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Overview Anti-seizure meds: Welcome to pharmacology by Lecturio. 00: We're going to cover today an overview of the seizure medications that we use in practice. 00: When we take a look at seizure control, we have to look at it in terms of the principles of therapy. 00: behind each type of medication. 00: We have many points of entry that we can use to control seizures. 00: The first and probably the most obvious of which is the sodium channels. 00: We can block the sodium channels with different medications. 00: Now remember that sodium channel blockade can be a rate dependent phenomenon, or it can prolong your refractory periods. 00: So there's a very nice way of reducing the hyper excitability of the synaptic cleft that we see in seizures. 00: Now, many drugs act on the sodium channel. 00: Drugs like phenytoin, or drugs like carbamazepine, even lamotrigine are sodium channel active agents. 00: Most of the sodium channels are on the postsynaptic membrane, but there may be relevant sodium channels on the presynaptic membrane that is being acted upon by some of these drugs. 01:
The other way that we act on these synaptic cleft is acting on the GABA A activity. 01: Now, that is the chloride channel. 01: It also is quite important in membrane depolarization. 01: Benzodiazepines increase the frequency of opening through which chloride travels through the channel, and barbituates increase the duration through which these agents are traveling through the channel. 01: So here's a picture a beautiful picture of a GABA receptor. 01: And you can see that it's made up of several subunits. 01: there is a Gamma subunit, there's an alpha subunit, and that spans across the membrane so there is an extracellular component and there is an intracellular component to the GABA receptor. 02: GABA itself will attach to certain areas on the receptor on the extracellular surface. 02: So you can see there that we've outlined two areas where GABA can attach. 02: The benzodiazepines attach between two of the units of the GABA receptor. 02: Flumazenil interacts right next to it Flumazenil remember, is an antidote to benzodiazepine overdose. 02: And there's one other drug called zolpidem, which actually interacts in an area very close to the other benzodiazepines, but not quite at the same area. 02:
Gabapentin works on the alpha-delta subunit of the presynaptic calcium channel. 04: Whereas, it's a related drug pregabalin also sold as Lyrica works on the alpha subunit. 04: So there you can see several areas where calcium channels are particularly relevant both on the presynaptic terminal button and on the postsynaptic membrane itself. 04: Finally, we have Potassium channel activation. 04: This can occur on the presynaptic terminal button or on the postsynaptic channel. 04: This causes membrane hyperpolarization, so you get a prolonged refractory period. 04: An example of this kind of medication is Retigabine. 04: Valproic acid may also act on these potassium channels. 04: We can't really be too sure, but we think that this is a particularly useful way for valproic acid to interact with the different membranes. 05: Okay, there you have it. That's an overview. 05: We're going to go over each of these drugs in a little bit more detail. 05: But I hope that maybe this overview will put into perspective all of the drugs that we use and seizure control.
Treatment Strategies – Antiseizure Medications
So, these are the lists of the different anti-seizure medications. 00:
Let's go through treatment strategies for each of the different type of seizure activity. 00: You will also cover this lecture in your neurology course in more detail. 00: Today, we're just going to focus on the pharmacology of these drugs. 00: Let's start off with valproic acid. 00: So, you can see that it's used in multiple different treatment strategies, right from absence seizures or myoclonic seizures to partial and tonic-clonic seizures. 00: Valproic acid has a number of side effects, and they can be quite frequent. 00: And in some studies we've shown up to 35 % of patients experience some kind of side effect from valproate. 00: Nausea, drowsiness and vomiting via the chemoreceptor trigger zone activation can be experienced with patients on valproic acid. 00: It does have a boxed warning, also called black box warning. 00: What a black box warning means is, is that the regulatory agencies have put it and mandated that all people be aware of potential problems of these drugs. 01: The first black box warning is hepatotoxicity. 01: The second black box warning is pancreatitis. 01: And the third black box warning are fetal abnormalities. It is a class D drug. 01:
I mentioned that earlier as being active against calcium channels. 02: It is the first choice for absence seizures. 02: It's a very effective drug for this particular problem. 02: It is not used in other seizure types. 02: It causes minimal sedation and minimal side effects. 03: It can interact with valproic acid, but we still use it with caution in combination because the protective index of this drug is so high. 03: One of the things you have to be aware of when you're talking about this molecule is that it actually can increase phenytoin levels as well. 03: So, there is a potential drug interaction between it and other agents. 03: Let's move on to lamotrigine. So, when you look at this set of slide, you can see that lamotrigine is used extensively in epilepsy. 03: We use it for myoclonic seizures, partial seizures and tonic-clonic seizures. 03: It's also used as an adjunctive agent. 03: Lamotrigine is also called Lamictal in some markets. 03: It's commonly used in partial seizures. 03: It blocks the sodium channel.
