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Chapter 20 Antimicrobial Medications
Biology 261 Dr. Santos Medgar Evers College
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Chemotherapeutic- a chemical used to treat a disease
Antimicrobial drug- a chemical used to treat microbial infections
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History and development
1- Paul Ehrlich developed Salvarsan to treat syphilis in laboratory animals.
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Discovery of Antibiotics
In 1928, Alexander Fleming discovered that the fungi Penicillium produces a chemical that kills bacteria. He called this substance penicillin.
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Features of Antimicrobial drugs
1- Made naturally by certain microorganisms. Many come from microorganisms that normally reside in soil. 2- Commercially they can be made in large numbers in a laboratory. 3- In a lab, they can be modified to alter their chemical and physical characteristics.
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Antibiotics that have been chemically altered are called semi-synthetic.
4- selective toxicity Useful antimicrobial drugs cause greater harm to microorganisms than to the human host. They do this by interfering with essential biological structures or pathways that are common in microorganisms but not humans.
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Therapeutic index The toxicity of a given drug is expressed as its therapeutic index. A high therapeutic index means that the drug is less toxic to a patient because the drug acts on a biochemical process of bacteria that is not found on humans.
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A drug with a low therapeutic index must be carefully monitored in the patient’s blood to ensure toxic levels are not reach.
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5- antimicrobial action
Those drugs that inhibit bacterial growth are called bacterio-static. These drugs depend on the host’s natural immune system to clear the pathogen from the body. Sulfonamides, erythromycin, and tetracyclines are examples of bacterio-static drugs. Antibiotics that actually kill bacteria are bacteriocidal.
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Those drugs that kill bacteria are called bactericidal.
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6- Antimicrobial drugs that affect a wide range of bacteria are called broad spectrum antimicrobials. These are important during life threatening acute infections when there is no time to culture and identify the agent of disease. 7- Antimicrobials that affect a limited range of bacteria are called narrow-spectrum antimicrobials.
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8- Combining drugs to fight infection must be carefully monitored
8- Combining drugs to fight infection must be carefully monitored. 3 situations to know! A- antagonistic when one drug interferes with the action of another. B- synergistic when one drug enhances the effectiveness of another drug
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C- Additive When the effect is neither antagonistic or synergistic
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9- half-life The rate of elimination of a drug in the body after it has been metabolize. The half life is the time required for the body to eliminate one half of the original concentration in the serum. *Half life determines the size of dosage and frequency of the dosage.
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Mechanisms of action of antimicrobial drugs
1- inhibit cell wall synthesis 2- inhibit protein synthesis 3- inhibit nucleic acid synthesis 4- inhibit metabolic pathways 5- inhibit cell membrane integrity 6- special drugs used against Mycobacterium tuberculosis
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Cell wall synthesis Antimicrobial drugs that inhibit cell wall synthesis include the penicillins, cephalosporins, and other beta lactam drugs.
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The beta lactam drugs include penicillin, cephalosporin, monobactam, and carbapenem.
They all share a chemical structure called a beta lactam ring. The beta lactam drugs competitively inhibit a group of enzymes that catalyze formation of peptide bridges between adjacent glycan strands in the final stages of peptidoglycan formation.
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Penicillin
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amoxicillin
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Mechanisms of penicillin resistance
1- restrict transport 2- modify target site 3- beta lactamases
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The cephalosporins Contain the beta lactam ring!
Are grouped into 1st, 2nd, 3rd ,and 4th generation cephalosporins. They include cephalexin, cephradine, ceflacor, cefibuten, and cefipime.
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Bacitracin These drugs interfere with cell wall biosynthesis by interfering with the transport of precursors across the cytoplasmic membrane. They are only used as topical ointments due to their toxicity.
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Inhibiting protein synthesis
All cells synthesize proteins Can exploit differences between prokaryotic and eukaryotic ribosomes Prokaryotes have 70S, eukaryotes have 80S ribosomes Mitochondria also have 70S ribosomes May account for some toxicity of these drugs Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Macrolides Prevent the continuation of protein synthesis. Streptogramins Each interferes with a distinct step of protein synthesis. Chloramphenicol Prevents peptide bonds from being formed. Lincosamides Prevent the continuation of protein synthesis. 50S Oxazolidinones Interfere with the initiation of protein synthesis. 30S Tetracyclines and glycylcyclines Block the attachment of tRNA to the ribosome. Aminoglycosides Block the initiation of translation and cause the misreading of mRNA. 25
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Drugs against nucleic acid synthesis
1- the fluoroquinolones inhibit the enzyme topoisomerase which helps maintain DNA in a supercoil state. 2- the Rifamycins block prokaryotic RNA Polymerase from initiating transcription.
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Drugs against metabolic pathways
1- sulfonamides block the action of an enzyme that normally binds to PABA, a substrate in the folate pathway. They closely resemble PABA, so the enzyme binds to it and the entire pathway is blocked.
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2- trimethoprim These drugs inhibit the bacterial enzyme that catalyzes a metabolic step following the one inhibited by sulfonamides.
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Drugs that interfere with cell membrane integrity
1- polymyxin alters the permeability of the cell membrane leading to leakage and cell damage. 2-Daptomycin inserts into the membrane leading to cell damage and eventually death.
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Special medications against Mycobacterium
1- first line drug such as Isoniazid inhibits the synthesis of mycolic acid, an important component of the cell wall. 2- Ethambutol inhibits enzymes used to synthesize other cell wall components. 3- Rifampin, an antimicrobial drug used to block the process of transcription by blocking RNA Polymerase. 4- Ampicillin, a broad spectrum penicillin.
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