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Yes. Okay. Okay. Are you able to see that? Sure. On the screen. Yes, that's great. Ok, thanks, everyone. Okay, so my name is even juice If McArdle uh, I'm a pharmacist. That's working a variety of different specialties. Um, in the nth us on the primary secondary and tertiary care of the health systems in the UK And today we'll be looking at the pharmacology of pain in analgesia, um, specifically focusing on narcotic, non narcotic analgesic and and suits. So it's what's the member and that this lecture is from a pharmacist perspective. So in some instances, it should help when they're going to to treat, prescribe and to consider co morbidities of patient's that you may see in your care some of the topics that we recover in the session. Um, what is pain? Uh, differential types of pain. Treatment of pen. I look at the World Health Organization analgesia, cutter and the aim of pain management. Uh, and treatment nonnarcotic anesthesia. I'm narcotic analgesia. And finally, we were looking at and see. It's, uh, non steroidal anti inflammatory drugs. Okay, So what is pain? Uh, very subjective to an individual. And if you ask 10 different people what pain is ordinarily, you would tend to get 10 different answers. So the World Health Organization has tried to define pain and in a way that would maybe shoot a wide variety of patient's are subjected you to in your care. Uh, health. Uh, sorry to interrupt. I don't know if you've moved from moved on from the first slide, but it's not showing on the screen. Yeah, the first slide, the slide showing should be showing. Is that not coming through? No, no, it's still on the first one. Sorry if you're still sorry. Is it still Are you still on the first slide? No. So it's not showing that you've moved on from there, right? OK, no problem. So it might be better to cover it this way. Can you see that? Is that the second you're on the second one now? Yeah. Yeah, that's showing. Okay, no problem. We can We can look at it this way, then, if the slideshow isn't working, um, so as mentioned, we were looking at the different types of pain and high pain. It's actually defined. So the world health and, uh, organization, who defines piano as an unpleasant century or emotional experience associated with actual or potential tissue damage or described in terms of such damage. And the International Association for the Study of P. E N I. S P defines pain relatively similarly again, an unpleasant century or emotional experience associated with actual or potential tissue damage or described in the terms of such damage. So I think one of the things that I wanted to look at first, um, just before we go through the pharmacologic treatments of pain and his pain management that is non pharmacologic. It's a very common method of non pharmacologic. Treatment, you see, is the rice treatment, which is the four components of rest ice compression and elevation and vice treatment. Rice therapy is the immediate application of rest ice compression and delegation to a minor soft tissue injury like a sprain. So rice is a popular first day of treatment designed to help manage swelling, pain and blood flow. I think essentially, um, when looking at pain management, essentially, we oftentimes we might not get to, uh, administer medications right away, or we might not get too. I have a patient get to the hospital, so if we can ascertain that it's a soft tissue injury, which is very common injury We certainly see in pharmacy. Uh, one would recommend using that method of non pharmacologic treatment, which is rice. Of course, elevation is very easy, and we can elevate our limbs. Or we can help a patient elevate their limbs. Compression, of course. Fire compression bandage or the administration or over wrap bandage ice might not always be possible, but we can certainly get cold treatment by flannels that are dies and water otherwise or ice packs and, of course, rest um, with any injury. Ordinarily, if there's pain, the patient should rest, so differential types of pain. So, of course, there's many types of pain that we can see, um, in hospitals and primary care and secondary care. And some of the more common types of pain seen in practice include, uh, acute pain, which is pain occurring as the result of an injury or trauma such as a compound fracture. Uh, chronic pain, uh, which is longstanding pain persisting beyond the usual recoverable recovery period of an injury or pain that's associated with a chronic health condition such as arthritis neuropathic pain, Uh, which is pain caused by, uh, lesion or disease of the tomato century nervous system such as peripheral neuropathy. Uh, we will touch on neuropathic pain in terms of some of the treatments. Um, quite a difficult pain to treat. And certainly we tend to see, um, high instances of neuropathic pain and subjects that have quite progressive or progressed diabetes that is poorly controlled. That's one very common type of fan museum deputies. Um, because, of course, peripheral neuropathy can be a complication or co morbidity associated with