Unknown Speaker 00:00 Hi, welcome Speaker 1 00:07 to Rosalind Franklin University, College of Pharmacy top 200 drugs podcast. Speaker 2 00:12 This podcast is produced by the pharmacy faculty members to supplement study material for students learning the top 200 drugs we're hoping that our real life clinical pearls and discussions from practicing pharmacists will help you study for your next drug quiz. Speaker 3 00:28 And now on to the show. Welcome to spring week two of Rosalind Franklin University's top 200 drugs podcast. I'm your co host, Dr. Kane, Dr. Holmes. I'm Dr. Weatherton, and this week, we'll be discussing sleep agents, hypnotics, benzodiazepines and neuropathic pain medications. So without further ado, we're going to start with the first drug class. We have four top 200 drugs, and they're all benzodiazepines. So before we get into those specific drugs, let's just talk about benzodiazepines as a drug class as a whole. Speaker 4 00:59 So all benzodiazepines are indicated for four different indications, anxiety, sleep, muscle relaxant and seizure disorders. All benzodiazepines can do all four properties, but are more commonly used for probably anxiety andor sleep. Speaker 5 01:16 Speaking of four, when I think of the benzos, I remember that they're all schedule four as far as the DEA is concerned as well. Speaker 3 01:23 So why would the DEA give them a schedule for classification? Speaker 4 01:26 As we know, a lot of benzodiazepines are commonly abused. They do have street value, and they have an addiction potential based on their potential to cause euphoria. Speaker 3 01:37 So anytime I think of how benzodiazepines work, I think of alcohol because they work on the same receptor, which is the GABA receptor. Obviously, it's a simplistic view of it, but it's essentially how they work. So the effects that a patient gets when taking a benzodiazepine isn't really all that different than the effect that they get with Speaker 5 01:53 alcohol, sure. So some things that those might include, they might be sedated or have an impaired memory, they might also stumble around or be unsteady and be prone to fall. Are there any other things that I'm forgetting? Speaker 4 02:04 Well, speaking of forgetting, perhaps memory impairment, we tend to see these side effects more pronounced in elderly individuals, but any age patient can be susceptible to these side effects. Speaker 3 02:16 And obviously these side effects are going to be magnified if you're taking other agents that are also seen as depressants, specifically alcohol being one of the worst offenders of that. Speaker 5 02:25 Yes, the benzos are relatively safe when taken by themselves, particularly when compared to other things like barbiturates. However, when you mix them with alcohol, they really do become dangerous drugs. Speaker 4 02:35 And I always like students and providers to remember that patients do have withdrawal from alcohol, as they also have withdrawal from benzodiazepines, and patients can die from both types of withdrawals. So they are very similar. Again, as Dr. Kane mentioned, their mechanism of action is on GABA. They both are GABA agonists, so when you take them away, the patient is at serious risk. Speaker 3 02:59 So without further ado, let's go ahead and start with our first drug, which is alprazolam. The brand name is Xanax. Speaker 5 03:05 One way that you could possibly remember that is that alprazolam, the generic, starts with ALP, like the mountains, and Xanax starts with an X, like Xmas or Christmas. So if you think of yourself spending Xmas in the Alps, that might help you to remember that alprazolam is Xanax, Speaker 4 03:22 so alprazolam, or Xanax, does have a rapid onset and short duration. It doesn't have a lot of active metabolites. It's important to remember that this rapid onset is responsible for why this medication is one of the most commonly abused benzodiazepines. Speaker 3 03:40 It may be not clinically relevant, but something that would be relevant for patient education is one of the street names for alprazolam or Xanax are Xanax bars, or just bars. The reason is that the two milligram tablet can be split, just like a candy bar, into four different pieces. Yeah, it sort of looks like a ladder. So to kind of wrap up with alprazolam or Xanax. It comes as three different formulations, one which is the most common, which is an immediate release formulation. Speaker 5 04:08 There's also a controlled release Xanax product as well, which Speaker 3 04:11 is kind of funny, because we want Xanax to be relatively short acting medication, but then they formulated it to something to make it very long. Unknown Speaker 04:18 And then there's also an orally disintegrating tablet available. Speaker 3 04:21 So our next medication is Clonazepam, or Klonopin is the brand name. I'm told that this Speaker 5 04:26 is bozos favorite benzodiazepine, because it sounds like Clonazepam. Speaker 4 04:30 So Clonazepam is