Antibiotics

1. 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

2. 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.

3. 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 C
1111HH
1212OO
55NN
22ClCl
22

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

4. 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 Used in treatment of typhoid, pneumonia, ricketisia, urinary
tract infection, whooping cough, meningitis, plague, syphilis, tract infection, whooping cough, meningitis, plague, syphilis,
gonorrhea & dysentrygonorrhea & 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 As it is insoluble in water it has to be administered in the form
of fine particles.of fine particles.

5. 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% .

6. ..
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.

7. 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

8. 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

9. 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

10. ..
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.

11. 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.

12. 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

13. 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

14. 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

15. ..

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

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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

22. 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

23. 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”

24. 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

25. 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

26. 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

27. 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.

28. MODE OF ACTION
 It is rapidly absorbed orally but food delays absorption
 high tissue penetrability
 concentration in lung muscle and bone
Excreted 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.

29. 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 &
AIDS
Activity include gram +tve cocci and enterobacteriaceae
It cause seizuse at higher doses.
CARBAPENEMS