ppt anti-infective agents Flashcards
GERMICIDES
Anti-infective agents that are used locally.
GERMICIDES
Subtypes:
Antiseptics
Disinfectants
Antiseptics
are compounds that kill (-cidal) or
prevent the growth of (-static) microorganisms
when applied to living tissue.
Disinfectants
are agent that prevents transmission
of infection by the destruction of pathogenic
microorganisms when applied to inanimate objects.
THE IDEAL ANTISEPTIC
- Must have low-enough toxicity
- Must exert a rapid and sustained lethal action against microorganisms
- Should have a low surface tension
- Should retain activity in the presence of body fluids
- Nonirritating to tissues
- Nonallergenic
- Lacks systemic toxicity when applied to skin or mucous membranes
- Does not interfere with healing
Examples: bacitracin, polymyxin, silver sulfadiazine, neomycin
THE IDEAL DISINFECTANT
- Exerts rapid lethal action against all potentially pathogenic
microorganisms and spores - Good penetrating properties into organic matter
- Compatible with organic compounds (particularly soaps)
- Not inactivated by living tissue
- Noncorrosive
- Aesthetically pleasing (non-staining and odorless)
anti-sepsis
application of an agent to living tissues for the purpose of preventing infection
decontamination
destruction or marked reduction in the number or activity of microorganisms
disinfection
chemical or physical treatment that destroys most vegetative microbes or viruses, but not spores, in or on inanimate surfaces
sanitation
reduction of microbial load on an inanimate surface to a level considered acceptable for public health purposes
sterilization
a process of intended to kill or remove all types of microorganisms, including spores, and usually including viruses with an acceptably low probability of survival
pasteurization
a process that kills nonsporulating microorganisms by hot water or steam at 65deg-100dec C
Structural Activity Relationship (SAR)
Primary Alcohol (against S. aureus)
- Activity increases with molecular weight
- As chain length increases, van der Waals
interactions increase, and the ability to
penetrate microbial membranes increases. - As water solubility decreases, the apparent
antimicrobial potency diminishes with
molecular weight - Branching of the alcohol chain decreases
antibacterial potency.
1 alcohol> 2 alcohol> 3 alcohol
alcohol MOA
protein & carbohydrate denaturation
protein denaturation
Alcohols disrupt hydrogen bonding in proteins, leading to denaturation and loss of function.
They interfere with the tertiary and quaternary structures of enzymes and structural proteins, making them non-functional.
Denatured proteins can aggregate, leading to cellular dysfunction and death.
Carbohydrate Denaturation
Alcohols can alter cell wall polysaccharides, disrupting the integrity of bacterial cell walls.
This weakens the peptidoglycan layer in S. aureus, making the bacteria more susceptible to osmotic stress and lysis.
Alcohols may also interfere with carbohydrate-based cell signaling and adhesion, preventing proper bacterial function.
ETHANOL (Ethyl Alcohol, Wine Spirit)
- A product of fermentation from grain and many other carbohydrates.
- by synthetic sulfuric-acid–catalyzed hydration of ethylene
Definition of Alcohol (US)
means that substance known
as ethyl alcohol, hydrated oxide of ethyl, or spirit of wine, from whatever source or whatever process produced, having a proof of 160 or more and not including the substances commonly known as whiskey, brandy, rum, or gin.”
Denatured Alcohol (methylated spirits or denatured rectified spirit)
is ethanol that has been rendered unfit for use in intoxicating beverages by the addition of other substances.
Completely denatured alcohol
contains added wood alcohol (methanol) and benzene and is unsuitable for either internal or external use.
Specially denatured alcohol
is ethanol treated with one or more substances so that its use may
be permitted for a specialized purpose.
Specially denatured alcohol Examples:
iodine in alcohol for tincture of iodine, methanol, and other substances in
mouthwashes and aftershave lotions, and methanol in alcohol for preparing plant extracts.
Primary Medicinal Use of Alcohol
Externally used as:
- Antiseptic
- Preservative
- Mild counterirritant
Rubbing alcohol is used as
- Astringent
- Rubefacient
- Mild local anesthetic.
Ethanol
- has even been injected near nerves and ganglia to alleviate pain.
- has a low narcotic potency
- has been used internally in diluted form as a mild sedative, a weak vasodilator, and a carminative.
The accepted bactericidal concentration of 70% alcohol is not supported by a study that discovered that the kill rates of microorganisms suspended in alcohol concentrations between 60% and 95% were not significantly different.
alcohol concentrations between 60% and 95% exhibit similar kill rates for microorganisms.
