drraythe's version from 2016-04-29 15:01

split in sonc is a good escuse to break this up

Question Answer
human med example (equivalent for vet he said): they say we've been having unnecessarily long treatment durations. instead of 500mg dose for 10d we could do 750mg dose for 5d. explain how this works with the stupid graph if you give a HIGHER dose, it increases the cMAX, so there is a higher area under the curve (AUC), so can get away with a shorter duration (since it is a conc dependant drug)
benefits of shortening the duration of tx by upping dose in conc-dependent drugs....less time in general is nice, less exposure of our good flora to the abx, less chance of creating resistance (but cant just keep upping dose or you will run into adverse effects). They also tried with diff drugs and had similar results
they saw in the human example (equivalent for vet he said) that you can treat at a higher dose for a shorter period of time. When they did this, what did levels of resistance do?see LESS emergence of resistance (so really now trying to minimize time we're treating)
what other factors should you consider if you would rather treat a patient with a high conc for a short amount of time rather than low conc for longer?depends on inoculum size, and time of onset of dz and tx. The sooner you are able to start tx pt with a high conc, the less time you need to kill all the bact
early intervention with a high dose microbial results in...the animal being cured in a short period of time
how does inoculum size the conc you'll need ?will need higher conc
Inoculum size and in vitro antimicrobial susceptibility--> explain what these graphs mean, explain the clinical implication Increased bacterial load requires higher concentrations of antibiotics! X axis is bacterial load (the 2E4 means 2 to the power of 4). Y axis is minimum inhibitory concentration. Their relative MIC goes up the denser the bacterial load-- meaning we need more of abx to kill the bact. This is the case when comparing many diff abx (see graph). implication is that the later on you are on the onset of the dz, there will be more bact in the pts, so need higher dose.
(i still dont really get this one) Inoculum size and in vitro antimicrobial susceptibility--> explain what this graph means, and explain the clinical implication Active marbofloxacin concentrations against a low inoculum have no activity against a high inoculum. Y axis is the mean inoculum growth (note that they start at diff numbers), and X axis is the abx concentration (NOT TIME). If its a high innoculum, the conc of marboflox initially is not enough to cause a 50% dec in bacterial growth.
will a high volume of distribution be more or less likely to get into cells?more
Vd looks atpenetration into tissues and ion disassociation
if the drug has a low Vd, where will it be in the body?cant penetrate cells so will stay in extracellular fluid
which 4 drugs have a low Vd?Aminoglycosides, aminocyclitols, sulfadimethoxine, penicillins
which 4 drugs have a high Vd?potentiated sulfonamides, fluoroquinolones, macrolides, tetracyclines
pKa is aka? what does it tell you about how the rug behaves?aka the disassociation constant.
If you have a basic drug, where will it accumulate?in an acidic environment (bc they ionize so they stay there) (and vice versa with an acidic drug)
If you inc the pH in the stomach (make it more basic), what happens to oral dose of penicillin which is an acidic drug?it will be ionized and will not be absorbed
what is an amphoteric drug?can be acidic or basic, basically
what are the acidic drugs (3)penicillins, cephalosporins, sulfonamides
what are the amphoteric drugs? (2)fluoroquinolones and tetraccyclines
what are the basic drugs? (easier to remember the acidic and ampho ones, 5 of basic ones)aminoglycosides, macrolides, chloramphenicol, florfenicol, trimethoprim
explain how this graph is about time-dependant killing so, the first graph is looking at AUC/MIC, the second graph is looking at cMAX/MIC (these are basically the same) and the last (right most) graph looks at the time above the MIC. you see inc AUC/MIC doesnt lead to inc killing, inc cmax doesnt inc killing, only inc the time inc the killing (as evidenced by a downward trend of colony forming units)
explain how this graph is about conc-dependant killing so, concentration depends on the AUC/MIC. and that is the first graph (leftmost). Concentration can also be judged by the max concentration peak (cMAX) over MIC, but it is not as accurate at AUC. In both those graphs you see a downward trend in the number of colony forming units, implying that they are being killed. but inc the time without the conc, you do not see a downward trend, so it is not effective when used this way
explain this graph, what is it telling us about?This is talking about bact resistance to abx. So we are looking at the concentration time curve, you see the Tmax and Cmax (time at which the conc reaches its maximum). so then you have your wild population- and there are always some bugs with resistant genes (this happens naturally). So usually we work with the MIC- if we're below it, we're not selecting everything, so we arent killing resistant back and non-resistant bact (so the ratio stays relatively similar). for the second dotted line, we DO exceed the MIC, which will kill all the susceptible bacteria. but it DOESNT kill the resistant bact, and now that is all you have (end up with higher load of resistant bact). How do we prevent this? we use a HIGHER dose, which is the MPC (mutant prevention concentration)- if we exceed the MPC, this conc WILL kill everything. (whether or not its a conc (AUC/MPC) or a time dependant drug, and time/MPC for time dependant drugs) the tan part of the graph is the mutant selection window which will be diff for each kind of bact (can be bigger or smaller)
what is the MPC?the mutant prevention concentration-- the dose which is high enough to wipe out everything to prevent only resistant bact from proliferating
explain how these graphs talk about MPC (mutant prevention concentration) look where the MIC and MPC are on the graph (x axis) and compare to the freq of resistance (y axis). Then note if they are talking about drug "a" or drug "b". So between MIC and MPC is the MSW (mutant selection window) and within that mutant selection window, the number of bact WILL go down, but it wont go down completely, bc not killing mutants. to kill the resistant, need to further inc conc of abx above the MPC. So then, if you can do it for one drug, can do it for 2 drugs at the same time. so sideways is conc of drug a, and up and down is conc of drug b. Overlap the two graphs and you get the one with the angle sign on it-- so at a certain conc of drug a and certain conc of drug b, we can find the smallest mutant selection window possible (double headed arrow). So, when you need to kill everything, you look where they have the strongest combined effect than on their own. And you can use a lower conc of the drugs and get a good effect