Antibiotics Antibiotics

Antibiotics are the chemical substances obtained from various micro Antibiotics are the chemical substances obtained from various micro organismsorganisms

First discovered antibiotic is Penicillin by Alaxander Flemming in 1940First discovered antibiotic is Penicillin by Alaxander Flemming in 1940 Antibiotics are used to cure diseases caused by bacteria such as pneumonia, Antibiotics are used to cure diseases caused by bacteria such as pneumonia,

tuberculosis, meningities tuberculosis, meningities

Conditions for a substance to act as antibiotics are as follows:Conditions for a substance to act as antibiotics are as follows: Should be effective at low concentrationShould be effective at low concentration Should not have toxic side effectsShould not have toxic side effects Must be effective against pathogensMust be effective against pathogens Should be stored for a long time without appreciable loss of its activityShould be stored for a long time without appreciable loss of its activity Should be highly stable so that it can be isolated easily and absorbed readilyShould be highly stable so that it can be isolated easily and absorbed readily Should be available at low costShould be available at low cost Should be completely eliminated from the body after its administration has Should be completely eliminated from the body after its administration has

been stoppedbeen stopped

Classification of antibioticsClassification of antibiotics

Classification based on chemical structureClassification based on chemical structure::

Cyclic structure– cyclopentane , cyclohexane and Cyclic structure– cyclopentane , cyclohexane and clycloheptane derivativesclycloheptane derivatives

Tetracycline antibiotics - tetracyclineTetracycline antibiotics - tetracycline Aromatic antibiotics - ChloramphenicolAromatic antibiotics - Chloramphenicol Amino Glycoside antibiotics - streptomycinAmino Glycoside antibiotics - streptomycin Macrolides antibiotics – Erythromycin.Macrolides antibiotics – Erythromycin.

Chloramphenicol Chloramphenicol Discovered by Ehrlich in 1947Discovered by Ehrlich in 1947 Obtained by culture of “Streptomyces Venezuelae”Obtained by culture of “Streptomyces Venezuelae”

PropertiesProperties Stable neutral compoundsStable neutral compounds Bitter in tasteBitter in taste Sharp melting point Sharp melting point Soluble in organic solvents and sparingly soluble in waterSoluble in organic solvents and sparingly soluble in water Optically active Optically active Molecular formula CMolecular formula C1111HH1212OO55NN22ClCl22

On hydrolysis it gives dichloro acetic acid & optically active baseOn hydrolysis it gives dichloro acetic acid & optically active base On reduction with Sn/ HCl followed by diazotization & coupling On reduction with Sn/ HCl followed by diazotization & coupling

with with ββ-naphthol – orange red dye-naphthol – orange red dye On acetylation in pyridine–shows the presence of two OH groupsOn acetylation in pyridine–shows the presence of two OH groups

Therapeutic uses Therapeutic uses

Effective against gram +ive and gram –ive bacteria Effective against gram +ive and gram –ive bacteria It’s the first broad spectrum antibioticIt’s the first broad spectrum antibiotic Inhibits the growth of stephalococcus, streptococcus bacillusInhibits the growth of stephalococcus, streptococcus bacillus Used in treatment of typhoid, pneumonia, ricketisia, urinary tract Used in treatment of typhoid, pneumonia, ricketisia, urinary tract

infection, whooping cough, meningitis, plague, syphilis, gonorrhea infection, whooping cough, meningitis, plague, syphilis, gonorrhea & dysentry& dysentry

Employed in acute infections due to Haemophilus influenzaEmployed in acute infections due to Haemophilus influenza Can be used in the treatment of skin and eye infectionCan be used in the treatment of skin and eye infection It is absorbed in a intestinal tract and diffused into tissues.It is absorbed in a intestinal tract and diffused into tissues. As it is insoluble in water it has to be administered in the form of As it is insoluble in water it has to be administered in the form of

fine particles.fine particles.

Structure, activity, relationship of Structure, activity, relationship of ChloramphenicolChloramphenicol

Modification of para nitro phenyl group:Modification of para nitro phenyl group: If the nitro group of phenyl ring of chloramphenicol is replaced by other If the nitro group of phenyl ring of chloramphenicol is replaced by other

substituents like CN , their physiological activity is reducedsubstituents like CN , their physiological activity is reduced

Shifting the nitro group from para position , reduces the anti-bacterial Shifting the nitro group from para position , reduces the anti-bacterial

activityactivity

If phenyl ring of choloramphenicol is replaced by alicyclic or If phenyl ring of choloramphenicol is replaced by alicyclic or

hetrocyclic ring, then the resulting antibiotic is found to be less effectivehetrocyclic ring, then the resulting antibiotic is found to be less effective

Modification of Dichloroacetamide chainModification of Dichloroacetamide chain If chloro group is replaced by bromo group , the antibacterial activity is If chloro group is replaced by bromo group , the antibacterial activity is

only 80% .only 80% .