Concentrations of alcohol below 60% are also effective, but
longer contact times
are necessary.
alcohol concentrations above 70% can be used
safely for preoperative
sterilization of the skin
metabolism of alcohol
Step 1:
Ethanol to Acetaldehyde
Enzyme: Alcohol dehydrogenase (ADH)
Acetaldehyde is
a toxic compound responsible for hangover symptoms like nausea and headaches.
metabolism of alcohol
Step 2:
Acetaldehyde to Acetate
Enzyme: Aldehyde dehydrogenase (ALDH)
Antabuse (disulfiram)
inhibits aldehyde dehydrogenase (ALDH), leading to the buildup of acetaldehyde, a toxic intermediate in alcohol metabolism.
DEHYDRATED ETHANOL (absolute ethanol)
- Contains not less than 99% w/w of C2H5OH
- Prepared by azeotropic distillation of an ethanol–benzene mixture (water-free).
- Primary use: Chemical Reagent or Solvent
*NOT INGESTED!
Dehydrated Ethanol (Absolute Ethanol) – Why Is It NOT for Ingestion?
*contains not less than 99% w/w of ethanol (C₂H₅OH) and is prepared by azeotropic distillation using benzene to remove all water
*1. Toxicity Due to Benzene Residue ☠️
Benzene is used in the final dehydration step to remove water.
Even in trace amounts, benzene is a highly toxic and carcinogenic substance.
- Highly Concentrated and Corrosive 🔥
99% ethanol is extremely dehydrating and damaging to tissues.
Can cause severe irritation to the mouth, throat, esophagus, and stomach.
High concentrations lead to rapid alcohol poisoning, affecting the central nervous system (CNS).
- Rapid Absorption and Overdose Risk 🚨
Absolute ethanol is absorbed too quickly, causing severe intoxication and possibly respiratory depression, coma, or death.
Unlike drinking alcohol (diluted ethanol, ~40% in beverages), the body cannot process pure ethanol safely.
- Industrial and Laboratory Use Only 🧪
Not intended for human consumption, mainly used as a solvent, disinfectant, or chemical reagent in research and industrial applications.
ISOPROPYL ALCOHOL (Isopropanol, 2-propanol)
- Considered a suitable substitute for ethanol in most cases but must not be ingested.
- prepared by the sulfuric-acid–catalyzed hydration of propylene.
ISOPROPYL ALCOHOL
- Antiseptic for the skin and disinfectant for surgical instruments.
- Rapidly bactericidal in concentration range of 50% to 95%.
- 40% concentration is considered equal in antiseptic efficacy to a 60% ethanol in water solution.
- Used in pharmaceuticals and toiletries as solvent and preservative.
ETHYLENE OXIDE (C2H4O)
- Mechanism of the germicidal action:
- Involves the alkylation of functional groups in nucleic acids and proteins by nucleophilic opening of the oxide ring.
ETHYLENE OXIDE (C2H4O) – Uses
- Used to sterilize temperature-sensitive medical equipment and certain pharmaceuticals that cannot
be heat-sterilized in an autoclave. - Ethylene oxide forms explosive mixtures in air at concentrations
ranging from 3% to 80% by volume. - Carboxide:
- Commercial sterilant containing 10% ethylene oxide and 90% carbon dioxide by volume.
FORMALDEHYDE SOLUTIONS (Formalin)
- Officially contains not less than 37% w/v of formaldehyde (HCHO) with methanol added to retard polymerization.
FORMALDEHYDE SOLUTIONS (Formalin)
Germicidal action:
- Believed to involve direct, nonspecific alkylation of nucleophilic functional groups (amino, hydroxyl, and
sulfhydryl) in proteins and nucleic acids. - TOXIC!
- Irritating to mucous membranes
- Causes hardening of the skin
- Can cause severe gastrointestinal distress
- Causes contact dermatitis
- Carcinogenic
GLUTARALDEHYDE Disinfectant Solution
- Glutaraldehyde (Cidex, a 5-carbon dialdehyde) is used as a dilute solution for sterilization of equipment and instruments that cannot be
autoclaved. - Stabilized in alkaline solution (2% buffered at pH 7.5-8.0)
Phenol, USP
- Remains the standard to which the activity of most germicidal substances is compared.
