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46 Cards in this Set
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- Back
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antimicrobrials |
target bacterial/fungai cell wall synthesizing enzymes bacterial ribosomes DNA synthesis enzymes Viral replication targets |
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cell wall & membrane active antimicrobrials
beta lactams |
group of Abx contain beta lactam ring PCN cephalosporins monobactams carbapenems |
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Beta-lactam MOA |
inhibit bacterial growth-interferes with transpeptidation reaction of bacterial cell wall synthesis -bact. CW rigid outer layer unique to bacteria(surrounds Cytoplasmic membrane & protects cell- composed of peptidoglycan polymers linked by side chains pcn binding protein removes terminal alanine side chain-allowing cross linking -BL=structural analogues to this alanine chain ( mimic natural structure of bacterial wall, bind covalently to PCNbinding protein, renderin it useless
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methods of BL resistance BL & alter target pcn bind prtn |
BL- inactivate beta lactams alter target pcn-bind prtn- -low affinity for BL binding -mech for MRSA |
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BL resistance methods- Impaired drug peneatration efflux pumps |
IMpaired drug peneatration -down reg or alteration of porins -common for gram - bacteria Efflux pumps -force drugs out of cell |
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PCN |
all pcn share common core -variations in side chain determine properties of each drug -integrity of rings structure is essential for biologic activity of these drugs -common path of drug resist. in this class is BL enzymes -most stable in gastric acid (oral admin good) |
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PCN classes Traditional PCN (PEN V, Pen G) |
most active against gram + organisms, gram - cocci, and non beta lactamase producing anaerobes susceptible to hydrolysis by beta-lactamases |
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PCN class- Antistaphyloccocal PCN Dilcoxacillin, nafcillin, oxacillin |
active vs staphylococci & streptococci resist to staphyloccal beta-lactamases |
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PCN classes -Extended spectrum PCN Amoxicillin, piperacillin, ticarcillin |
activity similar to traditional pcn plus more - oragnisms also susceptible to Beta-lactamases |
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PCN pharmacokinetics |
acceptable GI absorption but not all acid stable -Dicloxacillin, amoxicciln, ampicillin have best oral bioavailability 1-2hr apart form meals Highly prtn bound-good fluid/tissue distrib. -concentration most tissues=serum conc. rapid exc. by kidneys HL PCN G-->30min HL ampicilin -->60min |
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PCN ADRs- |
N/V diarrhea 2nd infection- candidiasis non-allergic rash: delayed 24-48hr hypersensitivity rxn: 2-30min post admin -all PCN cross reactive -5-8% claim PCN rxn -0.05% of recipients suffer anphylaxis -more common rxn are pruritis rash desensitization is possible if necessary |
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Cephalosporins |
structurally similar to PCN more stable to many beta-lactamses broader spectrum activity grouped by activity into 4 generations |
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Cephalosporin 1st generation |
used for skin & soft tissue infections primarily active vs gram + bacteria |
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cephalosporin 2nd generation |
same activity as 1st generation plus Klebsiella, proteus, E. Coli |
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cephalosporin 3rd generation |
used for broader indications -more active vs gram (-) bacteria |
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cephalosporin 4th generation |
primarily active vs gram + bacteria resistant to beta-lactamase |
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cephalosporin pharmacokinetics |
oral formulations well absorbed from GI -widely distrubuted to most tissues, some highly bound to prtn -some are metabolized to less active compounds, most excreted via kidneys as unchanged drug |
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cephalosporin ADR |
hypersensitivity -anaphylaxis, rash, fever, etc. very low cross sensitivity with PCN cross reactivity more likely in early gen ceph. -tox more common - site rxn- pain after IM injedction,phlebitis -renal damage -bleeding DO |
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drug modifying agents -Probenecid
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increases pcn concentration by inhibiting renal tubular secretion of weak acids |
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drug modifying agents -beta-lactamase inhibitors |
clavulanic acid, sulbactam, tazobactam -resemble beta-lactam drugs -posess weak antibacterial activity -inhibit beta-lactamases, extend spectrum of beta-lactams |
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Monobactams Aztreonam(azactam) (other beta-lactams) |
only active against aerobic gram - rods stable with many beta lactamases no gram + activity no cross sensitivity w/ PCN rash most common ADR |
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(other beta lactams) Carbapenums Doripenum(dorabax), Ertapenem (invanz), imipenem(primaxin), meropenem(merrem) |
broad spectrum drugs resistant to most beta lactamases imipenem given with cilastatin(dehydropeptidse inhibitor) to inhibit renal dehydropeptidation possible cross sensitivity to PCN Common ADR: N/V diarrhea, rash, local rxn |
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Vancomycin(Vancocin) |
ONLY vs gram + bacteria-large glycopeptide, not absorbed orally -oral Tx only for C. difficile -parenteral therapy by IV admin for serious infections such as endocardititis, meningitis, or highly PCN resistant bacteria -binds to terminal alanine of peptidoglycan polymers, inhibiting elongation of peptide, weakening the cell -resistance mediated by altering terminal binding amino acid 90% elim by glumerular filtration common ADR: phlebitis, chills, fever, flushing |
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Daptomycin- cubicin |
similar spectrum to vanc. more rapid bactericidal -activity vs vanco resist strains of enterococci & S aureus poorly absorbed orally, toxic to muscle (IV only) incorporates into cell membrane & alters polarity =cell death myopathy -common adr ineffective tx pneumonia r/t antagonistic effect that pulm surfactatnt has on dapta |
