Antibiotics

TABLE OF CONTENTS
1. INTRODUCTION
2. HISTORY OF ANTIBIOTICS
2.1. 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.

ANTIBIOTICS



ANTIBIOTICS
1. INRODUCTION
Antibiotics are drugs that are used in the treatment or prevention of bacterial infections. Strictly speaking, antibiotics are natural substances produced by micro-organisms as opposed to semi-synthetic or synthetic antibiotics, which are either natural substances artificially modified or totally human created respectively.
Antibiotics form part of a wider range of antimicrobial agents, a group which also includes antifungal, antiviral, antiprotozoals and disinfectants. This group is also known as chemotherapeutic agents.
Antibiotics are drugs derived wholly or partially from certain microorganisms and are used to treat bacterial or fungal infections. They are ineffective against viruses. Antibiotics either 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




2.1. EARLY HISTORY
 In 3500 BC the Sumerian doctors would give patients beer soup mixed with snakeskin’s and turtle shells. Babylonian doctors would heal the eyes by using an ointment made of frog bile and sour milk.
 The Greeks used many herbs to heal ailments.
 All of these "natural" treatments contained some sort of antibiotic.


2.2. MODERN HISTORY

Louis Pasteur observed that bacteria could be used to kill other bacteria.
In 1929 Fleming, left A Petri dish of staphylococci bacteria uncovered. When he returned, he noticed that there was mold growing on it. Upon further examination, he saw that the area around the mold had no bacteria growing. He named the mold Penicillium, and the chemical produced by the mold was named penicillin, which is the first substance recognized as an antibiotic..
In the late 1940's streptomycin, chloramphenicol, and tetracycline were discovered and introduced as antibiotics.





2.3. Penicillin-THE FIRST MIRACLE ANTIBIOTIC


Penicillin core structure
Penicillin (sometimes abbreviated PCN or pen) is a group of Beta-lactam antibiotics used in the treatment of bacterial infections 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 kill bacteria. Bacteria are single-cell organisms. If bacteria make it past our immune systems and start reproducing inside our bodies, they cause disease. We want to kill the bacteria to eliminate the disease.

An antibiotic is a selective poison. It has been chosen so that it will kill the desired bacteria, but not the cells in your body.
Certain bacteria produce chemicals that damage or disable parts of our body. So you take an antibiotic to kill the bacteria.
 An antibiotic is a selective poison. It has been chosen so that it will kill the desired bacteria, but not the cells in your body. Each different type of antibiotic affects different bacteria in different ways. For example, an antibiotic might inhibit a bacterium's ability to turn glucose into energy, or its ability to construct its cell wall. When this happens, the bacterium dies instead of reproducing. At the same time, the antibiotic acts only on the bacterium's cell-wall-building mechanism, not on a normal cell's.
 Antibiotics do not work on viruses because viruses are not alive. A virus is just a piece of DNA (or RNA). A virus injects 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 NATURAL
o SEMI SYNTHETIC
Chemotherapeutic agents (synthetic antibiotics): Antimicrobial agents of synthetic origin examples are sulfanilamide, isoniazid, ethambutol, AZT, nalidixic acid and chloramphenicol. Therapeutic agent as a "synthetic antibiotic".
Natural Antibiotics: Antimicrobial agents produced by microorganisms that kill other microorganism
Three bacterial colonies growing on this plate secrete antibiotics that diffuse into the medium and inhibit the growth of a mold.
.
Semi synthetic antibiotics are molecules produced a microbe that are subsequently modified by an organic chemist to enhance their antimicrobial properties e.g. Amoxillins,Ampicillin.

5. CHEMOTHERAPEUTIC SPECTRUM

5.1. Broad spectrum antibiotic: The term broad-spectrum antibiotic refers to an antibiotic with: activity against a wide range of disease-causing bacteria. A good example of a commonly used broad-spectrum antibiotic is levofloxacin.
5.2. Narrow spectrum antibiotic: Ideally, they activity is limited to few bacterias.e.g.PENCILLIN (5)
6. Mechanism of Action
Variation in site of action can indicate why certain antibiotics operate against certain bacteria, but not others.
The principle sites of action are:
1. Cell wall synthesis
2. Cell membrane function
3. Protein synthesis
4. Nucleic acid synthesis

