Antimicrobial Agents

Lesson title: Antimicrobial Agents Materials: Book, Pen and SAS Lesson Objectives: At the end of the lesson, you should be able to: 1. Classify the mechanism of actions of antibacterial, antifungal, antiprotozoal, anthelmintic and antiviral agents 2. Recognize occurrence of antimicrobial resistance 3. Create interventions to prevent antimicrobial resistance Productivity Tip: In the previous modules, you encountered the different microorganisms and understood their metabolism and growth. In this module, you can now connect those knowledge to this topic – identifying drugs or agents that target microbial diseases. A very fundamental topic as future pharmacist as this module will help you as you to dispense certain prescription drugs. Many drugs to memorize but it’ll be worth it. A. LESSON PREVIEW/REVIEW Introduction (2 mins) Another aspect of controlling the growth of microorganisms involves the use of drug to treat (and hopefully to cure) infectious diseases in other words, using drugs to control the growth of pathogen in vivo. Although we most often hear the term chemotherapy used in conjunction with cancer, it actually refers to the use of any chemical (drug) to treat any disease or condition. The chemicals (drugs) used to treat diseases are referred as chemotherapeutic agents. By definition, a chemotherapeutic agent is any drug used to treat any condition or disease. For thousands of years, people have been discovering and using herbs and chemicals to cure infectious diseases. Native which doctors in Central and South America long ago discovered that the herb, ipecac, aided in treatment of dysentery, and that a quinine extract of cinchona bark was effective in treating malaria. During the 16 th and 17 centuries the alchemists of Europe searched for ways to cure smallpox, syphilis and many other diseases that were rampant during the period of history. Unfortunately, many of the mercury and arsenic chemicals that were used frequently caused more damage to the patient than to the pathogen. The chemotherapeutic agents used to treat infectious diseases are collectively referred to as antimicrobial agents thus it is any chemical (drug) used to treat an infectious disease, either by inhibiting or by killing pathogens in vivo. Drugs used to treat bacterial diseases are called antibacterial agents, whereas those used to treat fungal diseases are called antifungal agents. Drugs used to treat protozoal diseases are called antiprotozoal agents, and those used to treat viral diseases are called antiviral agents. Characteristics of and Ideal Antimicrobial Agent The ideal antimicrobial agent should: 1. 2. 3. 4. 5. 6. Kill or inhibit growth of pathogens Cause no damage to the host Cause no allergic reaction in the host Be stable when stored in solid or liquid form Remain in specific tissues in the body long enough to be effective Kill the pathogen before they mutate and become resistant to it Good to know! Unfortunately, most antimicrobial agents have some side effects, produce allergic reactions, or permit development of resistant mutant pathogens. This module is consists of five topics, classifying antimicrobial agents: I. II. III. IV. V. Antibacterial agents Antifungal agents Antiprotozoal agents Anthelmintic agents Antiviral agents Activity 1: What I Know Chart, Part 1 (5 mins) Instructions: In this chart, reflect on what you know now. Do not worry if you are or not of your answers. This activity simple serves to get started on thinking about our topic. Answer only the first column, “what I know”. Leave the third column “what I learned” blank at this time. What I Know Questions: What I Learned (Activity 4) What is susceptible? What is inhibition? What is a drug of choice? B.MAIN LESSON Activity 2: Content Notes THE HISTORY OF CHEMOTHERAPY By definition, an antibiotic is a substance produced by a microorganism that is effective in killing or inhibiting the growth of other microorganisms. Although all antibiotics are antimicrobial agents not all antimicrobial agents are antibiotics, therefore, the terms are not synonyms, and care should be taken to use the terms correctly. Antibiotics are produced by certain moulds and bacteria, usually those that live in soil. The antibiotics produced by soil organism give them a selective advantage in the struggle in the struggle for the available nutrients in the soil. Penicillin and cephalosporins are examples of antibiotics produced by moulds, bacitracin, erythromycin, and chloramphenicol are examples of antibiotics