[02-MIDTERMS-MEDORG] ANTI-INFECTIVE AGENTS

John Lister

In 1867, he introduced phenol for antiseptic principles.

(Lister’s principle caused dramatic decrease in postsurgical infections).

Phenol (carbolic acid)

John Lister used this as wash for the hand.

Paul Erlich

Who is the Father of Chemotherapy?

Paul Erlich

Disciple of Robert Koch, began to work with set of antibacterial dyes and anti-parasitic organic arsenicals.

Anti-microbial activity

Paul Erlich’s goal is to develop compounds that retain _________ activity at the expense of toxicity to human host.

Magic bullets

These are antimicrobial agents that selectively attack pathogens without significant toxicity to the host.

Paul Erlich

Who discovered that the anti-microbial properties of dyes are parallel to staining activity (first demonstration of selective toxicity)?

Salvarsan

This is the first anti-syphilitic drug.

Compound 606

Salvarsan is also known as?

Selective Toxicity

Main tenet of modern antimicrobial therapy.

• The property of certain chemicals to kill one type of organism while not harming other.

1920s

What year is the most successful anti-infective agents based on Group-IIB element mercury and the Group-VA elements arsenic and antimony.

Group-IIB element mercury and the Group-VA elements arsenic and antimony

These are the basis for anti-infective agent.

H.W Thomas

In 1920, when he discovered the most successful anti-infective agents based on the group-IIB element mercury and the group-VA element arsenic and antimony, Atoxyl.

Atoxyl

Sodium arsanilate and arsphenamine was used for sleeping sickness and these are drugs derived from synthetic dyes.

• Gentian violet

• Methylene blue

What are some examples of dyes where atoxyl was discovered?

Atoxyl

Somewhat effective were a few chemical conjurers of the quinine molecule.

Some of these agents represented significant achievements in anti-infective therapy but they also possess some important limitations.

• Mercury

• Arsenic

• Antimony

Atoxyl contains elements used against parasites, exemplifying the use of heavy metals as therapeutic agents despite their potential toxicity.

Germicides

Anti-infective agents that are used locally.

Antisepsis

Definition and Standard for Removing Microorganism:

Application of an agent to living tissue for the purpose of preventing infection.

Disinfection

Definition and Standard for Removing Microorganism:

Chemical or physical treatment that destroys most vegetative microbe or viruses, but not spores, in or inanimate surface.

Decontamination

Definition and Standard for Removing Microorganism:

Destruction or marked reduction in the number of activity of microorganism.

Sanitation

Definition and Standard for Removing Microorganism:

Reduction of microbial load on an inanimate surface to a level considered acceptable for public health purposes.

Sterilization

Definition and Standard for Removing Microorganism:

A process intended to kill or remove all types of microorganism, including spores, and usually including viruses with an acceptable low probability of survival.

Pasteurization

Definition and Standard for Removing Microorganism:

A process that kill non-sporulating microorganism by hot water or steam at 65-100c.

• Chemical type of the compound

• Biological property

• Therapeutic indication

What are the Classification of Anti-infectives?

Antiseptics

Local Anti-Infectives:

Applied to living tissue.
Must have low toxicity that it can be used directly on skin or wounds.

• Bactericidal

• Bacteriostatic

Cidal

Compound that kills.

Static

Prevents the growth.

Disinfectant

Local Anti-Infectives:

Applied to inanimate objects.
Exerts a rapidly lethal action against all potentially pathogenic microorganism and spored.

Coagulation and denaturation of cell protein

What is the mechanism of action of local anti-infectives?

• Formalin

• Phenol — Alcohol

What are some examples of strong coagulators?

• Iodine

• Cresol

• Phenol

What are some examples of denaturants?

Alcohol

Classification of Anti-infectives:

The activity of alcohols against microorganisms is the result of their ability to denaturate important proteins and carbohydrates.

• Ethyl alcohol

• Isopropyl alcohol

What are the two (2) most commonly used antiseptics and disinfectants?

Protein and carbohydrate precipitation

What is the mechanism of action of alcohol?

8-carbon atom (octanol)

Structure-Activity Relationship: Alcohol

What is the molecular weight carbon atom of alcohol?

