Speaker 1 00:00 Alex, welcome to HelixTalk, a podcast presented by the Rosalind Franklin University, College of Pharmacy. We're hoping that our real life clinical pearls and discussions will help you stay up to date and improve your pharmacy knowledge. This podcast contains general information for educational purposes only. This is not professional advice and should not be used in lieu of obtaining advice from a qualified health care provider. And now Narrator - Dr. Abel 00:29 on to the show. Dr. Sean Kane 00:31 Welcome to HelixTalk. Episode 24 I'm your co host, Dr. Kane. I'm Dr. Schuman, and I'm Dr. Patel, and today we're doing a little bit different of an episode. We're going to go through three different patient case vignettes and talk about kind of our preferred management or preferred therapies for some of these patients. So the first patient that we're going to dive into is a patient who's depressed. So this patient is a 31 year old male who has hypertension, currently on hydrochlorothiazide for their hypertension, 25 milligrams once a day, and they're presenting with signs and symptoms consistent with depression, and the patient is seeking medication therapy, in addition to counseling that they're already receiving for their depression. The one caveat to this patient case, though, is that they're very worried about sexual dysfunction. This 31 year old male is married, wanting to have children in the next year or two is really worried about kind of losing the Mojo in the bedroom because of any antidepressant that he may initiate, but at the same time, is really ready to kind of get over the depressive symptoms that he's been Speaker 2 01:31 having, right? And this is something that comes up fairly frequently when we're looking at that and we look at some of the agents, and we can kind of look, we sometimes think of it as a class based issue. So the one thing that comes up a lot of times is that for an individual to take the SSRIs for a while, this is something they even, even can sometimes call the flattening of your affect. It's something called Prozac poop-out. Speaker 3 01:54 Very, very interesting phrase that that is. But, you know, I've noticed this side effect in elderly patient. You know, I'm not saying that patients who are of reproductive age and wants to start a family or have issues with that patients of older age. And I just had a patient who's a 45 848, year old male, and he's not married at the point, but he does not like the fact that, you know, the citalopram that he's been getting, it's causing issues on his performance. So he wants to stick around with that, because he's lost some weight. He's been motivated, you know, exercising. Been out of the bed, feeling good about it, however, not very happy with the performance issues. So he does not want to increase the dose, but going back to this patient again, so what would be recommend for him? Speaker 2 02:41 Well, a lot of it, real quick, is the issue ends up being a couple two folded. It's serotonergic medications. It's not necessarily an SSRI thing or another class. It's the serotonin. And so medications that purely increase serotonin over time, you seem to maybe lose a little bit of regulation of dopamine or norepinephrine. And so that's where you kind of end up with it. Well, I'm not repressed, but I just kind of feel flat. And then there can also be there can also be some issues, I think, with polarization of things and leading to difficulty with orgasm. But so it's serotonin as well as some anticholinergic so in this case, you kind of like anything. What I really try to do is make sure to address patient specific and so in this case, a couple options we have would be to what we kind of see a clearer the SSRIs in general, especially Paxil, is probably the worst of Paroxetine. So we look at that's the worst for sexual dysfunction, probably again, both being an SSRI, so serotonin plus being an anticholinergic. So then we look, we can consider the SNRIs, but venlafaxine or Effexor, and even this is something I was reading, and reading some of the newer guidelines can be a little bit more likely because it still is more serotonergic of those SNRIs and so in that case, you could consider duloxetine or Cymbalta, which is about 5050, of the serotonin and norepinephrine reuptake. Again, keeping in mind, though, that as you bring on the more of the norepinephrine reuptake that hypertension could come into play. Dr. Sean Kane 03:59 So would you say that this patient's concerns about sexual dysfunction are well founded, and that this is a well described adverse event that is common, or is it rare enough that the patient could potentially start an SSRI and kind of see if he does have sexual dysfunction? Speaker 2 04:13 Unfortunately, it is fairly common. So for you, I for me, I laugh to let the patient, I will try to let the patients know, because one of the things that can happen that I notice in practice is that some individuals, you know, if they, if you kind of a fool me once, so that if they have a side effect, and you know that they may swear off all medications with for that treatment if they have that first discontinuation. So I try