..

Modification of 1,3 propane diolModification of 1,3 propane diol The propane diol group is essential for its antibacterial The propane diol group is essential for its antibacterial

activityactivity If the length of the propane is altered, the drug is deactivated If the length of the propane is altered, the drug is deactivated If the bulkier substituents are introduced activity is If the bulkier substituents are introduced activity is

decreaseddecreased

STEREOCHEMISTRY:STEREOCHEMISTRY: cholramphenol has two asymmetrical carbon atom.cholramphenol has two asymmetrical carbon atom. It can form 4 optically active isomers-D & L threo isomers It can form 4 optically active isomers-D & L threo isomers

and D & L erythro isomers.and D & L erythro isomers. Erythro isomers- toxic & not used in medicineErythro isomers- toxic & not used in medicine L-threo isomer-biologically inactive.L-threo isomer-biologically inactive. D-threo isomer – biologically active.D-threo isomer – biologically active.

Toxicity Nitro group may contribute to bone marrow depression

and Fatal blood dyscrasia

Dosage Adult dosage- 500mg every 6 hrs

MODE OF ACTION It inhibits the growth of bacteria.

DOSAGE FORMS available as: capsules, ear drops, eye ointment

Penicillin Penicillin Widely used antibiotic Widely used antibiotic Extracted from mould of “Penicillin notatum”Extracted from mould of “Penicillin notatum” Belongs to a group of antibiotic called β-lactam Antibiotic Belongs to a group of antibiotic called β-lactam Antibiotic Basic structure contains thiozoline ring fused with β-lactam Basic structure contains thiozoline ring fused with β-lactam

ringring Two rings constitute the fundamental nucleus of group of Two rings constitute the fundamental nucleus of group of

antibiotics referred as “PENICILLIN”antibiotics referred as “PENICILLIN” Chrysogunum- highest yield of penicillinChrysogunum- highest yield of penicillin

Therapeutic usesTherapeutic uses Penicillin is effective against gram +ive and gram –ive coccai and some Penicillin is effective against gram +ive and gram –ive coccai and some

gram +ive bacilligram +ive bacilli It is bacteriostatic in action, but at certain concentration it acts as It is bacteriostatic in action, but at certain concentration it acts as

bactericidal agents.bactericidal agents. Inhibits synthesis of bacterial cell wall Inhibits synthesis of bacterial cell wall Non-toxic even in large doses.Non-toxic even in large doses. Effective against pneumocccal infections, streptococcal infections, Effective against pneumocccal infections, streptococcal infections,

staphylococcal infections, meningococcal infections.staphylococcal infections, meningococcal infections. Used in the treatment of diphtheria, gangrene, tetanus, etcUsed in the treatment of diphtheria, gangrene, tetanus, etc Used topically, orally or parentallyUsed topically, orally or parentally In oral therapy, the dosage must be given in larger doses as it is inactivated In oral therapy, the dosage must be given in larger doses as it is inactivated

by gastric acids by gastric acids Sodium or potassium salt are used for injectionSodium or potassium salt are used for injection Calcium salt can be used as an ointment or as powderCalcium salt can be used as an ointment or as powder

..

Adverse effects Adverse effects adverse effects like vomiting, nausea, anyphyxis and allergic adverse effects like vomiting, nausea, anyphyxis and allergic

reactionsreactions Natural penicillin are inactivated faster by HCL acids, variety Natural penicillin are inactivated faster by HCL acids, variety

of semi synthetic and synthetic penicillin are produced that are of semi synthetic and synthetic penicillin are produced that are made effectivemade effective

All these have allergic reactions similar to those produced by All these have allergic reactions similar to those produced by natural penicillin.natural penicillin.

