hey all welcome back to the real life pharmacology podcast I am your host Eric Christensen pharmacist I appreciate you taking the time to listen today uh today is uh we're going to talk about acetool estras Inhibitors more specifically uh the acetoin esterase inhibitor I see used in practice most uh which is denail the brand name for that medication is AOSP and it is uh utilized in the management of uh dementia mostly Alzheimer's dementia with a few Exceptions there so uh getting into the mechanism of action uh so in in dementia and Alzheimer's dementia specifically uh there is uh what researchers have found is that there's low coleric activity and this activity through acetylcholine and other uh mediators um is reduced and it's obviously very important for memory memory recall and things of that nature so that uh reduced activity obviously what the drug is going to Target is try to uh preserve those molecules in the brain which hopefully helps patients symptomatically okay two very very important points with this mechanism of action so it does not stop dementia and it does not reverse dementia so those are two very very important things that uh patients caregivers must understand the progression of dementia is going to continue on they're going to continue to get worse the goal the hope of the medication is that it helps somewhat with symptoms maybe a little bit of memory recall um but they are going to continue uh to get worse over time so that's very important to remember that these are not a cure for dementia and patients need to be and caregivers need to be educated about that so kind of wrapping up uh this mechanism of action so acetylcholine esterase Inhibitors they inhibit the enzyme that breaks down acetycholine so it helps preserve more acetylcholine uh in the brain and that hopefully again improves a little bit of memory and and potentially functioning there so that's how the the drug Works overall but again doesn't stop dementia doesn't reverse dementia now there is a few important points with dosing uh typical starting dose uh for Denzil is about 5 milligrams and um maybe after 4 weeks 6 weeks somewhere in there maybe about a month uh we can increase that dose uh up to 10 Mig now I have seen doses uh up to 20 Mig and there is a 23 mgram dosage form at least at this time it's really expensive much more expensive uh than doing the generic uh 5 to to 10 mgram dosing there so uh you know do you get much more bang for your buck uh honestly I I would say you you definitely see more adverse effects um you know how much more benefit and is it worth it that's always a clinical risk versus benefit type assessment that you want to discuss with uh patients caregivers and really try to identify what the exact goals of therapy are with these agents so I mentioned those adverse effects particularly as you start escalating do is and with acetool and esterase Inhibitors uh GI upset nausea diarrhea that is by far uh the most common adverse effects you're going to see uh with deoil and because of this uh we usually dose this medication at night which is kind of unique because a certain percentage of patients will actually get insomnia from this medication okay it's it's fairly low I think it's less than 10% if I recall right uh don't quote me on that percentage but I definitely have seen it happen in practice so in that situation in geriatrics we run into the problem so many times of poly Pharmacy and so let's say in the prescribing Cascade so let's say we start Denzil and we're dosing it at night now all of a sudden they aren't sleeping so we add you know another poor medic ation zadam or Dien hydramine meds that aren't tolerated very well in the elderly and so on and so forth they they cause other side effects and that type of thing so it's it's really important to um pay attention to when we're starting drugs increasing drugs and make sure they're not adding to some of those uh side effects so uh GI upset nausea diarrhea definitely most common uh insomnia can happen with those GI ad ver effects I did want to mention about the potential for weight loss uh this can often be challenging in dementia because many de dementia patients are at risk for weight loss uh due to those cognition issues uh swallowing issues can happen as well so sometimes weight loss is challenging to tell whether it's dementia versus the medication but you have got to remember to look at the acetool asteras inhib look at dapil uh if you do have a patient that has been losing weight it definitely can contribute to weight loss and again primarily because of those GI side effects uh now rarely uh braidic cardia is a possibility with uh denail so if you think about and I'll talk a little bit more about this in drug interactions and some of those meds but if you think about other drugs that might lower the pulse or lower the heart rate um we could potentially you know worsen that or drop that heart rate further with the acetool esterase Inhibitors not real strong of an effect uh you know it's not like a a beta blocker for example um but if you've got somebody that's kind of already borderline low it could drop it a little bit further so something to definitely uh pay attention to uh other you know kind of wacky unique side effects I I have seen uh pych changes you know where maybe patients will be actually more confused maybe they'll hallucinate um maybe they'll have more anxiety so you you may see some some wacky things like that and you know I think a good thing to think about is any drug that works in the brain uh probably has the potential uh to cause various types of CNS side effects um that's kind of a vague generality but I I think it definitely holds true when you start talking about um the complexity of the brain and using drugs uh that Target the brain uh one other one I'll throw out there um urinary incontinence frequency it may contribute or exacerbate that and the way I I really think about at least some of these adverse effects is the adverse effects are going to be opposite of the effects of anti-cholinergic medications so let's take that last one urinary frequency and continence well we use anticholinergics to sometimes treat those side effects so there's there's a good example of opposing effects another example atropine which is used in uh acute management of bradicardia so it can stimulate that heart rate in bradicardia whereas the acetylcholinesterase again opposite effects it might drop that heart rate some uh another adverse effect diarrhea um constipation happens with anticholinergics with the acetool esterase Inhibitors diarrhea is much more prevalent and common so you can kind of see those opposing effects and that's really uh ties into the the mechanism of action there so let's take a quick break and then I'll I'll elaborate a little bit more on on some of the really important drug interactions um but we'll take a quick break from our our sponsor here we've been 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hydroxyzine you've got Dien hydramine those types of drugs that have anticolon energic effects oxybutinin another one that just came into my head um but those types of drugs that have centrally acting uh systemic anticholinergic effects can block or blunt the response to the acetylon esteras Inhibitors okay these drugs oppose each other uh with the way their mechanism works so always always think of do I have it my patient who has dementia who has memory problems are they on anti-cholinergic medications already before you're even going to consider adding another medication for dementia because there definitely is the possibility that let's say patients taking uh overthe counter Dien hydramine for sleep there definitely is the possibility that that is contributing to their uh confusion and maybe mental cloudiness so definitely think about that uh before a patient has diagnosed with Alzheimer's dementia and placed on uh medication therapy because the drugs uh will oppose uh one another there so that's definitely the the biggest one I think of when I think of Denzil and the acetool esteras Inhibitors another one you know I I mentioned the adverse effect of braic cardia so I am paying close attention particularly in patients who have maybe a lower resting heart rate to begin with OR and or they're on drugs that drop pulse which many elderly patients are on drugs like beta blockers uh drugs like certain uh certain Kel channel blockers the D DM the Verapamil so those are are good examples of meds that can drop the pulse rate and if we add on a cetlin esterase inhibitor it could um maybe exacerbate that maybe make somebody who's borderline uh drop them a little bit further so again pretty rare but something definitely uh to think about so those are the two big things that I think about with drug interactions uh we're going to wrap up the the podcast for today uh go snag your free resource at reif pharmacology ccom uh it's over a 31 page PDF on the top 200 drugs where I highlight really really important stuff that you're likely to be tested on at some point uh throughout your Pharmacy medical um career if you have to take a pharmacology class so really cool resource there go get that for free simply for um following the the podcast there uh leave us a rating review on iTunes greatly greatly appreciated uh to those who have already done so but certainly that helps us um get in front of a bigger audience and lets uh more individuals learn and understand uh medications at a better and higher level I'm going to sign off for today thank you guys so much for listening um it's been an unbelievable uh first year here and I I can't thank you enough for all the support take care guys have a great rest of your day