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71 Cards in this Set
- Front
- Back
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What are the structure of aminoglycosides
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six membered rings, with amino group, linked to 2 or more sugars
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What is the name of the aminoglyocisde ring
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aminocyclitol
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What are the 3 main aminoglycoides
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Tobramycin
Amikacin Gentamicin |
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Are aminoglycodies bacterial or static
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Bacertical
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What is main MOA of aminoglycoides
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distrupting protein synthesis by binding to the 30S ribosome
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What 2 routes to aminoglyocisdes eneter the periplasmic space
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Diffusion porin
phospholodi bilayer |
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Once the drugs are in the periplasmic space, how are they transfer acroos the mebrane
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ELECTRON TRANSPORT
NEED O2 |
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So if aminoglycides require oxgen to pass the membrane, what baceria do they NOT treat
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ANAEROBICS
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Once aminoglycosides are INSIDE the bacteria, they bind
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to the 30S riboones, and interfer with mRNA
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Although most inhibitors of microbial protein synsther are bacteroSTATIC, aminoglycodies are bactericidal, what is other MOA
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compete with Mg2 and Ca+ that link lipoplosaccarhisa, dn may result in holes in the cell well mebrane, resulting in holes in the cell membrane
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What are the MAJOR mechanism of resistance with aminoglycosides
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Target site modication (ribosmonal mutations RARE)
Enzyme inactivation---Aminoglyocisde modfiying enzymes Drug efflux (NOT_ Decreased drug penetration, into periplasmic space though alterion in porin |
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WAmoinoglyocidies modiying enzymes, do what once aminglycosides are IN the periplasmic space
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inactivation by phrophsorylation
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Aminoglycosides modifiny enzymes inlcude phophorotransferase, andenyltransferase, and actelytranferase, each aminoglycodies is inactivated differently, and is it consider a class resistance
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NO
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Spectrum of activity of Aminoglycosides
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Gram + aerobes (only in combination)
Gram - aerboes--including Pseudomas aerguinosa and Acinectorbacter ANANEROBES-no activity |
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Spectrum of activity of Tobramycin and Gentamicin
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Gentamicin--better Serraita
Tobramcin is better against P. aeruginosa |
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Amikacin is POOR substrate for
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amino-glycoside modfiying enzymes
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Amikacin is BEST for
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P. aeurginosa and acinteobacter---less maingolycisde modifying enzymes
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What is the absoprtion of aminoglycosides
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POOR only adminstered parentally
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What is distriubtion of aminoglyosides
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well--
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What is CNS distribtion
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POOR
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What is elimination of aminoglycosides
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KIDNEY
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What are the 2 main toxicities with AMINOGLYCOSIDES
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Neprhotoxicity
Ototoxocity |
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Nephrotoxocity occur in 25% of pts, b/c amingolycosides are elminated via glomerular filtration, and at HIGH doses and LONG time period, the drug
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accumated within proximal tuble and cause necrosis
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What are the MAJOR risk factors for nephrotoxciithy
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Dose, druation and underlaying renal disease
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Ototoxcity is another MAJOR adverse effect of aminoglycosides, what tones are usually affect and what else
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HIGH frequnecy tones, and also vestibular impairment
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Nephotoxcit is usually reversible, what is otoxicity
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result in PERMENANT loass
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In animal modies risk for toxcities is greater for gentamicin>tobramycin>amkiacin, but most clincian FEEL
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not enough evidence and suseptibily is MORE important
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What is example of combinatio of aminglycosdie for severe GRAM + infections
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endocarditis
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Most of the resistance of Aminoglycosides are carried on
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plasmids
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What was the first identifed quinolones
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Naldixic acid
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The addition of the Fluorine to C6 position did what
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increased biologocial activity, and floroquinoles were bone
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Also addition of the piperrzinyl at C7 was imporatant, and what made CIPRO
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also added cycloproyl group
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CIPROFLOXACIN was an EARTH-shattering development, WHY
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Braod spectum antibiotcis
GOOD ORAL vioability excellent tissue peentaion |
