抗菌药物组成（英文ppt）antibacterial

ANTI-BACTERIAL Compounds Germicide / antiseptic on skin bacteria make it from PABA: we can fool them using sulfanilamide so they die of vitamin deficiency a sulfanilamide Sulfapyridine Sulfadiazine Sulfathiazole sulfamethoxazole common in Canada PENICILLINS (Narrow spectrum antibiotics) History: Original mould: penicillin notatum (pencil shapes) discovered by Fleming while working on staph bacteria, left cover plate off and noticed bacteria did not grow near mould Flory (Oxford, 1940) found way to extract penicillin out of mould, tried it on London policeman with blood poisoning from shaving cut. Wartime: needed to make much more, (used bed pans in Oxford to grow mould) so in June 1941 took production to USA (15,000 gallon vessels) Mould now: penicillin chrysogenum found on a cantaloupe in Peoria, Illinois in 1943 gave better yields and is used to make Pen-G Penicillins: general formula includes the b-lactam ring Pen-V Ampicillin Amoxicillin Cloxacillin You can make those other than Pen-G by feeding the mould the appropriate acid, RCOOH Pen-G Pen-G has to be injected: 600-2400 mg/day IV in 3-4 doses Useful against most GRAM +ve plus pneumonia, meningitis, gonorrhea, gangrene, bone infections Others can be taken orally: Pen-V: 300mg per 8h, first oral one Amoxicillin: most common, 250-500 mg per 8h Ampicillin: best for urinary tract Cloxacillin: approved for some resistant bacteria Many people are allergic to Penicillins (especially G) can lead to death! HOW PENICILLINS WORK: b-lactam ring binds to a transpeptidase enzyme responsible for forming the cross links in the peptidoglycan layer (bacterial cell walls): as the cell grows it needs to constantly break these layers: If it cant expand, the cell bursts and dies BUT some bacteria have Penicillinase, an enzyme that cleaves the b- lactam ring and allows normal wall formation: resistant Five Penicillins are more resistant to Penicillinase: mainly reserved for Staph infections (egs. Nafcillin and Methicillin) CEPHALOSPORINS: from mould found in sewage (Sardinia 1950s) a cephalosporin Cefachlor (Ceclor) Cefepime (Maxipime) 250 mg/8h, 2g/day max 1 g/12h for 10 days Very popular (2B$/y) more effective than penicillins against Gram -ve types CPS lists 16 in use all start with Cef- Not affected by penicillinase but a cephalosporinase has now emerged WIDE SPECTRUM ANTIBIOTICS: MYCINS and TETRACYCLINES Streptomycin (from soil) in 1947 stops cell division, shuts down protein/RNA synthesis Too toxic for use, then last resort for TB Also from soil: the tetracyclines: Chlorotetracycline (Aureomycin) X=Cl, Z=OH tetra-cyclo = 4 rings Tetracycline (Terramycin, (A,B,C,D) Ambramycin,.) X=H, Z=OH More common ones now: Doxycycline (Vibramycin) X=H, Z=OH, no OH in ring B Minocycline (Klinomycin) X=NMe2, Z=H, no OH or Me in ring B Demeclocycline (Declomycin) X=Cl, Z=H, no Me in ring B Doses: 250-600 mg/6h They inhibit protein synthesis by binding to the ribosome, Kill most bacteria = broad spectrum including intestinal bacteria, so side effect is DIARRHEA Eat pro-biotic yogurt when on this (and shortly after stopping)! Was used against Legionnaires Disease (Chicago 1976) Ca salts, antacids bind to them: avoid milk and antacids Side effects: browning of teeth (acne treatment for teens) photosensitive skin reduced effectiveness of birth control pills Mostly excreted unchanged high levels can be found in sewage! Aside on Legionnaires disease: hundreds staying at one hotel fell ill (34 died) during the 1976 American Legion Convention in Chicago - discovered that the pneumonia-like illness was caused by a previously unknown bacterium, now known as Legionella pneumophillia. Turns out the bacteria proliferates in warm, stagnant water, in this case in the hotel air conditioning system. Subsequent outbreaks have occurred in 1999 (Netherlands flower show, 34 died), 2001 (Spain, hospital cooling tower, 6 died) and 2002 (UK, Art Center cooling tower, 7 died) AMINOSUGARS (AMINOGLYCOSIDES) ERYTHROMYCIN CLINDAMYCIN (Dalacin) Very widely used More toxic allergic reactions rare usually only for more serious infections cross placenta and go in to breast milk Dose: 1 g/day in 2-4 doses; up to 4 g/day in more serious cases VANCOMYCIN Last resort for many staph types: interferes with wall synthesis VRE = Vancomycin resistant enterococci (opportunistic gut infection) - in Canadian hospitals (see chart at right) DAPTOMYCIN used against VRE and methicillin resistant staph (MRSA)* (stops synthesis of cell membranes) * flesh eating disease 30% mortality QUINOLONES - CIPRO Quinolones are synthetic, made first in 1987 They block bacterial DNA replication by stopping the re-coiling of new strands, make KNOTS instead CIPROFLOXACIN: most active broad spectrum antibiotic available (Anthrax scare) Sales 2B$/y especially useful for lung infections, bones, urinary tract (oral or IV) Related: Norfloxacin (Noroxin) Et in place of cyclopropyl Some newer ones: Levofloxacin Trovafloxacin Gemifloxacin LEVAQUIN TROVAN wide use for TB Others: moxifloxacin; gatifloxacin; ofloxacin Trovan (2 x 200mg/day): In Canada about 360,000 pneumonia cases per year, still 7000 deaths Some strains of staph which are Vancomyin and Methicillin resistant are now resistant to Cipro Need to keep making newer classes: 2-Pyridones and Oxazolidinones Linezolid (ZYVOXAM) Antagonize enzymes: Bind the bacterial ribosome, shuts down protein synthesis NEWEST APPROACH EFFLUX PUMP BLOCKERS Some resistant strains pump antibiotic out of the cell: these block that pump action MICROCIDE have found a peptide that stops pseudomonas effluxing fluoroquinolones = drug ca. 8x more effective 2005: FDA granted fast track status to intravenous iclaprim for the treatment of complicated skin and skin structure infections (cSSSI) resistant staph ANTI-FUNGALS Tolnaftate, Tinactin, Pitrex Fungistop, Triactin topical only, inhibits steroid biosynthesis Griseofulvin (Fulvicin, Grisovin, Grisactin) hair and nail infections orally for ringworm made by mould penicillin griseofulvin: disrupts the microtubules Not if pregnant: teratogen Not with alcohol: tachycardia NYSTATIN (mycostatin) especially for yeast (candida) infections (mouth, throat, vagina, underarms) Method of action: binds to ergosterol, the main component of the fungal cell membran