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88 Cards in this Set
- Front
- Back
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sulfanamide structure + activity
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hydrophobic.
n1-substitution keeps the pKa @ physiological pH to improve solubility (no ionization) similar structure to sulfonylurea (DM med.) |
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sulfanamides effective against what type of bacteria?
comment on drug-resistance |
gram + and gram -
drug-resistant strains highly prevalent, thus sulfanamides aren't used anymore |
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MOA of sulfanamides
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folate synth inhibitors, thus bacterial DNA/RNA synth inhibitors
..binds to enzyme that forms folate and blocks it |
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possible mechanisms of resistance?
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alteration/mutations in folate enzyme (dihydropteroate synthase)
increase capacity of bacteria to destroy/inactivate drug incraese production of folate metabolite, so gain competative advantage |
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side effects of sulfonamides
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crystalluria (not common)
hypersensitivity rxns hypoglycemia |
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trimethoprim MOA
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inhibitor of bacterial dihydrofolate reductase. (does human too but 100k fold less)
synergistic in combo w/ sulfamethoxazole trimethoprim:sulfamethoxazole = 1:20 ratio |
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trimethoprim effective against which bacteria?
resistant in which type of bact and why? |
gram + and gram -
resistance in gram - b/c of acquired plasmids that code for altered dihydrofolate reductase |
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sulfonamides are used to treat..?
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UTI
in combo w/ trimethroprim: otitis, bronchitis, pneumonia |
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quinolones: name 1st, 2nd, and 3rd gen
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1st gen = nalidixic
2nd = norfloxacin, ciprofloxacin, ofloxacin 3rd = lomefloxacin, moxifloxacin, gatifloxacin, levofloxacin |
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chemistry of quinolones
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carboxylic group at c3
newer ones: flourines at c6 piperazine at c7 |
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1st gen characteristics + used for?
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narrow spectrum w/ excessive binding to serum
used for UTI |
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2nd gen characteristics + used for what kind of bact?
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more potent, less side effects, broader spectrum. longer half lives
against gram - |
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3rd gen characteristics + used for what kind of bact?
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long half lives
used in gram + |
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MOA of quinolones
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inhibit activity of gyrase so inhibits DNA/RNA replication
gyrase normally unwinds dna for replication |
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quinolone structure characteristics
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at N1, when r group replaced w/ H = loss of activity
C2 replaced w/ N = decreased activity C3 carboxylic = superior to esters, etc C6 addition of F = increased activity |
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quinolone antibac spectrum + resistance
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used in gram -
most anaerobic bact = less susceptible resistance: mutation in gyrase, defects in drug penetration |
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quinolone DDI
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chelation w multivalent ions like Ca2+, Mg2+ to form water-soluble complexes taht decrease potency
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side effects of quinolones
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N/V, abdominal discomfort, anorexia, convulsions (rare)
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ciprofloxacin used against?
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gram -
some gram + effects high bioavail |
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levofloxacin used for?
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resp tract infection
s. pneuomonia is more susceptible to levo than cipro |
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tetracyclines MOA and used against which bact
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inhibit protein synth by inhibt 30S unit of ribosome @ A site
used in gram + |
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resistance?
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high resistance, thus tetracyclines are becoming 2nd-line agents
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tetracyclines and intestinal flora and effects?
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incomplete absorp kills intestinal flora.
stool becomes softer, odorless, and yellow-green color |
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tetracycline resistance?
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decrease in influx or increase in efflux of drug
additional proteins formed to protect 30S subunit enzymes that deactivate tetracycline |
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tetracycline DDI
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chelation w/ multivalent ions like Fe2+, Al3+ to form insoluble complexes
shouldn't be coadministered w/ antacids and iron or w/ Ca2+ rich dairy products |
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tetracycline c4 epimerization + dehydration
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epimerization of c4 yields inactive form of 4-epitetracycline
dehydration: anhydrotetracycline is inactive and has deep color |
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doxycycline formation
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formed by replacing hydroyxl group with H
reduces toxicity to kidney caused by dehydration |
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tetracycline toxicity
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discoloration in teeth and bones as a result of precipitation
phototoxicity |
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macrolides characteristics + used for? against what type of bacteria?