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What are the MAINM 4 quinonles used today
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Ciprofloxainc
Levofloxacin Monofloxacin Gemifloacin |
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What are the 2 MAJOR sites of action for quinolones
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Toposiomerase II (DNA gyrase)
Topsoirase IV |
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Topisomerase II (DNA gryrase) consists of 2 subunits
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GyrA and GyrB
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Topisomerase IV consists Also OF 2 SUBUNITS,
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ParC and Par E
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The primary taget of DNA gyrase of Topoisomerase II is
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Gram -
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The primary target of Toposimerase IV is
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Gram + bacterai
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IN REALITY--inbhition of either results in SOME degree of activity against Gram + or -
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YES
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What is another MOA of Quinolones, which can result in
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SOS response--explosion of cell
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What is the MAJOR fxn of DNA gyrase in bacteria
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negative supercoils in the DNA, allow for packing
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GyrA is involved
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breaking and uniting strands
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GyrB is involved in
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ATP and allow DNA strand passage
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Quinolones interact MAINLY with DNA gyrase drug-enzyme complex, its primary binding site is
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on GyrA
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What do Quinolones PREVENT
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resealing of nicked DNA, and results in cell death
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What is the fnx Toposimerase IV
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seprates daughter chromsoenes are DNA replication
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Quinoles ineracts ALSO with Topoisomerase IV, and what site
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ParC
COMPLES of enzyme-DNA-drug |
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What is Quinoles prevent with TOPOISOMERASE IV,
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releasing of the nicked DNA--
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What are 2 MAJOR mechanism of resistance with Quinolones
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Alteration is target site---muations in DNA gyrase and topisomerase IV
Drug efflux |
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What is MAJOR mutation in gram - bacteria
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gry A mutations
minor gyr B |
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What is MAJOR mutation in gram +
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ParC
minor mar E |
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A single step mutation can lead to
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low level resistance
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Whereas a mutation in BOTH genes can lead to
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clincally revelvant rsistance
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What is the ORAL bioavialbity of Floroquinoles
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EXCELLENT
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Can you take fluoroquinoles with FOOD
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yes--not affected
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Florquinoes are well disribted, what is CNS penetration
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POOR
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Folorquinolones are ELMINATED, and expection
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RENALLY,
except Moxifloxin---heaptiallyt clearn |
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What is half-life of Fluoroquinolones
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LONG---4-13 hours
allow qd dosing cipo BID |
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What is spectrum of activity of Fluoroquinolones
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Gram + aeroes
Gemi >Moxi >Levo >Cipro Gram - (All enterobacteriaceae, moraxella, Haemophilus, Neissera Anerobic acity, Moxi Atypicals--EXCELLENT |
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Fluorquinoles have POOR activity against what Gram +
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MRSA or enterococcus
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What is the BEST class AND only for AYTYPCIALS
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Fluroquionoles
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What are the only 2 fluoroquinoles that treat Pseudmonas
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Cipro and Levo
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ALL things consider what are the SAFEST and best tolerated antiobotics
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Fuloroquiones
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Common SIDE effects of Fluoroquinolones inlcude
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GI
CNS RASH |
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Incidnce of RASH with fulorquinoes is NOT hypersenstive, is MORE commo nwith gemifloxacin, and what pts are at risk
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women <40, and longer duration
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What is the Black box warning with fluorquinoles
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tendonitis and tendon rupture
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Tendonits and Tendone ruputre is rare, occurs 1-2 weeks AFTER starting drug therapy, who are MOST at risk
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>60 ages and taking corticosteriods
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Fluoroquinolones are contraindicated in
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pregnancy and children <16
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What are the drug interactions with Fluoroquinolones (F+)
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Anatacids--or any prodtions with cations
Ferrous sulfate Sulcralfate |
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What is the only flurorquiones that inhibits CYP450, so interactions with warfarin and theophylline
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cipro
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