Antibacterial potency increases

Structure-Activity Relationship: Alcohol

MW up to 8-carbon atom (octanol).

Increase penetration to membrane

Structure-Activity Relationship: Alcohol

As the primary chain length increases.

Decreases antibacterial potency

Structure-Activity Relationship: Alcohol

Branching of the alcohol chain.

Primary > Secondary > Tertiary

Structure-Activity Relationship: Alcohol

Isomeric alcohols’ potencies decreases in the order of?

• Ethanol

• Rectified spirit

• Wine spirit

• Grain alcohol

• Spiritus vini rectificatus

What are the five (5) synonyms of ethyl acohol?

95%

What is the % of ethyl alcohol in commercial ethanol?

Azeotrope

Commercial Ethanol (95% EtOH):

This concentration forms an ______ with water that distills at 78.2c

78.2c

Azeotrope forms with water that distills at temperature?

Grain fermentation

Method of Preparation: Ethyl alcohol

Synthetically prepared by the sulfuric acid-catalyzed hydration of ethene.

Acetaldehyde

Alcohol is metabolized in the human body by a series of oxidations:

• Nausea, vomiting, and vasodilatory flushing.

Disulfiram (Antabuse)

Alcohol is metabolized in the human body by a series of oxidations:

• Block aldehyde dehydrogenase, allowing acetaldehyde to accumulate.

Ethanol

This is ineffective against spores.

• Solvent

• Fuel

• CNS depressant

What are the common uses of ethanol?

25%

What is the % of ethyl alcohol as antipyretic?

60-90%

What is the % of ethyl alcohol as germicidal?

70%

What is the % of ethyl alcohol as disinfectant?

1. Nerves

2. Ganglia

Medicinal Uses: Ethyl alcohol

Injected near (1)___ and (2)___ to alleviate pain.

Narcotic potency

Medicinal Uses: Ethyl alcohol

Ethyl alcohol has low?

• Mild sedative

• A weak vasodilator

• Carminative

What are the internal uses of ethyl alcohol (diluted form)?

Spirits

Pharmaceutical Uses: Ethyl alcohol

Ethanol as the sole solvent.

Tinctures

Pharmaceutical Uses: Ethyl alcohol

Hydroalcoholic mixtures.

Fluidextracts

Pharmaceutical Uses: Ethyl alcohol

Alcohol as cosolvent.

Denatured Alcohol

• Intoxicating beverages

• Unfit for human use

• In alc lamps

Denaturants

• Wood alcohol

• Acetone

• Benzene

Denatured Alcohol

Intoxicating beverages and unfit to human use.

Completely denatured alcohol:

• With wood alcohol and benzene

Rubbing Alcohol

Classification of Anti-infectives:

(CH₃CHOHCH₃) — 2 propanol

Uses: astringent, rubefacient, mild local anesthetic

68-72%

Rubbing alcohol contains how many % of isopropyl alcohol?

Sulfuric acid

Preparation of Rubbing Alcohol:

This acid is catalyzed hydration of propylene.

Isopropyl alcohol

Uses:

• Disinfectant for the skin and for surgical instruments.

• Bactericidal (50-95%)

• 40% isopropyl alcohol = 60% EtOH.

Azeotropic Isopropyl Alcohol

Uses:

• Used on gauze pads for sterilization of the skin prior to hypodermic injections.

Dehydrated Alcohol

Absolute alcohol

• NLT 99% w/w EtOH.

Preparation: Azeotropic Distillation of EtOH and benzene.

Diluted Alcohol

Mixture of alcohol and water containing 41-42% by weight.

41-42%

Diluted alcohol is a mixture of alcohol and water containing % by weight.

Glycerin (Glycerol)

1,2,3-propanetriol

• The first polyhydric alcohol which can yield both an aldose and a ketose.

Uses: solvent and humectant

Ethylene oxide (C₂H₄₀)

• Gas sterilant

• Used for temperature sensitive medical equipment?

• Forms explosive mixtures in air in concentrations ranging from 3-80%

Carboxide

• 10% ethylene oxide + 90% carbon dioxide by volume.

• without danger of explosion.

