Week 1Lecture 17:Vocab:Sterilizer – Kills all living organisms, including spores (bleach and sodium hypochlorite)Disinfectant- Kills microbes or pathogens on inanimate surfaces, may not kill spores(ethanol and phenol)Sanitizer- Reduce, but may not eliminate microbes (detergents)Bacteriostatic- Antimicrobials that inhibit microbial growth without killing them.Bacteriocidal- Antimicrobials that kill microbes.Bacteriolytic- Antimicrobials that kill microbes by lysing them (no cells left)Antiseptic- Nontoxic microbial compound used on living tissues. For wound or surgical sides (hydrogen peroxide; iodine)Germicide- A substance or other agent that destroys harmful microorganisms (antiseptic). Non-chemotherapeutic agent (too toxic for internal use of the body).Selective toxicity- The ability of a chemical or drug to kill a microorganism without harming its host.Tube dilution assay- Used to detect the minimal inhibitory concentration. A series ofincreasing concentrations of the antimicrobial agent are prepared in a culture broth medium. Each tube is inoculated and incubated to allow microbial growth to occur. Growth occurs in the tubes.Concepts:- Briefly review uses of disinfectants ad antiseptics; what types or radiation are usedo Disinfectants- Kill microbes on surfaces. Ethanol and phenol. o Antiseptics- too harmful to use iNSIDE the body, but used for wounds and surgeries. Hydrogen peroxide and iodine. o Types of radiation: UV (ultraviolet) and ionizing radiation Ultraviolet radiation- used for reducing microbial contaminants on surfaces Ionizing radiation- gamma- rays, x-rays, electron beams- used for sterilization of medical devices, food, mail- Review factors that influence effectiveness of antimicrobial agents; what forms of microbes are resistanto Antimicrobial agent factors: concentration of antimicrobial agent, duration of exposure of the microorganisms, temperature of the treatment, presence of other materials, level of microbial resistance tothe antimicrobial agento Microbial factors: population size, population and community composition, encasement within surface biofilmso Most resistant- microbial spores o Least resistant- vegetative bacteria and mostly enveloped viruses (remember they are enveloped so contained- easier to kill). Uncapsulated ones can spread.- How is the minimum inhibitory concentration determined?o By performing a tube dilution assay:o A series of increasing concentrations of the antimicrobial agent are prepared in a culture broth mediumo Each tube is equally inoculated and incubated to allow microbial growth to occuro Growth or not occurs- How is the disc agar diffusion test performed; how are the results interpretedo The test organisms is spread on the culture medium in an agar plate and then sterile antibiotics discs are applied. After incubation, the organism produces a confluent “lawn” of growth except in zones of inhibition around discs containing antibiotics to which the organism is susceptible. Lecture 18Vocab:Therapeutic index- LD50/ED50LD50- 50% lethal doseED50- 50% effective doseToxic dose- level at which drug becomes toxic to the hostTherapeutic dose- required for effective clinical treatmentTranspeptidase- penicillin binding proteins (penicillin inhibits peptidoglycan synthesis). Connects peptidoglycan.Monensin- An ionophore used in animal feedCeftriaxone- more resistant to B-lactamase than some other antibiotics and is used for treating penicillin- resistant bacteria such as Neiserria gonorrhoeae (peptidoglycan BREAKDOWN)Ionophore- A substance that is able to transport particular ions across a lipid membrane cellAntibiotics- naturally occurring chemical compounds that inhibit or kill microorganismsSelective pressure- use of antibiotics create selective pressures. This favors microbes that are resistant to the drug. Selects against microbes that are sensitive tothe drug.Concepts:- review the stages of the clinical trial system for drug evaluationo Drug discoveryo Phase 1 trials- evaluation of drug safety and sideeffects on small groups of 20-100 individualso Phase II- test for efficiency; randomized and “bling” placebo/drug trialso Phase III- larger scale tests on up to several thousand patients o FDA approval – typically takes a year or moreo Post –marketing/ phase IV- continued monitoring of the drug- review the modes of action of antimicrobial chemotherapeutic agentso Antibiotics of important microbial cellular processes Inhibition of critical pathway:- Synthetic growth factor analogs: sulfa drugs. Sulfa drugsanalogs of p-aminobenzoic acid sulfanilamide is mode of action: inhibits incorporation of p-aminobenzoic acidinto the vitamin folic acid. Bacteria can’t make folic acids, and this prevents them from growing. Isoniazid also inhibits an important pathway by inhibiting synthesis of mycolic acids in the Mycobaterium. This is a prodrug where the enzyme gets converted to its activeform when it gets into the bacteria. Inhibition of DNA/RNA synthesis- DNA gyrase inhibitors: nalidixic acid, ciprofloxacin, Novobiocin (NCN). Mode of action: DNA gyrase is an important factor in replication. Inhibition of cell wall synthesis: the B- lactam antibiotics- Penicillins inhibit cell wall synthesis - Penicillin G was the first B-lactam antibiotic discovered and produced commercially- produced by fungus- Effective mainly against gram positive organisms, since gram negatives have the outer membrane- Other B-lactam antibiotics were found that had activity against a broader range of bacteria - Mode of action: B-lactam antibiotics inhibit cell wall synthesis by preventing transpeptidase reaction o Penicilin binds to transpeptidases and stimulatesthe release of autolysins by bacteria which degrade the existing cell wallo Vacomycin is not a b-lactam antibiotic, but it binds to peptidoglycan precursors to prevent peptidoglycan synthesiso Cephalosporins- have similar activity to penicillins. This is produced by fungus. These areeffective against a range f bacteria and is more resistant to B-lactamase than some other antibiotics used for treating penicillin- resistant bacteria such as Neiserria gonorrhoeae. o B- lactamase is the enzyme that destroys B-lactam antibiotics Inhibition of protein synthesis- ARMT (30-50-30). Last 2 source- Streptomyces- Aminoglycosides- have structures of linked amino acids.Mode of action: inhibit protein synthesis (30s subunit of ribosome)- Rifampcin- inhibits transcription by RNA polymerase -
View Full Document
Unlocking...