Cyprus International UniversityFaculty of PharmacyPharmaceutical Toxicology-IIAn Essay by:Falah BibwatStudent Number: 20156473Supervised by: Lecturer Tugce ArkanTopic: Antibiotics 2017-20181. Antibiotic Antibiotics were invented by Alexander Flemming in 1928 (Diggins).
Antibiotics are chemical substances produced by various microorganisms and other living systems, and capable of inhibiting the growth of dangerous bacteria, viruses, and so on. Before the epoch of antibiotics began, there was not much that could be done for patients suffering from different infections, and death rates were much higher than today. For instance, the streptococcus pyogenes bacteria had caused about half of all post-birth deaths (Cleary); staphylococcus aureus was fatal in 80% of the cases. Tuberculosis and pneumonia bacteria were famous killers as well. Today, the discovery of antibiotics has enabled medicine to treat these communicable diseases (Tulkens) together with other diseases that were once considered terminal. Antibiotics can be bacteriostatic (those that prevent bacteria from multiplying) (Dodd) or bactericidal—those that exterminate the bacteria.
They penetrate a bacterial cell surface, causing changes in their mode of reproduction (Tulkens). Antibiotics can be prescribed to patients in various forms, such as topical application, orally, parentally, or as injections. Antibiotics are usually manufactured in two ways. One of them is natural and is known as biosynthesis; the other one is synthetic. Among the most commonly used antibiotics, one can name Penicillin, Cephalosporin’s, Aminoglycosides, Tetracycline’s, and Polypeptides Bacitracin.
They are drugs that have the ability to injure or kill an invading microorganism without harming the cells of the host. Because of biochemical differences that exist between microorganisms and human beings. The drug is carefully controlled to attack the microorganism while still being tolerated by the host.2. Selection of Antimicrobial AgentsSelection of the most appropriate antimicrobial agent requires knowledge of 1) The organism’s identity.2) The organism’s susceptibility to a particular agent.3) The site of the infection.4) Patient factors.
5) The safety of the agent,.6) The cost of therapy. Critically ill patients require empiric therapy that is, immediate administration of drug(s) prior to bacterial identification and susceptibility testing.A rapid assessment of the nature of the pathogen can sometimes be made on the basis of the Gram stain, cerebrospinal fluid CSF, pleural fluid, synovial fluid, peritoneal fluid, and urine. It is generally necessary to culture the infective organism to arrive at a conclusive diagnosis and to determine the susceptibility of the bacteria to antimicrobial agents. In the critically ill patient, such a delay could prove fatal, and immediate empiric therapy is indicated. The choice of drug in the absence of susceptibility data is influenced by the site of infection and the patient’s history.
Broad-spectrum therapy may be needed initially for serious infections when the identity of the organism is unknown or the site makes a polymicrobial infection likely.3. Antimicrobial drugs are classified as either bacteriostatic or bactericidal. Bacteriostatic drugs arrest the growth and replication of bacteria at serum levels achievable in the patient, thus limiting the spread of infection while the body’s immune system attacks, immobilizes, and eliminates the pathogens. If the drug is removed before the immune system has scavenged the organisms, enough viable organisms may remain to begin a second cycle of infection. Bactericidal drugs kill bacteria at drug serum levels achievable in the patient.
Because of their more aggressive antimicrobial action, these agents are often the drugs of choice in seriously ill patients. It is possible for an antibiotic to be bacteriostatic for one organism and bactericidal for another. For example, chloramphenicol is bacteriostatic against gram-negative rods and is bactericidal against other organisms, such as S. pneumoniae.
Adequate levels of an antibiotic must reach the site of infection for the invading microorganisms to be effectively eradicated.4. Effect of the site of infection on therapy: The blood-brain barrier1-The lipid solubility of a drug is therefore a major determinant of its ability to penetrate into the brain.