to be very clear about that, and again, let the individual make that ultimate decision. So if somebody, in this case, this individual who's fairly concerned that that's a big issue and a big part of his well being, so I would probably go ahead and just steer clear and given and so what we then focus on, I believe it, as long as the individual weight gain isn't a problem, maybe we look at mirtazapine. The way it works, one of its many receptor profiles, as a serotonin 5-HT2C antagonist, seems to be somewhat free of a little bit of that by some of its maybe downstream increase in dopamine. So it seems to be somewhat free of those issues. It can be somewhat activating. And so because of that, as long as the individual is okay with maybe some sedation, so take it at night, as well as potential for weight gain, that can be one that can be fairly devoid of some of those sexual side effects. Speaker 3 05:25 And how early after they start SSRIs or SNRIs, that they would see the side effect come about? Speaker 2 05:32 I understand it's usually within a first couple of weeks when you start to see it having that effect on the receptors, and you start seeing these downstream issues there. Speaker 3 05:41 And one of the things that you mentioned, Dr. Schuman is really important that, you know, some patients are truthful. They'll come and tell you, yes, it's helping me from for what indication we started this medication, but I have the side effect. What can we do instead of coming to you, oh, it caused the side effect. I stopped taking it because one of the issue of, you know, cold turkey. Quitting this medication is huge as well. Speaker 2 06:03 And again, another one, I should say, too, is Bupropion. Can be an option. Again, it really depends on that depression. If there's an, you know, an anxious type of depression with the anxious symptoms, then we do, again, have to be careful. Some individuals can be somewhat, too, you know, activated by that agent. And so it may not always be the best, but again, if it's a low energy depression, that can certainly be being an option too. Still, blood pressure may may be an issue with that medication that certainly can be usable. Dr. Sean Kane 06:30 So Dr. Schmidt to kind of summarize the two options that you're thinking of for this particular patient, you're going the mirtazapine route that would be taken at night, that would be more sedating with the potential issue of weight gain, or going the Bupropion route, which would be more of an activating medication if they're more prone to kind of an anxiety issue, maybe not the best medication for them. And kind of selecting between those two, and either agent lacking some of the serotonergic effects that are associated with the sexual dysfunction certainly. Speaker 2 06:59 And again, the best thing is being is being completely open with the patient that this is a relationship, so that they can be, that image can be the driving force behind you know, what is it going to be best for fitting with what their goals are. Dr. Sean Kane 07:10 And then, in thinking about those two agents, are there any patients that would be very poor candidates for either mirtazapine, Remeron or Bupropion, Wellbutrin, Speaker 2 07:19 certainly against an individual who, in previously has had issues with antihistamines, like diphenhydramine (Benadryl), making them groggy. There may be some residual sedation with that. And as of course, weight gain with mirtazapine can be an issue, and then with Bupropion, the big one would be risk of seizure. So if an individual has a seizure history, you know, especially if it's uncontrolled, then you have to really be careful of that medication as well as as I said, if there's any some underlying anxiety or hypertension that that dope and dopaminergic noradrenergic behavior could somewhat exacerbate that. And I Dr. Sean Kane 07:57 think oftentimes healthcare providers, when they think about risk of seizure, they may forget about the potential for a lowered seizure threshold. And someone who, let's say, has bulimia, anorexia, an alcoholic, someone who may have risk factors that could predispose them to having seizures, probably also not a great candidate for Bupropion, certainly, and as I understand it, mirtazapine has kind of a dose dependent effect. At lower doses, it may be more sedating than higher doses. Is that correct? Speaker 2 08:26 Yes, what happens is, at the lower doses, you see a lot of that antihistamine effect, and as it goes up higher, there's the receptor affinity isn't as great. So you kind of increase the level, and you sort of spread it out, and you see a blockade of alpha two receptors, both alpha two a and alpha 2c and so that activity then blocks some of those auto receptors and allows for some further down stream release of norepinephrine. And that norepinephrine is now what works in some of those arousal mechanisms, as well as could potentially contribute to, you know, some insomnia. It could be a concern. So at higher doses. You just want to watch some individuals, actually, once you reach the 3045, milligram range, we kind of shift it, and it becomes an Amn. And this is one of the there is, I