 Cell wall synthesis inhibitors Cell wall synthesis inhibitors 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 therapeutically useful antibiotics owe their action to inhibition of some step in the complex process of translation. The most important antibiotics with this mode of action are the tetracyclines, chloramphenicol.
 Effects on Nucleic Acids Some chemotherapeutic agents affect the synthesis of DNA or RNA, or can bind to DNA or RNA so that their messages cannot be read

7. Classes and properties of Antibiotics:

Chemical class Examples Biological source Spectrum (effective against)
Beta-lactams (penicillin and cephalosporin) Penicillin G, Cephalothin Penicillium notatum and Cephalosporium species Gram-positive bacteria
Semi synthetic penicillin Ampicillin, Amoxycillin Gram-positive and Gram-negative bacteria
Clavulanic Acid Clavamox is clavulanic acid plus amoxycillin Streptomyces clavuligerus Gram-positive and Gram-negative bacteria
Monobactams Aztreonam Chromobacter violaceum Gram-positive and Gram-negative bacteria


Chemical class Examples Biological source
Semisynthetic penicillin Ampicillin, Amoxycillin
Clavulanic Acid Clavamox is clavulanic acid plus amoxycillin Streptomyces clavuligerus
Monobactams Aztreonam Chromobacter violaceum
Carboxypenems Imipenem Streptomyces cattleya
Aminoglycosides Streptomycin Streptomyces griseus
Gentamicin Micromonospora species
Glycopeptides Vancomycin Streptomyces orientales
Lincomycins Clindamycin Streptomyces lincolnensis
Macrolides Erythromycin Streptomyces erythreus
Polypeptides Polymyxin Bacillus polymyxa
Bacitracin Bacillus subtilis
Polyenes Amphotericin Streptomyces nodosus
Nystatin Streptomyces noursei
Rifamycins Rifampicin Streptomyces mediterranei











8. Kinds of Antimicrobial Agents and their Primary Modes of Action



8.1.Cell wall synthesis inhibitors Cell wall synthesis inhibitors generally inhibit some step in the synthesis of bacterial peptidoglycan.
Beta lactams antibiotics Chemically, these antibiotics contain a 4-membered beta lactam ring. They are the products of two groups of fungi, Penicillium and Cephalosporium molds, the beta lactam antibiotics inhibit the last step in peptidoglycan synthesis.

 Natural penicillins, such as Penicillin G or Penicillin V, are produced by fermentation of Penicillium chrysogenum. They are effective against streptococcus, gonococcus
 Semi synthetic penicillin first appeared in 1959. Many of these compounds have been developed to have distinct benefits or advantages over penicillin G, such as increased spectrum of activity (e.g. Amoxycillin,methicillin)
 Clavulanic acid is a chemical sometimes added to a semi synthetic penicillin preparation. Thus, amoxycillin plus clavulanate is clavamox or augmentin. It inhibits beta lactamase enzymes and has given extended life to penicillinase-sensitive beta lactams.
 Cephalosporins are beta lactam antibiotics with a similar mode of action to penicillins that are produced by species of Cephalosporium. The have a low toxicity and a somewhat broader spectrum than natural penicillins.
Chemical structure of some Beta Lactam antibiotics.
 Bacitracin is a polypeptide antibiotic produced by Bacillus species. It prevents cell wall growth by inhibiting the release of the muropeptide.Since it is not absorbed by the gut; it is given to "sterilize" the bowel prior to surgery.
8.2. Cell membrane inhibitors disorganize the structure or 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 and thereby interfere with membrane function.
8.3. Protein synthesis inhibitors Many therapeutically useful antibiotics owe their action to inhibition of some step in the complex process of translation. The most important antibiotics with this mode of action are the tetracyclines, chloramphenicol, the macrolides (e.g. erythromycin) and the aminoglycosides (e.g. streptomycin).
 The aminoglycosides are products of Streptomyces species and are represented by streptomycin, kanamycin, tobramycin and gentamicin. These antibiotics exert their activity by binding to bacterial ribosomes and preventing the initiation of protein synthesis.

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 that exerts a bacteriostatic effect. It is effective against intracellular parasites such as the rickettsiae.
Chloramphenicol is entirely selective for 70S ribosomes and does not affect 80S ribosomes
The chemical structure of chloroamphenicol.
8.4 Effects on Nucleic Acids Some chemotherapeutic agents affect the synthesis of DNA or RNA, or can bind to DNA or RNA so that their messages cannot be read
 Quinolones are broad-spectrum agents that rapidly kill bacteria and are well absorbed after oral administration. Nalidixic acid and ciprofloxacin belong to this group.
The chemical structure of nalidixic acid.