MOA: germinal action

• alkylation of functional groups in nucleic acids and proteins by nucleophilic opening of the oxide ring.

• nonselective alkylating agent.

• extremely toxic and potentially carcinogenic.

Aldehyde

This is a formaldehyde solution.

• Formol

• Formalin

• Methanal

What are the three (3) synonyms of aldehyde?

Aldehyde

• Irritating to mucous membrane.

• Causes hardening of skin.

• Disinfect rooms, clothing and surgical instruments.

• NLT 37% of formaldehyde

Formaldehyde Solution

• Irritating to mucous membrane and causes hardening of skin.

• Used to disinfect rooms, clothing, and surgical instruments.

• Contains not less than 37% of formaldehdye with methanol to prevent polymerization.

• Undergoes oxidation or polymerization

Methanol

This is used to prevent polymerization of formaldehyde solution.

Glutaraldehyde

This is a disinfectant superior to formaldehyde, microbial activity against all microorganism, including spored and virus.

• Glutarol (Cidex)

• Pentanedial

What are the two (2) synonyms of glutaraldehyde?

Glutaraldehyde

Uses: Solution for sterilization of equipment and instrument that cannot be autoclaved.

Commercial Glutaraldehyde

• Stabilized in alkaline solution.

• The preparation actually consists of two components (glutaraldehyde and buffer).

• Activated solution contains 2% glutaraldehyde buffered at pH 7.5 to 8

• Retain over 80% of the original activity 30 days after preparation.

Phenol and Derivatives

Classification of Anti-infectives:

• Protein precipitant

• Remains the standard to which the activity of most germicidal substances is compared.

Protein precipitation

What is the mechanism of action of phenol and derivatives?

Phenol coefficient

Ratio of a disinfectant to the dilution of phenol required to kill a given strain of Salmonella typhi.

Phenol

This is a carbolic acid.

Germicide

Phenol as prostoplasmic poison.

Liquefied phenol

Simple phenol containing 10% of water — is convenient for adding phenol to various pharmaceutical preparation.

The water content, however, preclude its used in fixed oils or liquid petroleum.

10%

Liquefied alcohol is a simple phenol containing how much % of water?

P-chlorophenol

• Used in combination with camphor in liquid petroleum as an external antiseptic and anti irritant.

• Has phenol coefficient of about 4.

Chloro-m-Xylenol (PC-MX, Metasep)

• Nonirritating antiseptic agent.

• Broad-spectrum antibacterial and antifungal properties.

• Marked in a 2% concentration as a shampoo.

Chloro-m-Xylenol (PC-MX, Metasep)

Used topically for the treatment of tinea (ringworm) infections such as athlete’s foot and jock itch.

Eugenol

• Local anesthetic effect

• Antiseptic in mouthwashes

• Dental analgesic

Hexachlorphene (Phisohex, Gemophen, Surgicon)

• 2,2-methylenebis (3,4,6-trichloro) phenol

Uses:

• Antiseptic in low concentration (very effective against gran (+)

• 2-3% soaps, detergent creams, lotions, and shampoos for variety of antiseptic uses.

Hexachlorophene

Biphenolic compounds, such as ______, are generally more potent that the corresponding monophelic counterpart.

Hexachlorophene

Neurotoxic in infants bathed in this and in burn patients are cleansed with this agent.

Cresol

• This is a mixture of three isomeric methylphenols (ortho-, meta-, para-isomers).

• Obtained from coal tar or petrolatum by alkaline extraction into aqueous medium, acidification, and fractional distillation.

Chlorocresol

• 4-chloro-3-methylphenol - is slightly soluble in water.

• At low concentration at aqueous media, the compound is only useful as a preservative.

Thymol

• This is isopropyl m-cresol.

• Extracted from oil of thyme.

• Has fungicidal properties and used in alcoholic solution or dusting powder for treatment of tinea infection.

Resorcinol

• m-dihydroxtbenzene (Resorcin).

• Weak antiseptic

• 1 to 3% used in solution and in ointment.

• Pastes in concentrations of 10 to 25% for the treatment of skin conditions such as ringworm, eczema, psoriasis, and seborrheic dermatitis.