this term paper is on the topic of antibiotics

7/30/2019 this term paper is on the topic of antibiotics

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PROJECTON

ANTIBIOTICS

(Or g a n ic c h emist r y : 153)

BMITTED TO: SUBMITTED BY:

. Rupesh Manak Name : Harkiran Kaur

Course: B.Tech (hons.)

-MBA (BIOTECH)

Section: 269

Roll No.: R269A09

Regd. No.: 10800646

Subject: ANTIBIOITICS

(Org. chemist


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TABLE OF CONTENTS

1. INTRODUCTION

2. HISTORY OF ANTIBIOTICS2.1. EARLY HISTORY

2.2. MODERN HISTORY

2.3. THE FIRST MIRACLE ANTIBIOTIC

3. HOW DO ANTIBIOTICS WORK?

4. TYPES OF ANTIBIOTICS

5. CHEMOTHERAPEUTIC SPECTRUM

6. MECHANISM OF ACTION

7. CLASSES &PROPERTIES OF ANTIBIOTICS

8. KINDS OF ANTIBIOTICS &PRIMARY MODES OF

ACTION

8.1. CELL WALL SYNTHESIS INHIBITORS

8.2. CLL MAMBRANE INHIBITORS

8.3. PROTEIN SYNTHESIS INHIBITORS

8.4. EFFECT ON NUCLEIC ACIDS

8.5. COMPETITIVE INHIBITORS

9. BASIS OF BACTERIAL RESISTANCE TO

ANTIBIOTICS

9.1. MEDICAL PROBLEM OF BACTERIAL

RESISTANCE

10. HEALTH HAZARDS

10.1. SIDE EFFECTS AND ALLERGIES

11. RATIONAL USE OF ANTIBIOTICS

12. REFRENCES.


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ANTIBIOTICS

ANTIBIOTICS1. INRODUCTION


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Antibiotics are drugs that are used in the treatment orprevention of bacterial infections. Strictly speaking,antibiotics are natural substances produced by micro-

organisms as opposed to semi-synthetic or syntheticantibiotics, which are either natural substances artificiallymodified or totally human created respectively.

Antibiotics form part of a wider range ofantimicrobialagents, a group which also includes antifungal, antiviral,antiprotozoals and disinfectants. This group is also knownas chemotherapeutic agents.

Antibiotics are drugs derived wholly or partially from certainmicroorganisms and are used to treat bacterial or fungalinfections. They are ineffective against viruses. Antibioticseither kill microorganisms or stop them from reproducing,allowing the body's natural defenses to eliminate them.

Antibiotics can not fight infections caused by viruses, such

as:

Colds

Flu

Most cough and bronchitis, sore throat.

2. HISTORY OF ANTIBIOTICS


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2.1. EARLY HISTORY In 3500 BC the Sumerian doctors would give patients

beer soup mixed with snakeskins and turtle shells.Babylonian doctors would heal the eyes by using anointment made of frog bile and sour milk.

The Greeks used many herbs to heal ailments.

All of these "natural" treatments contained some sort ofantibiotic.


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2.2.MODERN HISTORY

Louis Pasteurobserved that bacteria could be used to killother bacteria.

In 1929 Fleming, left A Petri dish of staphylococci

bacteria uncovered. When he returned, he noticed that therewas mold growing on it. Upon further examination, he sawthat the area around the mold had no bacteria growing. He

named the mold Penicillium, and the chemical produced bythe mold was named penicillin, which is the first substancerecognized as an antibiotic..

In the late 1940's streptomycin, chloramphenicol, andtetracycline were discovered and introduced as antibiotics.
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2.3. Penicillin-THE FIRST MIRACLEANTIBIOTIC

Penicillin core structure

Penicillin (sometimes abbreviated PCN orpen) is a groupofBeta-lactam antibiotics used in the treatment ofbacterialinfections caused by susceptible, usually Gram-positive,organisms, which has the molecular formula R-C9H11N2O4S,where R is a variable side chain.

Penicillin was being mass-produced in 1944

3. How do antibiotics

work?

Antibiotics work to killbacteria. Bacteria are single-

cell organisms. If bacteria make it past ourimmune
http://en.wikipedia.org/wiki/Beta-lactam_antibiotichttp://en.wikipedia.org/wiki/Bacteriahttp://en.wikipedia.org/wiki/Infectionhttp://en.wikipedia.org/wiki/Gram-positivehttp://en.wikipedia.org/wiki/Side_chainhttp://science.howstuffworks.com/cell.htmhttp://health.howstuffworks.com/immune-system.htmhttp://en.wikipedia.org/wiki/Image:PenicillinPSAedit.jpghttp://en.wikipedia.org/wiki/Image:Penicillin-core.pnghttp://en.wikipedia.org/wiki/Image:Penicillin-core.pnghttp://en.wikipedia.org/wiki/Beta-lactam_antibiotichttp://en.wikipedia.org/wiki/Bacteriahttp://en.wikipedia.org/wiki/Infectionhttp://en.wikipedia.org/wiki/Gram-positivehttp://en.wikipedia.org/wiki/Side_chainhttp://science.howstuffworks.com/cell.htmhttp://health.howstuffworks.com/immune-system.htm


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systems and start reproducing inside our bodies, theycause disease. We want to kill the bacteria to eliminate thedisease.