Phenolic Coefficient
- the ratio of a dilution of a given test disinfectant to the dilution of phenol that is required to kill (to the
same extent) a strain of Salmonella typhi under carefully controlled time and temperature conditions.
Phenolic Coefficient – Drawbacks
- Phenols and other germicides do not kill microorganisms uniformly, so variations in the phenol coefficient will occur.
- The conditions used to conduct the test are difficult to reproduce exactly, so high variability between different
measurements and laboratories is expected. - Several phenols are actually more bactericidal than phenol itself.
Phenol – Structural Activity Relationship
- Substitution with alkyl, aryl, and halogen (especially in the
para position) groups increases bactericidal activity. - Straight-chain alkyl groups enhance bactericidal activity
more than branched groups. - Alkylated phenols and resorcinols are less toxic than the
parent compounds while retaining bactericidal properties.
Phenol –MECHANISM OF GERMICIDAL ACTION
denature bacterial proteins at low concentrations,
where as lysis of bacterial cell membranes occurs at higher concentrations.
PHENOL (or Carbolic Acid)
- Considered a protoplasmic poison
- caustic to skin, exerts local anesthetic effects, & must be diluted to
avoid tissue destruction and dermatitis. - Introduced by Sir Joseph Lister as a surgical antiseptic in 1867, and it is still used occasionally as an antipruritic in
phenolated calamine lotion (0.1%–1% concentrations).
LIQUEFIED PHENOL
- Liquefied phenol is simply phenol containing 10% water.
- The liquid form is convenient for adding phenol to various
pharmaceutical preparations because it can be measured and transferred easily.
p-CHLOROPHENOL
- used in combination with camphor in liquid petrolatum as an
external antiseptic and anti-irritant. - Phenol coefficient: about 4.
p-Chloro-m-xylenol (PC-MX; Metasep)
- A nonirritating antiseptic agent with broad-spectrum antibacterial and antifungal properties.
- Marketed in a 2% concentration as a shampoo.
- It has also been used topically for the treatment of Tinea (ringworm) infections such as athlete’s foot (Tinea pedis) and jock itch (Tinea cruris).
HEXACHLOROPHENE
- IUPAC Name: 2,2-methylenebis (3,4,6-trichlorophenol); (2,2’-dihydroxy-3,5,6,3’,5’,6’ hexachlorodiphenylmethane
(Gamophen, Surgicon, pHisoHex)
GERMICIDAL ACTION
* A biphenol generally possesses greater potency than a monophenol.
* Increased degree of chlorination increases its antiseptic potency further.
- BANNED by FDA (as OTC)
CRESOL –
mixture of isomeric methylphenols
o-cresol
m-cresol
p-cresol
- Phenol coefficient of 2.5.
- Drawback: unpleasant odor
CRESOL – Derivative
Amylmetacresol (component of Strepsils)
CHLOROCRESOL (4-Chloro-3-methylphenol)
Chlorocresol is only slightly soluble in water. At the low concentration that can be achieved in aqueous media, the
compound is only useful as a preservative.
THYMOL
- Isopropyl m-cresol is extracted from oil of Thymus vulgaris
(thyme, of the mint family) - Thymol has mild fungicidal properties and is used in alcohol solutions and in dusting powders for the treatment of Tinea (ringworm) infections.
EUGENOL
- 4-Allyl-2-methoxyphenol is obtained primarily from clove oil.
- Has both local anesthetic and antiseptic activity and can be
directly applied on a piece of cotton to relieve toothaches. - Also used in mouthwashes
- The phenol coefficient: 4.4.
RESORCINOL
- m-Dihydroxybenzene (resorcin), or resorcinol
- Weak antiseptic (phenol coefficient 0.4).
- Nevertheless, it is used in 1% to 3% solutions and in ointments and pastes
in concentrations of 10% to 20% for the treatment of skin conditions such as
ringworm, eczema, psoriasis, and seborrheic dermatitis. - Keratolytic agent
HEXYLRESORCINOL
- 4-Hexylresorcinol, or “hexylresorcinol”
- Effective antiseptic (both bactericidal and fungicidal)
- The phenol coefficient: 98
- As is typical for alkylated phenols, it possesses surfactant properties.
- Has local anesthetic activity (formulated into throat lozenges)
OXIDIZING AGENTS
Germicidal Activity
- Depend on their ability to liberate OXYGEN in the tissues.
- Inorganic compounds (hydrogen peroxides, several metal peroxides, sodium perborate, etc)
- Protein denaturation in microorganisms
- KMnO4
- Effective against anaerobic bacteria and can be used in cleansing contaminated wounds.
