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Real Life Pharmacology - Pharmacology Education for Health Care Professionals
On this episode of the Real Life Pharmacology podcast, I continue my education on the top 200 drugs. Raloxifene, prednisone, phenytoin, fish oil, and ezetimibe are covered in this podcast episode. Prednisone is a corticosteroid that may cause hyperglycemia, insomnia, GI upset, osteoporosis, HPA suppression, and hypertension as primary adverse effects. Raloxifene is classified as a SERM and can be used for osteoporosis and breast cancer. DVT and hot flashes are significant adverse effect concerns. Fish oil (Lovaza) is used to reduce triglycerides. Elevated triglycerides can increase the risk of pancreatitis. Ezetimibe inhibits the absorption of cholesterol through the gut. It lowers LDL but not to the extent of statins. Phenytoin is a narrow therapeutic index medication (NTI) that is used as an anticonvulsant. Ataxia, confusion, GI upset, and vertical nystagmus are potential signs of toxicity.
InpharmD's EBM podcast focuses on commonly asked DI questions. Every day, our queue gets tons of new questions asked from providers all around the country. Today's podcast focuses on the use of phenytoin to treat tacrolimus toxicity.
Seizures are part of the bread and butter in emergency medicine. Most of the time when these patients arrive in the ED, the seizing has stopped and there isn't much else for us to do. But in the cases where they seizures don't stop or when the patient has multiple seizures, do you know what meds to give and how much? How about second line? Third? Perhaps, even fourth line? In this episode Dr. Rod Fontenette goes over the latest in seizure management when first line benzos don't work, the appropriate dosing of those meds, and what to do in certain patient populations.
Dr. John Neustadt discusses How to Prevent and Reverse Osteoporosis with Dr. Ben Weitz. [If you enjoy this podcast, please give us a rating and review on Apple Podcasts, so more people will find The Rational Wellness Podcast. Also check out the video version on my WeitzChiro YouTube page.] Podcast Highlights 3:08 Epidemic of osteoporosis. Today we have an epidemic of bone loss termed osteopenia and osteoporosis in the US and one reason is because our society is getting older. In fact around the globe, there are now more people over age 65 than younger than five. About 80% of osteoporosis cases are women and the fastest rate of bone loss is as women go through menopause and the ten years after menopause. 4:03 Women more at risk. The main reason why women are more at risk for osteoporosis has to do with their loss of estrogen as they get older. Another risk factor for women is the use of antidepressant medications that artificially raise serotonin levels and there are serotonin receptors in the bones that stimulate increased osteoclastic activity, leading to more bone breakdown. As people get older they also tend to have more inflammation such as autoimmune diseases and they tend to have more insomnia, etc., which are both associated with poor bone health. The average American woman also only gets about 800 mg of calcium per day from their diet, which is below the recommendation. They are also not getting enough of the micronutrients found in fruits and vegetables, which puts them not only at increased risk of osteoporosis but also for cardiovascular disease, dementia, etc. Have less muscle mass also puts post-menopausal women at risk as well and partially due to not getting enough protein in their diet and also due to not doing enough exercise, esp. resistance exercise. Osteoporosis is a chronic disease, so it doesn't just have one cause. 7:54 Medications. There are a number of other common medications that result in a loss of bone mass. Proton pump inhibitors, acid blocking medication often prescribed for reflux and other gastrointestinal complaints, such as Prilosec, damage bone and increase fracture risk. PPIs block calcium, magnesium, and other minerals from being digested and absorbed from our food. Taking a PPI for four years results in a 60% increased risk of a hip fracture. As mentioned, SSRIs, antidepressants, increased bone loss and for every 19 people taking an SSRI, we would expect one to break a bone. There is also a long list of other medications that increase bone loss, including anticonvulsants like Phenytoin, prednisolone and other glucocorticoids, and aromatase inhibitors. 12:28 Detecting and assessing bone health. The standard of care is a bone density test through a type of x-ray called dual x-ray absorptiometry test, a DEXA test, and that detects the quantity of bone and that's used to diagnose bone. A T-score of -2.5 or lower is diagnostic of osteoporosis. While bone density is an important marker to look at, the most important factor is fracture risk, which depends upon a number of factors, only one of which is bone density. Bone density only predicts 44% of women who will break a bone and only 21% of men. There are various factors that can affect the accuracy of the bone density test, including which mean is used, how they are positioned including that the hips are internally rotated 15 degrees or if they are very thin or obese or have arterial calcifications or bad arthritis in their spine of if they are taking strontium. 17:10 Bone Turnover tests. There are tests that measure whether you are losing or gaining bone, including the C-Telopeptide test, which is a breakdown product of collagen in bone. If CTX is high it means you're breaking down collagen and that has been associated with an increase in fracture risk. The most consistent predictor of fractures in gait or mobility. Can you get up from a seated position on a chair or the floor to st...