An antibiotic is a selective poison. Ithas been chosen so that it will killthe desired bacteria, but not the

cells in your body.Certain bacteria produce chemicals that damage or disableparts of our body. So you take an antibiotic to kill thebacteria.

An antibiotic is a selective poison. It has been chosenso that it will kill the desired bacteria, but not the cells inyour body. Each different type of antibiotic affects different

bacteria in different ways. For example, an antibiotic mightinhibit a bacterium's ability to turn glucose into energy, orits ability to construct its cell wall. When this happens, thebacterium dies instead of reproducing. At the same time,the antibiotic acts only on the bacterium's cell-wall-buildingmechanism, not on a normal cell's.
http://health.howstuffworks.com/immune-system.htmhttp://science.howstuffworks.com/cell.htmhttp://health.howstuffworks.com/immune-system.htmhttp://science.howstuffworks.com/cell.htm


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Antibiotics do not work on viruses because viruses are notalive. A virus is just a piece ofDNA (or RNA). A virusinjects its DNA into a living cell and has that cell reproduce

more of the viral DNA. With a virus there is nothing to "kill,"so antibiotics don't work on it.

4. TYPES OF ANTIBIOTICS

o SYNTHETIC

o

NATURALo SEMI SYNTHETIC

Chemotherapeutic agents (synthetic antibiotics):

Antimicrobial agents of synthetic origin examples aresulfanilamide, isoniazid, ethambutol, AZT, nalidixic acidand chloramphenicol. Therapeutic agent as a "syntheticantibiotic".

Natural Antibiotics: Antimicrobial agents produced by

microorganisms that kill other microorganism
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5.2. Narrow spectrum antibiotic: Ideally, they activity islimited to few bacterias.e.g.PENCILLIN (5)

6. Mechanism of ActionVariation in site of action can indicate why certainantibiotics operate against certain bacteria, but not others.

The principle sites of action are:

1. Cell wall synthesis

2. Cell membrane function3. Protein synthesis4. Nucleic acid synthesis

Cell wall synthesis inhibitors Cell wall synthesisinhibitors generally inhibit some step in the synthesis of

bacterial peptidoglycan.Cell membrane inhibitors disorganize the structure or

inhibit the function of bacterial membranes.

Protein synthesis inhibitors Many therapeuticallyuseful antibiotics owe their action to inhibition of somestep in the complex process of translation. The mostimportant antibiotics with this mode of action are the

tetracyclines, chloramphenicol.

Effects on Nucleic Acids Some chemotherapeuticagents affect the synthesis of DNA or RNA, or can bindto DNA or RNA so that their messages cannot be read


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7. Classes and properties of

Antibiotics:

Chemical class Examples Biological sourceSpectrum(effectiveagainst)

Beta-lactamspenicillin and

cephalosporin)

Penicillin G,Cephalothin

Penicillium notatumand Cephalosporiumspecies

Gram-positivbacteria

Semi syntheticpenicillin

Ampicillin,Amoxycillin

Gram-positivand Gram-negativebacteria

Clavulanic AcidClavamox isclavulanic acidplus amoxycillin

Streptomycesclavuligerus

Gram-positivand Gram-negativebacteria

Monobactams AztreonamChromobacterviolaceum

Gram-positivand Gram-negative

bacteria


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Chemical class Examples Biological source

Semisyntheticenicillin

Ampicillin, Amoxycillin

Clavulanic AcidClavamox is clavulanicacid plus amoxycillin

Streptomyces clavuligeru

Monobactams Aztreonam Chromobacter violaceum

Carboxypenems Imipenem Streptomyces cattleya

Aminoglycosides Streptomycin Streptomyces griseus

Gentamicin Micromonospora species

Glycopeptides Vancomycin Streptomyces orientales

incomycins Clindamycin Streptomyces lincolnensi

Macrolides Erythromycin Streptomyces erythreus

Polypeptides Polymyxin Bacillus polymyxa

Bacitracin Bacillus subtilis

Polyenes Amphotericin Streptomyces nodosus

Nystatin Streptomyces noursei

Rifamycins Rifampicin Streptomyces mediterran


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8. Kinds of Antimicrobial Agents andtheir Primary Modes of Action


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8.1.Cell wall synthesis inhibitors Cell wall synthesisinhibitors generally inhibit some step in the synthesis ofbacterial peptidoglycan.

