PMOC/DDD (copy)

AWA PO PLS

Medicinal Chemistry

devoted to the discovery and development (organic, analytical, and biochemical aspects) of new agents for treating diseases

pharmacophore

 It is the region of a molecule containing the essential organic functional groups that directly interact with the receptor active site, therefore, conferring the biologic activity of interest.

chemotherapy

a drug treatment that can kill or inhibit the growth of cells

Ignaz Semmelweis

Father of Handwashing

Joseph Lister

Father of Antiseptic Surgery

Joseph Lister

Introduced antiseptic principles for use in surgery and post-traumatic injury by using phenol (carbolic acid)

Paul Ehrlich

Father of Chemotherapy

Paul Ehrlich

he discovered Salvarsan / Arsphenamine / Compound 606

anti-syphilis

use of salvarsan

paul ehrlich

he introduced selective toxicity principle

germicides

anti-infective agents that are used locally

1. antiseptic

2. disinfectant

2 primary subtypes of germicides

antiseptic

Compounds that kill (-cidal) or prevent the growth of (-static) microorganisms when applied to living tissue.

disinfectant

An agent that prevents transmission of infection by the destruction of pathogenic microorganisms when applied to inanimate objects

 Alcohols and Related Compounds

 Phenols and Their Derivatives

 Oxidizing Agents

 Halogen-Containing Compounds

 Cationic Surfactants

 Dyes

 Mercury Compounds (Mercurials)

 Preservative

LOCAL ANTI-INFECTIVES

Protein and Carbohydrate denaturation

MOA of Alcohols

Staphylococcus aureus

test organism for alcohols and related compounds

Alcohol and related compounds

MOA: Protein and Carbohydrate denaturation

↑ Molecular weight: ↑ Antibacterial potency (up to 8C)

Structure-Activity Relationship of Alcohols

↑ Molecular weight: _ Antibacterial potency

Branching: ↓ Antibacterial potency

• Primary > Secondary > Tertiary

Structure-Activity Relationship of Alcohols

Branching: _ Antibacterial potency

methanol

wood alcohol

↑ C = ↑ Nonpolar = ↓ soluble = ineffective

Structure-Activity Relationship of Alcohols

↑ C = ↑ Nonpolar = _ soluble = ?

ethyl alcohol, grain alcohol, wine spirit, or spiritus vini rectificatus

others names of ethanol

ethanol

Synthetically prepared from the hydration of ethylene

70%

most common % of ethanol

95%

% of commericial ethanol

>70%

% of ethanol used safely for preoperative sterilization of the skin

• antiseptic

• preservative

• mild counterirritant

• solvent

uses of ethanol

Denatured Alcohol

Ethanol that has been rendered unfit for use in intoxicating beverages by the addition of other substances

isopropyl alcohol

Aka Isopropanol or 2-propanol

isopropyl alcohol

70% rubbing alcohol

isopropyl alcohol

A colorless, volatile liquid with a characteristic odor and a slightly bitter taste

propylene

isopropyl alcohol is prepared from the hydration of ___

gas sterilant

use of ethylene oxide

ethylene oxide (3-80%)

alcohol which forms explosive mixtures in air

Alkylation

MOA of ethylene oxide

Glutaraldehyde Disinfectant Solution

Use: Dilute solution for the sterilization of equipment and instruments that cannot be autoclaved

Ethylene Oxide

Use: Sterilize temperature-sensitive medical equipment and certain pharmaceuticals that cannot be heat-sterilized in an autoclave

formalin: NLT 37% w/v formaldehyde and methanol

formaldehyde solution

embalming agent

use of formalin

Glutaraldehyde Disinfectant Solution

a 5-carbon dialdehyde

Protein denaturation

MOA of Phenol in low concentration

cell membrane lysis

MOA of phenol in high concentration

Salmonella typhi

test organism of phenols

Phenol coefficient

Defined as the ratio of a dilution of a given test disinfectant to the dilution of phenol that is required to kill a strain of Salmonella typhi

↑ bactericidal activity

Alkyl, aryl, and halogen substitution at the para position: _ bactericidal activity

phenol

aka carbolic acid

phenol

A colorless to pale-pink crystalline material with a characteristic “medicinal odor.”