In this episode, I sit down with Jimmy Pruitt of the PharmSoHard podcast and talk about my favorite; status epilepticus. Support the showFind ER-Rx: - On Instagram: @ERRxPodcast - On the website: errxpodcast.com - On YouTube Disclaimer: The information contained within the ER-Rx podcast episodes, errxpodcast.com, and the @errxpodcast Instagram page is for informational/ educational purposes only, is not meant to replace professional medical judgement, and does not constitute a provider-patient relationship between you and the authors. Information contained herein may be accidentally inaccurate, incomplete, or outdated, and users are to use caution, seek medical advice from a licensed physician, and consult available resources prior to any medical decision making. The contributors of the ER-Rx podcast are not affiliated with, nor do they speak on behalf of, any medical institutions, educational facilities, or other healthcare programs.
Download the cheat: https://bit.ly/50-meds View the lesson: Generic Name phenytoin Trade Name Dilantin Indication tonic clonic seizures, arrhythmias, neuropathic pain Action interferes with ion transport, shortens action potentials and decreases automaticity blocks sustained high frequency repetitive firing of action potentials. Therapeutic Class antiarrhythmics, anticonvulsants Pharmacologic Class hydantoins Nursing Considerations • monitor serum phenytoin levels • therapeutic levels 10-20 mcg/mL • use cautiously in all patients • can cause suicidal thoughts, ataxia, extrapyramidal symptoms, hypotension, tachycardia, arrhythmias, gingival hyperplasia, nausea, rash, drug induced hepatitis, agranulocytosis, Steven's Johnson syndrome • concurrent administration of enteral feedings may decrease absorption • monitor for hypersensitivity • assess seizures • assess hemodynamics
Download the cheat: https://bit.ly/50-meds View the lesson: https://bit.ly/MethylphenidateConcertaNursingConsiderations Generic Name methylphenidate Trade Name Ritalin, Concerta Indication ADHD, narcolepsy Action improves attention span in ADHD by producing CNS stimulation Therapeutic Class central nervous system stimulant Pharmacologic Class none Nursing Considerations • can cause sudden death, hypertension, palpitations, anorexia, hyperactivity, insomnia • may decrease effects of Warfarin and Phenytoin • do not use with MAOIs • monitor cardiovascular system • monitor for behavioral changes • monitor for dependence • do not consume caffeinated beverages “Drug Holiday” used to assess dependence and status
Join me as I talk about the pronunciations of phenytoin and isotretinoin.