Beta lactams antibiotics Chemically, these antibioticscontain a 4-membered beta lactam ring. They are the

products of two groups of fungi, Penicillium andCephalosporium molds, the beta lactam antibiotics inhibitthe last step in peptidoglycan synthesis.


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Natural penicillins, such as Penicillin G orPenicillinV, are produced by fermentation ofPenicilliumchrysogenum. They are effective against streptococcus,

gonococcus Semi synthetic penicillin first appeared in 1959. Many

of these compounds have been developed to havedistinct benefits or advantages over penicillin G, such asincreased spectrum of activity

(e.g. Amoxycillin,methicillin)

Clavulanic acid is a chemical sometimes added to asemi synthetic penicillin preparation. Thus,amoxycillin plus clavulanate is clavamox oraugmentin. It inhibits beta lactamase enzymes andhas given extended life to penicillinase-sensitive betalactams.

Cephalosporins are beta lactam antibiotics with a

similar mode of action to penicillins that are producedby species ofCephalosporium. The have a low toxicityand a somewhat broader spectrum than natural

penicillins.


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Chemical structure of some Beta Lactamantibiotics.

Bacitracin is a polypeptide antibiotic produced byBacillus species. It prevents cell wall growth byinhibiting the release of the muropeptide.Since it is notabsorbed by the gut; it is given to "sterilize" the bowelprior to surgery.

8.2. Cell membrane inhibitors disorganize the structureor inhibit the function of bacterial membranes.

Polymyxin is effective mainly against Gram-negative

bacteria and is usually limited to topical usage.Polymyxin bind to membrane phospholipids andthereby interfere with membrane function.

8.3. Protein synthesis inhibitors Many therapeuticallyuseful antibiotics owe their action to inhibition of some step

in the complex process of translation. The most importantantibiotics with this mode of action are the tetracyclines,chloramphenicol, the macrolides (e.g. erythromycin) andthe aminoglycosides (e.g. streptomycin).

The aminoglycosides are products ofStreptomycesspecies and are represented by streptomycin,kanamycin, tobramycin and gentamicin. These

antibiotics exert their activity by binding to bacterialribosomes and preventing the initiation of proteinsynthesis.


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The chemical structure of tobramycin.

Tetracyclines inhibit protein synthesis on isolated

70S or 80S (eukaryotic) ribosomes, and in both cases,their effect is on the small ribosomal subunit.

The tetracyclines have a remarkably low toxicity and

minimal side effects when taken by animals

The chemical structure of tetracycline.

Chloramphenicol has a broad spectrum of activity thatexerts a bacteriostatic effect. It is effective againstintracellular parasites such as the rickettsiae.


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Chloramphenicol is entirely selective for 70S ribosomes

and does not affect 80S ribosomesThe chemical structure of chloroamphenicol.

8.4 Effects on Nucleic Acids Some chemotherapeuticagents affect the synthesis of DNA or RNA, or can bind toDNA or RNA so that their messages cannot be read

Quinolones are broad-spectrum agents that rapidly killbacteria and are well absorbed after oral administration.Nalidixic acid and ciprofloxacin belong to this group.

The chemical structure of nalidixic acid.


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The chemical structure of ciprofloxacin.

8.5. Competitive Inhibitors The competitive inhibitors are

mostly all synthetic chemotherapeutic agents, chemicalswhich are structurally similar to a bacterial growth factor butwhich do not fulfill its metabolic function in the cell.

Sulfanilamide were introduced as chemotherapeuticagents by Domagk in 1935

The sulfonamides are inhibitors of the bacterial enzymes

required for the synthesis of tetrahydrofolic acid(THFSulfonamides are structurally similar to para aminobenzoic acid (PABA), the substrate for the first enzyme in


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the THF pathway, and they competitively inhibit that step.

Sulfanilamide is similar in structure to para-aminobenzoic acid (PABA), an intermediate in thebiosynthetic pathway for folic acid. Sulfanilamide cancompetitively inhibit the enzyme that has PABA as itsnormal substrate by competitively occupying the activesite of the enzyme.


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9. The basis of bacterialresistance to antibiotics

An antibiotic sensitivity test performed on an agarplate. The discs are seeded with antibiotics planted onthe agar surface. Interpretation of the size of thebacterial "zones of inhibition" relates to the possibleuse of the antibiotic in a clinical setting. The organismis resistant to the antibiotics planted on the plate at 5o'clock and 9 o'clock.

Bacterial resistance to an antimicrobial agent may be dueto some innate property of the organism or it may due toacquisition of some genetic trait as described below.

