Speaker 1 00:00 Hi. Welcome 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 1 00:29 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 health care provider. Dr. Sean Kane 00:41 This podcast is copyright Rosalind Franklin University of Medicine and Science, and now on to the show. Welcome to week nine of Rosalind Franklin University's top 200 drugs Podcast. I'm Dr. Kane, I'm Dr. Weatherton, and I'm Dr. Patel. So this week we're talking about opiates or narcotics, and we're going to kind of combine them all together as a drug class, talk about some of the counseling points, adverse effects, how they work, and then we'll go into each agent specifically. Now I understand that our body has its own pain killing system via endogenous opiate receptors. How do these agents interact with those receptors? Speaker 3 01:20 So all these agents are agonists at the mu, kappa or delta, opiate receptors. And how they work is they decrease the pain signaling and perception. Yeah. Dr. Sean Kane 01:31 So one thing that from a pharmacy standpoint, that I think is important with all opiates is that they have a side effect profile that is important to counsel patients on the big side effect that I think of with opiates is sedation or CNS depression, which is why it really shouldn't be taken with other CNS depressants, unless you know how it's going to affect you, and that would include alcohol as well. Speaker 4 01:51 Good point. Dr. Kane, I also understand that opiates can slow down a couple other bodily functions. What are those? Speaker 3 01:57 Dr. Patel, yeah, so related to CNS depression, since the respiratory centers are also located in the brain, it can also cause respiratory depression. Some other common side effects are GI related side effects. Would you mind mentioning those? Dr. Weatherton, Speaker 4 02:12 well, these agents can upset the stomach, but the big opiate specific side effect that I think of is constipation. It just stops things from moving along. Dr. Kane, is there any way to prevent that? Dr. Sean Kane 02:23 So really, any patient who's on chronic opiate therapy should be given a bowel regimen, something like a stimulant laxative and a stool softener. But even with that, constipation can be a big problem in patients who are taking high doses of narcotics. Speaker 4 02:37 So what you're saying is that it's better to stay ahead of the problem, absolutely. Dr. Sean Kane 02:41 So some of the other adverse effects that are common with opiates include something like rashes or itching. The reason is that with many of these opiates, we actually get a little bit of a histamine release, some more than others. Speaker 4 02:52 Now I know that histamine can open up blood vessels or vasodilate. Does that have any effects on blood pressure? Dr. Sean Kane 02:58 It absolutely does so in the ICU, in patients who have blood pressure problems, morphine, especially high doses of morphine is not a good option for those patients. So before we move into the actual agents, the last thing I wanted to mention is dosing. So as pharmacists, dosing of narcotics or opiates is very important. With that in mind, there's a number of things that when dosing an opiate we have to keep in mind with that are patient specific things. Speaker 4 03:21 One of those has to do with how often your patient takes opiates. Are they on chronic opiate therapy and they've developed tolerances to low doses and need high doses? Or are they opiate naive? In which case we really want to start with low doses, the lowest dose possible that can help their pain. Speaker 3 03:38 The other factor that is also important to look at while dosing these medication is patient's age. You want to be conservative in dosing opiates in older patients versus younger patients. Same goes along with the body weight and any signs of renal or hepatic impairment. Speaker 4 03:54 Without further ado, let's go ahead and move on to our first opiate. The first drug is morphine sulfate. Brand name is MS Contin, and this is a schedule c2 agent. One way that I know busy doctors will sometimes try to write morphine sulfate is MSO4. Is that an appropriate abbreviation Speaker 3 04:11 that is actually one of the prohibited abbreviations to be used according to JC, which is Joint Commission, so we never want to write MSO4. We always need to spell it out morphine sulfate, because that leads to prescription errors. Dr. Sean Kane 04:24 So as far as morphine is concerned, we consider it the prototypic opioid. It came about way back in the 1800s it's been used extensively throughout history. We know a lot about it. It comes in many different dosage forms. We have po which includes extended release, which is MS Contin, we have immediate release morphine. We have solutions. We have capsules and tablets. We have IV, intrathecal epidural and even rectal formulations of morphine, rectal, even rectal. Speaker 4 04:53 So you mentioned that the brand name of morphine