think, with pharmacy, that we try to be aware of and educating is this is a medication that's versatile, but the same time, you got to be aware of that and make sure the medication and it still fit in the right niche. Speaker 3 09:19 I think the lesson we take out of this case vignette is you always have to let your patient know of the side effects so they don't quit the medication cold turkey, and let them know also to bring about that complaint back to the provider, so we can find another option like mirtazapine, bupropion, yeah, Dr. Sean Kane 09:36 and I can't emphasize enough the importance of If the patient is capable giving them the option, outlining the pros and cons of either medication, and saying, What would you like? And if the patient is capable of making that decision, I think that they feel more empowered to deal with an adverse effect that they anticipated. So moving on to our next case vignette. This is a 55 year old female. She's African American. Slightly obese, has hyperlipidemia and hypertension. She comes into the clinic with a blood pressure of 165 over 85 and the issue here is how we were going to deal with the patient's hypertension. Currently, she's on no medications at all for her hyperlipidemia. She's diet controlled. Is kind of refusing a statin at this point, and diet and exercise have been recommended to her, but she's fairly non compliant with those lifestyle interventions, which is actually fairly common for many patients. So clearly, there's a lot of different medications that we can consider for this patient, anything from thiazides to aces, ARBs, calcium channel blockers, even beta blockers are on the table, but we have to think about the JNC eight guidelines, specifically beta blockers being kind of taken off of the table, although many patients still are on beta blockers. Is mono therapy for hypertension, with no compelling indication for that. Yeah. Speaker 3 10:51 I mean, I have seen in clinic too. You know, some patients are have side effects to certain first line medication, first line anti hypertensive, and we end up have to using beta blocker in them to control their high blood pressure, you know. So that is one exception to the use of beta blocker without the compelling indication. So in Dr. Sean Kane 11:12 thinking about some of the options for my personal preference, seeing that the patient is African American, I know that aces and ARBs may be less efficacious compared to, let's say, a calcium channel blocker in that patient. So that may drive me that direction. The other thing is things like angioedema, although it's very, very rare, it is more common in African Americans than non African Americans. So to me, that's kind of two points against selecting an agent like Lisinopril, which would be an ACE inhibitor, or, let's say, Losartan and ARB, given that we have other agents that may be better for the Speaker 3 11:44 patient, right? And according to the new guidelines too, since her systolic is 165 you know, we have to kind of consider the two medication approach, because she's already at that stage two hypertension. Some patients starting out with two medication approach, they are taken aback a little bit and say, you know, I was not on any medication. Why am I being started on two medication? What you can do is also look out for those combination meds that are out there if patients, you know, insurance covers it, so that's a good approach to perhaps calm patient down and increase the compliance. Speaker 2 12:16 And Dr. K, at what point or do you ever become concerned about edema with some of these calcium channel blockers? Dr. Sean Kane 12:22 Yeah, so many patients will complain of peripheral edema and weight gain from that edema. Definitely something that should be counseled on. And I think we should clarify a calcium channel blocker. In this instance, to me, would mean a dihydropyridine calcium channel blocker, so not deltas and not verapamil, but thinking things like amlodipine, nifedipine, those are my go to calcium channel blockers that I really like, but for very different reasons. Going back to the patient's compliance, one thing to think about, too is, regardless of whatever antihypertensive we give the patient, she is almost certainly going to need two antihypertensives to be well controlled. With that said, though, if we do too much too soon, it seems like she's already non compliant, doesn't want to take a statin, has some dietary and lifestyle modifications that she's resistant to. If we make her light headed or orthostatic, or she has other adverse effects, we may be losing some of her trust in our medication therapy. So maybe going a little bit slower, knowing she's not at goal could be a reasonable approach to her, knowing that she will need two drugs at some point. Speaker 2 13:26 I think that's why, again, comes down to communication with the individual, letting them you know the note know that you know this, this to drug regimen may be coming, so that it just doesn't, all of a sudden become you know, well, what happened? I thought we were doing well, absolutely. Dr. Sean Kane 13:39 And one thing to think about again with peripheral edema is if we