Trade – Dilantin Class – AnticonvulsantMOA – Depresses seizures by affecting the movement of sodium and calcium into neural tissue. Indication – Generalized tonic – clonic seizures.Contraindication – sinus bradycardia, sinoatrial block, second and third degree heart block, adam stokes syndrome, known sensitivity to hydantoins. Side effects – N/V, depression of cardiac conduction, sedation, nystagmus, tremors, ataxia, dysarthria, gingival hypertrophy, hirsutism, facial coarsening Dosing:Adult: 15-20mg/kg IV/IO ( not to exceed a push rate of 50mg/min)Pedi: 15-20mg/kg IV/IO ( at a rate of 1-3 mg/kg/min)
Bravo Packing: The dirty business of pet food slaughterhouses by Erin Wing at AnimalOutlook.org. Original post: https://animaloutlook.org/bravo-packing-the-dirty-business-of-pet-food-slaughterhouses/ Related Episodes: 193, 199, 200, 201, 211, 233, 217 Animal Outlook is a national nonprofit 501(c)(3) animal advocacy organization based in Washington, DC and Los Angeles, CA. Their mission: Working today to build a better tomorrow for all animals. We're strategically challenging the status quo of animal agribusiness through undercover investigations, legal advocacy, corporate and food system reform, and empowering everyone to choose vegan. How to support the podcast: Share with others. Recommend the podcast on your social media. Follow/subscribe to the show wherever you listen. Buy some vegan/plant based merch: https://www.plantbasedbriefing.com/shop Follow Plant Based Briefing on social media: Twitter: @PlantBasedBrief YouTube: YouTube.com/PlantBasedBriefing Facebook: Facebook.com/PlantBasedBriefing LinkedIn: Plant Based Briefing Podcast Instagram: @PlantBasedBriefing #vegan #Plantbased #veganpodcast #plantbasedpodcast #plantbasedbriefing #animaloutlook #animalcruelty #horsemeat #dogfood #dogs #zoos #salmonella #petfood #slaughterhouses #Listeriamonocytogenes #Pentobarbital #Phenytoin #undercoverinvestigation #fda #exoticanimals #exoticanimalfood #rawdogfood
Good morning and welcome to your Friday dose of Your Daily Meds.Bonus Review: Can substances pass freely from blood into the CSF?Answer: Nah. There is a barrier to diffusion of most polar molecules. Naturally, this is called the blood-CSF barrier. In this case, the barrier is due to the tight junctions between the epithelial cells (ependyma) of the choroid plexus. The endothelial cells in the capillaries of the choroid plexus have gaps allowing small molecules to pass between and cross the capillary wall.Paeds Question:Which of the following is NOT one of the primary mechanisms by which foetal lung fluid is cleared at the time of birth?Reduction of fluid secretion in the lungsExpulsion of lung fluid as the foetal chest is compressed during labourLymphatic resorption of lung fluid Resorption of lung fluid via capillariesReduced foetal urine output prior to labourHave a think.Scroll for the chat.Case:A 34-year-old woman, currently at 37 weeks’ gestation in her second pregnancy is reviewed in clinic.She reports headache, some visual disturbances and epigastric pain, although there has been no vomiting.On examination, she is hypertensive to 165/115 mmHg, has a tender abdomen worst over the right upper quadrant and is seen to have brisk reflexes.Which of the following is most suitable to administer given this woman’s clinical presentation?PhenytoinSodium valproateMagnesium sulphateCalcium gluconateCephazolinHave a think.Scroll for the chat.He’s Got Fluid:The foetal lung acts as a secretory organ prior to birth, with approximately 100-150 mL/kg body weight of fluid being produced in the lungs of the normal foetus. This foetal lung fluid, along with foetal urine, are the primary contributors to amniotic fluid volume. Lung fluid is cleared during the time of birth by several mechanisms, including:Reduction of fluid secretion in the lungsExpulsion of lung fluid as the foetal chest is compressed during labourResorption of lung fluid via lung interstitium into pulmonary lymphatics and capillariesOf these, resorption is the main mechanism by which lung fluid is cleared and a failure of this mechanism can lead to transient tachypnoea of the newborn. So a reduction of foetal urine output prior to labour is not one of the primary mechanisms by which foetal lung fluid is cleared at the time of birth.Pre-Nasty:Key to answering this question is recognising the pregnant woman with signs of preeclampsia with severe features.This is evidenced by headache and visual changes, symptoms of central nervous system dysfunction, epigastric pain and right upper