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Chemotherapy and Drug Resistance.pptx

  1. Chemotherapy and Drug Resistance Chemotherapeutic agents and antibiotics. Modes of action of antibiotics on microorganisms Amjad Khan Afridi Lecturer, Department of Health & Biological Sciences Abasyn University Peshawar
  2. • The use of drugs to treat a disease • Selective toxicity: – A drug that kills harmfulmicrobes without damaging the host Chemotherapy
  3. Antibacterial spectrum Range of activity of an antibiotic. A broad spectrum Antibiotic that can inhibit wide range of G- positive and G- negative bacteria e.g. Carbapenems, 3-4th generation cephalosporins, quinolones. A narrow spectrum Antibiotic that is active only against a limited number of bacteria e.g. penicillin G, 1-2nd generation cephalosporins, oxazolidone. Terminologies
  4. Effects of Combinations of Drugs •Synergism occurs when the effect of two drugs together is greater than the effect of either alone. •Antagonism occurs when the effect of two drugs together is less than the effect of either alone.
  5. Effects of Combinations of Drugs
  6. Antibiotic/Antimicrobial • Antibiotic: – Chemical produced by a microorganism that kills or inhibits the growth of another microorganism • Antimicrobial agent: – Chemical that kills or inhibits the growth of microorganisms
  7. AntimicrobialAgents • Disinfectant: •Antimicrobial agent used only on inanimate objects • Chemotherapeutic agent: •Antimicrobial agent that can be used internally • Bactericidal: •Agent that kills bacteria • Bacteriostatic: •Agent that inhibits the growth of bacteria
  8. II.HISTORY 7  1929 Penicillin discovered by Alexander Fleming  1940 Florey and Chain mass produce penicillin for war time use, becomes available to the public.  1935 Sulfa (sulfonamide-prontosil rubrum) drugs discovered by Gerhard Domagk in 1935.  1943 Streptomycin (aminoglycoside drugs) discovered by Selman Waksman.
  9. • Bacteria have their own enzymes for √ Cell wall formation √ Protein synthesis √ DNA replication √ RNA synthesis √ Synthesis of essential metabolites Mechanisms of Antimicrobial Action
  10. Modes of Antimicrobial Action
  11. Basic mechanisms of antibiotics
  12. Inhibition of cellwallsynthesis –Penicillins and cephalosporins stop synthesis of cell wall by preventing crosslinking of peptidoglycanunits. –Bacitracin and vancomycinalsointerfere here. – Excellentselectivetoxicity 12
  13.  The bacterial cell membrane is also called cytoplasmic membrane. Its maincompounds are proteins andlipids.  Polymyxins can selectively combine with phosphatide in the cell membrane and cause the increase of membranous permeability. As the result, some important materials will outflow from bacterial cellsandresult in death ofbacteria. 13 Inhibition of functions of cellularmembrane
  14. Acting on DNA replication Quinolones Ciprofloxacin Metronidazole Quinolones Fluoroquinolones Inhibition of nucleic acid synthesis Acting on RNA synthesis Rifampin Rifabutin
  15.  Dueto differences inribosomes  Eucaryotic cellshave80S(60S+40Ssubunits) ribosomes.  Procaryotic cellshave70S(50S+30Ssubunits) ribosomes.  Examples:  Chloramphenicol, Macrolides and Clindamycin bind to the 50Ssubunit.  Tetracyclines andAminoglycosides bind to the 30S subunit. 15 Inhibition of protein synthesis
  16. Sulfonamides Dapsone Trimethoprim Para Aminosalicylic acid Antimetabolites
  17.  Drug resistance is simply defined as the ability of disease-causing microorganisms to continue multiplying despite the presence of drugs that usually kill them.  When the bacteria show resistance to one drug, they are also resistant to some other drugs. This phenomenon is called cross drug resistance. 17 Resistance To Anti Bacterial Agents
  18. 1. Inhibition of drug uptake or blocking the entry (Change their cell membrane and cell wall permeability to the drug) 2.Produceenzymes that destroy the chemical structures of drugs 3. Alter or modified the target molecule. 4. Activation of drug efflux pump. Active efflux is a common resistance mechanism in a wide range of bacterial pathogens. It is responsible for the transport of such toxic compounds as drugs, toxins, and detergents. 19 Mechanisms of Antibacterial Resistance
  19.  Havehighly selective toxicity to thepathogenic  Microorganismsin hostbody  Haveno or lesstoxicity to the host.  Lowpropensity for development ofresistance.  Not induce hypersensitive in thehost.  Haverapid and extensive tissuedistribution  Befree of interactions with other drugs.  Be relatively in expensive 29 Ideal Antimicrobial Drug
  20. Prevention of Antibiotic Resistance Patients : • Take antibiotics exactly as the doctor prescribes. • Donot skip doses. • Complete the prescribed course, even when you feeling better. • Onlytake antibiotics prescribed for you. • Donot save antibiotics for the nextillness. • Discard any leftover medication once the treatment is completed. • Donot ask for antibiotics to yourdoctor. • Prevent infections by practicing hygiene and recommended vaccines. Health professionals: •Prescribe antibiotics only when they are absolutely necessary – giving them at the right dose and only for as long as they areneeded. •Avoid unnecessary overlaps in antibiotics. •Become familiar with resistance trends in your region.
  21. Minimal Inhibitory Concentration
  22. Thank You
  23. arpan

