Anti-infective Agents

Anti-infectives is a general term used to describe any medicine that is capable of inhibiting the spread of an infectious organism or by killing the infectious organism outright.

This term includes:

. Antiseptics and Disinfectant

. Antibiotics (antibacterial and antineoplastic)

. Antifungals

. Anthelmintics

. Antimalarials

. Antiprotozoals

. Antituberculosis

. Antivirals agents

History of Anti-infective Agents

. The origin of anti-infective therapy in the Western hemisphere dates back to the use of cinchona bark to treat malaria by the indigenous peoples in South America. This discovery was taken to Europe in the seventeenth century.

. These observations were used to develop the drug quinine, which is still used in the treatment of malaria today.

. The Chinese have a 5,000 year history of using herbal remedies that may still lead to new anti-infective agents

. Prior to their discovery agents such as mercury and arsenic were used for many different ailments (most notably, syphilis).

. Sulphanomide, which was derived from a yellow clothing die in Germany, was first developed and patented in 1932.

. Penicillin was first utilized in 1941 on a policeman in England. The policeman died during the course of the treatment.

ANTISEPTICS AND

DISINFECTANTS

They have specific use and their selectivity is very low.

Antiseptics

• An agent that kills or inhibits the growth of microorganisms

• are compounds that kill or prevent the growth of microorganism when applied to living tissue.

• Used on skin

Disinfectants

• Chemical agents that inhibit or kill microorganisms (surgical apparatus, periphery of the patient, and the objects used by the patient).

• Used on inanimate objects

• Can be accomplished by application of chemical agents, use of physical agents (ionizing radiation) dry or moist heat, superheated steam(autoclave, 120̊ C)

Requirements for antiseptics and disinfectants

• Must have a broad spectrum of action;

• Rapid onset of action;

• Should have a small latency period;

• Should have a high activity;

• Must be chemically resistant;

• High availability and low cost;

• Lack of local irritant or allergic effects on tissues; • Minimal absorption from the place of their application;

• Low toxicity.

Antiseptic drugs are used in:

• The treatment of skin infections

• Prevention of infections in cuts and wounds

• Cleaning the skin area of surgery from microorganisms

• Proflaxy and treatment of infections in mucosal areas such as mouth, nose and vagina that are open to environment

• As a scrub for surgeans and the medical personnel

THE PATHOGENS THAT CAN BE

TRANSMITTED

❖Human Immunodeficiency Virus ( HIV )

❖Herpes Simplex Virus types 1 and 2

❖Hepatitis B Virus ( HBV )

❖Streptococci

❖Staphylococci

❖Mycobacterium tuberculosis

❖Cytomegalovirus

❖some upper respiratory tract viruses

CLASSIFICATIONS OF ANTISEPTICS AND DISINFECTANTS

1. Those that denature proteins,

2. Those that cause osmotic disruption of the cell,

3. Those that interfere with specific metabolic processes.

• The first and second classifications are tend to kill the organisms.

• The third one affects cell growth and reproduction without killing the cell.

Classification of Antiseptics and Disinfectants

(according chemical structure)

I. Inorganic substances

1. Halogens:

• Iodine (2%, 3%, 5% alcochol solution)

• Iodinolum

• Ioddicerinum

• Povidon-Iod (Betadinum)

• Iodophorm

• Lugol’s solution

• Chloramine B

• Chlorhexidine bigluconate

• Pantocidum (Halazone)

2. Oxidizing agents:

• Hydrogen peroxide

• Potassium permanganate

3. Acids and alkalis:

• Boric acid

• Salicylic acid

• Solution of ammonia

4. Metallic salts:

• Hydrargyri dichloridum

• Hydrargyri amidochloridum

• Silver nitrate

• Copper sulfate

• Zinc sulfate

• Zinc oxide

II. Organic substances

1. Aldehydes:

• Formaldehyde (Formalinum)

• Glutaraldehide

• Hexamethylentetraminum

(Methenamine)

2. Alcochols:

• Spiritus aethylicus (Ethyl alcohol)

3. Phenol derivatives:

• Phenol (Phenolum purum,

Carbolic acid)

• Cresol (Tricresolum)

• Resorcinol

• Thymol

• Benzylbenzoat

4. Dyes:

• Methylenum blue

• Brilliant green (Viride nitens)

• Etacridin lactate

5. Detergents:

• Aethonium

• Decamethoxin

• Roccal

• Dimexid

6. Tar, resins, products of petroleum:

• Pix liquida Betulae (Birch tar)

• Ichthyolum

• Liniment by Vishnevsky

7. Nitrofuran derivatives:

• Nitrofurasone (Furacilinum)

8. Antiseptics from medicinal plants:

• Chlorophyliptum (from eucalyptus)

• Novoimaninum

HALOGENS

• The halogens and halogen – releasing compounds include some of the most effective antimicrobial compounds used for disinfection and antisepsis.