For example, lipid-soluble drugs, such as the quinolones and metronidazole, have significant penetration into the CNS. In contrast, ?-lactam antibiotics, such as penicillin, have low solubility in lipids. In infections such as meningitis, in which the brain becomes inflamed, the barrier does not function effectively, and local permeability is increased. Some ?-lactam antibiotics can then enter the CSF in therapeutic amounts.2-Molecular weight of the drug: A compound with a low molecular cross the blood-brain barrier, whereas compounds with a high molecular weight (for example, vancomycin) penetrate poorly, even in the presence of meningeal inflammation.3-Protein binding of the drug: A high degree of protein binding of a drug in the serum restricts its entry into the CSF.
In selecting an antibiotic, attention must be paid to the condition of the patient. For example, the status of the patient’s immune system, kidneys, liver, circulation, and age must be considered. In women, pregnancy or breast-feeding also affects selection of the antimicrobial agent.4.1 Safety of the agent Many of the antibiotics, such as the penicillins, are among the least toxic of all drugs, because they interfere with a site unique to the growth of microorganisms. Other antimicrobial agents (for example, chloramphenicol) are less microorganism specific and are reserved for life-threatening infections because of the drug’s potential for serious toxicity to the patient. 4.
2 Cost of therapy Often, several drugs may show similar efficacy in treating an infection but vary widely in cost. 4.3 Route of Administration The oral route of administration is chosen for infections that are mild and can be treated on an outpatient basis. In patients requiring a course of intravenous therapy initially or some antibiotics, such as vancomycin, the aminoglycosides, and amphotericin B, are so poorly absorbed from the gastrointestinal.4.4 Agents Used in Bacterial InfectionsThe clinically useful antibacterial drugs are organized into six families penicillins, cephalosporins, tetracyclines, aminoglycosides, macrolides, and fluoroquinolones plus a seventh group labeled Other that is used to represent any drug not included in one of the other six drug families. 4.
5 Narrow-spectrum antibiotics Chemotherapeutic agents acting only on a single or a limited group of microorganisms are said to have a narrow spectrum. For example, isoniazid is active only against mycobacteria.Extended-spectrum antibiotics Term applied to antibiotics that are effective against gram-positive organisms and also against a significant number of gram-negative bacteria. For example, ampicillin is considered to have an extended spectrum, because it acts against gram-positive and some gram-negative bacteria.4.6 Broad-spectrum antibioticsDrugs such as tetracycline and chloramphenicol affect a wide variety of microbial species and are referred to as broad-spectrum antibiotics. Administration of broad-spectrum antibiotics can drastically alter the nature of the normal bacterial flora and precipitate a superinfection of an organism such as Candida albicans, the growth of which is normally kept in check by the presence of other microorganisms.
5. Combinations of Antimicrobial Drugs It is therapeutically advisable to treat patients with the single agent that is most specific for the infecting organism. This strategy reduces the possibility of superinfection, decreases the emergence of resistant organisms, and minimizes toxicity. However, in treatment of tuberculosis there will be benefits from drug combinations.
5.1 Advantages of drug combinations Certain combinations of antibiotics, such as ?-lactams and aminoglycosides, show synergism; that is, the combination is more effective than either of the drugs used separately.Disadvantages of drug combinations Co-administration of an agent that causes bacteriostasis plus a second agent that is bactericidal may result in the first drug interfering with the action of the second. For example, bacteriostatic tetracycline drugs may interfere with the bactericidal effect of penicillins and cephalosporins.5.
2 Drug Resistance Bacteria are said to be resistant to an antibiotic if the maximal level of that antibiotic that can be tolerated by the host does not halt their growth. Some organisms are inherently resistant to an antibiotic. For example, gram-negative organisms are inherently resistant to vancomycin. 5.
3 Drug resistance may be mediated by a variety of mechanisms.1- Spontaneous mutation or acquired resistance and selection. 2- Lack of or an alteration in an antibiotic target site.3- Lowered penetrability of the drug due to decreased permeability.
4- Increased efflux of the drug.5- Presence of antibiotic-inactivating enzymes 6. Complications of Antibiotic TherapyA.