diabetic patients' and then noise susceptive pain, which is pain that originates with an injury involving noise receptors from somatic sources such as the skin of joints or visceral sources such as walls of organs, so acute or chronic links to noises at the pain they tend to be, um, oftentimes, with no susceptive neuropathic, they can link into chronic or acute so injuries causing nociceptive pain uh, include, uh, mechanical injuries, such as a traumatic injury to do a limb, a thermal injury or or thermal pain. Um can come as a result of burns, and then chemical injuries can come as a result of poison or or or workplace injuries that might occur when one is working with hazardous chemicals. Uh uh. So treatment depends. Um, treatment of pain can be, uh, invasive or noninvasive. And one such non invasive method of pain treatment would be pharmacologic, which is what we're going to look at here because we're looking at pharmacology of pain management and some of the medications that are available for pharmacologic treatment. So, as mentioned, pharmacologic treatment is a noninvasive method of pain treatment. Uh, the most common administration is, uh, systemic. Uh, via that way, treatment is administered orally or via an injection. Uh, oil administration maximizes patient autonomy, which is quite important because we want the patient to have control of of of of their condition often. Sorry to interrupt again, but I think you've been muted. Hello? Hello? Oh, yes. Now it's working again. Ah, sorry. So you can hear me. Yeah, I can hear. You know, I think you're muted or something for a few minutes. Okay. So I'll just come back to treatment of pain. So essentially higher on the music Children for pain management. So recognition of the source of pain as a vital step in achieving correct pain management, uh, patient centred approach So, as with any treatment, we need to take the patient's specifically, uh, into account because every patient is different in some way. So we want to account for patient's specific goals. So what does the patient wish to get from treatment? Very common. Um, question, uh, that that you do here, um, in in hospitals, when? When doctors are speaking to subjects and patient's. But perhaps more importantly, when we're looking at the patient centred approach, we need to account for co morbidities and contraindications. Okay, so many, um, chronic diseases can cause physical or emotional pain, but they would also be linked into a co morbidity or contra indication. And and essentially, these can impact treatment choice. So when we're looking at the variety of pharmacologic methods available for treatment of patient's, we really do need to look at co morbidities and contraindications is quite significant because these can impact treatment choice. Um, for example, Tramadol, which is an opiate, is cautioned for used an elderly patient's or those with impaired respiratory function. One of the reasons it's causing for you Chanel really is, is to do with something that will touch on later is an increased risk of falls. Um, and also those are impaired respiratory function. As we know, strong opiates and all opiates can cause respiratory depression. So we certainly need to take that into account. Uh, when we're looking to prescribe tramadol and other opiates, Uh, ibuprofen, a non steroidal anti inflammatory drug, is caution for use in patient's with the history of gastrointestinal disorders such as also rate of colitis. Uh, and there is a reason for that is there's an increased risk of serious gastrointestinal adverse events such as bleeding adulteration in the GI tract. So for a patient that would present, um, with a history of GI disorders, um, we would certainly look to consider the use of another pharmacologic methods for pain management. Uh, rather than, um, increase the risk of serious GI adverse events. And then we need to account for current pharmacologic therapy. And individual patient is currently on, um So, for example, if you have a patient that present for the atrial Febru a shin who is concurrently using a apixaban, we would be concerned, and we would need to consider the use of non steroidal anti inflammatory drugs, specifically ibuprofen, because the use of ibuprofen with Apixaban has a severe interaction, and that is the concurred Use of apixaban with ibuprofen should be avoided due to increased bleeding risk. So essentially the things we want to look at when we're choosing the analgesics. Recognition of the social pain and then a patient centred approach. Looking at patient's specific goals or outcomes, UH, accounting for co morbidities or contraindications uh, for disease drug, um, contraindications or or otherwise. And then we need to account for the current therapy that a patient is on. Okay, so what is the name of pain management and treatment, essentially for main things for main goals, it's a pain management and treatment. And those aims are to reduce the impact of pain on or in an individual, to improve the patient quality of life, to improve patient function and to improve mental state of patient's