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Pharm - Antimicro

Microbiology-Antimicrobials from First Aid 2013

Block cell wall synthesis by inhibition of peptidoglycan cross-linking? Penicillin, methicillin, ampicillin, piperacillin, cephalosporins, aztreonam, imipenem
What are the MOAs of penicillin? (1) Bind PBPs (2) Block transpeptidase cross-linking (3) Activate autolytic enzymes
What are the toxicities of penicillin? Hypersensitivity reaction, hemolytic anemia
What drug increases penicillin's half life in the kidney? Probenecid: used in WWII for battlefield infections.
What adaptations on the part of bacteria commonly provides resistance to penicillin? Beta-lactamases (penicillinase) cleave penicillin's beta-lactam ring.
What are the clinical uses for classic penicillin? Gram-positive: Strep pneumo, Strep pyogenes, Actinomyces, Neisseria meningitidis, and Treponema pallidum
What penicillin-derivatives are penicillinase-resistant? Oxacillin, nafcillin, dicloxacillin
What is the MOA and use for penicillinase-resistant penicillins? Same MOA but resistant to b-lactamase because of bulky R-group blocking access to b-lactam ring. Narrow spectrum: Staph aureus (but not MRSA, altered PBP site). "Use NAF for STAPH."
What are side effects of the penicillinase-resistant penicillins? Hypersensitivity reaction and interstitial nephritis.
What are the aminopenicillins? Ampicillin, amoxicillin; penicillinase-sensitive, but broader spectrum than the penicillinase-resistant drugs.
What should be given with ampicillin or amoxicillin to make it beta-lactamase-resistant? Clavulanic acid. Otherwise they will cleave the beta-lactam ring.
What is the coverage of the aminopenicillins? HELPSS kill enterococci: Haemophilus influenzae E. coli Listeria monocytogenes Proteus mirabilis Salmonella Shigella
What are toxicities of aminopenicillins? HS Rxn, ampicillin rash, pseudomembranous colitis
Ticarcillin and piperacillin are used for what type of infections? What should be used with them? Pseudomonas. Use with clavulanic acid.
What are the beta-lactamase inhibitors? "CAST": Clavlanic Acid Sulbactam Tazobactam
What are cephalosporins? Beta-lactam drugs like penicillin that inhibit cell wall synthesis but are less susceptible to penicillinases. They come in four generations.
Which organisms are typically not covered by the cephalosporins? "LAME:" Listeria Atypicals (Chlamydia, Mycoplasma) MRSA (exc. ceftaroline) Enterococci
First generation cephalosporins cover: "PEcK:" Proteus mirabilis E. coli Klebsiella
Second generation cephalosporins cover: "HEN PEcKS:" H. flu Enterobacter aerogenes Neisseria spp. Proteus mirabilis E. coli Klebsiella Serratia
Third generation cephalosporins cover: Serious gram-negative bacteria resistant to other beta lactams: Ceftriaxone: Neisseria spp. Ceftazidine: Pseudomonas
Fourth generation cephalosporins cover: Pseudomonas and many gram positives.
What are the toxic side effects of cephalosporins? H-S Rxns, Vitamin K deficiency, some cross-reactivity with other penicillins, increased nephrotoxicity of aminoglycosides
Aztreonam: MOA, Use, Tox MOA: PBP3 binder, beta-lactamase-resistant Use: Gram-negative rods only Tox: none; use with penicillin-allergic patients or those with renal disease who cannot tolerate aminoglycosides
What is imipenem/cilastatin? Broad-spectrum, beta-lactamse-resistant drug that is inhibited by renal dehydropeptidase, so give cilastatin to "make the kill lastin."
What is imipenem/cilastatin's coverage and side effects? Extremely broad: gram-positive cocci and gram-negative rods, but use is limited due to serious SFX, including seizures.