were to pick a dihydropyridine calcium channel blocker, the addition of an ace or an ARB has been shown to actually prevent some of the edema, the peripheral edema that patients can have with that so in that sense, you could almost argue in favor of giving a dual regimen up front to help avoid Some of those adverse effects. Speaker 3 14:01 So I can make out that you definitely want to give this patient a calcium channel blocker. Let's say she agrees to, you know, tackle on another medication right away. What will be your go to agent? Dr. Sean Kane 14:11 I think I've got to go Amlodipine for her. And I say that because in the intensive care unit, I actually really don't like Amlodipine. But for the outpatient use, Amlodipine is actually a very attractive option for a couple reasons. One of all the hydropyridine calcium channel blockers it has the longest half life, has a very slow onset of action and a very slow absorption profile, meaning that patients won't get reflex tachycardia. They won't get some of the orthostatic symptoms and things like that that they may get from a very rapid acting anti hypertensive. So in general, I find Amlodipine to be very gentle. With that said, though, in the ICU, I don't want it to be gentle. I want it to work now, and I want it to work very quickly and get to steady state very quickly. Given that the half life is more than two days, it's going to take a long time to get to steady state. So it's a great outpatient medication, not a great acute man. Management of hypertension medication. But in this instance, it's, in my mind, a very good agent for that patient. Do you guys have any calcium channel blockers that you happen to like? Speaker 3 15:09 Actually, my go to agent for calcium channel blocker is also Amlodipine. I've seen some patients from other providers who come to me and I fatapin. But then I even though, if it's not an XR formulation, I do worry about the reflex tachycardia and nifedipine, so I would definitely, if I were to start a patient on a new calcium channel blocker, I would probably go with the amyloid pain as well. Speaker 2 15:32 And I, again, I agree here for some of it's the somewhat simplicity of being able to use it in the outpatient setting as well as some formulary considerations at our facility becomes a nice and we can start kind of bringing to individuals, especially due to the half life and being some night, some compliance issues we occasionally will run into with some of the patients we see with various comorbidities and maybe some cognitive concerns as well being able to have a medication that there's not going To be this, these problems, you know, should there be some interruptions in therapy? That can be a very nice thing. So it Dr. Sean Kane 16:05 sounds like we're on board with Amlodipine or Norvasc, which is a dihydropyridine calcium channel blocker for this patient. So very briefly, then are you guys in favor of an additional agent at this time? Or would you wait the two weeks after starting five or 10 of Norvasc and kind of see where the patient's at. Speaker 2 16:23 And I generally run with the opinion of stuff, kind of, you know, optimizing with a single agent. A lot of it comes down to to pilbern. We have a lot of individuals who that it's the simple numbers game with their medications. The number of pills directly correlates with how they feel about how their healthcare is going, and the more pills they see, the more problems they feel they have, and the more confused and frustrated they get, which then leads to kind of the just all or nothing. Well, I give up approach and I and seeing that in some individuals, trying to be aware of that and stick with one agent as that can be something that I try to generally advocate Dr. Sean Kane 17:01 for so I know Dr. Patel mentioned it earlier. Would you not be in favor of Lotrel, which is benazepril with amlodipine in it? Speaker 2 17:07 Oh, I, I certainly would be in favor. And if the facility allows for the for the use of a medication like that, I would be all in favor something like that as that kind of best of both worlds approach. Again, I don't always have the luxury of being able to prescribe or recommend that medication, but, yeah, that's certainly be an option. Dr. Patel, Speaker 3 17:25 what about yourself? Yeah, I think we kind of have to consider a few other factors. Like this patient, you know, we said that she's not complying with diet and exercise, and most likely, you know, the likelihood of her being compliant with two medication might be a little bit hard. So I would take a different approach in her, and you just start her on one medication. But if I have a different patient where, you know, there's a long standing history of increased blood pressure, there's a strong family history of cardiovascular risk because of, you know, high blood pressure running in the family too, I probably would start with two low doses of two different medication with, you know, two different mechanism of action. And so my second approach would be adding another medication on in those patients, especially if you, if you have a nice track record of compliance and they're okay, they're