• Iodine and chlorine are the most effective halogens with bromine and fluorine being less active.

• Because of the irritating nature of the products of sodium hypochlorite, it is currently used primarily as a disinfectant.

The mechanism of antimicrobial action

• Denaturation of proteins of the protoplasm of microbial cells by reacting with the amino group of the proteins, displacing hydrogen.

• Denatured protein loses its activity.

• In the presence of organic substances halogen’s antimicrobial effect decreases.

Chlorine

When chlorine or the hypochlorites are added to water, the following reactions take place

Cl2 + H2O > HOCl + HCl

Ca(OCl)2 + H2O > Ca2+ HCl +2OCl-

Ca(OCl)2 + 2H2O >Ca(OH)2 +2HOCl

HOCl > H+ OCl-

The mechanism of antimicrobial action

➢the chlorination of amide nitrogen atoms in proteins and the oxidation of sulfhydryl group in proteins

Synthesis of Chlorine Compounds

In order to synthesize the compounds, in the first step, toluene was sulphonated with chlorosulphonic acid. Then reacting with ammonia yields to p-toluensulfonamide. After treating with chloride, in the presence of sodium hydroxide, chloramine-T and dichloramine-T were obtained. To yield halazone, methyl group of p-toluensulfonamide was oxidized with potassium bichromate or potassium permanganate

Iodines

• Iodine - active bactericidal element.

• At a dilution of 1: 20 000 - kill vegetative forms of bacteria for 1 min,

• Alcoholic solution of Iodine 5% (5 g of Iodine, KI -

2g, ethyl alcohol 95% 100ml)

• An irritant and a distraction action

Povidone- Iodine

Povidone-Iodine, (Betadine, Isodine) is a complex with the nonionic surfactant polymer, polyvinylpyrrolidone. This watersoluble complex releases iodine slowly. It provides a nontoxic, nonirritating, nonvolatile, and nonstaining form of iodine. Approximately 10% of available iodine is present in the complex.

Halogens (Iodine)

• LUGOL'S SOLUTION (Iodine-1 part, 2 part -KI, water-17 part)

• IODDICERINE (Iodine, dimethyl sulfoxide, glycerol)

• Fungicidal, antimicrobial, antiviral, antinecrotic, antioxidant effect.

• !!!The most active Iodine preparation!!!

• Doesn’t irritate tissue, does not cause pain reaction, deeply penetrates into the tissue.

Oxidizing agents

HYDROGEN PEROXIDE

• It is available as 30% and 3% solution. More common 3% solutions is used.

• H2O2 2H + O2

It is decomposed with release of molecular form of oxygen that is responsible for antimicrobial effect

• Releasing oxygen makes foam that cleans and deodorizes putrid wounds and ulcers.

• Hydrogen peroxide is used in treatment of infected wounds and to stop small bleeding.

Formaldehyde solution (Formalin)

• The most important member in this class is formaldehyde.

• At room temperature, this gas polymerizes, which limits its use in high concentrations at these temperatures.

• Many of these polymers release formaldehyde slowly at room temperature or faster when heated.

• Formaldehyde is also 37% (formaldehyde solution.) water-soluble at room temperature.

MECHANISM OF ACTION: dehydration of microbial cells protoplasm proteins causing its destruction.

• Is used as a disinfectant and deodorant, skin treatment with sweating (0.5-1%), disinfection tools (0.5%). For the preservation of anatomical objects.

Quaternary Ammonium Compounds (Inverted Soaps)

➢ The synthesis and antibacterial properties of quaternary ammonium salts were first described by Einhorn and Cottier in 1908.

➢ Their use as general antiseptics was introduced in 1935, at which time they were widely recognized as effective. germicides.

➢ These compounds have the advantage of being colorless, odorless, stable, and relatively nontoxic, and are equally active against many gram-positive and gram-negative bacteria.

➢ They are also called "inverted" soaps since they are cationic-active colloidal electrolytes instead of anionicactive soaps.

Detergents (surface active agent)

• Detergents - a substances with a high surface activity.

• Show antiseptic and cleansing action.

• Distinguish anionic and cationic detergents.

• Anionic detergents include ordinary soaps (sodium or potassium salts of fatty acids).

• As antiseptics mainly used cationic surfactants:

benzalkonium chloride, cetylpyridinium chloride, miramistim.

• Benzalkonium chloride has antibacterial, antiprotozoal and spermicidal action.

• Used for treatment of skin, mucous membranes, wounds, rinsing the bladder, urethra, and for contraception in women.

Quaternary Ammonium Salts

• Cetylpiridinium chloride

• 1-Hexadecylpyridinium chloride