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high oral efficacy and low toxicity
narrow antibact spectrum and poor GI tolerability used for upper and lower resp tract infections and some STD's gram + but not gram - (can't penetrate outter layer) |
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macrolide MOA
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binds to 50S unit of ribosome and blocks translocation of peptides from A to P site
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erythromycin (type of macrolide). types?
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A,B,C,D,E,F
B,C,D = intermediates for A formation A = best antibacterial activity given in enterically coated caps/tabs b/c can't tolerate acidic env like stomach |
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clarithromycin (macrolide)
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better tolerability under acidic conditions
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azithromycin
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greater stability + longer half life
stonger activity against gram - compared to erythromycin and clarithromycin |
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side effects of macrolides
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erythromycin: GIT, n/v/d/, abdominal cramps
both clarith and azith have better tolerability for pt than eryth |
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macrolide resistance
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decrease in permeation of drug into cell
modification of 50S unit of ribosome hydrolysis of the drug causing inactivity |
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b-lactam antibiotic characteristics
examples of these? |
b-lactam ring required for activity
kill/prevent growth of bacteria by targeting cell wall effective in low conc. naturally prod by fungi synth analogues: increased efficacy, decreased side effects, broader activity, active against drug-resistant bact penicillin + cephalosporins |
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b-lactams used to treat..?
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ear/nose/throat infections, resp infect (pneumonia), UTI, skin infect, certain STD's (gonorrhea)
before/after surgery/dental work |
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penicillin used for:
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pneumonia, strep pharyngitis, syphilis
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amoxicillin used for:
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pneumonia, ear infections, strept pharyngitis, UTI
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ceftriaxone used for:
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meningitis, UTI, gonorrhea
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cloxacillin used for:
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cellulitis
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bacteria classifications:
gram + and gram - |
gram +: retain gentian violet staining (b. subtilus, s. pyogenes, s. aureus)
gram -: will not retain gentian violet staining (e. coli, v. cholerae) |
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pseudomonas species characteristics
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gram - especially p. aeruginosa = resistant to many antibiotics
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b-lactam spectrum of activity
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NATURAL penicillins only active against gram + (narrow spectrum)
SYNTHETIC penicillins have greater activity against gram - (broad/extended spectrum) cephalosporins = both gram + and gram - aztreonam (a monobactam) = gram - |
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b-lactam MOA
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bact. cell wall: inhibit formation of polymeric peptidoglycan, which is unique to bact cell wall
interrupt cell wall cross-linking of peptidoglycan (NAM and NAG) results in bact. cell lysing (weak walls) since they interfere w/ crosslinking, penicillins are more potent against G+, than G- |
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penicillin structural charact
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4 membered b-lactam w/ 5-membered thiazolidine rinkg
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penicillin properties
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white crystalline materials. unpleasant taste. pka value of 2.5-3
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penicillin units of activity
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1 oxford unit = 0.6ug of penG sodium
larger salt = higher molecular weight = fewer units per mg 1mg penG sodium = 1.667 units 1mg of penG potassium = 1.530 units |
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penicillin inactivation/resistance
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b-lactamases = enzymes that open up the b-lactam ring and inactivate
80% of staph auerus = resistant to penicillins overexposure/overprescribing = resistance development |
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methicillin and nafcillin uses
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used in infections caused by staph that are penG resistant
these are resistant to b-lactam ring breaking |
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ampicillin, amoxicillin
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these are ACID STABLE (because of amino substitution)
high oral availability because a-amino group increases acid stability amoxicillin = more effective orally. must be taken with meals |
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b-lactamase inhibitor
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sulbactam given w/ ampicillin (unasyn). IM/IV
clavulanate given w/ amoxicillin (augmentin). orally w/ food |
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penicillin...extending activity spectrum against gram - bacteria. how?
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add ionizable (amino or carboxyl) or polar group to a-carbon of acyl group
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carbenicillin (a carboxypenicillin)
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one of the broadest spectrum penicillins
used in systemic and urinary tract infection that are resistant to ampicillin given orally |
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ticarcillin
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higher serum levels and duration of action than carbencillin.