suffering with pain or chronic pain. Uh, so as we mentioned earlier about the World Health Organization, the World Health Organization analgesic ladder, uh, was a strategy proposed by the World Health Organization in 1986 to provide adequate pain relief for consultations. It was developed following recommendations of international groups of experts, and it has undergone several modifications over the years, which, like anything healthcare doesn't stand still, new drugs coming to market and also new studies are undertaken throughout the lifespan of from 1986. So, of course there would be modifications to that energetic bladder. It's currently applied for managing cancer pain, but also occluding chronic noncancer painful conditions due to a broader spectrum of diseases. And they include degenerative disorders, musculoskeletal diseases, neuropathic pain disorders and other types of chronic pain. So I'm sure many of you are very aware of this already, but I think you know the significance of the WHO analgesic bladder is that it really should act as a as a prompt for when we are prescribing pain treatment. So if if a patient presents with mild pain, uh, the first step would be to prescribe a non opioid, with or without adjuvant analgesic. So essentially you could look at prescribing something like acetaminophen or paracetamol, or a non steroidal anti inflammatory, such as ibuprofen or naproxen. And of course, if one or either of those didn't help, you could add another argument into the treatment pathway for that patient. If a patient presents with mild to moderate pain. Step two, we would use an opioid for mild to moderate pain, plus a non opioid with it without adjuvant annual music's and then moderate to severe pain would be Step three. We would use an opioid for moderate to severe pain, plus a non opioid, with or without at and a drive internal music. Of course, if pain persists, we would move one step up. So if a patient is prescribed a non opioid and there's a little relief, we would step up to step to, uh, and so on. Similarly, if a patient presents with signs of toxicity or severe side effects, we would reduce the dose of the current drug in that step. Or we would move down one step. So I thought I would put this slide up because it's just relevant, relatively interesting, certainly from a pharmacy standpoint or pharmacologic standpoint. And it's that over the years, the World Health Organization pain ladder has been criticized with varying degrees of fairness, and the scientist critique of the pain ladder is that it was created in 1986 and has not been modified since that time, despite intervening breakthroughs in our understanding of pain, pain control and the introduction of new methods to treat pain. So, for example, opioid annual music's have expanded to include new agents, fast acting and controlled release formulations and fix those combination products. Furthermore, there have been new approaches to pain control, such as neuromodulation. Nerve blocks into chemical drug administration and non pharmaceutical protocols have also been developed. Furthermore, we have a better understanding of the multiple mechanisms underlying the most severe type of pain that we see to treat, which is cancer pain and also the phenomenon known as breakthrough pain. So it is something to consider. It's a very useful tool, um, the World Health Organization analgesic ladder. But, uh, you know, since 1986 has mentioned there's been a number of changes for the betterment of pain management. Uh, so no, not call it analgesia. So So what is it for? For this, I thought I would look at and discuss, uh, paracetamol or acetaminophen, which is very commonly used drug most over the counter, and it's in everybody's drug coverage around the world. So it's something that that we see a lot of, uh, it's indicated for use in mild to moderate pain and particularly shooted for musculoskeletal pain. So how how does it work? Well, we we do know that paracetamol exerts an analgesic and antipyretic effects. Okay, so we do know that it brings about pain relief and that it is also used very commonly for fever, uh, Children, Um, because of that antipyretic effect. So it's an analgesic effect that's mediated through the central nervous system. Although the mechanism of Axion is not fully understood, Um, which is quite an interesting point that paracetamol has mentioned It's a very commonly used drug across the world. Most people will have it in the drug cabinet at home or the medicines cabinet. Um, it's it's taken over the counter. It's purchased in many places every day across the world. Yet we still do not fully understand the mechanism, which which I just find extremely interesting. Um, but as mentioned, it's mediated. Its effect is mediated through the central nervous system, So cyclo oxygen is enzymes. Cox one and Cox two are inducible enzymes, and they released prostaglandins, and these first blandings specifically mediate pain, inflammation and fever. So that's an interesting point, as mentioned, that we know that it's very useful as a pain medication. We know it's