understanding the risk of long standing high blood pressure, which is stroke. So with all that education, if your patient's up to par, then we can definitely start another agent right then. Dr. Sean Kane 18:22 And there are you starting benazopryl, amlodipine, or do you have a different favorite combo product? Or would you separate out the two? Speaker 3 18:29 Well, most of the patients that I have, I they require either a $4 generic help. You know, they can't afford that medication, so I tend to look at that list and see what combinations are covered under the $4 so again, going back to what you said, Doctor treatment, instead of, you know, them feeling, oh my gosh, I'm taking two medications. Now, if you combine the two, there is maybe likelihood of improving some of the compliance issue as well. But there is a combination of calcium channel buffer as well as hydrochlorothiazide available that we can put patient on consider that as well. Dr. Sean Kane 19:03 Think that's a great, great thought. I think that many of the combo products you're able to titrate up, so starting low for the patient, if you wanted to, with two different agents, would probably be fairly similar in efficacy to starting with a more aggressive calcium channel blocker. So I think it kind of depends on patient insurance and what they feel about taking two medications versus one down the road and things like that. So I think all of those approaches are very reasonable. So our third and final patient is a 62 year old female who's Hispanic, who comes to the clinic. She's a type two diabetic, currently on Metformin, 500 milligrams. B ID, she is obese, BMI of 42 and her a 1c is 8.9% that was taken today in clinic. She does want to lose weight, so she's very concerned about going forward with adding a lot of anti diabetic medications that may cause her to gain weight. And she just wants to know where does she go from here to kind of optimize her diabetic therapy? Speaker 3 20:00 Yeah, I do see this commonly in the clinic too. You know, it's usually a conundrum of metabolic syndrome, and that's how the patients present to you. You know, they have issues with waist circumference, aka obesity, and then they come up with either hyperlipidemia or high blood sugars. And my go to approach, obviously, we all know, per the guidelines, is start patient on Metformin. Initially it was thought to be causing anorexia and have some that weight loss benefit, but more studies came out, and it says that it's more of a weight neutral type of medication. And so when we look at the goal of therapy, you know now the ADA has changed its focus and kind of the goal has become in the area of preserving that beta cell function, okay, giving medication that are either weight neutral or helping patients reduce weight, because we know there is a direct correlation of reduction in weight and reduction in A and C levels too. And then last, but not the least, give the medication that would cause least amount of hypoglycemia, especially in patients. She's 62 however, there are a lot of elderly patients out there, you know, and we had to be careful in how aggressive of an approach that we take and what kind of medication we choose, especially the big ones are sulfonylureas and insulins. Speaker 2 21:19 So then we kind of look at options, like, are you concerned about something like Glyburide in this individual at a fairly high starting nose issues like that. About weight gain? Yeah. Speaker 3 21:32 So sulfonylureas and Glyburide is definitely one of them that could potentially increase the production, or they're considered a sequestering of insulin from pancreas, basically, and insulin at the end of the day is known to cause baking. So yes and no, my residency training has been in the VA and we perform under a very strict formulary, which basically consists of basic, generic agents such as Metformin, pioglitazone, which is a thiazolidinedione, and so we were effectively able to manage patients on these agents. Interestingly enough, though, the new guidelines of American endocrinology society has come out, and if you follow the algorithm, the first obviously medication to prescribe is Metformin, but the second-line agent, they have moved sulfonylureas to the little bit of bottom of the totem pole, and then they've moved up the GLP-1 agonist, like Bydureon, as well as Victoza as the preferred second-line agent. And that, to me, is a little bit disturbing. I remember a lot of my clinician colleagues were not really happy about that recommendation as well. And there are a few reasons behind that too. Obviously, as you said, Dr. Kane, there is weight loss issue. You know, if this patient's obese, wants to lose weight, we know that Bydureon, which is a GLP-1 agonist, does give us a little benefit of weight reduction, when I say little, and clinical trial, that number has been anywhere from three kilograms to five kilograms. Okay, so it's not a huge difference in weight they were looking for. For a patient who has a Dr. Sean Kane 23:13 BMI of 42 I think it's important to think about how the patient achieves that weight loss. It's not like their metabolism revs up, and they just magically