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Antibiotics

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  • Antibiotics

    Antibiotics[SIZE="5"][/SIZE
    Introduction
    [Antibiotics (Greek anti, “against”; bios, “life”) are chemical compounds used to kill or inhibit the growth of infectious organisms. Originally the term antibiotic referred only to organic compounds, produced by bacteria or molds, that are toxic to other microorganisms. The term is now used loosely to include synthetic and semisynthetic organic compounds. Antibiotic refers generally to antibacterials; however, because the term is loosely defined, it is preferable to specify compounds as being antimalarials, antivirals, or antiprotozoals. All antibiotics share the property of selective toxicity: They are more toxic to an invading organism than they are to an animal or human host. Penicillin is the most well-known antibiotic and has been used to fight many infectious diseases, including syphilis, gonorrhea, tetanus, and scarlet fever. Another antibiotic, streptomycin, has been used to combat tuberculosis

    II History
    Although the mechanisms of antibiotic action were not scientifically understood until the late 20th century, the principle of using organic compounds to fight infection has been known since ancient times. Crude plant extracts were used medicinally for centuries, and there is an evidence for the use of cheese molds for topical treatment of infection. The first observation of what would now be called an antibiotic effect was made in the 19th century by French chemist Louis Pasteur, who discovered that certain saprophytic bacteria can kill anthrax bacilli. In the first decade of the 20th century, German physician and chemist Paul Ehrlich began experimenting with the synthesis of organic compounds that would selectively attack an infecting organism without harming the host organism. His experiments led to the development, in 1909, of salvarsan, a synthetic compound containing arsenic, which exhibited selective action against spirochetes, the bacteria that cause syphilis. Salvarsan remained the only effective treatment for syphilis until the purification of penicillin in the 1940s. In the 1920s British bacteriologist Sir Alexander Fleming, who later discovered penicillin, found a substance called lysozyme in many bodily secretions, such as tears and sweat, and in certain other plant and animal substances. Lysozyme has some antimicrobial activity, but it is not clinically useful.
    Penicillin, the archetype of antibiotics, is a derivative of the mold Penicillium notatum. Penicillin was discovered accidentally in 1928 by Fleming, who showed its effectiveness in laboratory cultures against many disease-producing bacteria. This discovery marked the beginning of the development of antibacterial compounds produced by living organisms. Penicillin in its original form could not be given by mouth because it was destroyed in the digestive tract and the preparations had too many impurities for injection. No progress was made until the outbreak of World War II stimulated renewed research and the Australian pathologist Sir Howard Florey and German-British biochemist Ernst Chain purified enough of the drug to show that it would protect mice from infection. Florey and Chain then used the purified penicillin on a human patient who had staphylococcal and streptococcal septicemia with multiple abscesses and osteomyelitis. The patient, gravely ill and near death, was given intravenous injections of a partly purified preparation of penicillin every three hours. Because so little was available, the patient's urine was collected each day, the penicillin was extracted from the urine and used again. After five days the patient's condition improved vastly. However, with each passage through the body, some penicillin was lost. Eventually the supply ran out and the patient died.
    The first antibiotic to be used successfully in the treatment of human disease was tyrothricin, isolated from certain soil bacteria by American bacteriologist Rene Dubos in 1939. This substance is too toxic for general use, but it is employed in the external treatment of certain infections. Other antibiotics produced by a group of soil bacteria called actinomycetes have proved more successful. One of these, streptomycin, discovered in 1944 by American biologist Selman Waksman and his associates, was, in its time, the major treatment for tuberculosis.
    Since antibiotics came into general use in the 1950s, they have transformed the patterns of disease and death. Many diseases that once headed the mortality tables—such as tuberculosis, pneumonia, and septicemia—now hold lower positions. Surgical procedures, too, have been improved enormously, because lengthy and complex operations can now be carried out without a prohibitively high risk of infection. Chemotherapy has also been used in the treatment or prevention of protozoal and fungal diseases, especially malaria, a major killer in economically developing nations (see Third World). Slow progress is being made in the chemotherapeutic treatment of viral diseases. New drugs have been developed and used to treat shingles (see herpes) and chicken pox. There is also a continuing effort to find a cure for acquired immunodeficiency syndrome (AIDS), caused by the human immunodeficiency virus (HIV),


    IIIClassification
    Antibiotics can be classified in several ways. The most common method classifies them according to their action against the infecting organism. Some antibiotics attack the cell wall; some disrupt the cell membrane; and the majority inhibit the synthesis of nucleic acids and proteins, the polymers that make up the bacterial cell. for example :-
    Aminoglycosides
    These are products of actinomycetes (soil bacteria) or semi-synthetic derivatives of the natural products.
    Examples are:
    • streptomycin
    • kanamycin
    • neomycin
    • gentamycin
    The Chink in the Armor = the bacterial ribosome
    The 70S bacterial ribosome differs in several ways from the 80S eukaryotic ribosome. [The aminoglycosides bind to the 30S subunit of the bacterial ribosome and
    • interfere with the formation of the initiation complex
    • cause misreading of the mRNA.
    Although the eukaryotic ribosome in the cytosol is relatively unaffected by these drugs, ribosomes in the mitochondria are 70S and sensitive to their effects.