quadrant tenderness, potential signs of hepatic abnormality of HELLP (Haemolysis, Elevated Liver enzymes, Low Platelets) syndrome of severe preeclampsia, and brisk reflexes, potentially foreshadowing the seizures of eclampsia. Nasty.Given the features of severe disease in this woman, delivery must occur to minimise the risks of maternal and foetal complications, such as cerebral haemorrhage, hepatic rupture, renal failure, pulmonary oedema, seizure, bleeding of thrombocytopaenia, placental abruption or intra-uterine growth restriction. Of the options listed, magnesium sulphate is the most appropriate medication to administer as it has been shown to reduce the risk of eclampsia, and may be administered intravenously.Phenytoin and sodium valproate are other medications used for seizure prophylaxis, but are inferior to magnesium sulphate in this particular obstetric context. Calcium gluconate may be used to treat magnesium toxicity in the context of seizure prophylaxis with magnesium sulphate. Cephazolin is used as intrapartum antibiotic therapy in those mothers positive for commensal group B streptococcus infection and hypersensitive to penicillins to prevent neonatal streptococcus disease.Bonus: What is the difference between the blood-CSF barrier and the blood-brain barrier?Answer in Monday’s dose.Closing:Thank you for taking your Meds and we will see you Monday for your MANE dose. As always, please contact us with any questions, concerns, tips or suggestions. Have a great day!Luke.Remember, you are free to rip these questions and answers and use them for your own flashcards, study and question banks. Just credit us where credit is due. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit yourdailymeds.substack.com
Crystal delves into some brand new research about bovine digital dermatitis and Holy cow! There are too many cattle jokes in this episode. “But it's still a great one.” -CC --- Send in a voice message: https://anchor.fm/more-morgellons/message Support this podcast: https://anchor.fm/more-morgellons/support
Podcast summary of articles from the January 2021 edition of the Journal of Emergency Medicine from the American Academy of Emergency Medicine. Topics include shoulder dislocations, Phenytoin toxicity, Clonidine Toxicity, STEMI in the COVID era, spinal cord injury and board review on angioedema. Guest speaker is Dr. Paul Koscumb.
In Part 2 of this "Mini Grand Rounds" series, we discuss urgent therapy of patients in status epilepticus.Please click HERE to leave a review of the podcast!References:All references for Episode 47 are found on my Read by QxMD collection
This week it's all about the drug that's been in the news: lithium, and phenytoin, which has its own quirks. Listen to the end for some exciting news about next week's episode, and remember to follow us on Instagram, Twitter and LinkedIn, and join us in our Telegram groups, where you have access to exclusive content and the entire Primary HD team!
Real Life Pharmacology - Pharmacology Education for Health Care Professionals
On this episode of the Real Life Pharmacology podcast, I discuss the ins and outs of lamotrigine pharmacology. Lamotrigine has a very slow dose titration schedule due to the risk of drug induced rash. Sedation, GI upset, and CNS changes are the most common adverse effects associated with lamotrigine. Lamotrigine concentrations can be increased by valproic acid, so we tend to use lower starting doses. Phenytoin and carbamazepine can lower concentrations of lamotrigine.
Phenytoin is an anti-seizure medication that is commonly asked about on exams and NCLEX. Oh, and you’ll probably see it in your nursing school clinicals, too! In this podcast episode we’ll talk through this medication using the Straight A Nursing framework DRRUGS. Looking to go beyond the Five Rights of medication administration with my Bulletproof guide? Grab yours here and take your medication administration practice to an even higher level: https://straightanursing.ck.page/fc69f2501b Are you facing a dosage calculations exam that has you shaking in your Danskos? Enroll in Dosage Calculations Bootcamp here: https://straightanursing.mykajabi.com/dosage-bootcamp Read the show notes here: https://www.straightanursingstudent.com/phenytoin/
The Elective Rotation: A Critical Care Hospital Pharmacy Podcast
Show notes at pharmacyjoe.com/episode459. In this episode, I ll discuss why IV phenytoin cannot be diluted lower than 5 mg/mL. The post 459: Why can IV phenytoin not be diluted lower than 5 mg/mL? appeared first on Pharmacy Joe.