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Bacterial static protein syntehsis-inhibting antimicrobrials |
tetrocyclines, macrolides, clindamycin, streptogramins,chloramphenicol, linezolid |
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Tetracyclines mechanism |
bind to 30S of bacterial ribosome- prevent addition of further AA active vs gram + and - bacteria all orally bioavailable except tigecycline, which is synthetic analogue of minocycline excreted in feces and urine |
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Tetracyclines- |
Tx h. pylori, acne, lyme dx rigecycline IV to tx more serious infections bacterial resistance include -reduced influx or inc. efflux mechanisms -ribosomal protection by binding site interference -enzymatic inactivation -Doxcycline, minocycline, tigecyclien are more resitant to tetra. resist mech. due to poor binding efflux mechanisms |
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tetracycline ADR and CI |
bind to multivalent cations (Ca,Mg, Fe)given oral complex w/ growing bones/teeth CI:preg./lactate/kids<8 -N/V, Diarrhea(irritate GI) --> somtimes Cdif. -sunlight sensitivity enhanced |
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Macrolides
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-bind 50s of bacterial RNA-prevent chain elong. -active vs Gram+ &- bacteria oral bioavaialble(erythromycin w/ enteric coat) azithromycin QD dose -slow release from tissue HL:2-4days |
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macrolides |
rythromycin(ery-tab) clarithromycin(biaxin) azithromycin(zithromax) |
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Macrolides use ,resistance |
common used to tx CAP, chlamydia, substitutes for PCN allergy -bacterial resistance: reduced membrane permeability & efflux -production of esterases that hydrolyze macrolides -modificaiton of ribosomal binding site |
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macrolides ADR |
n/V, diarrhea - GI intoleranace due to stim of gut motility, epsecially erythromycin -many drug interactions: CYP3a4(not including azithro) |
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Clindamycin- cleocin |
derivative of lincomycin binds to 50S (same as macrolides) cross resistance high oral bioavail., Gram + activity
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clindamycin use and ADR |
tx skin/soft tissue infections, some MRSA activity, dental prophylaxis for pt w/ valve defects ADR: n/v, diarrhea,rash C. DIFF |
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Streptogramins quinopristen-dalfopristen(synercid) 30:70 mixture |
-bind to 50S (macro/clindo) -gram + activity -admin IV only -CYP3A4 metabolism -used in vanc resist E. Faecium ADR- related to infusion |
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Chloramphenicol use, binding, admin, elim, ADR |
binds 50s broad spectrum Gram + & - admin oral/parenterally as a PRODRUG w/ wide distribution to tissues -elim primarily in urine following glucuronidation -not common admin-can be sub for PCN ADR: include N/V diarrhea, candidasis, red cell suppresion @ high doses. CYP450 interactions |
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Linezolid-Zyvox |
Gram + activity unique binding site w/in 50s (23S) results in no cross resistance to other drugs of variety 100% bioavail after oral admin Tx vanc resist E Faecium, CAP, skin/soft tissue infections ADR: reversible dec. in PLT count (thrombocytopenia) in 3% of pt, anemia, neutropenia, Serotonin Syndrome |
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bacterial protein synthesis inhibiting antimicrobrials |
aminoglycosides |
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aminoglycosides streptomycin, neomycin, amikacin, gentamicin, tobramycin |
Gram - activity used w/ another class of med for synergistic effect (beta lactam / Vanc) -irreversible inhibitors of prtn synthesis -binds to specific 30s ribosomal proteins --> peptide formation interference & misreading of mRNA to create jumbled or toxic peptides -lethal to cell(hence bacteriocidal) |
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aminoglycosides |
absorbed very poorly from oral dosing- excreted mostly in feces IM provides fair absorption-IV is best dosed TID but can be QD potential for dec. tox w/ similar efficy in Tx - concentration dependent killing -post-antibiotic effect excrete in urine and tx endocarditis ADR: oto and nephrotoxicity- (^ occurence >5days & w/ renal insufficiency |
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Sulfonamides mechanism & resist |
P-aminobenzoic acid analogues inhibit purine production in bacteria- interfere w/ DNA replication resist occurs w/ abundance of PABA -enzymes have low affinity for sulfonamides, or permeability is decreasesd for sulfonamides |
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sulfonamides ADR, use, admin |
topical, oral non/absorbable used w/ Trimethoprim for synergism inhibit both Gram + & - bacteria ADR: n/v diarrhea, rash, hypersensitivity rxn, SJS, photosensitivity, headache, drug interactions, crystaluria |
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Trimethoprim mech. & resist |
-folate analogue inhibits dihydrofolic acid production-another step in process --> purines for dna syntehsis -combines w/ sulfonamide activity provides better results, reducing chance for resistance -resist occurs w/ abundance of dihydrofolate reductase,enzyme has low affinity for trimeth. or permeability dec. for trimeth.
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trimethoprim dose and Tx |
oral & IV preperation more lipid soluble --> ^ Vd give in ratio 1: 5 trimethoprim - sulfamethoxazole - Tx UTI some MRSA tx |
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Fluoroquinolones mecanism Tx |
Nalidixic ACID analogues block DNA synth by interfering w/ DNA gyrase prevent relaxation of supercoiled DNA which is required for normal transcription QD dosing in levo, gemi,gati ^ activity vs Gram - and some + cations disrupt absorption-cross resistance growing fast Tx UTI, bacterial diarrhea newer meds improved availability significantly |
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fluoroquinolones ADR |
N/V, diarrhea,colitis, renal/hepatic failure, angina atrial flutter, BBW: tendonitis/tendon rupture -elderly @ ^ risk, delay onset for months AVOID in pregnancy no kids <18
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