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24 Cards in this Set
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penicillins (chemistry and action)
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1. Beta lactam ring fused to thiazolidine ring with side chain
2. bactericidal, T>MIC, irreversibly binds to penicillin-binding proteins (transpeptidases) which inhibits petidoglycan structure. cell lysis through osmotic pressure |
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natural penicillin
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1. penicillin VK (PO), penicillin G (IV)
2. gram + aerobes (strep but not S. aureus) 3. tx: sensitive Streptococcus, group A strep pharyngitis, syphilis |
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penicillinase-resistant: nafcillin (IV), oxacillin (IV), methicillin, cloxacillin (PO), dicloxacillin (PO)
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1. gram + aerobes (broad): MRSA, Strep. spp.
2. no gram - activity 3. different than other penicillins- liver metabolized, excreted in bile, highly bound 4. tx: MRSA (cellulitis, endocarditis) |
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extended spectrum penicillins (aminopenicillins, carboxypenicillins, ureidopenicillins)
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Aminopenicillins: ampicillin (IV), amoxicillin (PO)
1. gram + aerobes (including Enterococcus) and some gram - 2. tx: enterococcal endocarditis, RTI, UTI, endocarditis prophylaxis carboxypenicillins: Ticarcillin (IV) 1. less potent with gram + aerobes v. ampicillin. inc gram - activity 2. associated with electrolyte disturbances Ureidopenicllins: Piperacillin (IV) 1. ~ to ampicillin, with inc gram - tx: nocosomial |
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penicillin pharmacokinetics
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1. absorption: most degraded by gastic acid. must be given IM or IV. (amoxicillin is oral)
2. Vd: distributes to most tissue. 5-20% of serum levels in CNS (must dose accordingly) 3.metabolism: minimal 4. excretion: renaly excreted in active form (helpful for UTI). dose adjustment for renal disease |
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penicillin adverse effects
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1. hypersensitivity: skin rash, anaphylaxis, cross sensitivity between penicillin and cephalosporins
2. GI: nausea, ab pain, diarrhea (oral agents) 3. neuro: sz, coma, myoclonus 4. electrolyte: Na overload, hypo/hyperkalemia (high dose IV) 5. other: interstitial nephritis, eosinophilia, serum sickness, fever, hematologic effects |
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penicillin resistance
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1. bacterial B-lactamase cleaves B-lactam ring and inactivates drug
2. alterations in PBP (MRSA) 3. alterations in outer membrane permeability (gram -) |
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Beta lactamase inhibitors: Clavulanic acid
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1. mechanism: irreversible, non-competitive B-lactamase inhibitor
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Carbapenems (imipenem/ cilastatin (IV), meropenem (IV), doripenem (IV), ertapenem (IV))
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1. mechanism: similar to penicillin, T>MIC. cilastatin given with imipenem to prevent renal dehydropeptidase metabolism to nephrotoxic product
2. spectrum: very broad (last line). gram +/- activity (Pseudomonas), anaerobic, and extended spectrum beta lactamase (ESBL) organism 3. PK: only IV. similar to penicillin 4. adverse: GI problems, hypersensitivity (cross react with penicillin), higher sz incidence |
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Vancomycin
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1. mechanism: inhibits glycopeptide cell wall synthesis. bactericidal. AUC/ MIC
2. gram + aerobes and anaerobes. (MRSA) 3. tx: MRSA, gram + infection with B lactams anaphylaxis, second line C.diff (PO) 4. PK: moderate Vd (poor CSF), excreted unchanged via renal (watch serum trough and adjust for renal disease) 5. adverse: -"red man syndrome" with rapid IV infusion - hematologic: neutropenia -hypersensitivity: rash, anaphylaxis, vasculitis (desquamating skin rash and renal failure) - ototoxicity and nephrotoxicity 5. resistance: enterococci (VRE), VISA, VRSA |
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Protein synthesis inhibitors: Aminoglycosides (gentamicin)
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gentamicin (IV), tobramycin (IV), amikacin (IV)
1. mechanism: irreversibly binds to 30s ribosome causing misreading. bactericidal. Cmax/ MIC. PAE 2. spectrum: gram +/-. used with B-lactam ab for Staph, strept, enterococcus. activity against protozoa and mycobacteria 3. resistance: reduced 30s affinity, reduced intercellular transport, plasmid-mediated modifying enzymes 4. PK: requires IM/IV, Vd to extracellular space (highly polar. no CNS), excreted active in urine 5. adverse: nephrotoxicity (long term and with vanco), irreversible ototoxicity |