produced by bacteria. Although originally produced by microorganisms, many antibiotics are now synthesized or manufactured in pharmaceutical laboratories. Also many antibiotics have been chemically modified to kill a wider variety of pathogens or reduce side effects; these modified antibiotics are called semisynthetic antibiotics. Semisynthetic antibiotics include semisynthetic penicillins, such as ampicillin and carbenicillin. Antibiotics are primarily antibacterial agents and are used to treat bacterial diseases. PAUL EHRLICH ‒ Father of Chemotherapy ‒ He coined the term selective toxicity and chemotherapy • Selective toxicity: means that the drug is harmful to a pathogen without being harmful to the host • Chemotherapy: the use of drugs to treat a disease ALEXANDER FLEMING ‒ Discovered Penicillin in 1928 ‒ In 1928, Alexander Fleming observed that the growth of the bacterium Staphylococcus aureus was inhibited in the area surrounding the colony of a mold that had contaminated a Petri plate HOWARD WALTER FLOREY AND ERNST BORIS CHAIN, ‒ Purified penicillin and demonstrated its effectiveness in the treatment of various bacterial infections. SELMAN WAKSMAN ‒He isolated streptomycin (the first antituberculosis drug) and subsequently discovered antibiotics such as chloramphenicol, tetracycline, and erythromycin in soil samples. SPECTRUM OF ANTIMICROBIAL ACTIVITY NARROW SPECTRUM ‒ drugs that are effective against few types of bacteria. ‒ Advantage: will cause less resistance of the bacteria as well as it will deal only with specific bacteria ‒ Disadvantage: can be used only if the causative organism is identified. BROAD SPECTRUM ‒ drugs that are effective against several different classes of bacteria. Both gram positive and negative ‒ Advantage: there is less need to identify the infecting pathogen before treatment. ‒ Disadvantages: Children increased risk of developing childhood asthma and may give rise to drug resistance EXTENDED-SPECTRUM - Effective against gram-positive organism and a significant number of gram-negative organisms BACTERICIDAL – means killing of microorganism BACTERIOSTATIC – inhibition of metabolism and reproduction of microorganism Good to Know! When are bactericidal antibiotics preferable to bacteriostatic antibiotics? 1. Immunocompromised patients 2. Infections that are immediately life-threatening 3. Infections that are protected from the host’s immunity THE ACTION OF ANTIMICROBIAL DRUGS To be acceptable, an antimicrobial agent must inhibit or destroy the pathogen without damaging the host. To accomplish this, the agent must target a metabolic process or structure possessed by the pathogen but not possessed by the host. The five most common mechanisms of action of antimicrobial agents are as follows: 1. Inhibiting Cell Wall Synthesis 2. Inhibiting Protein Synthesis 3. Injuring the Plasma Membrane 4. Inhibiting Nucleic Acid Synthesis 5. Inhibiting the Synthesis of Essential Metabolites 1. Inhibiting Cell Wall Synthesis TARGETS: • Penicillin-binding proteins • PBP 1a and 1b are transpeptidases involved in peptidoglycan synthesis associated with cell elongation. • PBP 2 a transpeptidase involved in maintaining the rod shape of bacilli. • PBP 3 transpeptidase required for septum formation during cell division. • PBP 4 through 6 are carboxypeptidases responsible for the hydrolysis of D alanine–D-alanine terminal peptide bonds of the cross-linking peptides. 2. Inhibiting Protein Synthesis - Binds to 30s ribosomes • Aminoglycoside • Tetracycline - Binds to 50s ribosomes • Chloramphenicol • Erythromycin/Macrolides • Lincosamides 3. Injuring the Plasma Membrane TARGET: - Lipopolysaccharide, - inner and outer membranes 4. Inhibiting Nucleic Acid Synthesis - A number of antibiotics interfere with the processes of DNA replication and transcription in microorganisms. These drugs block bacterial topoisomerase or RNA polymerase 5. Inhibiting the Synthesis of Essential Metabolites Targets: - Folic acid synthesis enzyme - Mycolic acid synthesis enzyme TEST TO GUIDE CHEMOTHERAPY 1. DISK DIFFUSION METHOD Kirby-Bauer test - A bacterial culture is inoculated on an agar medium, and filter paper disks impregnated with chemotherapeutic agents are overlaid on the culture. - After incubation, the diameter of the zone of inhibition is used to determine whether the organism is sensitive, intermediate, or resistant to the drug. - Minimal inhibitory concentration (MIC) is the lowest concentration of drug capable of preventing microbial growth; MIC can be estimated using the E test.