Hinweis der Redaktion

  1. Disinfectant: Disinfectants can be split into two broad groups, oxidizing and nonoxidizing. Oxidizing disinfectants include the halogens, chlorine, iodine, bromine, and chlorine dioxide, and oxygen-releasing materials such as peracetic acid and hydrogen peroxide Chemotherapeutic agent: are used to directly or indirectly inhibit the uncontrolled growth and proliferation of cancer cells. They are classified according to their mechanism of action and include. alkylating agents. , antimetabolites.
  2. Prontosil Streptomycin: aminoglycoside drugs:  gentamicin, tobramycin, amikacin, plazomicin, streptomycin, neomycin, and paromomycin are approved by the US Food and Drug Administration (FDA) and are available for clinical use.
  4. DNA-dependent RNA polymerase. DNA gyrase is an essential bacterial enzyme that catalyzes the ATP-dependent negative super-coiling of double-stranded closed-circular DNA.
  5. 50S: Streptogramins, Oxazolidones
  6. Drug resistance: Drug resistance is simply defined as the ability of disease-causing germs (e.g., bacteria or viruses) to continue multiplying despite the presence of drugs that usually kill them. Extrachromosomal drug resistance: Antibiotic resistance plasmids are bacterial extrachromosomal elements that carry genes conferring resistance to one or more antibiotics.
  7. Drug resistance is simply defined as the ability of disease-causing germs (e.g., bacteria or viruses) to continue multiplying despite the presence of drugs that usually kill them.
  8. enzymatic degradation of antibacterial drugs, (2) alteration of bacterial proteins that are antimicrobial targets, and (3) changes in membrane permeability to antibiotics. Activation of drug efflux pump: Efflux pumps allow the microorganisms to regulate their internal environment by removing toxic substances, including antimicrobial agents, metabolites and quorum sensing signal molecules.
  9. XDR:Extensively drug-resistant  Many different definitions for multidrug-resistant (MDR), extensively drug-resistant (XDR) and pandrug-resistant (PDR) bacteria are being used in the medical literature to characterize the different patterns of resistance found in healthcare-associated, antimicrobial-resistant bacteria. Criteria for defining MDR, XDR and PDR in Enterococcus spp. MDR: non-susceptible to ≥1 agent in ≥3 antimicrobial categories. XDR: non-susceptible to ≥1 agent in all but ≤2 categories. PDR: non-susceptible to all antimicrobial agents listed.