Types of penicillin &PropertiesTypes of penicillin &Properties

Types of penicillinTypes of penicillin Natural penicillin Natural penicillin Semi synthetic penicillinSemi synthetic penicillin

PropertiesProperties Optically active Optically active Soluble in water Soluble in water Hydrolyzed by hot inorganic acidsHydrolyzed by hot inorganic acids Acid resistant Acid resistant Effective in treatment of respiratory tract infection, streptococcal infections Effective in treatment of respiratory tract infection, streptococcal infections

and pneumonococcal infectionsand pneumonococcal infections Methicillin is resistant to penicillinase and used in treatment of infection Methicillin is resistant to penicillinase and used in treatment of infection

resistant to benzyl penicillinresistant to benzyl penicillin Ampicillin is effective against influenza, gonorrhea, salmonella typhose, e-Ampicillin is effective against influenza, gonorrhea, salmonella typhose, e-

coli, etc. coli, etc.

Mode of actionMode of action

Bacteriostatic and bacteriocidalBacteriostatic and bacteriocidal

Anti-bacterial against organism mainly their growth phaseAnti-bacterial against organism mainly their growth phase

Interferes with synthesis of ribonucleic acid Interferes with synthesis of ribonucleic acid

TetracyclinsTetracyclins Tetracyclins compress a group namely:Tetracyclins compress a group namely:

TetracyclinsTetracyclins

ChlorotetracyclinsChlorotetracyclins

OxytertacyclinsOxytertacyclins

Most important anti-microbial propertyMost important anti-microbial property

Obtained from the species of actinomyces named as streptomyces Obtained from the species of actinomyces named as streptomyces

Precipitated from a culture medium maintained at a pH 8-10 in presence of divalent cationsPrecipitated from a culture medium maintained at a pH 8-10 in presence of divalent cations

Can be separated by ion exchange chromatography Can be separated by ion exchange chromatography

Therapeutic uses Therapeutic uses

Effective against gram+ive and gram –ive micro-organisms Effective against gram+ive and gram –ive micro-organisms BacteriostaticBacteriostatic Inhibit essential enzymes in bacterial cellInhibit essential enzymes in bacterial cell Prevent synthesis of ribosomes Prevent synthesis of ribosomes Used in treatment of infections such as pneumonia, Used in treatment of infections such as pneumonia,

actinomycosis, urinary infection, spotted fever, typhus fever, actinomycosis, urinary infection, spotted fever, typhus fever, gonorrhea, syphilis,plague, ricketisia, etc.gonorrhea, syphilis,plague, ricketisia, etc.

Oromycin is effective against many bacteria similar to Oromycin is effective against many bacteria similar to cholorominphenicol but is not as effective as cholorominphenicol but is not as effective as chloramphenicol against typhoid feverchloramphenicol against typhoid fever

..

Less toxic drug, tolerated by patientsLess toxic drug, tolerated by patients Tetramycin is more stable than oramycinTetramycin is more stable than oramycin Used in treatment of conjunctivitis, cholera, amoebic Used in treatment of conjunctivitis, cholera, amoebic

dysentery, etc. dysentery, etc. Its effective against pneumonococci, streptococci, H-Its effective against pneumonococci, streptococci, H-

influenza, e-coli, M-tuberculosisinfluenza, e-coli, M-tuberculosis Absorbed in duodenum and small intestine Absorbed in duodenum and small intestine Long duration of anti-bacterial actionLong duration of anti-bacterial action They form insoluble complexes with calcium and magnesiumThey form insoluble complexes with calcium and magnesium Substances like milk which contain calcium and antacids Substances like milk which contain calcium and antacids

reduce their absorptionreduce their absorption Not advisable for children and pregnant women Not advisable for children and pregnant women

Chemical propertiesChemical properties Yellow, odourless, crystalline powder with bitter tasteYellow, odourless, crystalline powder with bitter taste Sparingly soluble in waterSparingly soluble in water Oxidized by oxygen in air, they darken when exposed to air Oxidized by oxygen in air, they darken when exposed to air Amphoteric in nature , basicity is due to N-amino group and Amphoteric in nature , basicity is due to N-amino group and

acidity is due to phenolic groupacidity is due to phenolic group Form chelates with metal ionsForm chelates with metal ions Due to the presence of phenol, it gives colour with neutral Due to the presence of phenol, it gives colour with neutral

ferric chloride and forms azo dyeferric chloride and forms azo dye Gives florescence in presence of UV lightGives florescence in presence of UV light

StreptomycinStreptomycin

Belongs to the important amino glycosidic group of antibiotic Belongs to the important amino glycosidic group of antibiotic

It is given the name from streptomyces It is given the name from streptomyces

Organism producing the antibiotic is known as “Streptomyces Organism producing the antibiotic is known as “Streptomyces

Griseus”Griseus”