intermediate duration and does not have any active metabolites. It lasts for approximately 12 hours when taken orally. Speaker 5 04:40 So you might see a, dosed B, i, d, interestingly, this one is also available as an immediate release tablet and orally disintegrating as well. So the next drug on the list is diazepam, or Valium. The way that you might remember this is diazepam starts with di and Valium starts with V, a, l, I, if you put those together, you. Of Diwali, which is the Indian holiday. Speaker 4 05:02 So diazepam has a pretty rapid onset, but it's important to remember that has a longer duration than any of the other benzodiazepines, and it has a lot of active metabolites. Speaker 3 05:13 So I think of diazepam kind of like a shotgun, where you have this active metabolite, and it soon as it hits the liver, it has a shotgun effect into a ton of different active metabolites that all have different half lives and build up in patients who take it over time. Speaker 5 05:27 And the effect that lasts longest is actually the sedative effect, so patients may feel tired or sleepy longer than they're getting relief from their anxiety or having potentially anti seizure effect. When I think of valium or diazepam in the community setting, this is the benzodiazepine that I really think of that's used as Speaker 3 05:44 a muscle relaxant. It's true a lot of times in surgical patients in the ICU, we'll use diazepam if we have problems with muscle spasms, especially if we've cut part of the muscle to get to an underlying structure for surgery. Speaker 4 05:58 It's available as a tablet, an oral solution, an injection, and also a rectal gel, which is the brand name, a rectal gel with brand name, diastat. So this gel is used for seizure control, and the dose does need to be preset based on the patient's weight. Speaker 5 06:15 And as a pharmacist, you'll be doing that before you dispense the drug, you will adjust the dose on the diastat syringe and then lock it in so that you can be sure your patient's getting the Speaker 3 06:25 right dose. So the next medication is Lorazepam or Ativan. This is an intermediate acting benzodiazepine that has no active metabolites. So in the ICU, we use Lorazepam or Ativan quite a bit as an injection, but it's also available as an oral solution and also a tablet. So next Speaker 4 06:40 we're going to talk about zolpidem, brand name Ambien, which is used to treat insomnia. Speaker 3 06:45 So Dr. hoops, I've heard that this class of medication are non benzodiazepine hypnotics. What does that mean? Speaker 4 06:51 So non benzodiazepine hypnotics are different structurally than the benzodiazepines, but they still hit some of the GABA receptor. The mechanism of action is largely Speaker 5 07:04 unknown, and so these agents, even though they're not benzodiazepines, they are still schedule fours, and they still work on GABA. Is that correct? Yes. So what sort of counseling points might be important for these agents? Dr. Kane, Speaker 3 07:19 so one thing that I think is important, partially because you want it to act as soon as you take it, is that you really need to take this medication on an empty stomach, because if you don't, it takes longer for it to kick in, which means that the drug will stick around when you're ready to wake up in the morning. Speaker 5 07:33 I think that's an important point, Dr. Kane, because this agent lasts approximately six to eight hours. So when you're thinking of taking one a patient, they would need to really look at the clock and make sure that they have the time to sleep off the effects of this medication Exactly. Speaker 3 07:47 And if they don't, then they'll be waking up with effects again, that are similar to alcohol, where they'll be sedated, difficult to have concentration and potentially have issues with whatever they need to do the next day. Speaker 5 07:58 And I think that's why recently, the FDA has issued guidance saying that they should decrease the dosage of zolpidem used in female patients, because females tend to be smaller and have a higher risk of waking up in the morning with residual Unknown Speaker 08:11 effects of these drugs. Speaker 4 08:13 Yeah, a lot of patients will actually refer to this as an Ambien hangover. Other adverse drug reactions that might occur with Ambien includes sleep related activities. So patients have been reported to be sleep, driving, making phone calls, cooking, eating, not remembering anything they're doing. Sleep, sex even has been reported. Speaker 3 08:33 So as far as zolpidem or Ambien, we have the traditional immediate release formulation. We have CR controlled release formulation, Speaker 4 08:41 there's a sublingual tablet and a sublingual spray. So zolpidem, controlled release, also known as Ambien, CR, has only been shown in studies to improve sleep duration by about an hour, maybe two hours, so Speaker 3 08:55 really, you're only gaining a couple hours of sleep at best with the