sulfate that we're looking at this week is MS Contin, what's special about MS Contin, Dr. Sean Kane 04:59 so MS Contin is the extended release formulation of morphine, as opposed to an immediate release that has to be taken more often. And one Speaker 3 05:06 thing we also need to worry about when we're switching patients from IV to PO is that the IV dose does not equal to the PO dose. The conversion ratio is one to three. Speaker 4 05:17 So if I have a patient who needs 100 milligrams of IV morphine. How much oral morphine would they need? It would be 300 milligrams of oral morphine. Now, that's a lot of morphine. The more morphine the better. Well, it sounds like even though these agents are really good at helping pain, there could be real problems if patients overdose. I understand that there's a black box warning to this effect. Is that correct? Speaker 3 05:38 That is very correct. So FDA has a black box warning for potential fatal overdose, and it can occur with accidental ingestion as well. What we need to do in this case is give patient, patient specific handout and educate the patient. And this all falls under FDA side effect monitoring program called REMS. Dr. Sean Kane 06:00 So before we move on to the next agent, I just wanted to point out that morphine is probably the most prototypic agent that causes histamine release. So this is one of the reasons that we use it for things like myocardial infarction or a heart attack, is that it causes vasodilation, which could be beneficial in someone who has an occluded coronary artery. But a lot of histamine can also lead to some side effects, right? Absolutely. So with the histamine release, we see the hypotension, we see itching, and in some patients, we even see skin reactions that look like an allergy, but are more of a pseudo allergy, which is from the histamine release. Speaker 4 06:34 Ah, so not everybody who gets itching from morphine has a true allergy. So our next agent is codeine with acetaminophen. The brand name is Tylenol number three and Tylenol number four, and these are both DEA schedule three. Now we learned that morphine sulfate or MS Contin was a long acting agent, is codeine and acetaminophen also a long acting agent. Dr. Sean Kane 06:53 So it's not and really it's a difference of formulation. This is an immediate release formulation, so it has to be dosed fairly frequently, about every four to six hours. Speaker 3 07:02 But interestingly enough, when they go through the metabolism, they convert into morphine. Dr. Sean Kane 07:07 Not all patients will metabolize codeine into morphine in the same way. Some people can metabolize a lot more of the drug to morphine, so they're at risk for an overdose with it. Some patients can metabolize very little of it, so they see very little analgesic effect from codeine. Speaker 4 07:22 So I understand that Tylenol number three and four also has acetaminophen in it. Are there any issues with that? Speaker 3 07:28 Well, yeah, so the name being said, acetaminophen, we want to make sure that patients are not getting an overdose of Tylenol. So it becomes a patient education point for us to explain for them not to use more Tylenol. The total daily dose for Tylenol is four grams per day. Dr. Sean Kane 07:44 While we're on the topic, we actually had a podcast listener comment about our previous episode of our maximum Tylenol dose per day. So there's actually some confusion, not only in the consumer market, but even among the medical community. What is the FDA's current stance on the total amount of Tylenol that someone should consume per day. So all the way back to the 1970s the recommendation was no more than four grams per day. Recently, though, because of a number of Tylenol toxicity cases, because of combination products and because of higher doses of Tylenol in these combination products, it was brought up whether or not the maximum dose of Tylenol should be reduced. So the FDA has not changed their stance. Their stance still is four grams per day. But McNeil, one of the primary manufacturers of brand name Tylenol, has self imposed restriction, saying that their current labeling for 500 milligram tablets has a new maximum of 3000 milligrams, or three grams per day. Speaker 4 08:41 Well, it sounds like we need to be really careful watching our acetaminophen doses, how much acetaminophen and codeine are in each Tylenol three and Tylenol four tablet. Dr. Sean Kane 08:50 So Tylenol number three and four both contain the same amount of Tylenol or acetaminophen, which is 300 milligrams. The difference, though, between t3 and t4 is the amount of codeine that's in the product. Speaker 4 09:01 So Tylenol number three contains 30 milligrams of codeine per tablet, and Tylenol number four contains 60 milligrams per tablet. That's right. Dr. Weatherton, we talked about how codeine and morphine are similar cousins. Are the adverse effects of both agents fairly similar. Dr. Sean