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113 Cards in this Set
- Front
- Back
MOA of penicillins
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Bind PBPs to inhibit transpeptidation reactions in peptidoglycan cross-linking --> inhibit cell wall synthesis
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Mechanism of resistance to penicillin
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Beta-lactamases (staphylococci); structural change in PBPs (MRSA); change in porin structure (pseudomonas)
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Narrow spectrum penicillins
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Penicillin G and V. Strep, pneumococci, meningococci, treponema
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Very narrow spectrum penicillins
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Nafcillin, methcillin, oxacillin. Staph. If MRSA use vancomycin.
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Broad spectrum penicillins
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Ampicillin, amoxicillin. Gram+ cocci (except staph), Listeria, H. influenzae, E. coli. Borrelia and H. pylory: amoxi
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Extended spectrum penicillins
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Ticarcillin, piperacillin, azlocillin. Increased activity against gram- plus anti-pseudomonal
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Beta-lactamase inhibitors
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Clavulanic acid, sulbactam. Use in combination with broad and extended spectrum penicillins
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Pharmacokinetics of penicillins
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Most are eliminated via active tubular secretion. Nafcillin and oxacillin are eliminated in bile. Ampicillin undergoes enterohepatic circulation but is excreted by the kidney. Benzathine penicillin G repository form (t1/2: 2 weeks)
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Side effects of penicillins
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Hypersensitivity (5-7%). Urticarial skin rash to anaphylaxis. Interstitial nephritis (methicillin).
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First generation cephalosporins
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Cefazolin, cephalexin. Gram+ cocci (not MRSA), E. coli, Klebsiella pneumoniae, some proteus. Surgical prophylaxis
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Second generation cephalosporins
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Cefotetan, cefaclor, cefuroxime. Increased gram- coverage, including some anaerobes
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Third generation cephalosporins
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Ceftriaxone (IM), cefotaxime (IV), cefdinir, cefixime (oral). Gram+ and gram- cocci plus gram- rods. Enter CNS. Use in meningitis, sepsis
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Fourth generation cephalosporins
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Cefepime (IV). Enter CNS, resistant to betalactamases
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Pharmacokinetics of cephalosporins
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Active tubular secretion blocked by probenecid. Cefoperazone and ceftriaxone largely eliminated in bile.
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Side effects of cephalosporins
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Hypersensitivity (2%), rashes, fever, postive Coombs test, disulfram-like effect
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Drugs to use in case of penicillin/cephalosporin allergy
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Macrolides for gram+, aztreonam for gram- rods
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Imipenem and meropenem
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Resistant to betalactamases. Active against gram+ cocci, gram- rods and anaerobes. Use in life-threatening infections. Used IV. Imipenem is given with cilastatin to inhibit rapid renal metabolism by dehydropeptidase. Side effect: seizures
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Aztreonam
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Resistant to betalactamases. Used IV against gram- rods. No cross-allergenicity with penicillins or cephalosporins
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Vancomycin MOA
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Binds D-Ala-D-Ala pentapeptide to inhibit elongation of peptidoglycan chains. Does not bind PBPs.
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Uses of vancomycin
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MRSA, enterococci, C. difficile (backup drug)
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Resistance to vancomycin
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Terminal D-ala is replaced with D-lactate in muramyl pentapeptide
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Pharmacokinetics of vancomycin
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Used IV and orally (not absorbed) in colitis. Enters most tissues but not CNS. Eliminated by renal filtration. Long t1/2
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Side effects of vancomycin
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"Red man syndrome" (histamine release); permanent ototoxicity; nephrotoxicity
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Antibiotics that act on 30S ribosomal subunit
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Aminoglycosides, tetracyclines. "buy AT 30, CCEL at 50".