And it's unique for a number of reasons. 03: Number 1, it has very few side effects. 03: And that's like gold in epilepsy, right? Remember that a lot of epilectics are kids, so we want to make sure that they stay on their medications. 04: Kids who experience side effects are not going to take their pills. 04: It's very good at treating the depressive phase of bipolar disorder. 04: And it has been used as a mood stabilizer for some patients. 04: It's really the first new drug in about 30 years. 04: Lennox-Gastaut syndrome is also treatable with Lamictal or lamotrigine. 04: This is a syndrome that I encourage you to read up on and you will also cover this in your neurology lectures. 04: Let's move on to phenytoin. 04: Now, I just want to mention something very briefly, just because phenytoin is at the bottom of this list, does not mean that it's not an important drug. 04: It's probably one of the most important drugs in seizure control. 04: Phenytoin is also called Dilantin, it's used in tonic-clonic seizures and prevention of tonic-clonic seizures.
And that's where the gums overgrow the teeth. 06: The reason why I want to mention this to you is because if you have a patient picture on your exam with gingival hyperplasia where the gum seem to be hypertrophic, think about this drug. Remember that it is a category D drug, and remember that can also cause bone marrow suppression. 06: It can also cause a drop in your blood pressure. 06: One of the more feared side effects of this medication is TEN or toxic epidermal necrolysis. 06: One of the interesting things about this drug and it's very common on exams is that at lateral gaze, you will develop nystagmus when you're at a proper therapeutic level. 07: And on vertical gaze, you will develop nystagmus at toxic levels. 07: So, it's really nice quick and dirty trick to do in your office to determine whether or not the patient is on adequate doses of phenytoin or not. 07: Remember that if you abruptly discontinue this medication, you actually may precipitate seizure activity. 07: Let's move on to phenobarbital. 07: Phenobarbital, once again, just because it's on the bottom of the list, doesn't mean it's not important, it also is one of the most important agents that we use to treat seizures. 07: Phenobarbital is a barbiturate. It acts on the GABA receptor. 07: Remember that barbiturate acts at a different point on the receptor than the benzodiazepine.
Phenobarb is used in all types of seizures except for absence seizures. 07: Once again, that's a good exam question. 07: It is less well tolerated, and therefore it's our third line agent even though it's very effective. 07: It's our first line treatment for neonatal seizures. 08: And we sometimes use it for patients who have seizure secondary to ethanol withdrawal. 08: And we do use it sometimes in detoxification programs. 08: Newer benzodiazepines have replaced the use of phenobarbital, and that's mostly because the newer benzodiazepine are less sedating and they work quite well. 08: Now, remember that phenobarb is a powerful cytochrome P450 inducer. 08: So, you want to be aware that this is an agent that can change the serum levels of other drugs. 08: What's interesting is that it also can be used to reduce the toxicity of other drugs. 08: Side effects. The bigger side effect of course is sedation and hypnosis. 08: And that's because it is a sedative hypnotic medication. 08: And please refer to our sedative hypnotic lecture previous to get more information. 09: A special topic that I think we should discuss is status epilepticus. 09:
It may also change the way that the vesicle is being released into the synaptic cleft. 00: Side effects of this medication include sleepiness, which is quite frequent. 00: Rarer cases of psychosis and suicide. 00: Increased risk can occur with this medication. 00: Rare cases of Stevens-Johnson syndrome have been reported, and also rare cases of anaphylaxis can occur with Keppra. 01: All of these things do need to be monitored for. 01: Uses include focal epilepsy, partial complex epilepsy, and generalized epilepsy. 01: That's one of the newest agents. 01: I hope this information was useful. 01: Good luck on your exams. .Neuromuscular Blocking Drugs (NMBs) (Nursing) by Rhonda Lawes, PhD, RN Hi, welcome to our pharmacological video series. In this one, we are going to look at neuromuscular blockers. Now, before those drugs make sense, we want to introduce you to the neuromuscular junction. We'll call that the NMJ because that becomes a mouthful for me to say. So, we're going to talk about neuromuscular drugs. Now, let me just give you a little intro to these drugs. They will completely paralyze a patient, but they are awake at the same time. So, they can't move any skeletal muscle in their body, but they can hear, they can see, they can feel pain. Well, they can't really see because they can't raise an eyelid. So, let's talk about how