CR formulation correct. Speaker 4 09:00 But for some patients that aren't sleeping or having severe difficulties, that might make a difference. So the next drug we're going to talk about is zaleplon, or Sonata, which is a non benzodiazepine hypnotic. Speaker 5 09:12 So it sounds like it works similar to Ambien or zolpidem, but does zaleplon have any important differences? Speaker 3 09:18 Dr. Kane actually it does. So it has a faster onset in the shorter duration than zolpidem or Ambien does, so you don't have to worry about taking it with or without food. Its onset is about 30 minutes, with a peak effect of about 60 minutes, and it lasts about four hours, instead of about six to eight hours with zolpidem or Ambien. Speaker 4 09:36 And it's available as an oral capsule and also a four door Hyundai, Speaker 5 09:41 that's correct. Dr. Holmes, the Hyundai Sonata, also tends to put people to sleep. So the next drug on our list is gabapentin, or Neurontin. This drug, I believe, was invented to be an anti epileptic, to help with seizures, but it's really gained a lot of popularity helping with neuropathic pain, particularly in patients with diabetes, would you agree with that? Speaker 3 10:01 Dr. Kane, absolutely. So in the hospital, I've rarely seen it used as an anti seizure medication. You have to use very high doses compared to the doses that people commonly will use it for neuropathic pain, Speaker 4 10:12 and unfortunately, most patients can't tolerate that high dose due to the adverse drug reactions, which is why it's not used clinically that much. The ADRs that we tend to see most often are CNS, depression, some dizziness, which is often the dose rate limiting stuff. Speaker 5 10:30 Now we've talked a lot about sedation with other drugs in this podcast that work on the GABA receptor, so I'm going to guess that maybe Gabapentin has some activity there as well. Is that correct? Speaker 3 10:40 So we know it has something to do with GABA, but we don't really know how. So yes and no. Speaker 5 10:45 So some of the other adverse drug reactions that we see can be peripheral edema or fluid accumulating in the arms and legs, and this tends to be dose dependent, meaning that when you reduce the dose, theoretically, the edema should Speaker 3 10:57 improve as a counseling point, just like all of the other agents that we've discussed today, because this is a CNS depressant, we really should avoid other CNS depressants if we can, particularly alcohol. Speaker 4 11:08 One last thing to mention with Gabapentin is that there is a wide range of dosing. So many patients will respond for their neuropathic pain at lower doses, and some patients require pushing to the maximum dosage. Unknown Speaker 11:21 And how is Gabapentin or Neurontin supplied? Speaker 3 11:24 So we see it primarily as an oral tablet or capsule. We also have it as a solution. And then there's a new patent extender, extended release product called Gralise, which is a once daily Gabapentin dosage form. Speaker 5 11:35 Now, Dr. Kane, I noticed that you called this a patent extender. Can you explain just a little bit what you mean by that? Because I think it's important, yeah. Speaker 3 11:42 So a lot of times when drug companies come out with a product and they lose their patent, where a generic comes out, in order to gain traction in the market with the drug, they'll release a new formulation. It's the same product, it just releases over a longer period of time, or the dosing is a little bit different. That allows them to get a new patent, which means that they can regain brand name status for products and make money on it. Interesting, okay, the Speaker 4 12:04 next drug we're going to talk about is pregabalin or brand name Lyrica, which is structurally similar to Gabapentin and has similar uses for seizures and more commonly, neuropathic pain. Speaker 5 12:16 Now Gabapentin or Neurontin was not a controlled substance. Is pregabalin or Lyrica a controlled substance. Speaker 3 12:23 It's actually a schedule five controlled substance by the DEA, so it Speaker 5 12:27 has some possibility of abuse, but probably not a whole lot. Are there any patients who shouldn't get pregabalin or Lyrica? Dr. Holmes, Speaker 4 12:34 we should use it with caution and patients with heart failure, because it may exacerbate peripheral edema. And how does it come? It comes as an oral capsule and also a solution. And it should be noted that it's pretty expensive medication as Speaker 5 12:48 well, so it still is a branded medication without a generic right now? Is that right? That's right. So maybe, as Dr. Kane mentioned, when this brand name starts to expire, we may see a Lyrica controlled release as well, but only time will tell. Speaking of controlled release products for pain, the next agent on the list is lidocaine, which comes as the lidoderm patch. This is a patch that patients can slap on for long term pain relief, primarily neuropathic pain is