cresol

A mixture of three isomeric methylphenols

phenol

General protoplasmic poison

cresol

Occurs as a yellow to brownish yellow liquid that has a characteristic odor of creosote

Inexpensive antiseptic and disinfectant

uses of cresol

thymol

Has mild fungicidal properties for the treatment of tinea infections

thyme oil, thymus vulgaris

source of thymol

clove oil, Eugenia caryophyllata or Syzygium aromaticum

source of eugenol

eugenol

Has local anesthetic and antiseptic activity for the relief of toothache

Clove oil, Eugenia caryophyllata or Syzygium aromaticum

source of eugenol

Resorcinol

phenol derivative with weak antiseptic (PC: 0.4)

keratolyic agent

use of resorcinol

Liberation of oxygen

MOA of oxidizing agents

poor penetrability and transient effect

limitations of oxidizing agents

• Hydrogen peroxide

• Metal peroxides

• Sodium perborate

• KMnO4

inorganic oxidizing agents

Hydrous Benzoyl Peroxide

Keratolytic and keratogenic for the treatment of acne

clindamycin or erythromycin

hydrous benzoyl peroxide + (antibiotics) if acne is caused by bacteria

iodine-containing compounds

The oldest germicide still in use today.

1. Iodine

2. Chlorine

HALOGEN-CONTAINING COMPOUNDS:

Protein inactivation by iodination of aromatic residues and oxidation

MOA of Iodine

Iodine tincture

2% iodine in 50% alcohol with NaI

Strong iodine solution (Lugol’s solution)

5% iodine in water with KI

Iodine solution

2% iodine in water with NaI

Povidone-Iodine

An iodophor (10% I2 + nonionic surfactant)

Polyvinylpyrrolidone

nonionic surfactant of povidone-iodine

Presurgical and wound disinfection

Povidone-Iodine

1. Halazone

2. Chloroazodin

3. Oxychlorosene sodium

CHLORINE-CONTAINING COMPOUNDS

CHLORINE-CONTAINING COMPOUNDS

Generally used to disinfect water supplies

hypochlorous acid (HClO)

active of chlorine-containing compounds

Chlorination and oxidation of proteins

MOA of chlorine-contaning compounds

ph 7

chlorine-containing compounds have optimal effect at pH 7

cationic surfactants

Quaternary ammonium compounds

Cell membrane destabilization and lysis

MOA of cationic surfactants

Inactivated by soaps and other anionic detergents

disadvantage of cationic surfactants

 Cationic head group

 Long hydrocarbon tail

structural moieties of cationic surfactants

benzalkonium chloride

new generic name of merthiolate

1. Benzalkonium Chloride

2. Methylbenzethonium Chlroride

3. Benzethonium Chloride

4. Cetylpyridinium Chloride

5. Chlorhexidine Gluconate

cationic surfactants

diaper rash

use of Methylbenzethonium Chlroride

skin antiseptic

use of Benzethonium Chloride

Cetylpyridinium Chloride

The most active of a series of alkylpyridinium compounds

throat lozenge and mouthwash

available dosage forms of Cetylpyridinium Chloride

Chlorhexidine Gluconate

The most effective of a series of antibacterial biguanides

Preoperative skin disinfection, Wound irrigation, Mouthwashes, General sanitization

use of Chlorhexidine Gluconate

gram-positive

Dyes are active against gram-__ bacteria and many fungi

1. Gentian Violet

2. Basic Fuchsin

3. Methylene Blue

DYES

Gentian Violet

Occurs as a green powder or green flakes with a metallic sheen

yeast infection

use of Gentian Violet vaginal suppositories

Ringworm and yeast infection

use of 1% to 3% Gentian Violet solution

Anthelmintic (Strongyloidiasis and Oxyuriasis)

oral use of Gentian Violet

Basic Fuchsin

Component of carbol-fuchsin solution (Castellani’s paint)

• Ringworm

• Athlete’s foot

uses of Basic Fuchsin

methylene blue

A dye used in vital nerve staining

 Cystitis

 Urethritis

uses of methylene blue