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Antibiotics that act on 50S ribosomal subunit
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Chloranphenicol, clindamycin, erythromycin (macrolides), linezolid. "buy AT 30, CCEL at 50"
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Antibiotics that inhibit formation of initiation complex
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Aminoglycosides (30S), linezolid (50S)
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Antibiotics that block attachment of aminoacyl-tRNA to A site
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Tetracyclines (30S), dalfopristin (50S)
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Antibiotics that inhibit peptidyltransferase (peptide bond formation)
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Chloranphenicol (50S)
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Antibiotics that inhibit translocation
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Macrolides (50S), clindamycin (50S)
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Mecanisms of resistance to macrolides and clindamycin
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Methyltransferases alter drug binding site on the 50S ribosome; active transport out of cell
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Mechanism of resistance to tetracyclines
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Tetracycline pumps transport drug out of the cell
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Mechanism of resistance to aminoglycosides
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Conjugation enzymes
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Mechanism of resistance to sulfonamides
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Change in target enzyme decreases drug sensitivity; formation of PABA; use of exogenous folic acid
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Mechanism of resistance to fluoroquinolones
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Change in target enzyme decreases drug sensitivity; pumps transport drugs out of the cell
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Mechanism of resistance to chloranphenicol
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Formation of inactivating acetyltransferases
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Pharmacokinetics of aminoglycosides
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Polar compounds not absorbed orally or widely distributed. Renal elimination. Modify in renal dysfunction
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Aminoglycoside drugs
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Gentamicin, tobramycin, amikacin: gram- aerobic rods (pseudomonas, brucella, legionella); Streptomycin: TB, plague and tularemia; neomycin
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Side effects of aminoglycosides
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Nephrotoxicity (6-7%), ototoxicity enhanced by loop diuretics.
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Tetracycline drugs
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Tetracycline, doxycycline, minocycline, demeclocycline
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Uses of tetracyclines
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Chlamydia, mycoplasma, H. pylory, Rickettsia, Borrelia, Brucella, Vibrio
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Phamacokinetics of tetracyclines
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Metabolized by kidney (most), and liver (doxycycline). Decrease absorption of divalent cations by chelation.
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Side effects of tetracyclines
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Tooth enamel dysplasia, decreased bone growth (avoid in children), phototoxicity, contraindicated in pregnancy
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Drugs that cause phototoxicity
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Tetracyclines, sulfonamides, quinolones
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Drugs that are nephrotoxic
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Vancomycin, aminoglycosides, amphotericin B, cisplatin, cyclosporine
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Drugs that are ototoxic
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Aminoglycosides, loop diuretics
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Pharmacokinetics of chloranphenicol
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Orally effective, enters CNS, metabolized by hepatic glucoronidation, inhibits P450
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Side effects of chloranphenicol
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Dose-dependant bone-marrow suppression, "gray baby" in neonates (decreased glucoronosyl transferase)
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Macrolide drugs
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Erythromycin, azithromycin, clarithromycin
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Uses of Erythromycin
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Gram+ cocci, atypicals (chlamydia, mycoplasma, ureaplasma), legionella, campylobacter
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Uses of azithromycin
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Gram+ cocci, atypicals (chlamydia, mycoplasma, ureaplasma), legionella, campylobacter, more activity in respiratory infections
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Pharmacokinetics of macrolides
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Erythromycin and clarithromycin: metabolized by liver, excreted in bile, inhibit P450, not safe in pregnancy. Azithromycin: excreted by kidney, doesn't inhibit P450, safer in pregnancy
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Side effects of macrolides
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Stimulate motilin receptors and cause GI distress, reversible deafness, cholestasis, jaundice
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Drugs to avoid in pregnancy
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Aminoglycosides, erythromycin, clarithromycin, fluoroquinolones, sulfonamides, tetracyclines
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Uses of clindamycin
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Gram+ cocci, anaerobes, toxoplasmosis. Use in gram+ osteomyelitis. Can cause pseudomembranous colitis