Vancomycin: MOA, Use MOA: inhibits cell wall formation by binding the D-ala portion of cell wall precursors. Use: serious gram-positives, MRSA, Cdiff (oral only)
What are the side effects of vancomycin? Generally well-tolerated but has the potential for Nephrotoxicity, Ototoxicity, Thrombophlebitis, and "Red Man Syndrome": flushing prevented with antihistamines and a slow transfusion rate.
With bacterial protein synthesis inhibitors, what is the mnemonic for which ribosomal subunits each class binds to? But AT 30, CCEL at 50: 30S - Aminoglycosides 30S - Tetracyclines 50S - Chloramphenicol 50S - Clindamycin 50S - Erythromycin (Macrolides) 50S - Linezolid
What is the general mechanism of aminoglycosides? Bind to the 30S and inhibit formation of the initiation complex. "A initiates the Alphabet."
What is the menmonic for remembering the aminoglycosides and their side effects? "GNATS caNNOT kill anaerobes." Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin SFX: Nephrotoxicity (esp with cephalosporins) Neuromuscular blockade Ototoxicity (esp with Loop diuretics) Teratogenic
Why can't aminoglycosides kill anaerobes? They require O2 for uptake, and so are useless against anaerobes.
What is the general mechanism of tetracyclines? Bind to the 30S and prevent attachment of the incoming aa-tRNA. "Tetra = tRNA!"
Which tetracycline is safe to use in patients with renal failure? Why? Doxyclycline, because it is fecally-eliminated.
What should not be taken with tetracyclines? Milk, antacids, or iron tablet: divalent cations inhibit its absorption in the gut.
What is special about demeclocycline? Despite being a tetracycline, it is used more commonly as an ADH antagonist and diuretic in SIADH.
What are the toxic side effects of tetracyclines? Discoloration of the teeth, inhibited bone growth, photosensativity, c/i in pregnancy.
What is the coverage for tetracyclines? Borrelia burgdorferi, Mycoplasma pneumoniae, and especially the intracellulars (Rickettsia and Chlamydia).
How is tetracycline resistance conferred by bacteria? Efflux pumps are conjugated into cell by plasmids encoding transport pumps.
Macrolides: naming, MOA Nom: "-thromycin", e.g. erythromycin MOA: Binds to the 50S and blocks translocation of the growing peptide ("MacroSLIDES")
What are the macrolides' coverage and toxicity? Atypical pneumonias (Mycoplasma, Legionella, Chlamydia--pneumo or STD); gram-positive cocci in patients with penicillin allergies. Tox: MACRO: Motility, Arrhythmia (long QT), Cholestatic hepatitis, Rash, eOsinophilia
Chloramphenicol: MOA, Use, Tox MOA: Blocks peptidyl transferase at the 50S. Use: Meningitis, any cause Tox: aplastic anemia and "gray baby" syndrome (UDP-GT needed to clear in liver)
Clindamycin: MOA, Use, Tox MOA: Blocks peptide transfer at 50S Use: Anaerobes above the diaphragm (vs. Metronidazole below the diaphragm) Bacteroides, Clostridium, in lung abscesses or mouth anaerobes Tox: C.diff pseudomembranous colitis
How do sulfonamides (sulfa drugs) work? They work as PABA antimetabolites just upstream of the bacterial DHFR pathway, and so are bacterostatic.
What are sulfa drugs' coverage? Gram-positive, gram-negative, Nocardia, Chlamydia, good for simple UTIs
What are sulfa drugs' toxicities? H-S Rxn, oxidative stress in G6PDH-deficiency, nephrotoxicity, photosensitivity, kernicterus in infants, displace other drugs from albumin (like warfarin)
Trimethoprim: MOA, Use, Tox MOA: bacterial DHFR (like MTX) Use: USE WITH SULFAs for UTIs, Shigella / Salmonella, and PCP prophylaxis Tox: Megaloblastic anemia, leukopenia, rescue with leucovorin.
How are fluoroquinolones named? "-floxacin"
How do fluoroquinolones work? They inhibit DNA Topoisomerase II (gyrase).