particularly suited for musculoskeletal pain. And then that last point there, um, uh, the fact that that the fever is mentioned, Um, and that's evidently why we use it for both analgesia and the antipyretic effect. So with the Cox one and Cox two inducible enzymes, it's widely accepted. The paracetamol inhibits Cox one and inhibits Cox two through metabolism of the paradox. Ia's function of these ice, so enzymes. So whilst it's widely accepted that that fully understood so paracetamol is commonly given us an oral preparation very often, Um, uh, it does come another preparations, but oral preparation is the most common. Um, for adult dosing, Um, it's usually 1 g four times a day, with a maximum of 4 g daily, so that would be, uh, in the UK They come in 500 mg tablets, so that would be two tablets four times a day, 4 to 6 hours apart. Um, it's it's a great medication in that it's safe for use in neon. It's and Children, Uh, and as mentioned, it's often given for pyrexia with discomfort. So we do see it and and younger, younger people and Children and neo needs for pyrexia with discomfort. However, cautions for use uh, include patient's with increased risk of hypoto toxicity. So dose adjustment it needed, uh, for patient's with the body, we have less than 50 kg or those with risk factors of hepatic toxicity. Uh, the reason for this is that there is an increased risk of toxicity at normal therapeutic doses in these subjects. Okay, so in the National Health Service or the NHS settings in the UK, um, if the patient has poor liver function, if a patient has increased risk of a paddle toxicity or if a patient is below 50 kg, the dose is reduced to 500 mg four times a day to offset the risk of increased toxicity at normal therapeutic doses in these subjects. So just something to be mindful of, um, and then the last point on uh, Sudamina fan is that uh, partially mostly women often is that it is considered safe in pregnancy, which is which is great and at different times during the course of being pregnant. So it's considered safe in pregnancy. It's safe for use in neo needs. It's safe for use in Children. That's great, but we do need to think about cautions for use and nose with reduced, uh, paddle toxicity and also the over the body weight of less than 50 kg. Right? Uh, so another non narcotic analgesic, um, that we'll look at is pregabalin. Okay, so grappling is a medication that is structurally similar to gabapentin. Okay, so pregabalin as a medication reduces and modulates the synaptic release of several neuro transmitters and several studies indicate that the pharmacology of pregabalin requires binding to Alpha two Delta Subunit, uh, pro grabbing is an antagonist of vote educated calcium channels, and it specifically binds the Alpha two delta subunits to produce anti epileptic and analgesic actions. And Alpha two, Delta Liggins have analgesic, antico, anticonvulsant and fancy a lytic activity. So we are seeing it more and more used for patient's with neuropathic pain. Um, often neuropathic pain isn't well controlled with the use of of other animals music's and essentially you see the use of pregabalin and, of course, gabapentin used in patients with, uh, neuropathic pain. It's it's otherwise uncontrolled. Okay, So as you can see, it's indicated for use in peripheral and central neuropathic pain and the maximum daily dose for pregabalin is 600 mg, and that's in 2 to 3 divided doses. Now it is worth noting that in the UK, uh, gavlin has recently been reclassified as a schedule three controlled substance. Uh, and that's due to abuse potential. So if you have a patient that you may be concerned about abuse or they may be, um, the unshared of their pain uh, you know, as pain is subjective. Oftentimes, um, with schedule three or or other controlled substances in the UK there are there are, uh, legal implications in terms of what you can prescribe. Okay, so for a Schedule three controlled substance in the UK, it's 28 days. Um, with respect to dose adjustment for pregabalin, uh, we should consider those adjustment and compromise respiratory function in neurological disease, renal impairment, patient's over the age of 65 and those patients that are taking other central nervous system depressants, including opiates, and with respect to pregnancy, we need to avoid the use of pregabalin and pregnancy. Last, the benefit of treatment outweighs the risk. Uh, another very key point is that you should not abruptly withdrawal treatment, so we want to avoid abrupt withdrawal of treatment, uh, in negotiations that have been using the drug, and you should taper that off over the course of a period of time greater than one week. And also, it's like a few other of the, uh, analgetic medications available. It's cautioned and elderly due to risk of falls. So that's something that we do need to consider. Um, when prescribing pregabalin is the huge of the patient other medications, they may be on an increased risk of falls. Uh huh. Yeah. Mhm. So looking at narcotic, you know, G and I so very commonly across the the world, we see the use of opioids use for