Status epilepticus is the most common paediatric neurological emergency in the UK and the second most common reason for unplanned PICU admission in the UK. Dr Colin Gilhooley defines status epilepticus before discussing the EcLiPSE trial: Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial This was a UK wide trial across 30 Emergency Departments (including our own in Nottingham) comparing Phenytoin as the standard 2nd line treatment to Levetiracetam as an alternative with a smaller side effect profile. The result was (spoilers): NO SIGNIFICANT DIFFERENCE. Colin take us through the potential consequences of this, how this might change practice as well as what it was like to be involved in the trial and what deferred consent might mean in the future. You can find the blog for this episode at https://www.takeaurally.com/paediatric-emergency-medicine/2019/7/3/paediatric-status-epilepticus-amp-the-eclipse-trial As ever you can subscribe to Take Aurally through Apple Podcasts and Soundcloud AND we're also on Spotify: open.spotify.com/user/hk2tt55xd97pcz4xoj43nydyy Remember to follow us and NUH DREEAM on Facebook and Twitter We're now also on Instagram where you can find our whole collection of Take Visually infographics: www.instagram.com/takeaurally/
Real Life Pharmacology - Pharmacology Education for Health Care Professionals
Cimetidine blocks histamine 2 receptors which can suppress acid production and reduce symptoms of heartburn. One of the major downsides to cimetidine is that it has a ton of drug interactions. I discuss many of the common ones in this episode. Cimetidine is one of a few drugs that has the potential to cause gynecomastia. I discuss the mechanism of this adverse effect in this episode. Phenytoin concentrations can rise due to the use of cimetidine. I discuss this in the drug interactions section of this episode.
Our regular monthly round up, this month with Ian and Simon chatting through the best of the blog. The power of peer review: https://www.stemlynsblog.org/smacc2019-the-power-of-peer-review/ Virtual reality in PED: https://www.stemlynsblog.org/jc-virtual-reality-for-distraction-from-paediatric-procedural-pain/ Wellbeing for the broken: https://www.stemlynsblog.org/wellbeing-for-the-broken-part-3-the-podcast-st-emlyns/ Traumatic cardiac arrest https://www.stemlynsblog.org/wellbeing-for-the-broken-part-3-the-podcast-st-emlhttps://www.stemlynsblog.org/jc-should-we-use-chest-compressions-in-traumatic-cardiac-arrest-st-emlyns/ Should we cardiovert AF in the ED or wait? https://www.stemlynsblog.org/should-we-rapidly-cardiovert-af-in-the-ed-st-emlyns/ Prolonged field care in the ED https://www.stemlynsblog.org/prolonged-field-care-in-the-ed/ Keppra or Phenytoin for status epilepticus in kids https://www.stemlynsblog.org/jc-enter-sandman-which-agent-as-second-line-in-paediatric-status-epilepticus/
The Elective Rotation: A Critical Care Hospital Pharmacy Podcast
In this episode, I ll discuss an article about when to draw a free phenytoin level. Show notes at pharmacyjoe.com/episode402. The post 402: When do you need to draw a free phenytoin level? appeared first on Pharmacy Joe.
Real Life Pharmacology - Pharmacology Education for Health Care Professionals
Oh boy...Phenytoin is one of those medications that has a ton of clinical pearls. I've seen mistakes with phenytoin that has led to hospitalizations. You need to pay attention for this one! Also be sure to check out our Top 200 drugs and 3 highly testable pearls! A FREE 31 page PDF resource, simply for following the blog!
