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62 Cards in this Set
- Front
- Back
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what is involved in the cross linking of the precursor products to form the cell wall
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transpeptidation
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how do Beta lactams fool the enzyme
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they act as analog of D-ala-D-ala and bind to the PBP and appear like a substrate of enzyme and since transpeptidase can't distinguish between them it results in weaker cross linking therefore weaker cell wal
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how do gram + bacteria resist drugs
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by releasing enzymes into the environment and hope it destroys the drug
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how do gram - bacteria resist drugs
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they secrete enzymes into their periplasmic space and kill the drug they use a lot less essential enzymes than gram + bacteria
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what are the properties of Natural PCN
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good gram + coverage
good against non Betalactamase producing bacteria |
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what PCN can be used to treat syphilis
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natural PCN
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what are the properties of Penicillinase resistance penicillin
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not good against gram -
no anaerobic activity drug protected from hydrolysis by betalactamase |
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what are the properties of Aminopenicillins, ureidopenicillins, and Carboxypenicillins
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good gram - coverage
no protectection from hydrolysis due to lack of steric hinderance |
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what are the properties of betalactamase inhibitors
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intrinsically have no antibacterial activity so they always have to be used in conjunction w/ something else
structurally looks like Beta lactams |
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how do betalactamase inhibitors work
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due to their structure the enzyme recognizes them as potential substrate but once it comes into contact w/ the inhibitor they form a strong covalent bond therefore making the enzyme unable to hydrolyze the drug
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what are the suicidal inhibitors
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betalactamase inhibitors
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what are not inhibited by current Betalactamase inhibitors
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Bush class 1
due the the low affinity |
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how are PCN cleared
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renally
they are also cleared via hemodialysis |
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what are some of the adverse effects of PCN
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GI, skin, neutropenia, platelet aggregation (pt may have prolonged bleeding), CNS (due to high [ ] ), metabolic, hepatic (increase in transaminases) effects
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how can renal insufficiency lead to CNS effects w/ PCN
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since most PCN are cleared renally if someone has renal insufficiency and the dose is not adjusted then PCN may reach a high concentration causing CNS effects such as seizures and encephalopathy
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what metabolic effects happen w/ PCN
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electrolyte disturbances (hypokalemia, hypernatremia)
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what drug interactions do PCN have
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aminoglycosides
probenecid |
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how do PCN interact w/ aminoglycosides
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they can't be mixed in the same infusion bag because they have been shown to inactivate each other
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how do PCN interact w/ Probenecid
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in order to maintain a high concentration of PCN w/o having to pay more Probenecid could be used since it inhibits active renal secretion of PCN
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how are cephalosporins classified
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by spectrum of activity
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what is the spectrum of activity of the 5 generations of cephalosporins
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1st gram +
2nd 50/50 gram +/- 3rd 10/90 gram +/- 4th and 5th gram +/- |
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what are the properties of 2nd gen cephalosporins
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two groups
TRUE CEPHALOSPORINS - better activity against gram - CEPHAMYCINS - very good against anaerobic bacteria |
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what beta lactam has activity against MRSA
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5th gen cephalosporins
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what are the pharmacokinetics of the cephalosporins
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1st gen - can't be used to treat meningitis or CNS infections because they can't get through BBB
2nd get - can't use to treat meningitis (not enough penetration to reach high []) 3rd/4th - can get through BBB and reach high [] to treat meningitis |
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how are cephalosporins eliminated
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renally unchanged
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what are the adverse reactions of cephalosporins
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adverse reaction w/ MTT side chain resulting in the interference in the formation vit K clotting factors in the liver therefore increased risk of bleeding
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what are the drug intereactions of Cephalosporins
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alcohol
probenecid (for cephalosporins cleared tubularly) H2 antagonist/antacids (b/c drug won't completely dissolve at higher pH) |
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what are the properties of carbapenems
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coverage for gram+ gram- and anaerobes
not suceptible to hydrolysis by plasmid mediated beta lactamases |
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which carbapenem must be given w/ cilistatin and why
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imipenem must be given w/ cilistatin to prevent renal metabolism from occuring because its metabolite is toxic
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what bacteria are implicated for lower respiratory tract infection and carbapenem has no effect on them
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acinetobacter
p. aeruginosa ertapenem has no effect |
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what is MIC 50
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concentration required to inhibit 50% of the bacteria in the population, the higher the number the less potent the drug because more drug is required to inhibit the bacteria
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what is the function of the GABA Rc in the brain
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it serves as neuroinhibition and keeps the brain from excessively firing
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what are the adverse effects of carbapenems
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neurotoxicity due to inhibition of the GABA Rc which may lead to increased neurotransmissions leading to seizures/convulsions.