What are fluoroquinolones' coverage? Gram-negative rods in the urinary and GI tract, including Pseudomonas. Also: Neisseria, some gram-positives.
What are the toxicities of fluoroquinolones? Tendonitis, tendon rupture, myalgia, cartilage = "Quinolones hurt the attachments to your BONES," contraindicated in pregnancy, the eldery, and those taking steroids.
What are metronidazole's MOA and possible side effects? It creates free radical metabolites that are toxic to DNA. Tox: disulfiram-like with alcohol, headache, metallic taste
What is metronidazole used for? Antiprotozoan and some bacteria: "GET GAP"... Giardia Entamoeba Trichomonas Gardanella Anaerobes (Clostridium, Bacteroides) H. pylori Treats anaerobes BELOW the diaphragm, vs. clindamycin above it.
What is the triple-therapy for H. pylori? Proton pump inhibitor (Omeprazole) Metronidazole Clarithromycin
What is the standard cocktail for MTB treatment? RIPE: Rifampin Isoniazid (alone for prophylaxis) Pyrazinamide Ethambutol
What is the standard treatment for M. leprae? Dapsone and rifampin. Add clofazimine for the lepromatous form.
What is the prophylactic treatment for M. avium-intracellulare? Azithromycin Add rifampin, ethambutol if you contract it.
Isoniazid (INH): MOA, Use, Tox MOA: dec synthesis of mycolic acids Use: MTB treatment and prophylaxis (only one) Tox: INH "injures nerves and hepatocytes) Give Vit. B6 to prevent neurotoxicity. May cause drug-induced lupus.
Rifampin: MOA, Use, Tox Rifampin has four R's for treating MTB: RNA polymerase inhibitor Revs up CYP450 (hepatotox) Red/orange body secretions Rapid resistance if used alone
Pyrazinamide: MOA, Use, Tox MOA: unknown, thought to acidify MTB Use: MTB Tox: hyperuricemia, hepatotox
Ethambutol: MOA, Use, Tox MOA: dec carb polymerization of MTB cell wall Use: MTB Tox: optic neuropathy (red/green color blind)
What are each of the MTB drugs' classic side effects? Rifampin - red/orange fluids INH - neurotoxicity, lupus? Pyrazanimide - hyperuricemia Ethambutol - optic R/G color blindness Many cause hepatotoxicity.
How can you prophylactically prevent GC/chlamydial conjunctivitis in a newborn? Topical erythromycin ointment.
What prophylactic antibiotics should AIDS patients be on? TMP-SMX for PCP, toxoplasmosis. Azithromycin for M. a-i.
What are the last-resort antibiotics for MRSA, VRE? MRSA: vancomycin VRE: linezolid + streptogramims
Amphotericin B: MOA, Use, Tox MOA: binds ergosterol (fungi) to form pores Use: Serious, systemic mycoses: Blasto, Coccidio, Histoplasma, Mucor Systemic candidiasis Cryptococcal meningitis Tox: fever/chills ("shake and bake") IV phlebitis
Nystatin: MOA, Use MOA: like ampho, ergosterol binder Use: Topical/oral candidiasis only
Azole antifungals: MOA, Use, Tox MOA: inhibit ergosterol synthesis by inhibiting a fungal P450 enzyme Use: Local, less serious systemic mycoses Tox: Testosterone synthesis inhibition -> gynceomastia, esp. ketoconazole
Use flucanozole for... ...chronic suppression of cryptococcal meningitis in AIDS patients, or for Candida infections.
Use itraconazole for... ...Blastomycosis, Coccidiomycosis, or Histoplasmosis.