Other examples of amino glycosidic antibiotics are Other examples of amino glycosidic antibiotics are

gentamycins, neomycinsgentamycins, neomycins

Therapeutic usesTherapeutic uses

Used in treatment of tuberculosis, infections of e-coli, H-Used in treatment of tuberculosis, infections of e-coli, H-

influenza, plague, respiratory tract infection, meningitiesinfluenza, plague, respiratory tract infection, meningities

Bactericidal propertiesBactericidal properties

Disturbs the normal protein synthesis and bacteriaDisturbs the normal protein synthesis and bacteria

Destroyes the cell membraneDestroyes the cell membrane

PropertiesProperties

Colourless solidColourless solid Dissolves in water but soluble in organic Dissolves in water but soluble in organic

solvents solvents Optically active and Leavoratotary Optically active and Leavoratotary Basic in nature Basic in nature

StructureStructure

Streptomycin is made Streptomycin is made up of three basic up of three basic units:units:

StreptidineStreptidine L-streptoseL-streptose N- methyl L-N- methyl L-

glucosamine glucosamine

RifamycinRifamycin It is isolated from “Streptomyces mediterranei”It is isolated from “Streptomyces mediterranei”

Belongs to a new class of antibiotics called “Ansamycins”Belongs to a new class of antibiotics called “Ansamycins”

There are five types of rifamycis A,B,C,D,E There are five types of rifamycis A,B,C,D,E

Cant be administered orallyCant be administered orally

Given intravenouslyGiven intravenously

Therapeutic usesTherapeutic uses

Inhibits the growth of gram +ive bacteria such as e-coli, keri Inhibits the growth of gram +ive bacteria such as e-coli, keri bacilabacila

Effective against staphylococcus Effective against staphylococcus Acts by blocking the biosynthesis of nucleic acid of bacteria Acts by blocking the biosynthesis of nucleic acid of bacteria

Used in the treatment of tuberculosisUsed in the treatment of tuberculosis

PropertiesProperties

Reddish brown crystalline powderReddish brown crystalline powder Slightly soluble in water, completely in methanolSlightly soluble in water, completely in methanol It exist as a “zwitter ion”It exist as a “zwitter ion”

CephalosporinsCephalosporins Isolated from the fungi “Cephalosporium acremonium” in 1948Isolated from the fungi “Cephalosporium acremonium” in 1948 They are β-lactum antibiotic with same fundamental structure as penicillin They are β-lactum antibiotic with same fundamental structure as penicillin It contains dihydro-meta thiazine ring It contains dihydro-meta thiazine ring Most acid stable than penicillin Most acid stable than penicillin

Classification of cephalosporinClassification of cephalosporin

Cephalosporin NCephalosporin N

Cephalosporin PCephalosporin P

Cephalosporin CCephalosporin C

Cephalosporin C is true cephalosporinCephalosporin C is true cephalosporin

Therapeutic usesTherapeutic uses

Used in the treatment of urinary tract infections, streptococcal Used in the treatment of urinary tract infections, streptococcal infections, pneumonia, tonsillitis, skin infections, etc.infections, pneumonia, tonsillitis, skin infections, etc.

Inhibits cross linking of peptide units in bacterial cell wallInhibits cross linking of peptide units in bacterial cell wall

They have been divided into four generations This division is chronological order, the overall antibacterial

spectrum as well as potency. It is the most potent first generation fluoroquinolones active

against broad range of bacteria-aerobic gram -tve bacilli & gram

+tve bacteria at higher concentrations. important feature- tissue penetrability.

CIPROFLOXACIN

THERAPEUTIC USES

Effective against urinary tract infections,typhoid,bone,soft tissue

gynaecological and wound infections,respiratory infections,

tuberculosis, meningitis and conjunctivitis

First choice drug- typhoid cells since chloramphenicol,

amphicillil and cotrimaxazole are unreliable due to development

of resistance.

Used as a component of combination of multi drug treatment of

tuberculosis and respiratory infections.

MODE OF ACTION

It is rapidly absorbed orally but food delays absorption high tissue penetrability concentration in lung muscle and boneExcreted by urine

ADVERSE EFFECTS Produces nausea, vomiting and bad taste Cause head aches, anxiety & insomnia,some times rashes on

the skin. not admistered to children- damage to weight bearing joints.

Extremely potent and broad spectrum antibiotic. It is a β-lactone antibiotic resistant to β-lactinases. limiting feature of imipenim is rapid hydrolysis by enzyme

peptidase located in the border of renal tubular cells. effective in treatment of hospital acquired infections- cancer &

AIDSActivity include gram +tve cocci and enterobacteriaceaeIt cause seizuse at higher doses.

CARBAPENEMS