lose the weight. They feel bad, like they feel nauseous, they have diarrhea. It's not like it just magically falls off their body. It comes because they're not eating very much, because they don't feel like eating, because they Speaker 3 23:33 feel bad, right? And that would be the education point, if I were to prescribe that medication in this patient. Say, Hey, by the way, this doesn't happen overnight. You know, the reason you lose weight is because you're not able to eat so much, you know, and your diet habit will have to be changed to eating small meals, small, frequent meals, which not only will help control the sugar, but also help lose some weight. Speaker 2 23:56 Dr. Patel, do you find that the the route of administration is somewhat prohibitive toward its use. I know we, you know, talk about individuals kind of release. In my population, tend to prefer going with more of an oral route first before going to an invasive route. And that would be an issue at all. Speaker 3 24:11 Yeah, and you brought up a great point. So in a patient who wants to utilize weight neutral medication or pets that would help with weight loss, but not necessarily, go with injectables, such as GLP, one agonist. I'm talking about injectables. So cost consideration will also come in play. You're looking at a 62 year old patient. Fine, there's one example. However, there are a lot of elderly patients are out there. My approach in treatment is, if I'm going to recommend an injectable. Why not insulin? Why go have your patient take the biota injection two times a day? Why I can start a longer acting insulin once a night? And we know that's definitely going to work and bring down that ANC and so talking about A and C, GLP, one agonist, you know, depending on the formulation you use. The shorter acting ones had shown to reduce your A1C by about 1%. A couple of new long-acting products have been out in the market, like Exenatide ER (Bydureon), which has shown to decrease A1C by 1.5%. Our patient sits at 8.9%, so we're not looking to, and this is, again, these A1C reduction numbers come from clinical trials, so we kind of have to take them from the trial itself when we apply that to real clinical practice, right. Earlier examples of patients we talked about compliance issue. So is the patient's going to be compliant, especially Dr. King, you mentioned all this nausea side effect, you know, she might be cutting corners and say, Hey, I'm going to go have a dinner outside today, and I particularly do not want to feel nauseous afterwards, so I'm going to skip my biota dose today. So I Dr. Sean Kane 25:46 wonder if we can't kind of eliminate some options off the table, given the patient's a 1c her personal preferences and things like that, what I'm hearing is any injectable given where she's at, given where her a 1c is at, seems like overkill for this patient. Is that an accurate assessment? Speaker 3 26:01 You got that correct? Sorry, I was going in tantrums, kind of just going in different factors that I would consider in bringing down or boiling down to one particular agent. So forget the agents that would cause weight gain, which is sulfonylureas and insulin. Forget the agents that are injectable and expensive, GLP, one agonists, however, we can bring it down to a similar acting medication like Januvia. Those are DPP four inhibitors. Ultimately, DPP four is the enzyme that breaks down GLP and GIP in the gut. And so what we want to do is stop this breaking down of GLP and GLP ones. And so it's once a day oral medication, as long as the renal function is good, there are other agents out in the same category that do not even depend on renal function. So those modifications not required. Dr. Sean Kane 26:50 What are those medications? So we have you mentioned Sitagliptin or Januvia. Speaker 3 26:54 That's one. We have saxagliptin or an Elisa. And then there is Linagliptin, which is tragenta. So lenoglitin is the one that does not have renal dosing parameters. Dr. Sean Kane 27:05 And I can tell you, anecdotally, I've seen a lot more Linagliptin in the past six months, and I have probably even Sitagliptin or Januvia. I think the renal elimination stuff has really taken hold in terms of providers don't have to worry about creatinine clearance with lenogliptin, and I think they're probably more likely to use it just because they don't have to worry about it. Speaker 3 27:24 Funny, you say that, because that's the marketing strategy from the drug reps. Speaker 2 27:28 From my understanding too. I think certain formulas are taking notice of that as well when they're selecting agents. And the fact that it does have that versatility, I think, is attractive as well from a formulary standpoint, absolutely. Dr. Sean Kane 27:39 So I know that you mentioned pioglitazone, so can we kind of rule in or rule out the thiazolidinediones for this patient? Speaker 3 27:48 Yeah, absolutely. You know, thiazolidin diene also falls into a category of insulin sensitizer, so that's where that form is coming right now, you would say this patient's only on 500 milligram B ID, so we do have an opportunity to increase the dose 2000 milligrams VAD, or even if you want