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Linezolid
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VRSA, VRE, drug-resistant pneumococci. Side effect: bone marrow suppression (platelets)
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Streptogramin drugs
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Quinupristin-dalfopristin
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MOA of streptogramins
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Bind 50S ribosomal subunit
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Uses of streptogramins
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Vancomycin resistant staph (VRSA), vancomycin resistant enterococci (VRE), drug-resistant gram+ cocci
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Inhibitors of nucleic acid synthesis drugs
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Sulfonamides, trimethoprim, pyrimethamine
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MOA of sulfonamides
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Inhibits dihydropteroate synthetase which inhibits folic acid synthesis
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MOA of trimethoprim
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Inhibits dihydrofolate reductase which inhibits folic acid synthesis
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Uses of trimethoprim-sulfamethoxazole
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DOC in Nocardiosis; mycobacteria; gram+ cocci, E. coli, Salmonella, Shigella, H. influenzae, P. carinii, toxoplasma
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Pharmacokinetics of sulfonamides
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Hepatically acetylated; renally excreted metabolites cause crystalluria; high protein binding
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Side effects of sulfonamides
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Hypersensitivity, Steven Johnson, phototoxicity, GI distress, hemolysis in G6PDH deficiency
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Side effects of trimethoprim
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Bone marrow suppression, enterocolitis
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Quinolone drugs
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Norfloxacin, ciprofloxacin, ofloxacin, levofloxacin
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MOA of quinolones
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Bactericidal. Inhibit topoisomerase II (DNA gyrase).
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Uses of quinolones
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UTIs resistant to cotrimoxazole, PID (chlamydia, gonococcus), skin and bone infections by gram-, diarrhea to shigella, salmonella, E. coli, campylobacter
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Pharmacokinetics of quinolones
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Iron and Ca+ limit their absorption, eliminated by kidney active secretion (inhibited by probenecid)
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Side effects of quinolones
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GI distress, phototoxicity, rashes, tendonitis, increases QT interval, contraindicated in pregnancy and children
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Regimens used in H. pylori infections and ulcers
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BMT: bismuth, metronidazole, tetracyclines or clarithromycin, amoxicillin, omeprazole
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Uses of metronidazole
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Giardia, trichomonas, entamoeba, gram- anaerobics, clostridium (DOC pseudomembranous colitis)
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MOA and resistance to isoniazid
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Inhibits mycolic acid synthesis; prodrug requires conversion by catalase; resistance: deletions in katG gene encodes catalase needed for activation; deletions in inhA gene encodes acyl carrier protein, the target
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Side effects of isoniazid
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Age-dependant hepatitis, peripheral neuritis (use B6), sideroblastic anemia (use B6), hemolysis in G6PDH deficiency, drug-induced lupus in slow acetylators
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MOA and resistance to rifampin
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Inhibits DNA-dependant RNA polymerase; resistance via change in enzyme
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Side effects of rifampin
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Hepatitis, induction of P450, red-orange metabolites
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MOA of ethambutol
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Inhibits synthesis of cell wall component arabingalactan
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Side effects of ethambutol
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Dose-dependant retrobulbar neuritis --> decreases visual acuity and red-green discrimination
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Side effects of streptomycin
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Deafness, vestibular dysfunction, nephrotoxicity
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Polyene drugs
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Amp B, nystatin
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MOA of polyenes
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Formation of artificial pores in the ergosterol membranes disrupts membrane permeability
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Uses of amphotericin B
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Severe infections by Aspergillus, Candida, Cryptococcus, Histoplasma, Mucor, Sporothrix
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Uses of nystatin
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Topical localized infections; too toxic for systemic use
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Pharmacokinetics of amphotericin B
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Given by slow IV infusion, does not enter CNS, slow t1/2 > 2 weeks, hepatic metabolism and renal elimination
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Side effects of amphotericin B