where we see it used very often. Speaker 4 13:18 So patients use this patch on their body by applying it on for 12 hours, and then they have to take it off for 12 hours. They can use up to three patches at one time in various locations on their body, and the patch can be cut to put it where they need pain relief. Speaker 3 13:34 That's interesting, because a lot of times we can't cut patches because the way that it's made, the formulation relies on not being violated by being cut. Speaker 5 13:43 So speaking of cuts and scrapes and scratches, are there any patient counseling points that apply to the lidoderm patch? Speaker 4 13:49 So you'd only want to apply the patch to intact skin, so you have to avoid any kind of broken skin, as there is a risk of toxicity, of absorbing the lidocaine. Speaker 3 13:58 Similarly, you don't want to put anything hot, or be around something hot that could potentially increase the amount of lidocaine that goes through the patch into the skin. So you wouldn't want to put something like a heating pad, sit in a hot tub or have a heated blanket on top of you, because of the risk of toxicity with the lidocaine. Speaker 5 14:15 Now, this patch is cool because it works, you know, for potentially 12 hours or more at a time when I first slap it on, can I expect it to start relieving my pain immediately? Speaker 4 14:24 No, it's probably not going to work for about four hours. Is the average onset of action Speaker 3 14:30 once you're done with it? An important patient counseling point is that you need to fold the patch and put it, discard it in a safe place, away from animals or small children, because there's plenty of drug that's still left in the patch, even after you're done with it. Speaker 4 14:43 Now, a lot of patients will ask you if this patch is habit forming, or does it have potential for abuse, or is it a narcotic agent? So it's important to remind them that in no way is this a narcotic agent, or does it have a schedule. According to the DEA, this could be useful for a lot of patients that do have a history of substance or drug abuse. Speaker 3 15:04 So Dr. Weatherton, this seems like a pretty neat drug. We get pain relief without any CNS depression, and it's something that you can apply topically that lasts a long time. Are there any problems with the medication? Speaker 5 15:15 We can see actually some pigment changes of the skin in the areas where the patches are applied. So that's something we need to warn our patients about. They can also potentially rotate the site of application to minimize that. One other thing about this patch is it's new, it's branded, and so it's very expensive. I think it's about four or $5 a patch. What they won't tell you is that there are lidocaine ointments that also exist that potentially can relieve pain to a similar degree, although you would have to apply the ointment more frequently. There are some downsides of the ointment as well. Potentially, if patients have trouble, if they have pain right in the middle of their back and they can't reach it, maybe it's better to have somebody slap a patch on them and be done with it, rather than trying to apply ointment there a few times a day. Speaker 4 15:59 And as with all ointments, if they have close contact with another individual or pet, the other person or animal could get the ointment on them too, which is a risk, all right. Speaker 3 16:11 So moving on to our over the counter section, the first OTC top 200 drug is doxylamine. Brand name is Unisom. Speaker 4 16:18 So this is an antihistamine, a nighttime sleep aid. So we're using the antihistamine properties of this just for the purpose of sleep in this indication. Speaker 3 16:28 So this sounds a lot like Benadryl or diphenhydramine, right? Speaker 5 16:31 Correct? It is. It's a non selective antihistamine, although, from personal experience, and this is not a scientific explanation, Benadryl will make me drowsy, but doxylamine, when it's in things like NyQuil, it knocks me out completely. I'll wake up four hours later with a dry mouth and dry eyes and having slept like a log, and hopefully Speaker 4 16:55 you avoided the other ADR, such as constipation and urinary retention as well. Speaker 5 17:00 Yeah, one of the ways that we can remember these anticholinergic adverse effects are is the little nursery rhyme, can't see, can't spit, can't pee, Speaker 3 17:10 can't defecate. And I think it's important to know how quickly it starts acting and how long it acts. So doxylamine or Unisom will take about one to two hours at most for its full onset, and then it will last about four hours. Speaker 5 17:26 Moving on, I think we need to get to this nasal agent called Nasalcrom or cromolyn. Dr. Kane, what's the Speaker 3 17:34 deal with cromolyn? So cromolyn is a preventative medication that stabilizes mast cells, so when you are exposed to an allergen that might normally cause your nose to run, this prevents the allergic reaction