Antibiotics & Homeopathic Antidotes.
Dr. Sayeed Ahmad D. I. Hom. (London)
I. - 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 anecdotal 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. Slow progress is being made in the chemotherapeutic treatment of viral diseases. New drugs have been developed and used to treat shingles 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).
III. - CLASSIFICATION
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. 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.
A. Mechanisms of Action
Most antibiotics act by selectively interfering with the synthesis of one of the large-molecule constituents of the cell�the cell wall or proteins or nucleic acids. Some, however, act by disrupting the cell membrane (see Cell Death and Growth Suppression below). Some important and clinically useful drugs interfere with the synthesis of peptidoglycan, the most important component of the cell wall. These drugs include the �-lactam antibiotics, which are classified according to chemical structure into penicillins, cephalosporins, and carbapenems. All these antibiotics contain a �-lactam ring as a critical part of their chemical structure, and they inhibit synthesis of peptidoglycan, an essential part of the cell wall. They do not interfere with the synthesis of other intracellular components. The continuing buildup of materials inside the cell exerts ever greater pressure on the membrane, which is no longer properly supported by peptidoglycan. The membrane gives way, the cell contents leak out, and the bacterium dies. These antibiotics do not affect human cells because human cells do not have cell walls.
Many antibiotics operate by inhibiting the synthesis of various intracellular bacterial molecules, including DNA, RNA, ribosomes, and proteins. The synthetic sulfonamides are among the antibiotics that indirectly interfere with nucleic acid synthesis. Nucleic-acid synthesis can also be stopped by antibiotics that inhibit the enzymes that assemble these polymers�for example, DNA polymerase or RNA polymerase. Examples of such antibiotics are actinomycin, rifamicin, and rifampicin, the last two being particularly valuable in the treatment of tuberculosis. The quinolone antibiotics inhibit synthesis of an enzyme responsible for the coiling and uncoiling of the chromosome, a process necessary for DNA replication and for transcription to messenger RNA. Some antibacterials affect the assembly of messenger RNA, thus causing its genetic message to be garbled. When these faulty messages are translated, the protein products are nonfunctional. There are also other mechanisms: The tetracyclines compete with incoming transfer-RNA molecules; the aminoglycosides cause the genetic message to be misread and a defective protein to be produced; chloramphenicol prevents the linking of amino acids to the growing protein; and puromycin causes the protein chain to terminate prematurely, releasing an incomplete protein.
B. Range of Effectiveness
In some species of bacteria the cell wall consists primarily of a thick layer of peptidoglycan. Other species have a much thinner layer of peptidoglycan and an outer as well as an inner membrane. When bacteria are subjected to Gram's stain, these differences in structure affect the differential staining of the bacteria with a dye called gentian violet. The differences in staining coloration (gram-positive bacteria appear purple and gram-negative bacteria appear colorless or reddish, depending on the process used) are the basis of the classification of bacteria into gram-positive (those with thick peptidoglycan) and gram-negative (those with thin peptidoglycan and an outer membrane), because the staining properties correlate with many other bacterial properties. Antibacterials can be further subdivided into narrow-spectrum and broad-spectrum agents. The narrow-spectrum penicillins act against many gram-positive bacteria. Aminoglycosides, also narrow-spectrum, act against many gram-negative as well as some gram-positive bacteria. The tetracyclines and chloramphenicols are both broad-spectrum drugs because they are effective against both gram-positive and gram-negative bacteria.
C. Cell Death and Growth Suppression
Antibiotics may also be classed as bactericidal (killing bacteria) or bacteriostatic (stopping bacterial growth and multiplication). Bacteriostatic drugs are nonetheless effective because bacteria that are prevented from growing will die off after a time or be killed by the defense mechanisms of the host. The tetracyclines and the sulfonamides are among the bacteriostatic antiobiotics. Antibiotics that damage the cell membrane cause the cell's metabolites to leak out, thus killing the organism. Such compounds, including penicillins and cephalosporins, are therefore classed as bactericidal.
IV - TYPES OF ANTIBIOTICS
Following is a list of some of the more common antibiotics and examples of some of their clinical uses. This section does not include all antibiotics nor all of their clinical applications.
