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CHEM 1004 (13)
Chapter 15

Chapter 15 cont'd - Antibiotics

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CHEM 1004
Gerald Buchanan

Chapter 15 cont’d: Antibiotics ● Antibiotics have saved the most lives ● Kill bacterial infections and cure the illness by destroying bacteria cell walls ● Dr. Joseph Lister - Found that mould inhibited the growth of bacteria ○ ‘Discovered’ antiseptic surgery by killing bacteria ○ ‘Listerine’ named after him ● Listerine and other mouthwashes contain up to 25% alcohol. Long term use increases risk of oral cancer. Kills some germs but, many more remain ● Serious infections such as gingivitis and trench mouth require much stronger mouthwash than any over the counter available ● Sulfa Drugs (Sulfanilamide) - The first antibacterial drugs ○ Benzene sulfonamides. Not antibiotics but inhibit bacteria growth by disrupting folic acid synthesis ● Antibiotics isolated from moulds or bacteria, eg. penicillins, cephalosporins, erythromycin, streptomycin, but sometimes ‘synthetic’ ● Antibacterial Agent - Antimetabolite (starves the bacteria, often of folic acid), eg. sulfa drugs ● Penicillin - Discovered in 1928 by Alexander Fleming by growing Staphylococcus bacteria on an agar medium ○ Grew a pure mould culture and discovered it was Penicillium notatum. Then isolated the pure antibiotic named penicillin ○ Penicillins are Beta-Lactams. The first class of 'broad spectrum' antibiotics; still the most prescribed worldwide. ○ Pharmaceutical grade Penicillin obtained for fermentation ● The Process of making Penicillium ○ Start “cold stored” penicillium culture on agar plate ○ Transfer to “shake flasks” ,with food (Sugars) and nutrients (ammonium salts), aa’s needed for growth ○ Resulting suspension can be transferred to seed tanks for further growth ○ Transfer to larger fermentation tank (30,000 gallons) ○ After 3-5 days , isolation temp, pH, mixing essential, sterilized air pumped in ● Semi-Synthetic Derivatives of Penicillin ○ Original penicillin was excreted too rapidly-urine recycling in early patients for recovery of the drug ○ Chemists modify original structure for different properties and bioavailability ○ Varied structures indicate varied 'mechanisms' to kill bacteria ● Beta-lactams(penicillins) - breakdown cell walls ● tetracyclines/erythromycin/streptomycin - inhibit various aspects of protein synthesis ● fluoroquinolones('cipro') - inhibit DNA replication Antibiotics and Their Uses: ● Penicillins – ear/skin/respiratory/digestive/urinary infections, syphilis, scarlet fever. ● Tetracyclines – respiratory/urinary infections, acne, bronchitis, whooping cough, typhus fever. ● Cephalosporins – ear/throat/skin/urinary infections ● Chloramphenicol – typhoid fever, meningitis, eye/ear infections ● Erythromycins – skin/eye/respiratory/tissue infections, diphtheria. ● Spectinomycin – gonorrhea ● Gentamicin – bone/skin/lungs/abdomen infections ● Over The Counter Antibiotics: Cefaclor(cephalosporin), Bacitracin, Neomycin Antibiotic Resistance ● Partly due to overuse (abuse?), partly because bacteria have short life-cycles there is a serious and increasing problem of emergence of antibiotic-resistant bacteria. ● Antibiotics use would only be permissible to treat sick animals Antimalarials: ● Malaria is transmitted by female Anopheles mosquito. Microscopic parasites in saliva- multiply in human red blood cells ● No antimalarial drugs because no money in it for the Pharmaceutical industry ● Quinine - Bark of the South American cinchona tree ○ An alkaloid ○ Also antipyretic, analgesic, anti-inflammatory, anti-smallpox ○ British added it to water to prevent malaria ● Chloroquine: Synthetic Antimalarial Drugs ○ Used to prevent and treat malaria ○ Dangerous in overdose. Malaria parasites now have developed widespread resistance to it Viruses ● A virus contains a core of DNA or RNA, but never both, wrapped in a protective shell (usually protein). Cannot grow and reproduce by itself ● Viruses are parasites. They invade other organisms (the host), take over their 'metabolic machinery' to reproduce and eventually kill those cells and move on. Viruses do not have a lot of metabolic reactions to 'mess up' chemically. ● Fighting Viruses ○ Vaccines - A weakened strain of the virus is injected into the host so that antibodies can be produced against that specific virus. These antibodies are then always ready to protect against future exposure to that particular virus. ■ *Can occur 'naturally' if you survive an attack of, eg. chicken pox/measles/polio. Doesn't work for colds/flu/HIV ● H1N1 Vaccine Production ○ Old method: inject circulating flu virus and 1 other into eggs: 2 viruses mix and match their genes via genetic mutations ○ Pick out the desired seed strain for H1N1 and then reinject into millions of eggs to grow the vaccine ○ Takes 5-6 months in total ○ Modern Method - Reverse genetics. Stitching together the wanted genes. ● Antiviral Agents: ○ General - Stop DNA synthesis with modified nucleic acids ○ For HIV - Inhibit production of the protein sheath with non-nucleosidic compounds ● An antibody is a specific protein that is synthesized by white blood cells to eliminate/inactivate a pathogen that enters our body. These 'invading' compounds are
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