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Pharm - Antimicro
Microbiology-Antimicrobials from First Aid 2013
| Question | Answer |
|---|---|
| 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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