gentamicIn irreversibly binds 30s
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Protein synthesis inhibitors: tetracylines (doxycycline)
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doxycyline (IV/PO), minocycline (PO), tetracycline (PO), tigecylcine (IV)
1. mechanism: reversibly binds to 30S. prevents tRNA binding. bacteriostatic 2. spectrum: (broad) - gram+ aerobes (Strept and Staph. some MRSA) - gram - (H.influenza - gram - anaerobes - RIckettsiae, lyme disease, brucellosis, cholera, syphilis, Chlamydia, Mycoplasm, Legionella 3. PK: oral (binds with Ca, Mg, Al, Fe [dairy products] thereby decreasing absorption), distributes to most tissue (concentrated in bile, liver, kidney, spleen, skin, bone) -undergoes glucuronidation -metabolites excreted in urine/ bile 4. adverse: photosensitivity (rash), tooth discoloration, GI, 5. contraindicated in pregnancy and children. alters calcification of bones and cartilage stability |
tetra prevents tRNA binding
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Protein synthesis inhibitors: Macrolides (azithromycin)
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erythromycin (PO/IV), clarithromycin (PO), azithromycin (IV/PO), telithromycin (PO)
1. mechanism: reversibly binds 50S ribosome. bactericidal/ static (dose dependent) 2. spectrum -erythromycin: gram + (Strep, Staph); gram - (H. influenza). less activity against anaerobes -azithromycin: ~ to erythromycin, with more H. influenza activity and Chlamydia, Mycoplasm, Legionella activity 3. tx: RTI, pts. allergic to penicillin 4. PK: oral absorption; high Vd but no CNS (drug concentrates in neutrophils and macrophages); hepatic metabolism. acts as CYP450 inhibitor (many drug interactions! not as much with azithromycin); excreted in bile/ urine 5. adverse: GI, thrombophlebitis, cholestatic hepatitis, hearing loss, allergy (rare) |
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Protein synthesis inhibitors: Clindamycin (IV/PO)
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1. mechanism: binds to 50S ribosome, inhibits protein synthesis, bacteriostatic
2. spectrum: - gram + cocci (penicillin alternative) - gram +/- anaerobes - pulmonary, abdominal, pelvic infections, anaerobic coverage 3. PK: -PO or IV. Vd to most tissue except CSF - undergoes oxidative metabolism. excreted in urine/ bile in inactive state 4. adverse: diarrhea (C. diff overgrowth); allergy; metallic taste; neutropenia; thrombocytopenia |
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Protein synthesis inhibitors: others
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Daptomycin
- binds to cell membrane, causes depolarization, and disrupts DNA/RNA/protein synthesis - rapidly bactericidal - gram + aerobes (MRSA, VRE) - IV only - highly protein bound - minimal metabolism/ renal excretion Quinupristin/ dalfopristin (IV): -binds to 50S ribosome. -bacteriostatic/ cidal dependent on organism - gram + aerobes (MRSA and VRE faecium) - high Vd, no CSF Linezolid (IV/PO) - binds 50S ribosome - bacteriostatic - gram + aerobes (MRSA, VRE) - IV/ PO at same dose - high Vd - oxidized. renal and nonrenal elimination - adverse effects with SSRI's because of MAO inhibition of drug |
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Nucleic acid/ chromatin structure inhibitors: Quinolones (levofloxacin)
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1. mechanism: inhibit topoisomerase II (gyrase) and IV. arrests DNA replication
-bactericidal. Cmax/ MIC 2. spectrum - 2nd generation (ciproflaxin, levofloxacin): some gram +, high gram - (Pseudomonas) - 3rd generation (gatifloxacin, moxiflxacin): more gram + (S. pneumoniae) -4th generation (trovafloxacin): anaerobic activity 3. tx: gram - infection, RTI, anthrax, gastroenteritis, osteomyelitis, prostatitis 4. PK: IV/PO. good absorption (including bone, prostate); renal excretion 5. adverse: GI upset, HA, dizzy, rash, photosensitivity, QT prolongation, hypo/hyperglycemia 6. contraindicated in pregnancy (affects cartilage development) |
QT
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Nucleic acid/ chromatin structure inhibitors: Nitroimidazoles (Metronidazole)
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1. mechanism: damages DNA (reduction of nitro groups produces cytoxic products); bactericidal
2. spectrum: gram -/+ anaerobes, protozoa (amobea, giardia, trichomonas) 3. tx: C. diff, anaerobic infections 4. PK: high oral. IV/PO at same dose. high Vd (high CSF) - hepatic metabolism to active metabolites. excreted in urine/ feces -adjust for renal and hepatic disease! 5. adverse: metallic taste, disulfiram rxn (tx for ETOH abuse), peripheral neuropathy |