Kane 09:17 They really are, because one does get metabolized to the others, so we see the same adverse effect profile. Speaker 3 09:23 Some patients might not be tolerating codeine as well. So you can recommend that they take this medication with food. Dr. Sean Kane 09:30 So for our next medication, the generic name is oxycodone, and the brand name is Oxycontin, and this is a DEA schedule two. Wow. I hear the word Speaker 4 09:39 Contin in this just like MS Contin, does that mean that OxyContin is a long acting agent as well it Dr. Sean Kane 09:44 is so OxyContin is an extended release formulation, just like MS Contin is, and it's Contin, it's not cotton. Is it? No, a very common misconception is it's OxyContin as opposed to Oxycodone. Speaker 4 09:59 So you're saying. Oxycodone is not the fabric of our lives. Dr. Sean Kane 10:02 It is not so. Dr. Patel, if you were counseling a patient between the differences of oxycodone and morphine, what would you tell that patient? Speaker 3 10:09 I would tell the patient that they would have less nausea and vomiting with oxycodone or OxyContin compared to morphine. However, the pain efficacy is equal. Yeah. And what is all the hoopla about the new formulation of oxycodone that I've been hearing in the market. Speaker 4 10:24 Well, OxyContin had the unfortunate nickname of hillbilly heroin, and while that's not politically correct, what it means is that this was a very abused drug in the past. In response to this, the manufacturer changed the OxyContin tablet so that it's not as easy to crush, because people would crush it up and abuse it that way. Also, the tablet can't be dissolved, because if it is dissolved, the active ingredient will form into a gel that's not easy to be melted and injected. So the next medication is very similar. It's oxycodone with acetaminophen. So combination product. The two brand names are Percocet and Roxicet, and this is also a DEA schedule two medication. Speaker 3 11:06 So what will be the difference between oxycodone and oxycodone with Tylenol in it? Speaker 4 11:11 Well, OxyContin is designed to be a long acting medication for basal pain control. Oxycodone and Acetaminophen is not an extended release product. So it's more short Dr. Sean Kane 11:22 acting, and also, by adding the Tylenol component, we could get some synergistic effect with analgesia that we wouldn't get with the oxycodone alone. Speaker 4 11:30 So the next drug on our list is another combination agent. This one is hydrocodone and acetaminophen, which has about a million brand names, but the two we're going to be talking about are Lortab and Vicodin Dr. Sean Kane 11:41 and these are both DEA schedule three medications. So the brand names are kind of interesting, at least historically, the brand name indicated how much acetaminophen was in each product. So historically, Lorcet had 650 milligrams, Lortab had 500 milligrams. Norco had 325, milligrams, and Vicodin also had 500 milligrams. Now, though, Vicodin only has 300 milligrams because of a new FDA warning about hepatotoxicity with products that are formulated with more than 325 milligrams of acetaminophen. Unknown Speaker 12:11 What is hepatotoxicity? Unknown Speaker 12:13 Hepatotoxicity would be the damage to the liver? Speaker 4 12:16 Well, there sure are a lot of formulations of this drug. Is it only in pill form? No. Speaker 3 12:20 Actually, this product is also available in many different formulations, such as capsules, tablets, solution and even an elixir. The next medication on our list is also a combination of hydrocodone and ibuprofen. The brand name is Vicoprofen, and this is a schedule three medication in Illinois. So just like the hydrocodone and Tylenol, this medication is also short acting. Speaker 4 12:44 Why might someone prescribe Vicoprofen or hydrocodone and ibuprofen over Vicodin, which is hydrocodone and acetaminophen, Dr. Sean Kane 12:51 having the ibuprofen or an NSAID component provides anti inflammatory effects, but it also comes with some adverse effects, like GI upset stomach ulcers, GI bleeding, and even renal impairment. Speaker 4 13:03 So we've talked about some short acting agents, but I understand that fentanyl, or Duragesic is a long acting agent. It's a controlled substance scheduled two or c2 medication as well. Dr. Patel, what's the deal with fentanyl? Speaker 3 13:17 Fentanyl is actually a very potent medication, so potent that it's dosed in micrograms. Dr. Sean Kane 13:24 So the interesting thing about fentanyl is that it's completely synthetic, so it structurally has no relationship to morphine. So in patients who have a true morphine allergy, fentanyl is completely okay to give to that patient. Speaker 3 13:35 And what I'm amazed by fentanyl is the variety of formulations that are available in the market. What's available? Dr. Patel, so I've seen the medication being available in Patch form in the inpatient setting. We can use it in the IV