The chemical structure of ciprofloxacin.

8.5. Competitive Inhibitors The competitive inhibitors are mostly all synthetic chemotherapeutic agents, chemicals which are structurally similar to a bacterial growth factor but which do not fulfill its metabolic function in the cell.
 Sulfanilamide were introduced as chemotherapeutic agents 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 amino benzoic acid (PABA), the substrate for the first enzyme in the THF pathway, and they competitively inhibit that step.

Sulfanilamide is similar in structure to para-amino benzoic acid (PABA), an intermediate in the biosynthetic pathway for folic acid. Sulfanilamide can competitively inhibit the enzyme that has PABA as its normal substrate by competitively occupying the active site of the enzyme.



9. The basis of bacterial resistance to antibiotics

An antibiotic sensitivity test performed on an agar plate. The discs are seeded with antibiotics planted on the agar surface. Interpretation of the size of the bacterial "zones of inhibition" relates to the possible use of the antibiotic in a clinical setting. The organism is resistant to the antibiotics planted on the plate at 5 o'clock and 9 o'clock.
Bacterial resistance to an antimicrobial agent may be due to some innate property of the organism or it may due to acquisition of some genetic trait as described below.
• Inherent (Natural) Resistance - Bacteria may be inherently resistant to an antibiotic. For example, a streptomycete may have some natural gene that is responsible for resistance to its own antibiotic.
• 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: a spontaneous mutation in the bacterial chromosome imparts resistance to a member of the bacterial population. In the selective environment of the antibiotic, 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 another organism. Some bacterium develops genetic resistance through the process of mutation and selection and then donates these genes to some other bacterium through one of several processes for genetic exchange that exist in bacteria.

9.1.The medical problem of bacterial drug resistance:
Obviously, if a bacterial pathogen is able to develop or acquire resistance to an antibiotic, then that substance becomes useless in the treatment of infectious disease caused by that pathogen. So as pathogens develop resistance, we must find new (different) antibiotics to fill the place of the old ones in treatment regimes. Hence, natural penicillins have become useless against staphylococci and must be replaced by other antibiotics; tetracycline, having been so widely used and misused for decades, has become worthless for many of the infections where it once worked as a "wonder drug".

10. Health Hazard
• Today’s society has access to more antibiotics than ever before,. Antibiotic cures for different ailments are used frequently by the human population. This proliferation of antibiotic use has some dangerous repercussions.
• 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 the human population consuming this livestock. Attempts to correct, this eruption of hazardous effects of antibiotic use have been targeted towards the FDA and Department of Agriculture to reduce the use of antibiotics in livestock food, and towards physicians to utilize antibiotics more prudently.

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. Mild allergic reactions consist of an itchy rash or slight wheezing. Severe allergic reactions (anaphylaxis) can be life threatening
11. Rational use of antibiotics:
1. Right diagnosis should be made either clinically or by laboratory.
2. Proper selection of drug—
§ Specificity
§ Safe drug &proper combination
3. Right dose—usually we give initially loaded dose followed by maintenance dose.
4. Right duration—at least 3-5 days antibiotic should be continued.
5. Status of the patient—
§ Age of the patient.
§ Immune system of the patient.
12. REFRENCES

1. ^Drews, Jurgen (March 2000).”Antibiotic Discovery”.
Science 287 (5460):1960-1964.
2. ^Mary Bellis.”The History of Antibiotics”.
Baylor University Medical Center proceedings 14(1):106-107.
3. ^ Gruchalla RS, Pirmohamed M (2006).”Clinical
Practice. Antibiotic allergy”.N. Engl.J. Med.354 (6):799
4. ^ Antunez C, Blanca-Lopez N, Torres MJ, et al (2006).
“Natural Antibiotics and Their Spectrum”.
5. ^ Pechichero ME (2007).”Antibiotic Resistance”.J.
Allergy Clin. Immunol.117 (2):404-10.
6. Web Sites:
http://www.nlm.nih.gov/medlineplus/antibiotics.html
http://en.wikipedia.org/wiki/Penicillin
http://wikimedia.org/wikipedia/commons/thumb/8/82/Penicillin-core.png/800px-P
http://www.textbookofantibiotics.net/control.html
http://www.answers.com/topic/broad-spectrum-antibiotics
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