Penicillins are bactericidal, inhibiting formation of the cell wall. There are four types of penicillins: the narrow-spectrum penicillin-G types, ampicillin and its relatives, the penicillinase-resistants, and the extended spectrum penicillins that are active against pseudomonas. Penicillin-G types are effective against gram-positive strains of streptococci, staphylococci, and some gram-negative bacteria such as meningococcus. Penicillin-G is used to treat such diseases as syphilis, gonorrhea, meningitis, anthrax, and yaws. The related penicillin V has a similar range of action but is less effective. Ampicillin and amoxicillin have a range of effectiveness similar to that of penicillin-G, with a slightly broader spectrum, including some gram-negative bacteria. The penicillinase-resistants are penicillins that combat bacteria that have developed resistance to penicillin-G. The antipseudomonal penicillins are used against infections caused by gram-negative Pseudomonas bacteria, a particular problem in hospitals. They may be administered as a prophylactic in patients with compromised immune systems, who are at risk from gram-negative infections.
Side effects of the penicillins, while relatively rare, can include immediate and delayed allergic reactions�specifically, skin rashes, fever, and anaphylactic shock, which can be fatal.
Like the penicillins, cephalosporins have a �-lactam ring structure that interferes with synthesis of the bacterial cell wall and so are bactericidal. Cephalosporins are more effective than penicillin against gram-negative bacilli and equally effective against gram-positive cocci. Cephalosporins may be used to treat strains of meningitis and as a prophylactic for orthopedic, abdominal, and pelvic surgery. Rare hypersensitive reactions from the cephalosporins include skin rash and, less frequently, anaphylactic shock.
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.
Tetracyclines are bacteriostatic, inhibiting bacterial protein synthesis. They are broad-spectrum antibiotics effective against strains of streptococci, gram-negative bacilli, rickettsia (the bacteria that causes typhoid fever), and spirochetes (the bacteria that causes syphilis). They are also used to treat urinary-tract infections and bronchitis. Because of their wide range of effectiveness, tetracyclines can sometimes upset the balance of resident bacteria that are normally held in check by the body's immune system, leading to secondary infections in the gastrointestinal tract and vagina, for example. Tetracycline use is now limited because of the increase of resistant bacterial strains.
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.
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.
V. - PRODUCTION
The production of a new antibiotic is lengthy and costly. First, the organism that makes the antibiotic must be identified and the antibiotic tested against a wide variety of bacterial species. Then the organism must be grown on a scale large enough to allow the purification and chemical analysis of the antibiotic and to demonstrate that it is unique. This is a complex procedure because there are several thousand compounds with antibiotic activity that have already been discovered, and these compounds are repeatedly rediscovered. After the antibiotic has been shown to be useful in the treatment of infections in animals, larger-scale preparation can be undertaken.
Commercial development requires a high yield and an economic method of purification. Extensive research may be needed to increase the yield by selecting improved strains of the organism or by changing the growth medium. The organism is then grown in large steel vats, in submerged cultures with forced aeration. The naturally fermented product may be modified chemically to produce a semisynthetic antibiotic. After purification, the effect of the antibiotic on the normal function of host tissues and organs (its pharmacology), as well as its possible toxic actions (toxicology), must be tested on a large number of animals of several species. In addition, the effective forms of administration must be determined. Antibiotics may be topical, applied to the surface of the skin, eye, or ear in the form of ointments or creams. They may be oral, or given by mouth, and either allowed to dissolve in the mouth or swallowed, in which case they are absorbed into the bloodstream through the intestines. Antibiotics may also be parenteral, or injected intramuscularly, intravenously, or subcutaneously; antibiotics are administered parenterally when fast absorption is required.
In the United States, once these steps have been completed, the manufacturer may file an Investigational New Drug Application with the Food and Drug Administration (FDA). If approved, the antibiotic can be tested on volunteers for toxicity, tolerance, absorption, and excretion. If subsequent tests on small numbers of patients are successful, the drug can be used on a larger group, usually in the hundreds. Finally a New Drug Application can be filed with the FDA, and, if this application is approved, the drug can be used generally in clinical medicine. These procedures, from the time the antibiotic is discovered in the laboratory until it undergoes clinical trial, usually extend over several years.
VI. - RISKS AND LIMITATIONS
The use of antibiotics is limited because bacteria have evolved defenses against certain antibiotics. One of the main mechanisms of defense is inactivation of the antibiotic. This is the usual defense against penicillins and chloramphenicol, among others. Another form of defense involves a mutation that changes the bacterial enzyme affected by the drug in such a way that the antibiotic can no longer inhibit it. This is the main mechanism of resistance to the compounds that inhibit protein synthesis, such as the tetracyclines.