nitro destroy DNA
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Cephalosporins (cefazolin, cefuroxime, cefoxitin, ceftriaxone, cefepime)
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1. similar action to penicillin
2. no action against Enterococci 1st generation: (Cefazolin (IV), Cephalexin (PO) - broad gram + aerobes (strep, MSSA) - narrow gram - tx: skin infection, UTI, surgical prophylaxis 2nd generation: (Cefuroxime (IV/PO)) - less broad gram + aerobes (Strep, less staph) - more gram - activity (not Pseudomonas) - tx: RTI, CAP 3rd generation: (Ceftriaxone (IV)) - less gram + (strep less staph) - broad gram - - inc ability to cross CSF - tx: PNA, gram -, meningitis 4th generation: Cefepime (IV) - broad gram + aerobes (~to 1st) - broad gram - aerobes (including Pseudomonas) -tx: nocosomial 3. PK: ~ to penicillin 4. adverse: ~ to penicillin |
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Folate synthesis inhibitors: sulfamethoxazole and trimethoprim
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1. mechanism
- sulfonamides: analogue of PABA, inhibits dihydropteroate synthestase, which converts PABA to dihyropteroaste, which is converted to folic acid - Trimethoprim: inhibits DHF reductase, which converts DHF to THF (required for purine/ pyrimidine synthesis - folate inhibitors are bacteriostatic 2. spectrum: gram + aerobes (MRSA), gram - aerobes, Listeria, Shigella, Pneumocystis jiroveci (fungus) 3. tx: UTI, PCP, Stenotrophomonas 4. adverse: exfoliative dermatitis, Stevens-johnson syndrome (hypersensitivity rxn-severe erythema multiforme), fever, pancytopenia (dec [RBC, WBC, platelets]), photosensitivity 5. contraindicated in near term pregnancy. risk of kernicterus |
sulFa
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Anti-mycobacterials (isoniazid, rifampin)
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Isoniazid
1. mechanism: unstable electophilic inhibts cell wall mycolic acids. bactericidal (selective for mycobacteria) 2. spectrum: mycobacterium (M. tuberculosis-TB, M kansasii, M. xenopi) 3. adverse: hepatic toxicity (inc. with age), peripheral neuropathy Rifampin 1. mechanism: blocks RNA polymerase. inhibits transcription. prokaryotic specific 2. spectrum: broad. mycobacterium, gram +/-, leprosy 3. PK: oral absorption, enters CSF, hepatic metabolism, eliminated with bile 4. induces cytochrome P-450 (many drug interactions) |
isoniazid = ilectrophilic
rifampin= RNA inhibition |
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Antifungals: Amphotericin B
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1. mechanism: binds to ergsterol leading to inc permeability. fungicidal
2. spectrum: yeasts (Candida, Cryptococcus, histoplasmosi, blastomycoses); molds (Aspergillus, mucormycosis) 3. PK: only IV, high Vd, renal excretion 4. adverse: affects cholesterol in mammals, causing cytokine release and nephrotoxicity; infusion related reactions, K and Mg wasting |
tear the cell wall
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Antifungals: Azoles (fluconazole)
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1. mechanism: depletes [ergosterol] by inhibiting fungal P450 (converts lanosterol to ergosterol). cell wall instability. fungistatic
Fluconazole (IV/PO) - active against Candida, Coccidioides, Cryptococcus (FCCC) - IV or PO at same dose - distributes to tissue and CSF - some liver metabolism. excreted in urine Itraconazole (PO) - broad. active against Candida, Cryptococcus, coccidiodes, histoplasma, blastomycoses, aspergillus - oral capsules need acidic environment. solution does not - metabolized in liver and GI. excreted in bile and feces - inhibits CYP3A4 (drug interactions) Voriconazole (IV/PO) - very good against Aspergillus - IV or PO - metabolized in liver and GI. excreted in bile and feces |
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Antifungals: Echinocandins
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caspofungin (IV), micafungin (IV), anidulafungin (IV)
1. mechanism: inhibits synthesis of glucan (component of fungal cell wall) 2. spectrum: Candida, Aspergillus 3. tx: invasive candidiasis 4. PK: -only IV -highly bound -hydrolysis and N-acetylation in liver (not by P450) -eliminated in bile, feces, urine 5. adverse: nephrotoxicity, increased liver enzymes |
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Antifungals: Flucytosine (PO)
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1. mechanism: enters fungal cell via cytosine permease (not found in mammals). deanimated and inhibits thymidylate synthetase, blocking DNA synthesis. fungistatic
2. spectrum: chromoblastomycosis. combo drug for candidiasis and cryptococcsis 3. PK: oral, distribution to CSF, excreted in urine 4.adverse: bone marrow toxicity. contraindicated in pts with depressed bone marrow and hepatic dysfunction |
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