III Pharm.D Medicinal chemistry-Local antiinfective agents

1. LOCAL
ANTI-INFECTIVE
AGENTS
BY
KENCHA SWATHI
ASSISTANT PROFESSOR
BANGALORE
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2. ANTI -INFECTIVE AGENTS-INTRODUCTION
 In 1867,Joseph Lister introduced antiseptic property
principles by using phenol as a spray on an incision site & on
wounds.
 In 1881-1900,Paul Ehrlich –Microbiologist –discovered
selective toxicity by using dyes and arsenicals.
 Prior to Ehrlich’s studies,the local antimicrobial properties of
phenol and iodine were well known,but systemic agents are
cinchona for malaria and ipecac for amoebic dysentry.
 Ehrlich also discovered salvarsan as the effective antisyphilitic
drug.
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3.  Antiinfective agents are classified as:
1.Local antiinfective agents
2.Preservatives
3.Antifungal agents
4.Synthetic antibacterial agents(Urinary antiinfective
agents)
5.Anti tubercular agents
6.Anti protozoal agents
7.Anthelmintics
8.Antiscabies & antipedicular agents
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4. LOCAL ANTIINFECTIVE AGENTS
 Drugs or chemical agents which are used locally
for infections are called as local antiinfective
agents
 Local antiinfective agents contains two
categories:
a) Antiseptics
b) Disinfectants
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5. ANTISEPTICS
 Definition:Chemical compounds that kill(cidal) or
prevent the growth of microorganisms(static)
when applied to living tissues
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6. Ideal properties of antiseptics for showing good activity
 Rapid and sustained lethal action against microorganism
 Low surface tension so that it wil spread into the wound
 Should retain its activity in the presence of body fluids
 Should be non irritating to tissues
 Should be non allergic
 Should lack systemic toxicity when applied to skin
 Should not interfere with healing property.
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7. DISINFECTANTS
 A disinfectant is an agent that prevents transmission of
infection by the destruction of pathogenic microorganisms
when applied to inanimate objects.
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8. Ideal properties of a disinfectant for showing good activity
 Rapid lethal action against all potentially pathogenic
microoganisms.
 Good penetration into organic matter
 Compatible with organic compound
 Should not inactivate by living tissue
 Should be Non corrosive
 Aesthetically pleasing
 Should be Non staining
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9. CLASSIFICATION
1.Alcohols and related compounds: Ethyl alcohol,Isopropyl
alcohol,Formaldehyde,Ethylene oxide,Glutaraldehyde
2.Phenols and their derivatives: Phenol,Parachloro phenol,Resorcinol,Hexyl
resorcinol,Hexachlorophene,Cresol,Chlorocresol
3.Oxidising agents: Hydrogen peroxide,Hydrous benzoyl peroxide
4.Halogen containing compounds: Tincture Iodine,Halozone
5.Cationic surfactants: Benzal konium chloride,Cetyl pyridinium chloride
6.Dyes: Gentian violet,Methylene blue
7.Nitrofuran derivatives: Nitrofurazone,Furazolidone
8.Mercury compounds: Nitromersal,Thiomersal
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10. ALCOHOLS & RELATED COMPOUNDS
C₂H₅OH HCHO
(Ethyl alcohol) (Formaldehyde)
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(Isopropyl alcohol)
(Ethylene oxide)
(Glutaraldehyde)

11. PHENOLS AND THEIR DERIVATIVES
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Phenol Parachloro phenol Resorcinol
Hexyl resorcinol Hexachlorophene

12. Swathi Pharma Jnan
Cresol
Chlorocresol

13. OXIDISING AGENTS
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Hydrogen peroxide Hydrous benzoyl peroxide

14. HALOGEN CONTAINING COMPOUNDS
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Iodine(I₂) Halozone

15. CATIONIC SURFACTANTS
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Benzalkonium chloride Cetyl pyridinium chloride

16. DYES
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Gentian violet Methylene blue

17. NITROFURAN DERIVATIVES
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Nitrofurazone Furazolidone

18. MERCURY COMPOUNDS
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Nitromersal Thiomersal

19. MOA OF Alcohols and related
compounds
 R-Non polar & OH – polar group
 Primary alcohol shows more penetration,more active,more cost as the
length of the carbon chain increases. Eg:n-Propyl alcohol
 Secondary alcohol shows less penetration,less active Eg:Isopropyl
alcohol
 When R increases,penetration increases,action decreases as more
vanderwalls forces are present.
 Formaldehyde –mode of action is alkylation.
 It alkylates the groups present in the proteins and nucleic acids.
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20.  As the primary alcohol chain length increases vanderwalls
interaction increases and the ability to penetrate the cell
membrane increases.As water solubility decreases the
antimicrobial potency decreases with molecular weight.
 So branching of the alcohol chain decreases the antimicrobial
potency.
 The germicidal action of HCHO is slow but powerful.The
mechanism of action is to direct non-specific alkylation of
nucleophilic functional groups like amino,sulphydryl OH group
present in proteins and nucleic acids to form carbinal derivatives.
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21. MOA of phenols
 Phenols in low concentrations they denature
proteins(bacterial proteins)
 Phenols in high concentrations they produce lysis
(breakage) of bacterial cell membrane.
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22. MOA of Oxidising agents
 They liberate oxygen/oxygen free radicals.
 Anaerobic microorganisms are affected by this liberation,they will
die.
 The germicidal action of oxidising agents depend on their ability to
liberate oxygen in the tissues.
 All these agents react in the tissues to generate O2/Oxygen free
radicals.
 These agents are effective against anaerobic microorganisms.
 They are used in cleaning contaminated wounds.
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23. MOA of Halogen containing compounds
 Tincture Iodine: Iodine will inactivate proteins by iodination
of aromatic residues like phenyl allyl group,tyrosyl group.
 I₂ can oxidise the S-H group by oxidation of sulphur
containing groups.
 Chlorine containing compounds releases Cl₂ and chlorinate
amide nitrogen atoms so that amido N₂ is halogenated and
also oxidation of sulphur containing groups.
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24. MOA of Cationic Surfactants
 Cationic surfactants will dissolve and disperse in
the cell membrane and then destabilise and
cause lysis of the cell membrane.They will also
interfere with the enzymes present in the cell
membrane.
(Dissolve – Disperse- Destabilise- Lysis)
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25. MOA of Dyes
 These dyes act on cell membranes.
 The difference in susceptibility of the organism is
related to cellular characteristics.
 These cationic dyes are active against gram+ve
bacteria and many fungi.
 Gram-ve bacteria are generally resistant.
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26. MOA of Nitrofuran derivatives
 The complete mechanism is not fully understood
but they are mutagenic and carcinogenic under
certain conditions.
 The cellular effects are due to DNA damage
caused by metabolic reaction products of the
nitrofurans.
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