    Tetracyclines
    These are natural products derived from soil actinomycetes or their semi-synthetic derivatives. Examples:
    • chlortetracycline (trade name = "aureomycin")
    • oxytetracycline (trade name = "terramycin")
    • doxycycline
    The Chink in the Armor = the bacterial ribosome
    Tetracyclines bind to the 30S subunit of the bacterial ribosome. They prevent the transfer of activated amino acids to the ribosome so protein synthesis is halted.
    Polypeptides
    The most common of these are the polymixins.
    They behave as detergents, increasing the permeability of the membranes that encase bacteria and causing the contents of the bacterial cell to leak out.
    Rifampin
    This semi-synthetic antibiotic binds to the bacterial RNA polymerase and prevents it from carrying out its role in transcription. Its affinity for the equivalent eukaryotic enzyme is much lower. Rifampin is also known as rifampicin.


    Cycloserine
    Cycloserine inhibits synthesis of the bacterial cell wall but by a different mechanism than the beta-lactam antibiotics discussed above. Cycloserine is an analog of D-alanine and blocks the incorporation of D-alanine into the peptide bridges in the bacterial cell wall (look back). It is derived from an actinomycete.
    Another method classifies antibiotics according to which bacterial strains they affect: staphylococcus, streptococcus, or Escherichia coli, for example. Antibiotics are also classified on the basis of chemical structure, as penicillins, cephalosporins, aminoglycosides, tetracyclines, macrolides, or sulfonamides, among others.
    Aminoglycosides
    Streptomycin is the oldest of the aminoglycosides. The aminoglycosides inhibit bacterial protein synthesis in many gram-negative and some gram-positive organisms. They are sometimes used in combination with penicillin. The members of this group tend to be more toxic than other antibiotics. Rare adverse effects associated with prolonged use of aminoglycosides include damage to the vestibular region of the ear, hearing loss, and kidney damage.
    Aminoglycosides are typically aminosugars linked together by glycosidic linkages.








    CHEMICAL STRUCTURE
    © John Heritage 2004, 2006
    Macrolides
    The macrolides are bacteriostatic, binding with bacterial ribosomes to inhibit protein synthesis. Erythromycin, one of the macrolides, is effective against gram-positive cocci and is often used as a substitute for penicillin against streptococcal and pneumococcal infections. Other uses for macrolides include diphtheria and bacteremia. Side effects may include nausea, vomiting, and diarrhea; infrequently, there may be temporary auditory impairment.

    Chemical structure of a macrolide with a 16-membered ring
    © John Heritage 2004, 2006


    Sulfonamides
    The sulfonamides are synthetic bacteriostatic, broad-spectrum antibiotics, effective against most gram-positive and many gram-negative bacteria. However, because many gram-negative bacteria have developed resistance to the sulfonamides, these antibiotics are now used only in very specific situations, including treatment of urinary-tract infection, against meningococcal strains, and as a prophylactic for rheumatic fever. Side effects may include disruption of the gastrointestinal tract and hypersensitivity. © John Heritage 2004, 2006


    Chemical structure of sulphamethoxazole, a sulphonamide

  • #2
    الله يجزاك خير.. كان عندي مشكلة مع الـ classification بس الحمد لله انحلت
    إن الحلم، الذي لا تستطيع أن تنزله من فضاء الخيال وتتحسسه ، وتحس به جزءا منك، وأنت جزء منه، سوف تضطر أن تصعد إليه.. لشئ واحد فقط..

    من أجل أن تهوي من عليائه فتتهشم...

    ثم تعود بعدها لتجمع حطامك..

    حطام قلبك المثخن بالخيبات..

    وحطام ذاكرتك الملأئ بالتجارب الفاشلة...

    أي قلب لك بعدها قادر على أن ينهض، يداوي جراحه.. يلملم حطامه ..
    _______________________________________________
    د. محمد الحضيف

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    • #3
      أما أنا فكان عندي مشكلة بـ Antibiotics كلها .. لكن انحلت ولله الحمد :sm180:

      مشكورة أختي منى .. ومتشكرين أوي .. :sm199:

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