from happening in the first place. Speaker 4 17:48 So can I take this when I get a runny nose around cats? Speaker 5 17:52 Well, Dr. Holmes, it may work for that. However, the package insert recommends that you take this agent, starting regularly a week before you're ever around cats. Do you have that in your calendar a week Speaker 4 18:04 ahead of time? Never predicts my exposure to cats. Speaker 5 18:07 And that's one of the problems with this agent. It's it's a fairly good preventative agent, but you have to take it so far in advance that not many people can predict. Speaker 3 18:15 The other good thing about this agent is that we really see almost no side effects from it, very well tolerated, and really the only patient complaints we get are patient complaints that you would get with any other type of nasal spray, which is a better taste in your mouth and maybe a runny nose. So the final medication that we'll be talking about today is phenylephrine, and it has a number of different brand names, from Sudafed PE to Neo-Synephrine. It's available in a lot of different products, combination cold products, nasal sprays, a number of different medications. So you mentioned that one of the brand names is Sudafed PE and I see a lot of patients confused by that brand name. So is phenylephrine the same thing as what's in Sudafed? No, it's not. So what happened was the makers of Sudafed started making this phenylephrine product because the government had enforced that all Sudafed products be put behind the counter. So this is an alternative agent that can't be made into methamphetamine that really isn't as potent as the original Sudafed. Speaker 5 19:13 Yeah, so the bioavailability is pretty poor on this agent. It's below 40% and a lot of patients just say it's just not as Speaker 4 19:20 effective as Sudafed. Dr. Weatherton Let us know some considerations of using the nasal formulation compared to the oral formulation. Speaker 5 19:29 So the nasal formulation works by constricting the blood vessels in the nose, reducing the edema in the area and sort of opening things back up again. It works pretty quickly with relatively minimal side effects. However, there's a big downside in that it can't be used for more than about three to five days in a row. The problem with use extended beyond that is when the patient stops using it, they could potentially get what's called rebound congestion, where everything reverses and the congestion is much worse than when they started. Speaker 3 19:59 So Dr. Weatherton. You mentioned that the way this medication works is by constricting blood vessels. Does that mean that we can't use the tablet form in certain patient populations where maybe that wouldn't be a good idea. Speaker 5 20:10 That's a great point. Dr. Kane, we don't want to use this agent in people with uncontrolled hypertension, so we also want to avoid it in patients who are maybe predisposed to heart disease, either patients with pre existing heart disease or diabetics or other patients of that nature, really. Speaker 3 20:24 The other counseling point I mentioned with phenylephrine or even Sudafed for that matter, is that it could keep a patient up at night. So insomnia is a concern because these are stimulant like effects. So it would be like having a cup of coffee at night if you're going to take your PE at night too. Speaker 4 20:38 I would also use caution in patients that do have anxiety disorders, because it could exacerbate their anxiety disorders, or patients with perhaps hyperthyroid disease, this could make some of the symptoms worse Excellent. Speaker 3 20:53 So to review the medications that we've covered today, the first was alprazolam or Xanax, Unknown Speaker 20:59 the next was clonazepam or Klonopin, Speaker 4 21:01 then we talked about diazepam or Valium, Unknown Speaker 21:04 then Lorazepam or Ativan, Unknown Speaker 21:06 zolpidem or Speaker 4 21:07 Ambien, zaleplon or Sonata Gabapentin or Neurontin, pregabalin or Lyrica, lidocaine, or the lidoderm patch, Speaker 3 21:18 doxylamine or Unisom cromolyn or Nasalcrom Speaker 4 21:22 and phenylephrine or Neo-Synephrine and multiple other brand names. Speaker 3 21:28 Well, that concludes week two of the spring quarter of the Rosalind Franklin University's top 200 drugs podcast. I'm your co host, Dr. Kane. Speaker 5 21:36 I'm Dr. Weatherton And I'm Dr. Holmes. Study hard. Speaker 1 21:41 This has been an educational production by the Rosalind Franklin University College of Pharmacy. Speaker 3 21:46 This podcast is copyright Rosalind Franklin University of Medicine and Science. Speaker 1 21:50 No participants have any conflicts of interest to disclose. This podcast is for educational purposes only and is not intended to treat a particular patient. This information should not be used in lieu of the judgment of a healthcare provider. The theme music for this podcast is an excerpt of Metro Mix by sea salt released under Creative Commons.