analogies. Yeah, And these opioid drugs include coding tramadol, boot, panwarfin, oxycodone, fentanyl and, of course, morphine. The very commonly used drug. And, uh, I see you. See. See you, um, would be, um, injectable, fentanyl and morphine. Uh, where I was at the weaker end of the opioid scale. We tend to see, uh, codeine and tramadol orally, Boop and morphine. We commonly see that used as a patch okay, in the in the UK and then oxycodone. Uh, similarly, um, that could be used in a variety of different, uh, mode of administration. So the opioid drugs as a whole essentially produce analgesia by actions at at several levels of the nervous system. Uh, in particular, opiates cause inhibition of neurotransmitter release from the primary afferent terminals in the spinal cords and activation of descending inhibitory controls in the mid brain. So opioids in have a neural transmitter release a several levels. Um, as we mentioned and, um, one of those is to inhabit calcium entry, and this dampens transmission transactions, processing and modulation of pain signals. Um, opioids inhibit neuro. Transmit a release by enhancing outward movement of potassium ions. And this is the most likely MEChA mechanism for post synaptic hyper polarization on the inhibition of neurons induced by opioids to be too nervous. System and opioids inhibit neurotransmitter release by inhibiting a dental eight cyclers a. C uh, the enzyme which converts adenosine. Try philosophy at 80 p to cyclic adenosine monophosphate at C A. M p. All three types of opioid receptors couple to a dentist at cyclist, so inhibition of a dental at cyclers may result in inhibition of neurotransmitter release. So a couple of things to think about meth, narcotic analgesia or opiates? Um, is tolerance under, uh, dependence? Okay, so tolerance levels can go up when a patient is prescribed. Uh, long period. Uh, opiate Vogue's, um uh, and also dependent. So it's things we need to think about. Um, tolerance can be induced by chronic high are chronic exposure to morphine, morphine and other opioids. Um, and then tolerance means that higher doses of opioids are required to produce a therapeutic effect. So it's something that needs to be considered, um, in the UK narcotic analgesic SAR mainly controlled drugs due to abuse potential. Um, and as I mentioned with respect to, um, controlled drugs in the UK uh, and a previous slide, there are limits on the prescribing quantities that we can actually use or prescribe to one subject or one patient at any one time. Um, with narcotics. We also need to have caution and elderly or or patient's over the age of 65 due to increase risk of cognitive impairment and falls when exposed to narcotics or other centrally acting drugs. And one of the reasons for that is that the narcotic analgesics increased the anti cholinergic burden score. An anticholinergic anticholinergic burden is a strong predictor of cognitive and physical impairment. So it is something that I wanted to touch on the anti cholinergic burden score, which is something we need to consider, Uh, particularly in early early patient's when we're prescribing pain management. Um, which is why I put the next slide in, which is the anti cholinergic burden in pain management. Okay, so joy is contributing the anticholinergic burden and risk of fall or fall related injury among older adults with mild cognitive impairment, dementia and multi or multiple chronic conditions. Okay, so this is not an exhaustive list, but as you can see here, we have some drugs for the 90 colonic burden score of not some drugs and anti colonic burden Score of one with two and with three. Okay, so I've highlighted tramadol and code in here because they have an anti cholinergic burn score of one. And there there was, uh, an interesting, uh, study that was done looking at the anticholinergic burden score and, uh, and and the different drugs that are used in elderly Um, and that's something that that they found that the same daily anticholinergic burden score was associated with a different degree of risk, depending on the anticholinergic burden. Readings of the individual drugs the comprised to score. Okay. So combinations of Level two and Level three drugs, which is these two columns, had the greatest risk of fall or for related injury. Relatively other individuals with the same daily anticholinergic burden score and local potency anti cholinergic drugs taken modestly together increase the hazard of a fall or for related injury. So essentially I've been working in care of the elderly or older, patient or patient's that that have cognitive impairment, dementia or multiple chronic conditions. We need to consider that the more we load patient's with the 90 colonizing burden, the greater the risk of side effects to potentially their cognition, but also to their falls. So when we look at this slide, caution and elderly, or over 65 you to increase risk of cognitive impairment and falls when exposed in narcotics or other centrally acting drugs, this is when we would look at the anticholinergic burden score of the different drugs and and add