HypersensitivityHypersensitivity reactions to antimicrobial drugs or their metabolic penicillins, can cause urticaria (hives) to anaphylactic shock.B. Direct toxicityHigh serum levels may cause toxicity by directly affecting cellular processes in the host. Aminoglycosides can cause ototoxicity by interfering with membrane function in the hair cells of the organ of Corti.
C. SuperinfectionsDrug therapy, particularly with broad-spectrum antimicrobials or combinations of agents, can lead to alterations of the normal microbial flora of the upper respiratory, intestinal, and genitourinary tracts, permitting the overgrowth of opportunistic organisms, especially fungi or resistant bacteria. These infections are often difficult to treat.7. Sites of Antimicrobial ActionsAntimicrobial drugs can be classified in a number of ways.
These include.1) By their chemical structure (for example, ?-lactams or aminoglycosides),2) By their mechanism of action (for example, cell wall synthesis inhibitors), 3) By their activity against particular types of organisms (for example, bacteria, fungi, or viruses). Doubtlessly, antibiotics are deemed as one of the most important sorts of medicines. Throughout the history of medicines the chemists, biologists, and scientists from divergent realms craved to pay a special heed to the antibiotic medicines due to its significance power in curing diseases and saving human’s life. However, one must be very careful while using the antibiotics as besides their great benefits they might cause harm to adults and child when used improperly. Furthermore, the antibiotics must not be used for viral diseases treatment, because the diseases generated out of viruses can never get cured by antibiotics as the human body automatically gets recovered from these common viral infections when the illness has run its course. On the other hand, the antibiotics play effective and crucial rule in recovering the bacterial infections which human beings and divergent types of animals may have. Usually, the antibiotics, or sometimes called antibacterial medicines, may success in healing the bacterial infections by fighting and killing the bacteria through attacking the walls of the infected cells and disintegrate them; in this sense, the antibiotics terminate the growth of the bacteria.
However, there are some types of bacteria called; the resistant bacteria; which develop resistance against antibiotics and cannot get killed or terminated. The repeated use of the same antibiotic or the improper use of the antibiotics make the resistant bacteria to grow more powerful and resist the medicines; as a consequence they may cause dangerous and serious harm to the patients. Therefore, the patients can be recovered from the resistant bacteria through using a different type of antibiotics and of course with a good clinical observation and consultation of doctors. Antibiotic resistance and its spread Antibiotic-resistant bacteria are a natural consequence of antibiotic use, but development and spread of these pathogens can be hastened or slowed by the way antibiotics are used. Antibiotic-resistant bacteria arise as the natural result of mutation and natural selection within a population of organisms—say, an infection in a human host—faced with an agent that eliminates most of its members. Those that survive because of mutations that circumvent the effect of the antibiotic (through a variety of mechanisms) can multiply and give rise to larger numbers of antibiotic-resistant bacteria.
In the absence of alternative antibiotics or other control mechanisms, these antibiotic-resistant bacteria can spread to other people just like any other bacterial infection (for example, through personal contact or inhalation of droplets from coughing). If they are robust enough, they can become widespread. Complicating matters, in many cases bacteria acquire resistance to antibiotics through the transfer of genetic material from other species of bacteria.
In addition, resistance to one antibiotic may confer resistance to related antibiotics. Antibiotic resistance cannot be prevented. Every time antibiotics are used, whether they save a life or are used to no effect (to treat viral rather than bacterial infections, for example), the effective lifespan of that antibiotic and perhaps related drugs is shortened. The tension between individual good and collective good is central to the issue. The average patient suffering from a cold or an ear infection wants immediate relief and sees a prescription for antibiotics as the ticket to recovery, and the physician may be only too. To sum up the whole subject, it is of a high significance to say that everyone must know how important the antibiotics are, how they work in healing bacterial infections, and how to cure the bacterial infections which are not recovered because of the resistant bacteria.
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