Inherent (Natural) Resistance - Bacteria may be

inherently resistant to an antibiotic. For example, astreptomycete may have some natural gene that isresponsible for resistance to its own antibiotic.


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Acquired Resistance - Bacterial populations

previously-sensitive to antibiotics become resistant,due to:(1) mutation and selection; (2) exchange of

genes between strains and species

Vertical evolution is strictly a matter of Darwinian

evolution driven by principles of natural selection: aspontaneous mutation in the bacterial chromosomeimparts resistance to a member of the bacterialpopulation. In the selective environment of theantibiotic, the wild types (non mutants) are killed and

the resistant mutant is allowed to grow and flourish.

Horizontal gene transmission (HGT) is the

acquisition of genes for resistance from anotherorganism. Some bacterium develops geneticresistance through the process of mutation andselection and then donates these genes to some other

bacterium through one of several processes for geneticexchange that exist in bacteria.

9.1.The medical problem ofbacterial drug resistance:Obviously, if a bacterial pathogen is able to develop oracquire resistance to an antibiotic, then that substancebecomes useless in the treatment of infectious diseasecaused by that pathogen. So as pathogens developresistance, we must find new (different) antibiotics to fill the


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place of the old ones in treatment regimes. Hence, naturalpenicillins have become useless against staphylococci andmust be replaced by other antibiotics; tetracycline, having

been so widely used and misused for decades, hasbecome worthless for many of the infections where it onceworked as a "wonder drug".

10. Health Hazard

Todays society has access to more antibiotics thanever before,. Antibiotic cures for different ailments areused frequently by the human population. Thisproliferation of antibiotic use has some dangerousrepercussions.

By using antibiotics at inappropriate time, the only

effect on the body is the increased destruction of

beneficial bacteria.

An example of the hazards of this can be seen in

Hospital-acquired infections.

Antibiotics erroneously used by farmers in the food of

their livestock have massive repercussions on thehuman population consuming this livestock. Attempts

to correct, this eruption of hazardous effects ofantibiotic use have been targeted towards the FDA andDepartment of Agriculture to reduce the use ofantibiotics in livestock food, and towards physicians toutilize antibiotics more prudently.


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10.1. Side Effects and Allergies: Common side effects of antibiotics include upset

stomach, diarrhea. Some side effects are more severe and,depend on the antibiotics.

Antibiotics can also cause allergic reactions. Mildallergic reactions consist of an itchy rash or slightwheezing. Severe allergic reactions (anaphylaxis) can belife threatening

11. Rationa l use of antibiotics:1. Right diagnosis should be made either clinically or bylaboratory.

2. Proper selection of drug

Specificity

Safe drug &proper combination

3. Right doseusually we give initially loaded dosefollowed by maintenance dose.

4. Right durationat least 3-5 days antibiotic should becontinued.

5. Status of the patient

Age of the patient.

Immune system of the patient.


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12. REFRENCES

1. ^Drews, Jurgen (March 2000).AntibioticDiscovery.

Science 287 (5460):1960-1964.

2. ^Mary Bellis.The History of AntibioticsBaylor University Medical Center proceedings

14(1):106-107.3. ^ GruchallaRS, Pirmohamed M (2006).ClPractice. Antibiotic allergy.N. Engl.J. Me(6):799

4. ^ Antunez C, Blanca-Lopez N, Torres MJ, e(2006).

Natural Antibiotics and Their Spectrum5. ^ Pechichero ME (2007).Antibiotic

Resistance.J.Allergy Clin. Immunol.117 (2):404-10.

6. Web Sites:http://www.nlm.nih.gov/medlineplus/antibiomlhttp://en.wikipedia.org/wiki/Penicillinhttp://wikimedia.org/wikipedia/commons/thu82/Penicillin-core.png/800px-P
http://www.nlm.nih.gov/medlineplus/antibiotics.htmlhttp://www.nlm.nih.gov/medlineplus/antibiotics.htmlhttp://en.wikipedia.org/wiki/Penicillinhttp://wikimedia.org/wikipedia/commons/thumb/8/82/Penicillin-core.png/800px-Phttp://wikimedia.org/wikipedia/commons/thumb/8/82/Penicillin-core.png/800px-Phttp://www.nlm.nih.gov/medlineplus/antibiotics.htmlhttp://www.nlm.nih.gov/medlineplus/antibiotics.htmlhttp://en.wikipedia.org/wiki/Penicillinhttp://wikimedia.org/wikipedia/commons/thumb/8/82/Penicillin-core.png/800px-Phttp://wikimedia.org/wikipedia/commons/thumb/8/82/Penicillin-core.png/800px-P


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http://www.textbookofantibiotics.net/controhttp://www.answers.com/topic/broad-spectrantibiotics

THANK YOU
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