them up. And I've worked with the number of professors and consultants, and very often times One of the things they asked was that the junior doctors or the pharmacists, which would have been me in that case is to look at the anticholinergic burden score to tally it up. And then that would actually be written in the notes and often times, if someone you know had had quite significant cognitive impairment or someone had quite significant risk of falls, we may look to utili pain management and with with the drug that did not contribute to the anti cholinergic burden. So just something to consider, especially in an elderly patient when we're prescribing narcotic analgesics. Mhm. So I wanted to look at, uh, morphine because, as I said, it's a very commonly used drug in intensive care and critical care units across, uh, the world, and it's commonly given in severe acute and chronic pain. Okay, so it's commonly given orally in a modified release preparation for severe acute chronic pain. Um, we do see injection indications and acute pain and hospital settings or end of life care, as mentioned. We we need to have caution and elderly um, for a number of reasons. We need to have caution and respiratory impairment, hypertension and obstructive ball disorders. So with respiratory impairment as we know it causes respiratory depression. More things are quite significantly potent, uh, narcotic. So it can cause respiratory depression. And that's what we need to be mindful of. Hypertension. Summary related to that and then obstructive bowel disorders. Um, so opiate, um, cause constipation, and that's something we need to be mindful of. So if if somebody had obstructive pollen disorders, we need to be mindful of using a drug that can cause quite serious or significantly worsening constipation. Um, also, if a patient is subsequently described a c n s the present, we need to monitor and adjust the dose, um, interactions, Uh, if we're prescribing a modified release preparation, alcohol causes rapid release from a modified release preparation. So we need to avoid alcohol, um, at all times when using or prescribing a modified release preparation. And then I wanted to just briefly, like a breakthrough pain. So it was modified release preparations that that were that were tight. It has been once, twice daily, once 11 tablet or two tablets every 12 hours to control serious pain. It has now transpired that in some instances, twice daily or 12 hourly modified release preparations may not cover the full 12 hour period. Okay, Um, and that's where the brakes repaying phenomenon comes in. So it's common that immediate release preparations of weaker opiates maybe co prescribed in tandem with the twice daily preparations. Whatever there is a risk with co prescribing narcotics, and that's an increased risk of tolerance, dependence and abuse. So it's something that often if we have breakthrough pain, we might want to seek, uh, you know, a senior doctor's advice in the hospital. Or we might want to speak to pain management, um, nurse specialist or other, uh, colleagues, stakeholders that may be able to advise because essentially, we want to reduce the risk of tolerance, dependence, uh, and abuse. And with with opiates, um, you want to avoid abrupt withdrawal after long term treatment, so gradual withdrawal of treatment is needed for narcotics? Uh, so the last sort of energetic medications that we're looking at are the non steroidal anti inflammatory energy sticks or or insets uh, commonly prescribed Ansaids, uh, include ibuprofen, uh, particular Phonak, naproxen and then say it's listed above, have the following mechanism of actions. So these drugs work by inhibiting Cox one and cox two Uh, These are involved in the synthesis of key biological mediators, namely Prostaglandins and Cox one and Cox two enzymes produced prostaglandin hate Cynthia's, which converts are rec a Danek acid, the prostaglandins. So by inhibiting Cox one and Cox two, that happens the production of prostaglandins. And, as we mentioned before, prostaglandin mediate the process of information, pain and fever. And as a result, the use of an said there was a direct link to reduction of information on pain. So with respect to the nonsteroidal anti inflammatory, uh, logistics, the most commonly used drug that that I know of in in this group And I'm sure most people know of this Khyber proofing and I've Griffin has a number of common indications, and that is pain and inflammation and rheumatic disease and other musculoskeletal disorders, uh, mild to moderate pain, including dysmenorrhea and pain and inflammation of soft tissue injuries. With respect to, uh, preparations administrations, oil preparation is the most common. Uh, the usual dose is 1.2 g in 3 to 4 divided doses. The maximum daily dose is 2.4 g and 3 to 4 divided doses. However, I must stress, um, and my over 10 years as a pharmacist. Um, it's only a handful of times that I have seen 2.4 g prescribed as a maximum daily dose. It's much, much, much more common that we see the maximum daily dose as 1.2 g and 3 to 4 divided doses. And, you