and various trans mucosal forms are also available, such as buccal lozenges, sublingual tablets, nasal spray and even sublingual spray, Speaker 4 14:00 fentanyl under the brand name durajizik. I understand that it's available as a patch. If I have a pain in my leg, can I just slap this patch on for quick pain relief? Speaker 3 14:10 No, actually, the patch doesn't start working until after 12 to 36, hours after you apply the patch. Dr. Sean Kane 14:17 So in addition to it taking a long time to start working, it also takes a long time for it to stop working. So it's not something that as soon as you remove it, the drug effect is gone. And actually there's a lot of drug that is left on the patch. An important counseling point to tell patients is that they should fold the patch and flush it down the toilet so that an animal or children cannot be exposed to the medication. Speaker 3 14:38 So we talked about all the opioid agents. And one important thing when it comes to contraindication is to keep in mind that these medications are contraindicated in patients who have paralytic ileus, gi obstruction, acute or severe asthma and along the line, respiratory depression. Speaker 4 14:57 Well now moving along to the last medication, which really moves things along as well. It's bisacodyl or Dulcolax. Dr. Kane, I understand that this is a stimulant type laxative. Can I use it to study not that kind of stimulant? Dr. Weatherton, so this has a direct irritation effect on the GI mucosa, and it causes a motility action that would be advantageous in patients who have constipation, and it Speaker 3 15:21 also alters water and electrolyte secretion. And this produce produces that intestinal fluid accumulation, and that's how it moving. It moves things along. Dr. Sean Kane 15:32 One important thing about the formulation of bisacodyl or Dulcolax is it's an extended release formulation. The reason is that because one of the ways it works is by irritating the GI mucosa. If it irritated your stomach, you'd get very nauseous. So it will not release its formulation until it's passed through the gastric area. Speaker 3 15:52 And thus, it's really important for us to educate the patient not to crush or split the pill. Speaker 4 15:57 Are there any other non oral dosage forms of bisacodyl or Dulcolax. Dr. Sean Kane 16:01 So one of my favorites in the ICU is the suppository form of bisacodyl or Dulcolax. And the reason is that it works so quickly, and it's very effective, how quickly Dr. Kane within minutes, all the way up to about an hour for the rectal suppository form, as opposed to about six to eight hours for the oral formulation. Wow. Speaker 4 16:20 So I really don't want to use that to study unless you want to study in the bathroom. So the Dr. Sean Kane 16:24 one thing that I think is important to counsel patients when they're constipated is that bisacodyl or Dulcolax can cause pretty severe abdominal cramping, nausea and vomiting. That's because it stimulates and irritates the gut, right? It does, and because it produces so much motility, it can cause cramping in the intestine Speaker 3 16:43 going along the same line. This should not be used in patient who have abdominal obstruction. Speaker 4 16:48 One important thing to tell your patients who may be considering using a bisacodyl suppository over the counter is to unwrap the suppository. It sounds simple, but the medication won't work if it's still in the wrapper. Dr. Sean Kane 17:01 And Dr. Weatherton, what is the wrapper made out of tin foil? Unknown Speaker 17:05 Exactly. Dr. Kane, so Dr. Sean Kane 17:07 this week, we talked about morphine sulfate. Brand name is MS Contin This is schedule two, codeine Speaker 4 17:12 and acetaminophen. Brand name, Tylenol three and Tylenol four, which are schedule three agents, Speaker 3 17:17 oxycodone, brand name, OxyContin. And this is a schedule two, Dr. Sean Kane 17:21 oxycodone, acetaminophen as a combination product. Brand names are Percocet and Roxicet, and these are both DEA schedule two. Speaker 4 17:29 We talked about hydrocodone and acetaminophen brand names Lortab and Vicodin, among others. And that's a schedule three, controlled substance. Speaker 3 17:36 Then came along, hydrocodone in combination with ibuprofen. Brand name is Vicoprofen. This is also a schedule three agent. Dr. Sean Kane 17:44 Fentanyl. Brand name is Duragesic, and this is a DEA schedule two medication. Speaker 4 17:49 And finally, in a very stimulating discussion, we talked about bisacodyl or Dulcolax. Dr. Sean Kane 17:55 Well, that concludes week nine of this Rosalind Franklin University, top 200 drugs podcast. I'm your co host, Dr. Kane. I'm Dr. Weatherton And Unknown Speaker 18:03 I'm Dr. Patel. Study hard. Speaker 1 18:08 This has been an educational production by the Rosalind Franklin University, College of Pharmacy. Theme music for this podcast is an excerpt of Metro Mix by seesaw, released under Creative Commons.