Author: Erik Verzemnieks, M.D. Educational Pearls: ● Common causes of nystagmus: Congenital disorders, CNS diseases (MS, CVA), Intoxication ● Drugs associated (ETOH, Ketamine, PCP, SSRI, MDMA, Lithium, Phenytoin, Barbiturates) ● If a patient has nystagmus and is intoxicated, consider other drugs and etiologies as potential sources References: Alpert JN. (1978). Downbeat nystagmus due to anticonvulsant toxicity. Annals of Neurology. 4(5):471-3. Rosenberg, ML. (1987) Reversible downbeat nystagmus secondary to excessive alcohol intake. Journal of Clinical Neuroophthalmology. 7(1):23-5. Weiner AL, Vieira L, McKay CA, Bayer MJ. (2000). Ketamine abusers presenting to the emergency department: a case series. Journal of Emergency Medicine. 18(4):447-51.
The post Phenytoin (Dilantin) Nursing Pharmacology Considerations appeared first on NURSING.com.
Multiple Sclerosis Discovery: The Podcast of the MS Discovery Forum
[intro music] Host – Dan Keller Hello, and welcome to Episode Forty of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller. This week’s podcast features an interview with Raj Kapoor who discusses a clinical trial of the epilepsy drug, phenytoin, for MS. But first, a few updates on the latest developments at MSDF. We posted an essay by Dr. Katie Lidster of the National Centre for the Replacement, Refinement, & Reduction of Animals in Research, a U.K.-based scientific organization. In her essay, she points out that Dr. Kapoor’s phenytoin study was made possible by the prior development of a refined mouse model of MS that is more humane than experimental autoimmune encephalomyelitis, which results in paralysis. To find Dr. Lidster’s article, go to msdiscovery.org and click first on News and Future Directions and then on Essays and Opinions. Our Drug-Development Pipeline includes continually updated information on 44 investigational agents for MS. During the month of April, we added 9 new trials, we updated information on 28 trials, and we've added 42 other pieces of information. The drugs with important additions and changes are alemtuzumab; BAF312; BIIB033, which is also called anti-LINGO-1; daclizumab; dalfampridine; dimethyl fumarate; fingolimod; glatiramer acetate; interferon beta-1a; interferon beta-1b; laquinimod; mitoxantrone; natalizumab; phenytoin; rituximab; RPC1063; and teriflunomide. To find information on all 44 compounds, visit msdiscovery.org and click first on Research Resources and then on Drug-Development Pipeline. According to our curated list of the latest scientific articles related to MS, 42 such articles were published last week. We selected two of them as Editors’ Picks. One is a review of the role of microRNA in MS. The other is an analysis of the cost of MS drugs in the U.S. This study reports several startling facts. For example, first-generation MS drugs, which cost $8000 to $11,000 annually when they were first released, now cost $60,000 a year. And disease-modifying therapies cost two to three times more in the in the US than in comparable countries. This study ties in nicely with our interview with Dr. Kapoor. Phenytoin has been off patent for many years and is dirt cheap. Good news for MS patients? Maybe not. Paradoxically, phenytoin’s low cost may mean that it will never be fully developed for use in MS. To see our curated list of recently published papers, go to msdiscovery.org and click on Papers. [transition music] Now to the interview. Dr. Raj Kapoor is a neurologist at the National Hospital for Neurology and Neurosurgery in London, England. Interviewer – Robert Finn Hello, this is Bob Finn. I'm at the American Academy of Neurology meeting Washington, D.C., and I'm talking with Dr. Ray Kapoor, who's presenting a very interesting study on a trial of phenytoin – also called Dilantin – in optic neuritis. Dr. Kapoor, welcome. So my first question is why phenytoin and why optic neuritis? Interviewee – Raj Kapoor So phenytoin we use because it works as a sodium channel blocker, and this is based on years of experience and validation in animal models over the years about how neuroprotection could be achieved in MS. And it turns out that sodium channels are quite important for neurodegeneration in the setting of inflammation. And work in London that we've done, work in Yale has validated animal models that say that if you block sodium channels you can achieve neuroprotection. So why phenytoin? Well that comes down to why optic neuritis? We wanted to test sodium channel blockade in a relapse. And optic neuritis has a lot of advantages because you can study the visual system in so many ways. So why phenytoin? Because we think there's a window of opportunity, and a relapse degeneration occurs pretty rapidly. You need to treat quickly to switch off the mechanisms of neurodegeneration. And phenytoin has the advantage that we can load it very quickly and achieve therapeutic levels. So we have here a model of neuroinflammation and neurodegeneration, which we can study using multiple