IM and IV only, not orally |
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ureidopenicillins
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more active than carboxypenicillins against most kelbsiellas, pseudomonas, hemophilus
IM and IV, not orally |
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narrow spectrum penicillins
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penG, penV
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narrow spectrum penicillinase-resistant
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methicillin, mafcillin, oxacillin, cloxacillin, dicloxacillin
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moderate spectrum
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amoxicillin, ampicillin
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broad spectrum
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augmentin (amoxicillin + clav acid)
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extended spectrum
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piperacillin, ticarcillin, mezlocillin, carbenicillin
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adverse effects of penicillins
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common: N/D, rash, yeast/candidiasis overgrowth
infrequent: fever, vomiting, dermatits/swelling/redness pain + inflammation at injection site |
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penicillin allergy
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10% of population is allergic
rashes, itchy eyes, swollen lips/tongue |
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cephalosporin structural characteristics
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4 membered b-lactam ring + 6-membered dihydrothiazine ring
acid hydrolysis of 3C group prevents oral administration, thus must be given parenterally |
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cephalexin + used for?
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moderate antibac spectrum
good oral activity used for: UTI |
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oral cephalosoporins (cefaclor, loracarbef)
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orally active and used for h. influenzae
inactive against pseudomonas |
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b-lactamase resistance of cephalosporins
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more resistant than ampicillin, particularly gram + lactamases
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mod to increase b-lactamase resistance?
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add methoxy group to 7alpha position
...forms cephamycin class |
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cephamycin class
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cefotetan
IV, not orally short half-life effective against gram - bact and penicillin-resistant |
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oxime cephalosporins (cefotaxime)
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b-lactamase resistant
excellent broad spectrum against gram - and gram + IM and IV, not orally |
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oxime cephalosporins (cefuroxime)
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parenterally and orally
UTI not effective against pseudomonas |
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oxime cephalosporin(ceftriaxone)
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good for resp infection
combo w/ azithromycin for pneumonia gonorrhea and meningitis |
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oxime/ammonium cephalosporins (ceftazidime)
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ceftazidime
better against pseudomonas aeruginas |
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oxime/ammonium cephalosporins (cefepime)
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similar to ceftazidime but superior coverage of gram +
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oxime/ammonium cephalosporins (cefpirome)
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gram -
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1st gen cephalosporin (oral)
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cephalexin, cephradine, cephadroxil
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1st gen cephalosporin (parenteral)
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cephalothin, cephapirin, cefazolin
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2nd gen cephalosporin moderate spectrum with anti-haemophilus activity
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cefaclor, loracabef, ceprozil, cefuroxime, cefamandole
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2nd gen cephalosporin (mod spect w/ anti-anaerobic bacteriodes) activity
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cefoxitin, cefotetan
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3rd gen cephalosporin (broad w/ anti-pseudomonas)
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ceftizoxime, cefotaxime, ceftriaxone
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3rd gen w/ better anti-pseudomonas
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ceftazidim, cefoperazone
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4th gen cephalosporin (enhanced against gram + and better b-lactamase stability
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cefepime, cefpirome
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adverse reactions to cephalosporins
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relatively nontoxic and selective aginst bacteria but can cause allergic and hypersensitive rxn
some cephalosporins can cause hypoprothrombinemia and severe bleeding problems |
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monobactams
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b-lactams taht are monocyclic w/ only 1 ring.
natural products from soil bacteria weak antibacterial, but highly resistant to b-lactamase |
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synthetic monobactam (aztreonam)
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very broad spectrum against gram -
limited gram + resistant to G b-lactamase injection only not oral |
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carbapenem characteristics
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thienamycin
4-membered b-lactam w/ 5-membered ring like penecillin, but structurally different (no sulfur group) |
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thienamycin activity
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gram + and gram -
ultra-broad spectrum b-lactam antibiotics as compared w/ penicillin and cephalosporins IV only highly resistant to b-lactamase |
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bei
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near, with, at the house of
(dat.) |