Flucytosine: MOA, Use, Tox MOA: inhibit DNA/RNA synthesis (fungal 5-FU) Use: systemic mycoses and cryptomeningitis, in combination with Amphotericin B Tox: bone marrow suppression
Caspofungin, micafungin: MOA, Use, Tox MOA: inhibit beta-glucan synthesis in walls Use: invasive aspergillosis Tox: GI upset, histamine release -> flushing
Terbinafine: MOA, Use, Tox MOA: inhibits fungal squalene epoxidase Use: dermatophytes, esp onychomycosis Tox: abnormal LFTs, vision disturbances
Griseofulvin: MOA, Use, Tox MOA: fungal MT inhibitor Use: Tinea dermatophytes, also accum in nails Tox: teratogen, carcinogen, P450 (warfarin)
What antiprotozoan therapy is indicated for toxoplasmosis? Pyrimethamine
What antiprotozoan therapy is indicated for Trypanosoma brucei? Suramin and melarsoprol
What antiprotozoan therapy is indicated for T. cruzi? Nifurtimox
What antiprotozoan therapy is indicated for leismaniasis? Sodium stibogluconate
Chloroquine: MOA, Use, Tox MOA: blocks heme breakdown; it accumulates Use: Plasmodium other than falciprum Tox: Retinopathy
Why can't you use chloroquine to treat Plasmodium falciprum? What should be used instead? It's too resistant (due to a membrane pump). Instead use proguanil/atovaquone.
List some anti-helminthic drugs. Mebendazole, pyrantel pamoate, ivermectin, praziquantel
What anti-helminthic drug should be used for flukes (trematodes) such as Schistosoma? Praziquantel
Zanavimir, oseltamivir: MOA, Use "Tamiflu," inhibits neuraminidase in influenza A and B.
Ribavirin: MOA, Use, Tox MOA: inhibits guanine nucleotide synthesis Use: RSV, chronic Hep C Tox: severe teratogen, hemolytic anemia
Acyclovir: MOA, Use, Tox MOA: activated by HSV/VZV to inhibit viral DNA polymerase Use: HSV, VZV Tox: none, viruses cam mutate resistance
Gancyclovir: MOA, Use, Tox MOA: similar to Acyclovir, activated to inhibit viral DNA Polymerase Use: CMV, esp in immunocomp'd patient Tox: leuko- and thrombocytopenia, renal tox
Foscarnet: MOA, Use, Tox MOA: pyroPHOSphate analog, inhibits DNA Poly Use: CMV (retinitis) or HSV when Gancyclovir and Acyclovir fail Tox: nephrotoxicity
Cidofovir: MOS, Use, Tox MOA: inhibits viral DNA polymerase Use: CMV retinitis, HSV rest. to acyclovir Tox: nephrotox, administer with probenecid!
What is the cocktail indicated HIV? HAART with three drugs: 2 NRTIs (nucl rev transcriptase inhibitors) 1 NNRTI, protease inhib., or integrase inhib.
Protease inhibitors: naming, Tox "-navir," Navir tease a protease! Tox: hyperglycemia, lipodystrophy, GI upset indinavir = nephrotox, hematuria
NRTIs: names, MOA, Tox "-vudine," Have vu dined with my NRTIs? MOA: nucleotide that competitively inhibits viral reverse transcriptase Tox: BM suppression, peripheral npy, lactic acidosis
NNRTIs: names, MOA, Tox "-vir-" on the inside of the word. MOA: non-nucl that inhibits rev transcriptase Tox: same as for NRTIs
Raltegravir: MOA, Tox MOA: the only integrase inhibitor Tox: hypercholesterolemia
Interferons: MOA, Use, Tox MOA:
Effect in pregnancy: sulfonamides Kernicterus
Effect in pregnancy: aminoglycosides Ototoxicity
Effect in pregnancy: fluoroquinolones Cartilage damage
Effect in pregnancy: clarithromycin Embryotoxicity
Effect in pregnancy: tetracyclines Discolored teeth, inhibited bone growth
Effect in pregnancy: Ribavarin Teratogenic
Effect in pregnancy: Griseofulvin Teratogenic
Effect in pregnancy: Chloramphenicol "Gray baby," anemia
Created by: wmwebb89



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