techniques. And we have a drug that we can load and inhibit those mechanisms quickly. MSDF I find it fascinating that optic neuritis, which is one of the many symptoms of multiple sclerosis, can be used as a model for multiple sclerosis itself. Dr. Kapoor The important thing there is it's part of the model. And the key is that we have – in MS – two processes going on. We have inflammation flaring up and leading to relapses like optic neuritis; and then, there is perhaps an allied or even a second process going on, which is the slow grumbling degeneration that leads to progression of disability. Now, we've studied both, but what we're focusing on in this study is that acute process that leads to relapses, you know, attacks which occur from time to time. I mean they're quite important in themselves because they don't always recover. We know that with every attack – even if there's apparent recovery – there is underlying damage to the nervous system. So to protect the nerves in any case is self-serving; it's a good idea. But what we are hoping is that this may even be a key to preventing progression, and that would really be a worthwhile target. MSDF So you say you chose phenytoin because of its effects as a sodium blocker. What's the connection between sodium and neurodegeneration? Dr. Kapoor What we found many years ago was that in areas of inflammation there can be nerve damage. And the inflammation drives nerve damage through a number of pathways, but one of them is that it actually indirect leads to sodium accumulation inside the nerve fiber, the axons. This has been well worked out in ischemia, as well. So sodium enters axons; it can't leave through the normal sodium pump because they're metabolically inhibited by the inflammation itself. And the sodium exchanges with calcium. So there's a sodium/calcium exchange in the membrane of nerve cells, and if you load them with sodium then sodium has to get out and gets out by driving the influx of calcium, and that's dangerous; that kills axons. So the whole process can be inhibited by inhibiting sodium entry. Now there's another thing that's very important, which is in acute inflammation one of the things that drives it is microglia, activated microglia release chemicals such as nitric oxide, which in themselves drive the whole inflammatory damaging cascade. But it turns out – and this is work from Yale – that actually the microglia themselves have sodium channels, and that their functioning can be inhibited by inhibiting those same channel. So what phenytoin is doing is it's actually inhibiting not only the cascade that damages the axons but is actually inhibiting the cells which are driving the inflammation and causing the damage in the first place. MSDF Now, is there any indication that phenytoin may be working in this way more centrally than the optic nerve? Dr. Kapoor It's very unlikely because the mechanism that we've testes is really something well characterized as inflammation within the optic nerve. And we are measuring the damage and the effects of treatment by actually imaging the retina looking at retrograde degeneration from the optic nerve lesion. So I think it's very unlikely given the timescale – you know, we're treating within a couple of weeks of onset, we're having a readout within six months – that it's doing anything other than what we're asking of it, which is a readout of what's going on in the optic nerve and retina. MSDF If I understand you correctly, even if this is working exactly the way you want it to be, it's not going to be doing anything for people with central damage. Is that correct? Dr. Kapoor Well I think the thing to understand here is it may do in MS where damage is happening everywhere. This is really a proof of concept. We've tried our very best to isolate the damaging process and to work out whether the theory works. So yes, there may be more general implications, and we think there probably are. But it's important to note that really what we're doing here is choosing a very clearly defined model to test the hypothesis. MSDF Now one of the advantages of phenytoin is that it's generic; it's dirt cheap. But is that a liability, as well? Dr. Kapoor Yeah, this is a very important point. So we're talking here about this whole issue of repurposing drugs. And we think that there may be many different drugs on the shelf which may have a role in treating diseases like MS. Now for us that was an advantage. This is an investigator led study, and it was funded by charitable means from the National MS Society and UK MS Society. So that's an advantage because the drug is really cheap. But of course, in terms of development, the commercial reality is that there's very little money in this. And so to take this further, it makes it harder not to have a drug that makes money. MSDF So what's the solution to that problem? Dr. Kapoor We don't know. I mean there are lots of ways that we're taking this forward. I mean you may know that there is a thing