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Infusion-related: fever chills, muscle rigor, hypotension alleviated by NSAIDs, antihistamines, meperidine, steroids. Dose-dependant: nephrotoxicity, decreased GFR, tubular acidosis, anemia
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Azole drugs
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Ketoconazole, fluconazole, itraconazole, clotrimazole
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MOA of azoles
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Fungicidal by inhibiting 14-alpha-demethylase which converts lanosterol to ergosterol
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Uses of ketoconazole
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DOC for Paracoccidioides; backup for Blastomyces, Histoplasma; Oral use in mucocutaneous candidiasis or dermatophytoses
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Uses of fluconazole
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DOC for esophageal and invasive candidiasis and coccidioidomycoses. Prophylaxis and suppression of cryptococcal meningitis
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Uses of itraconazole
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DOC in blastomycoses and sporotrichoses
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Uses of clotrimazole
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Used topically for candidal and dermatophytic infections
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Pharmacokinetics of ketoconazole
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Orally effective; absorption decreased by antacids; metabolized by liver enzymes; inhibits P450
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Pharmacokinetics of itraconazole
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Orally effective; absorption increased by food; metabolized by liver enzymes; inhibits P450
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Pharmacokinetics of fluconazole
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Orally effective; enters CSF; eliminated in the urine in unchanged form
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Side effects of azoles
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Decreased synthesis of cortisol and testosterone --> decreased libido, gynecomastia, menstrual irregularities; Increased liver function tests and rare hepatotoxicity
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Drugs that block viral penetration and uncoating
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Amantadine, enfurvitide
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Drugs that inhibit viral DNA polymerases
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Acyclovir, foscarnet, ganciclovir
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Drugs that inhibit viral RNA polymerases
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Foscarnet, ribavirin
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Drugs that inhibit viral reverse transcriptase
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Zidovudine, didanosine, zalcitabine, lamivudine, stavudine, nevirapine, delavirdine, efavirenz
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Drugs that inhibt viral aspartate protease
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Indinavir, ritonavir, saquinavir, nelfinavir
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Drugs that inhibit viral neuraminidase
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Zanamivir, oseltamivir
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Drugs used to treat herpes
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Acyclovir, ganciclovir, foscarnet
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Acyclovir
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Activated by viral thymidine kinase, inhibitor and chain terminator of DNA polymerase. Use for HSV ans VZV. Side effects: crystalluria, neurotoxicity
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Ganciclovir
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Activated by viral thymidine kinase, inhibitor and chain terminator of DNA polymerase. Use for HSV, VZV, CMV, AIDS retinitis and transplant patients. Side effects: hematotoxicity, crystalluria, rash
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Foscarnet
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Inhibits viral DNA and RNA polymerases. Use for HSV, VZV, CMV, AIDS retinitis, transplant patients. Side effects: nephrotoxic acute tubular necrosis, hypocalcemia (tremors, seizures)
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Zidovudine (ZDV, AZT)
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Converted to triphosphate that inhibits reverse transcriptase and causes chain termination. Resistance by mutations of RT gene.
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Drug interaction of zidovudine (ZDV, AZT)
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Increase levels of ZDV: azoles, cimetidine, indomethacin, probenecid, TMP-SMX. Decrease levels of ZDV: rifampin
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Side effects of ZDV
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Neutropenia, anemia, granulocytopenia, headache, myalgias, neuropathy, lactic acidosis
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MOA enfuvirtide
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Binds gp41 and inhibits fusion of HIV-1 to CD4 cells
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Needle stick HIV prophylaxis
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ZDV + 3TC + indinavir
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Pregnancy HIV prophylaxis
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ZDV trimester 2 and 3 plus 6 weeks to neonate reduces vertical transmission by 80%. Or ZDV intrapartum reduces transmission by 50-60%
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Amantadine
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Blocks attachment, penetrationa and uncoating of Influenza A. May decrease flu symptoms. Side effects: nervousness, insomnia, atropine-like effects
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Uses of interferons
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Antiviral: HBV, HCV; antiumor: Kaposi, CML, multiple myeloma, renal CA; Immunoregulatory: mutiple sclerosis
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