to maximize to 2550 milligrams. However, your patient might have to take it three times a day, and likelihood of you know, compliance with that might be also should be considered. So increase that Metformin, rather than using a medication that would do pretty much the same, basically, insulin sensitizing effect, which would also be diazoline and Dione, I would say, use another type of mechanism of action. So talking about Januvia again, or DPP four inhibitors, you know, they not only help with an overall control of the sugar. So control the AMAC, which is the fasting blood sugar, but they also help with postprandial control of the sugar too. And so instead of your patients using sulfonylurea or taking prandial insulin, they can be on DPP, four inhibitors, and there has been shown to reduction in postprandial glucose explosions as well. Dr. Sean Kane 29:05 I wonder if pioglitazone or rosiglitazone, those thiazolidinediones, would have edema associated with them that the patient may believe is part of weight gain. I don't know if that would be a common adverse effect or not that a patient would experience. Speaker 3 29:18 Yeah, so thiazolid and ions, we know those do definitely come with some cardiac conditions, you know, edema, weight gain, increase in L of T's, and in patients who have situations of heart attack, or even, you know, congestive heart failure, like symptoms, we have to get them off of basal and Dione, because that's one of the black box warning too. And so, yes, it is once a day medication. We can start at 15 milligrams, once a day, and then go to 30 and 45 milligrams. However, the caveat with diazoline Dione is because they work at a nuclear level, and they change the expression of glute, four receptors on the nuclear. Is, we are looking at an effective or pharmacodynamically the effect of sugar lowering, or even seeing improvement, is not seen until about two to three months, you know, four to six weeks down the line, we see the effect of it, versus talking about metformin and Januvia, you know, they shoot, they show the effect in about one to two weeks. Speaker 2 30:20 So from a patient compliance issue, I can imagine then that if somebody is taking a medication and still not seeing a beneficial effect, and then you can say, you know, why am I still bothering with this? This isn't working. I don't want to take it. I can imagine that would be a concern. Speaker 3 30:35 Yeah, absolutely, absolutely. So again, talking to them about it, you know, explaining how the medication work. It's very, very important being a pharmacist, you know, my approach to having any diabetic management patient is to first say, Bring all your medication. I'm going to tell you how these medications work. And you'll be surprised after knowing how the medications work, what kind of effect and side effect they have on their blood sugar. They are more compliant because, just because they feel that they have the knowledge and they need to do whatever they need to do in order to lower their blood sugar. Dr. Sean Kane 31:08 So we've neglected to talk about my favorite diabetic drug class, the sglt, two Speaker 3 31:14 inhibitors. Oh yes, the newest one in the market. Dr. Sean Kane 31:17 The newest ones. These are my favorite because of the adverse effect profile. So for the listeners who aren't familiar, this drug class increases the amount of glucose that's excreted in the urine, and it does have a weight reduction effect, because you are essentially getting rid of calories that you would have had in your bloodstream anyway. Of course, there's one tiny problem with putting too much sugar in your urine, Speaker 3 31:40 and as you would imagine, those are urinary tract infections. And these are not just bacterial infection. It could be Mycotic infections as well, Dr. Sean Kane 31:48 and that's in men and women. So at least in the clinical trials, again, about 10% of women and three to 4% of men would have these Mycotic or fungal infections of their genitals because of this drug class, right? Speaker 2 32:00 That's a tough trip. I mean, that's be honest. That's that's a challenging trade off for somebody to start thinking about a medication, no matter how seemingly, you know, miraculous the mechanism is to think about these things in terms of real health risks. Speaker 3 32:14 And I'll give you two examples. I had a female patient who recently was on an antibiotic course or UTI, maybe it wasn't used by hyperglycemia as it is, because she's diabetic, she comes to me and she talks about Invokana, which is canagliflozin, because she saw a commercial, and would she be a good candidate for it? I bring about this side effect as part of the education? And she said, No, I'm not going to venture it. I have another patient who is a school bus driver cannot use insulin. We have a man on Bydureon. However, we needed additional control, and so he explored an Invokana. And then we oh, we get all right, we'll give it a try. You know, it's not going to reduce your ravency by a great deal, but we'll give it a try. Surprisingly, he agreed, despite knowing these side effects, and he agreed to use it, he has been using it, and has shown great