called the Progressive MS Alliance, which is an international body of MS societies, which is trying to work its way through questions exactly like this establishing industry relations. And it may be that they're a scope for industry to step in. And governments step in sometimes. I mean in the U.K. we have a trial running at the moment which is using funds from government to do a moderately sized Phase 2/Phase 3 trial of neuroprotection. So I think, actually, this all depends on the results. If the results are good, then we hope that either through industry or through government or, indeed, through charitable means there may be a way through. Just to get back to your question, I think that, you know, repurposing is a problem because clearly the commercial angle is far less prominent. MSDF Is one possible solution to find a drug that's still under patent? Dr. Kapoor Indeed, that would be a remarkable thing to do. But of course, a trial in the beginning would then need commercial collaboration. But certainly that's an angle. MSDF So assuming that your research is confirmed and extended and phenytoin proves to be truly neuroprotective, when in the course of MS is it likely to be useful? Dr. Kapoor So by definition, phenytoin is going to be useful for relapses. The idea that relapses sometimes leave damage and that a drug like phenytoin or phenytoin itself prevents some of that damage speaks for itself. The real question, though, comes down to whether progressive MS is also driven by similar mechanisms. We did a trial of lamotrigine, which is another sodium channel blocking anticonvulsant, and published the results about five years ago now. And that trial was reportedly negative for its primary outcome, which was brain atrophy; could we reduce the rate of loss of brain volume. I suppose what we've done is to go back to that trial and look at positive signals there because after all the question is do sodium channel blockers prevent progressive MS or prevent progression? And in fact, it turns out that there was some remarkable positive signals in that trial. So I have the knowledge that phenytoin should be useful for relapsing MS. But I also have a hunch that it may be useful for progressive MS, as well. MSDF Now there's a flipside to the fact that phenytoin is so easily available, and that is that physicians listening to this podcast or to other news reports may consider prescribing it off-label. How would you counsel somebody considering that? Dr. Kapoor I think it's difficult for somebody to use phenytoin in that way because the way the trial was designed was to treat people in a very narrow window after the onset of a relapse. Now people may say well, you know, the next time I see a patient who has a relapse, you know, can't walk or the vision is affected I will immediately prescribe phenytoin. The difficulty I have there is that this remains a very attractive study but hasn't proved the point. And phenytoin is not without its side effects. You know, I'm always somebody who's evidence led, and so I would counsel against using drugs without even further evidence. This is one Phase 2 study after all. I think the temptation will be there nevertheless. MSDF And if a physician falls to that temptation, what should he or she look for? Dr. Kapoor Well again, this is the point. We have shown a concept works. You know, we have shown that phenytoin, by a number of measures, prevents nerve damage. I think the difficulty – and I need to be very clear about this – is that with acute optic neuritis where vision generally recovers we didn't see better recovery with phenytoin. So again, perhaps another answer is that if I treat somebody with a relapse with phenytoin I'm not really sure that I may be protecting nerves, but am I producing a better outcome? So that may be another reason to say let's wait for a better drug or a better trial. MSDF That's a very good point. So is there anything I haven't asked that I should have asked, or anything you'd like to add? Dr. Kapoor No, I think that really the way I want to convey the result is that it's a robust result. I mean what I'll be presenting is that on a number of measures the drug worked. I think it worked with a modest amount of success. I see this is opening a door. I don't see this as the final answer to a problem. You know, if you think about it, we've been looking for a long time for a neuroprotective drug in MS and a strategy. And I think this is opening a door, which I think needs to be opened a lot wider. MSDF Dr. Kapoor, thank you very much. Dr. Kapoor Thank you. [transition music] MSDF Thank you for listening to Episode Forty of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the non-profit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is vice president of scientific operations. Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances. We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org. [outro music]
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