know, ultimately, the lowest effective dose should be used for the shortest possible duration. So it's just something to consider that very rarely would we actually prescribe above 1.2 rams and 3 to 4 divided doses. Very, very, very rarely. And so I've mentioned that we're talking about oral preparations and, uh, ultimately that systemic use for indication is relating to pain or pyrexia. And just to reiterate the point, the lowest effect of those should be used for the shortest possible duration. Some cautions for use of, uh, ibuprofen, uh, cardiac impairment and NSAID me and for renal function. That's such a direct link to cardiac and permit history of gastrointestinal disorders such as all spirit of colitis, uh, chrome disease and uncontrolled hypertension. Uh, with respect to pregnancy, we want to avoid the use of ibuprofen unless the potential benefit white ways. The risk and then interactions again. We need to consider interaction to the older analgesic. Some other drugs that we would prescribe an interaction with other medications that that that I felt were important to highlight include apixaban because there is an increased bleeding risk if using apixaban uh, ibuprofen, uh, together, uh, clopidogrel again, An increased bleeding risk infusing ibuprofen and clopidogrel together, uh, and then ciprofloxacin. And the reason why there was an interaction there is that I person potentially increases the risk of seizures when given with ciprofloxacin. So these are some of the reference sources that I've used, um, with respect to developing this, the lectures today which can be provided it needs to be. And I just want to thank you all for listening. And, of course, if there is any questions you can get to those Yeah, um, there were two questions, um, in the chat. That's how I look like that to know that's mhm. So how do you usually decide to use between gabapentin and for gavlin? Um, uh, it's an interesting question. Gabapentin is, um, less potent is my understanding so essentially I mean, there's no established guidance, For example, on converting between gabapentin and pregabalin. Um, gabapentin. You can use a lower dose essentially, and what I mean by that is that they there's a greater number of incremental increases in gabapentin prescribing versus for goblin prescribing. So if you think somebody has mild or milder neuropathic pain, um, you could use a lower dose of gabapentin and incrementally build that up a little bit easier than you could with pregabalin. Um, so I think you know, that's why it would be beneficial to to maybe start on on gabapentin versus pregabalin. And but, of course, as well as if there are other contraindications or otherwise, um, you would always want to check those. But I tend to see more pregabalin you used, um, in those with diabetic neuropathy and in elderly patient's with neuropathic pain. I tend to see more gabapentin, and my understanding is it's because there is a as I mentioned, you can increase gabapentin 300 mg or even 100 mg could be the lowest dose, uh, all the way up to 3.6 g, uh, in one day, whereas per goblin has a lower maximum dose and the lower the lowest strength that you can get in per goblin in the UK is 25 mg capsules. So the increments are greater and the higher that the the maximum daily dose is lower. Uh, in terms of grams. And what that means is that, as I say, you have those incremental increases which are easier to obtain. Uh, that's complimenting. And the only question How do you usually decide? Uh, which different types of opioids again? That comes down to, uh, the individual, um, prescribing medic. Um, but also, uh, you could look at using the lower strength. So, for example, coding coding phosphate, um is weaker opiate than than tramadol? Uh, and then a stronger opiate than tramadol would be buprenorphine. So it's just about looking at what are the most potent, um, or or or the most potent opiates and stepping up. Um, but But similarly, if a patient wasn't tolerating anything orally or if a patient was was with no by mouth or a patient was, um you know, uh, suffering from a missus or being sick and they were in the hospital, they could use a low strength patch and pooping morphine has a patch, but quoting and tramadol, don't So? So there's a number of factors to play. Um, when looking at the different type of opioids, I don't think there's any more questions in the chat. But if anyone wants to add anything now, mhm. Um, otherwise, since we have a few minutes left, if you could please do the feedback form, then I post in the chat. Um, there's also the link for the next lecture and 11, um, and the link for the WhatsApp group. Then you WhatsApp Group for all the information about the CRF medical school program, Um, if you go through the chat, So if you complete the feedback form now, um, and let me know that you've completed it, then I can send this difficult through. Um, thank you, everyone. And thank you very much for the lecture. No problem. Thanks everyone for joining. And yeah, all the best with your studies and everything else. Thank you. Thank you. Uh, take care right