improvement in his blood sugars. Dr. Sean Kane 33:07 So I think that kind of wrapping it up, at least for me, we've narrowed it down to two things. One would be modifying the Metformin dose that the patient's currently on, and two, thinking about something like Sitagliptin or a DPP four inhibitor. For me, at least, I'm going to rule out our sglt Two inhibitors, knowing that down the road, we could explore that with the patient, but I just don't feel like that would be my first step for a patient who's only on Metformin with a reasonable ANC. What do you Speaker 3 33:34 guys think that's absolutely right for? First and foremost, these are new agents in the market. Obviously, no generics are out there. They're expensive. If you look at most insurance plans, they're going to be either, you know, fourth or fifth tier, preferably, maybe have some sort of quantity limit or prior authorization required to, Speaker 2 33:53 yeah, I think for me start, you know, start to look at and considering that DPP four and hey, we're keeping in mind that I believe that our ability to then get well below that goal may be somewhat difficult with singularly bringing out that agent. So potentially, a combination of then going back and maybe optimizing the Metformin on top of that may be Dr. Sean Kane 34:11 a palatable option. Just for completeness sake, the patient should be educated as they increase their Metformin dose of the GI side effects, which are very common with metformin, are going to be more common for a little while, while the patient's body kind of adjusts to that new dose. So diarrhea, nausea, gas, bloating, things like that. They're going to have some more of those adverse effects with an acute increase in their dose, but it will improve over time. Speaker 3 34:35 Yeah, and that, that time period is about one to two weeks for most patients. So do educate your patient about that. You know, starting patient on your DPP force to kind of have to be telling them about what's been out recently in the studies, too, pancreatitis, right? Risk of acute pancreatitis. So tell your patients about how to detect the signs of acute pancreatitis. You know, acute abdominal pain, acute onset of nausea. Vomiting, acute, generalized fatigue, maybe it's a mild grade fever as well. Dr. Sean Kane 35:05 So Dr. Patel, I'm gonna ask you to pick your regimen for this patient here, specifically. Speaker 3 35:11 Okay, so I will go ahead and increase this patient's Metformin from 500 milligrams two times a day, 2000 milligrams, two times a day, and then, after doing all the education needed bringing patient on board, I would like to start the DPP four inhibitor, just because we would get some post prandial coverage as Dr. Sean Kane 35:31 well. And which DPP four inhibitor Are you gonna back? Speaker 3 35:34 I will go ahead Januvia, or sodagliptin, 100 milligrams daily. But before I start that dose, I'll make sure that patient's renal function is up to par. The other renal dosing consideration to keep in mind, if the grant in clearance is between 30 and 50, decrease the dose to 50. And if it's less than 30 milliliters per minute, then decrease your dose to 25 Dr. Sean Kane 35:57 milligrams per day. So just to clarify, then, it's not that you can't use januvier acidagliptin and chronic kidney disease, you just have a dose adjustment, and with lenogliptin, there's no dose adjustment. And that's really the clarification. Speaker 3 36:10 I agree with that clarification. Earlier, we mentioned that, you know, lenoglitin is more attractive because we don't have to worry about renal function. What we really meant is that, yes, Januvia still can be used, however, we can't be using at a full dose potential, so if the patient's renal function is kind of fluctuating, go ahead and put them on the glyptin, and you won't have to worry about adjusting the dose. Dr. Sean Kane 36:31 So Dr. Schuman, do you agree with Dr. Patel increasing Metformin to 1000 B ID and initiate sitagliptin? Speaker 2 36:37 Certainly the I may consider the order of them a little differently again, just to want to, you know, be avoid any kind of GI distress right after that. But certainly I think that that combination Dr. tau proposed is a great way to both in terms of economically as well as for looking at overall patient outcomes inside of that profile. Dr. Sean Kane 36:57 I think that sounds great. So as listeners, if you enjoyed this podcast format where it's kind of case based, and we're kind of going back and forth, please let us know we're available at HelixTalk.com you can find our contact information there. If you have any topic suggestions, you can find us there as well. To suggest any topics. We really appreciate five star reviews and iTunes to help other other students and healthcare practitioners find us. And with that, all sent off. I'm Dr. King, I'm Dr. Schuman, Speaker 3 37:23 and I'm Dr. Patel, and I was always study hard. Narrator - Dr. Abel 37:26 Thank you for listening to this episode of HelixTalk. This is an educational production, copyright Rosalind Franklin University of Medicine and Science. For more information about the show, please visit us at HelixTalk.com. You.