea (ringworm) infections
Hexachlorophene
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Biphenol
Greater potency than a monophenol
2% to 3% in soaps, detergent creams, lotions and
shampoos
Cresol
 Alkyl, aryl, halogen (para position)
 Straight-chain > branched
 MOA
 low conc  protein denaturation
 high conc  membrane lysis
Phenol
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carbolic acid
colorless to pale-pink crystalline
“medicinal odor”
General protoplasmic poison
Caustic
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Mixture of methylphenols
Obtained from coal tar, inexpensive but has
unpleasant odor
Chlorocresol
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4-chloro-3-methylphenol
Preservative
CCS
Thymol
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Tx of oral ulcerations or in dental care
Hydrous Benzoyl Peroxide
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Isopropyl m-cresol
From oil of Thymus vulgaris (thyme, mint family)
Use: mild fungicidal properties and dusting powders
Eugenol
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In pure powder form  explosive
+ 30% water to make it safer
Keratolytic and keratogenic (thickness of the skin)
Induces proliferation of epithelial cells
Tx of acne
HALOGEN-CONTAINING COMPOUNDS
Povidone-Iodine (Betadine)
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4-allyl-2-methoxyphenol
From clove oil (Syzygium aromaticum)
Use: local anesthetic and antiseptic, toothaches,
mouthwashes
Resorcinol
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m-Dihydroxybenzene (resorcin)
antiseptic and keratolytic (causes stratum corneum
to slough)
Hexylresorcinol
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Sensation of numbness to the tongue
Antiseptic (bactericidal, fungicidal)
Local anesthetic
Formulated in throat lozenges
OXIDIZING AGENTS
 MOA: active liberate oxygen in the tissues
 Effective against anaerobic bacteria
 Bubbles dislodge debris
 Example: hydrogen peroxide and potassium
permanganate
 Limitation:
 Poor penetrability
 Transient effect
Iodophors - active complexes of iodine with reduced
volatility and irrittating property
Example:
 Iodine + PVP (polyvinylpyrrolidone)
 Nontoxic
 Non-volatile
 Non-staining
 Non-irritating
CHLORINE-CONTAINING
 used in water disinfection
 example: NaOCl and Ca(OCl)2
 MOA:
1) Chlorination of amide
2) Oxidation of –SH in proteins
 Optimal effect at pH 7
IODINE-CONTAINING
Elemental iodine – oldest germicide
Iodine tincture – 2% iodine in 50% alcohol
Strong iodine solution – 5% iodine in water
Iodine solution – 2% iodine in water
Kl or NaI is added to:
 Increase solubility of iodine
 Reduce its volatility
Halazone
Carbamide Peroxide
 Gly-Oxide
 Stable complex of urea and hydrogen peroxide
CCS
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P-Dichlorosulfamoylbenzoic acid
Photosensitive
Very soluble in alkaline solutions
Drinking water disinfectant
Methylbenzethonium Chloride
 Tx of diaper rash (C. albicans)  NH3
Benzethonium Chloride
 Similar to benzalkonium chloride
Chloroazodin
Cetylpyridinium Chloride
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N,N-Dichlorodicarbonamidine
Insoluble in water
Unstable in light or heat
Use: lavage and irrigation, wound dressing
Long lasting because of its extremely slow reaction
with water
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Q. nitrogen is replaced with aromatic pyridine ring
Most active in a series of alkylpyridinium
compounds
Chlorhexidine Gluconate
Oxychlorosene Sodium
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Slowly release HOCl
Rapid-cidal effect
Treat localized infections
Remove necrotic tissues
Counteract odorous discharge
CATIONIC SURFACTANTS
 Quaternary ammonium compounds
 Has surface-active properties due to polar head and
non-polar tail
 Resistant to spores
 MOA: dissolution of cell membrane 
destabilization  lysis
Advantages:
 Highly water-soluble
 Non-toxic
 Stable
 Non-staining
 Non-corrosive
 Good penetration
Disadvantages:
 Inactivation by soaps and anionic detergent
 Tissues debris, blood, serum reduce activity
 Adsorbed a glass, talc
 Slower action than iodine
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Most active of a series of antibacterial biguanides
Technically NOT a quaternary ammonium
compounds
Similar properties to cationic surfactants
DYES
 Colorless LEUCOBASE in alkaline condition
 Cationic dyes are effective for gram (+)
Gentian Violet
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Crystal violet, methyl violet
Vaginal suppositories for yeast infections
Orally as anthelminthic
Basic Fuchsin
 A component of carbol-fuchsin solution (Castellani’s
paint)
 Topical – tx of ringworm (athlete’s foot)
Benzalkonium Chloride
 Antiseptic for skin and mucous membrane at
concentration 1:750 to 1:2000
CCS
Methylene Blue
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Tx of cystitis and urethritis
Bacteriostatic
Blue green urine and stool
MERCURIALS
Inorganic salts
 Mercuric chloride (corrosive sublimate)
 Mercurous chloride (calomel)
 Ammoniated mercury
 Mercury oxide
 Compatible with other constituents
 Stable
Parabens
 Esters of p-hyroxybenzoic acid
 Antifungal
 Low toxicity with humans
 Undergo rapid hydrolysis
 Activity increases with MW
 Methylparaben – molds
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Limitations:
 Low water solubility
 Irritations
 Hypersensitivity reactions
Organomercurials
1) Non-ionizable (Hg-C)
2) Ionizable (Hg bonded to O, N, S)
 More lipid soluble
MOA: covalent bonding with –SH in proteins
 Reversed by:
 Cysteine
 Dimercaprol (Minamata poisoning)
(BAL) British Anti-Lewisite
 Bacteriostatic effect
 Inactivated by serum
 Not very effective on spores
Nitromersol (methapen) and Thimerosal (Merthiolate)
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Non-irritating to mucous membranes
Nonstaining
PRESERVATIVES
 Added to preparations to prevent microbial
contamination
 Maintain sterility in parenteral and ophthalmic
preparations
Propylparaben – yeast; preferred for drugs in oil
or lipophilic bases
Butylparaben
Ethylparaben
Chlorobutanol
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Bacteriostatic
Unstable in heat, pH >7
Benzyl Alcohol
 Unesterified form in oil of Jasmin
 Esterified form in gum benzoin, storax resin, peru
balsam, tolu balsam
 Commonly used in injectable vials (1-4%)
 Local anesthetic
Phenylated Alcohol
 Orange oil, rose oil, pineapple oil
 Used in perfumery
Benzoic Acid
An ideal preservative
 Effective at low concentration
 Non-toxic
CCS
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Gum benzoin, peru balsam, tolu balsam
White crystalline solid
Slightly soluble in water
Antiseptic
Preservative at low pH
Sodium Benzoate
 Preservative in acidic pH
 Benzoic acid is released
Sodium Propionate
 Most effective at low pH
Sorbic Acid
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2,4-hexadienoic acid
Used in syrups, elixirs, ointements and lotions
Potassium Sorbate
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Same as sorbic acid but more water soluble
Phenymercuric Nitrate
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Efficacy reduced in the presence of serum
Phenylmercuric Acetate
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Occurs as white prisms
CCS