- LIMITATIONS
- generally poor penetrability into infected tissues and organic matter.
- Action of the oxidizers is typically transient
CARBAMIDE PEROXIDE TOPICAL SOLUTION
- Carbamide peroxide (Gly-Oxide) is a stable complex of urea
and hydrogen peroxide. - Formula: H2NCONH2 H2O2
- Commercial preparation: 12.6%w/v carbamide peroxide in
anhydrous glycerin. - Used as both an antiseptic and disinfectant.
- Effective in the treatment of oral ulcerations or in dental care.
HYDROUS BENZOYL PEROXIDE
- Hydrous benzoyl peroxide (Oxy-5, Oxy-10, Vanoxide)
- In its pure powder form, it is EXPLOSIVE
- 5% & 10% concentrations, both used as keratolytic and keratogenic.
- It is used in the treatment of acne.
IODOPHORS
- Elemental iodine (I2)
- Iodine tincture (2% iodine in 50% alcohol with sodium iodide)
- Strong iodine solution (Lugol’s solution, 5% iodine in water with
potassium iodide) - Iodine solution (2% iodine in water with sodium iodide)
- One of the most effective and useful of the germicides.
IODOPHORS
GERMICIDAL ACTION
- It probably acts to inactivate proteins by iodination of aromatic residues (phenylalanyl and tyrosyl) and oxidation
(sulfhydryl groups). - Bactericidal and fungicidal
POVIDONE-IODINE
- Betadine, Isodine, polymer polyvinylpyrrolidone [PVP]–
iodine)
The complex is extremely water-soluble. - Soluble and releases iodine very slowly
- Used in presurgical disinfection of the incision site; to treat infected wounds and damage to the skin
- Effective for local bacterial and fungal infections.
CHLORINE-CONTAINING COMPOUNDS
- Inorganic
- HClO
- NaOCl
- Ca(OCl)2
- Organic:
- N-chloro compounds
CHLORINE-CONTAINING COMPOUNDS
Plausible mechanisms of germicidal action:
- Chlorination of amide nitrogen atoms and the oxidation of sulfhydryl groups in proteins.
- Optimal antiseptic effect at around pH7
HALAZONE
p-Dichlorosulfamoylbenzoic
* photosensitive compound
* halazone is used to disinfect drinking water.
CHLOROAZODIN
- N,N-Dichlorodicarbonamidine (Azochloramid)
- Unstable to light or heat (explodes above 155°C)
- Soluble enough in water to be used in very dilute solution to disinfect wounds, as packing for dental caries, and for lavage and irrigation.
- The antiseptic action of chloroazodin is long lasting because of its extremely slow reaction with water.
OXYCHLOROSENE SODIUM
- Oxychlorosene (Clorpactin) is a complex of the sodium salt of
dodecylbenzenesulfonic acid and hypochlorous acid. - Has rapid-cidal action against most microorganisms, including both Gram-positive and Gram-negative bacteria,
molds, yeasts, viruses, and spores.
CATIONIC SURFACTANTSQUATERNARY AMMONIUM COMPOUNDS
- Ionized in water and exhibit surface-active properties.
- The compounds, with a polar head group and nonpolar
hydrocarbon chain, form micelles by concentrating at the
interface of immiscible solvents. - The surface activity of these compounds, exemplified by
lauryl triethylammonium sulfate, results from two structural moieties:
(a) a cationic head group, which has a high affinity for water and
(b) a long hydrocarbon tail, which has an affinity for lipids and nonpolar solvents.
QUATERNARY AMMONIUM COMPOUNDS
- Benzalkonium Chloride
- Methylbenzethonium Chloride
- Benzethonium Chloride
- Cetylpyridinium Chloride
- Chlorhexidine Gluconate
DYES
- Cationic dyes are active against Gram-
positive bacteria and many fungi; Gram-
negative bacteria are generally resistant. - The difference in susceptibility is probably related to the cellular characteristics that underlie the Gram stain.
Gentian Violet/Crystal Violet/Methyl Violet
- Vaginal suppository for treatment of yeast infection and anthelmintic for strongyloides and oxyuriasis
- Strongyloides: feet penetration
Basic Fuchsin
Ingredient of carbolfuchsin (Castellani’s paint);
Treatment of fungal infection, ringworm and athletes foot
Methylene Blue
- At low conc – tx of methemoglobinemia
- At high conc – cause of methemoglobinemia
- Antidote for (CN-) cyanide poisoning (with NaNO2 and Na2S2O4)
INORGANIC MERCURY COMPOUNDS
- Elemental Mercury – syphilis
- Mercuric Chloride and Mercurous Chloride (Calomel) – antiseptic
- Ammoniated mercury [Hg(NH2)Cl] – for skin infections such as impetigo, psoriasis, and ringworm.