All these forms of resistance are transmitted genetically by the bacterium to its progeny. Genes that carry resistance can also be transmitted from one bacterium to another by means of plasmids, chromosomal fragments that contain only a few genes, including the resistance gene. Some bacteria conjugate with others of the same species, forming temporary links during which the plasmids are passed from one to another. If two plasmids carrying resistance genes to different antibiotics are transferred to the same bacterium, their resistance genes can be assembled onto a single plasmid. The combined resistances can then be transmitted to another bacterium, where they may be combined with yet another type of resistance. In this way, plasmids are generated that carry resistance to several different classes of antibiotic. In addition, plasmids have evolved that can be transmitted from one species of bacteria to another, and these can transfer multiple antibiotic resistance between very dissimilar species of bacteria.
The problem of resistance has been exacerbated by the use of antibiotics as prophylactics, intended to prevent infection before it occurs. Indiscriminate and inappropriate use of antibiotics for the treatment of the common cold and other common viral infections, against which they have no effect, removes antibiotic-sensitive bacteria and allows the development of antibiotic-resistant bacteria. Similarly, the use of antibiotics in poultry and livestock feed has promoted the spread of drug resistance and has led to the widespread contamination of meat and poultry by drug-resistant bacteria such as Salmonella.
In the 1970s, tuberculosis seemed to have been nearly eradicated in the developed countries, although it was still prevalent in developing countries. Now its incidence is increasing, partly due to resistance of the tubercle bacillus to antibiotics. Some bacteria, particularly strains of staphylococci, are resistant to so many classes of antibiotics that the infections they cause are almost untreatable. When such a strain invades a surgical ward in a hospital, it is sometimes necessary to close the ward altogether for a time. Similarly, plasmodia, the causative organisms of malaria, have developed resistance to antibiotics, while, at the same time, the mosquitoes that carry plasmodia have become resistant to the insecticides that were once used to control them. Consequently, although malaria had been almost entirely eliminated, it is now again rampant in Africa, the Middle East, Southeast Asia, and parts of Latin America. Furthermore, the discovery of new antibiotics is now much less common than in the past.
ANTIBIOTICS AND HOM�OPATHIC ANTIDOTES
Adverse Effects of Penicillin
Fever with cold feet. Bell., Cupr-ac.
Wheezing and Pseudoasthmatic attack. Aspidosperma (Quebracho)
When skin eruptions are simultaneouslypresent. Grind.
Anorexia (with Mycin group of drugs likeAureomycin). Abrot.
Peripheral Neuritis. Ant-t.
Brachiaglia Nocturna (with the pronounced symptoms of pins and needles). Sec., Act-s.
Pruritus. Apis and Grind. 10 drops mixed in a cup of milk andapplied locally.
Skin lesions from Penicillin. Agar., Sulph.
Chronic cough after Penicillin. Penicillin 3x or 30, Seneg. 30 or 200.
In cases when Srepto Peniciliin had been used. Streptococcin 30 or Staphelococcin 30 (as an intercurrent remedy.
Heart depressing effects of Penicillin. Ars-a.
Harmful effects of Penicillin. Ars-a., Thuj., Nux-v., Sil.
Specific to counteract the effects of Penicillin. Ars-a.
Diarrhoea from Antibiotics (especially Mycins). Nit-ac.
Allergic reactions to Antibiotics. Sulph., Penicillin, Streptomycin.
Headache due to Streptomycin. Bell.
#. Effects of Chloromycetin: cases of typhoid (where Chloromycetin was given). ----- Chloromycetin 30, 200 or 1M (according to patient�s Constitution). With Placebo for a week. In second week Typhoidinum 200 or 1M (with Placebo for a fortnight).
Intestinal effects of Aureomycin. Aureomycin leaves a very weak liver and severe troublewith the bowels. In this case, a pure constitutional treatment with careful observation of idiosyncrasies is most effective.
#. Effects of Allergy (in general). Ill effects of Penicillin. ----- Carb-v. (Dilutions used: 2x, 3x, 6x, 12x).
1. Contributed by Dr. M. Maureen Dale and Dr. Joel Mandelstam (MS Encarta Encylop�dia 2002).
2. Homoeopathy and Adverse Reactions of Allopathic Drugs by Dr. Sayeed Ahmad.
Copyright with Dr. Sayeed Ahmad 2004
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