neurotoxicity may also occur due to risk factors that increase the concentration of carbapenems in the blood |
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in relation to neurotoxicity how does imipenem compare to meropenem
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imipenem is far more epileptogenic meaning it binds better to the GABA Rc
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what are the monobactams
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aztreonam
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what is structurally unique about the monobactams
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they lack an adjacent side chain and therefore lack coverage against gram positive bacteria and anaerobes
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what beta lactam can be used when someone is clinically hypersensitive to PCN/cephalasporins
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monobactams due to them being strucuturally distinct
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what are monobactams often used in conjunction with
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a drug with gram positive coverage
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patients with hypersentivity to what may exhibit cross reactivity with aztreonam
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ceftazidime
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what is the relationship between concentration and antimicrobial effect for beta lactams
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concentration independent killing
saturation at rate of killing at concentration above 4-6x MIC |
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what is the relationship in general pharmacology
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straight relationship
need to know how well pt is handling the drug so you can design the drug to keep up w/ the pt metabolism/elimination to have a prolonged effect |
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why is the first dose the most critical when giving antibiotics
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what we usually do is we give a small dose of drug observe a therapeutic response and then titrate up and down BUT with antibiotics what we see by the bed side is not really the drugs effect but the indirect consequence of the immune function therefore can't use titration process
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what is the inverted U phenomenom
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when you give a lil drug you'll kill some of the drug resulting in a selective pressure that allows a resistant sub population to proliferate and they'll continue to increase but will decline with increasing drug exposure
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what occurs in sub-optimal exposure
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when a small exposure occurs you offer selective pressure allowing amplification of the resistant subpopulation since you've killed off their competitiors
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how do you insure you kill all subpopulations
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try to minimize the fluctuations between peak and trough by giving a continuous infusion or frequent doses
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what is the inoculum effect
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if you have few bacteria drug will do well in killing them all but if you have a lot of bacteria drug will be overloaded and can't kill them all
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what are important pharmacodynamic considerations for Beta lacatms
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time above MIC
concentration independent killing |
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what is structurally essential for antibacterial activity
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beta lactam ring
rest of the structure deals with how good it binds to bacterial species |
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what is beta-lactamases that are encoded by chromosomes
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chromosomes are carried in the genome and are species specefic so they can only be passed on to their offspring
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what is beta-lactamases that are encoded by plasmid
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plasmid are mobile genetic material that are transfered from bacteria species to species easily
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what are constitutive enzymes
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bacteria produce a constant amount of enzymes regardless of the external stimuli
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what are inducible enzymes
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bacteria are able to sense their external environment and titrate the enzymes to w/e they need
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what are the classification of bacteria and what do they mean
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AMBLER - classified by AA sequences of enzymes and seeing how homologous the AA residues are to each other
BUSH-JACOBY - classified based on functional properties such as substrate specificity of enzymes and their ability to be inhibited by inhibitors |
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which form of classification is used clinically and in research
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ambler = research
bush-jacoby = clinical |
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what bush class is inhibited by EDTA and why
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bush class 3 molecular class B since there is metal (Zn/Cobalt) maintaining their 3D structure EDTA will take away the metal and collapse the enzyme making it lose its function
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what are the stably derepressed mutants
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bush class 1 chromosomal B lactamases
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what is meant by stably derepressed mutants
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the bacteria are constantly producing the maximum amount of enzyme at all times due to their repressor genes being mutated
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what should you avoid using in the class 1 B lactamases and why
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3rd gen cephalosporins would select out for the resistant mutants resulting in only the stably derepressed mutants being left and they'd already be producing their max amount of enzymes so pt would be fine but get worse after 48 hrs
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what is the mechanism by which ESBLs work
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plasmid mediated
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what should you avoid using when treating ESBL
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3rd gen cephalosporins and Aztreonam both are inactivated by ESBL producing organisms
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what do you use to treat ESBLs
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carbapenems
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how do bacteria alter their permeability to PCN
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since PCN enter gram - bacteria via porins bacteria can reduce or stop producing them and prevent the drug from entering
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