- Mercuric oxide – eye infection.
- NOT RECOMMENDED
ORGANIC MERCURY COMPOUNDS
- Employed as antiseptics, preservatives, or diuretics.
- Two general classes:
A. compounds with at least one carbon–mercury bond
a. does not ionize readily
B. compounds with mercury bonded to heteroatoms (e.g., oxygen, nitrogen, sulphur)
a. ionize partially or completely
MECHANISM OF GERMICIDAL ACTION
* Reacts with sulfhydryl (-SH) groups in enzymes and other proteins to form covalent compounds of the type R-S-Hg-R.
PRESERVATIVES
- Used to prevent microbial contamination and maintain sterility
- Ideal preservative:
- effective at low concentrations against all possible microorganisms;
- nontoxic and compatible with other constituents of the preparation; and
- stable for the shelf life of the preparation.
p-Hydroxybenzoic Acid Derivatives
*“Parabens”
* Have antifungal properties
* Activity generally increases with molecular weight, but the methyl ester is most effective against molds,
whereas the propyl ester is most effective against yeasts.
* The more lipid-soluble propyl ester is the preferred preservative for drugs in oil or lipophilic base.
p-Hydroxybenzoic Acid Derivatives
- Methylparaben
- Propylparaben
- Butylparaben
- Ethylparaben
PRESERVATIVES
Others
- Chlorobutanol
- Benzyl Alcohol
- Phenylethyl Alcohol
- Benzoic Acid
- Sodium Benzoate
- Sodium Propionate
- Sorbic Acid
- Potassium Sorbate
- Phenylmercuric Nitrate
- Phenylmercuric Acetate
alcohols
1- Ethanol (Ethyl Alcohol, Wine Spirit)
*Denatured Alcohol (methylated spirits or denatured rectified spirit)
*Completely denatured alcohol
*Specially denatured alcohol
2- DEHYDRATED ETHANOL (absolute ethanol)
- ISOPROPYL ALCOHOL (Isopropanol, 2-propanol)
- ETHYLENE OXIDE (C2H4O)
aldehydes
- FORMALDEHYDE SOLUTIONS (Formalin)
- GLUTARALDEHYDE Disinfectant Solution
PHENOLS and their Derivatives
- PHENOL (or Carbolic Acid)
- LIQUEFIED PHENOL
- p-CHLOROPHENOL
- p-Chloro-m-xylenol (PC-MX; Metasep)
- HEXACHLOROPHENE
- CRESOL – mixture of isomeric methylphenols
- CHLOROCRESOL (4-Chloro-3-methylphenol)
- THYMOL
- EUGENOL
- RESORCINOL
OXIDIZING AGENTS
- CARBAMIDE PEROXIDE TOPICAL SOLUTION
- HYDROUS BENZOYL PEROXIDE
HALOGEN CONTAINING AGENTS
- POVIDONE-IODINE
CHLORINE-CONTAINING COMPOUNDS
- HALAZONE
- CHLOROAZODIN
- OXYCHLOROSENE SODIUM
DYES
- Gentian Violet/Crystal Violet/Methyl Violet
- Basic Fuchsin
- Methylene Blue
made the first antiseptic to disinfect wounds and spray the air of his operating theater with carbolic acid steam
Joseph Lister
Antibacterial Dyes and Antiparasitic Organic Arsenicals
PAUL EHRLICH
Principle of Selective Toxicity
The property of certain chemicals to kill one type of organism
while not harming another.
* Antibacterial Dyes
* Organic Arsenicals
* Compound 606, Salvarsan
Paul Ehrlich
ANTI-INFECTIVE AGENTS
CLASSIFICATION
- Therapeutic indication
- Chemical type of the compound
- Biological property
ANTI-INFECTIVE AGENTS
CLASSIFICATION
- Local Anti-Infectives
- Preservatives
- Antifungal Agents
- Synthetic Antibacterial Drugs
- Antitubercular Drugs
- Antiprotozoal Agents
- Anthelmintics
- Antivirals
- Antineoplastic Antibiotics