these drugs work. So, where do they work? Well, I just told you, didn't I? They work at the neuromuscular junction. Now, you probably already figured this out, but let me break that down. Sometimes, we use so many words so quickly in education that you kind of miss this. So, I want to break down neuro and muscular. That is where the nerves and the muscles communicate. So, the neuromuscular junction is where they meet up, the nerves and the muscles. So, this is where this medication acts. Now, neuromuscular blockers. Well, blocker tells us it's stopping something. Right? So, what are they stopping? Well, they work after the synapse or postsynaptically. That's not some kind of crazy movie in the future. We are talking about after the synapse. They work at the acetylcholine receptors of the motor nerve endplate, and that's what causes the paralysis of skeletal muscles. Now, you have skeletal muscles all over your body including your diaphragm. So, if you don't mind, write yourself a little note including diaphragm because when that becomes paralyzed, the patient can't breathe on their own. So, neuromuscular blocker medications, they work after the synapse or postsynaptically. They block the acetylcholine receptors of the motor nerve endplates. 02: Now, in case you don't have a good frame of reference, don't worry. That is why we are doing this video. We'll help you understand it, and it will make perfect sense. I promise. But the end result, paralysis of skeletal muscles. So, paralyzing the muscles that are used for breathing, so that is the problem. It's usually not our goal to paralyze the respiratory muscles, but the diaphragm is a thin piece of skeletal muscle. So, when we use these drugs, we often use them with anesthesia or we use it with patients who are critically ill, but both groups of these patients need to be on mechanical ventilation or ventilator support because they can't draw in a breath on their own. Now, it doesn't affect the CNS. Remember, we talked about that in the introduction. So, to me, this is like that bizarre feeling where people say, "I was awake for my surgery." Now, those are stories that are usually on TV. But a neuromuscular blocker doesn't affect the CNS because remember it works where the nerves meet the muscles. So, the patient is fully awake and aware of pain. So, that's why general anesthetics are used, or analgesics or sedatives have to be given to the patient when you give a neuromuscular blocker. It's only the appropriate thing to do. Now, they are really helpful in surgery and in areas where we need the patient to be very still as long as you're aware of the risks. They are able to breathe on their own, but they still will be aware unless you give them other medications in addition to the neuromuscular blockers that will help sedate them or deal with pain. So, let's break down how they work. We have got a graphic here for you to help you walk through the process and recognize the players. Let's talk about skeletal muscle paralysis. It sounds kind of weird, doesn't
Remember when when we are going to be treating persons with Alzheimer's disease, the medications treat the symptoms. 01: You are not going to be treating Alzheimer's itself because this is a progressive chronic brain disease. 01: And so we're not treating the brain itself. 01: What we're treating is to help the person with the symptoms that they're trying to live with. 01: Controversial treatments for Alzheimer Disease include Aducanumab (Aduhelm) and Vitamin E. Aducanumab is a monoclonal antibody directed against amyloid beta and has received FDA approval for use in mild Alzheimer cases. 01: Alzheimer cases. 01: It's particularly adept at reducing amyloid levels in the brain, which is a hallmark of the disease. 01: However, it's important to note that we do not have solid evidence that this reduction translates into clinical benefits for patients. 01: There are also risks associated with Aducanumab, necessitating close monitoring, , including both clinical and imaging assessments. 02: Therefore, its routine use is not currently recommended, and it is graded 2C. 02: Treatment with Aducanumab should be a shared decision between the patient and physician, weighing the potential benefits against the known risks and considering the uncertainties involved. 02:
When it comes to Vitamin E, this is an option we might consider for those with mild to moderate AD. 02: At a dose of 1000 international units twice daily, Vitamin E might slow disease progression, although any benefit is likely modest. It's not universally endorsed by experts, particularly due to concerns about risks in patients with existing cardiovascular conditions. 02: Now, there are some environmental and therapeutic strategies. 02: These strategies are going to be delivered by professionals who have, as their professional training, a well known body of tools. 03: For example, occupational therapists will be working to help the person to keep dexterity. 03: We may have Milieu therapy where they're going into a situation like the hospital or perhaps an extended care facility for persons who have dementia, where the whole environment is set up to increase their functioning and to slow down this progression of loss. 03: We're also thinking about family education because a person who has spent their lifetime being the head of the family is now going to require quite a bit of support. 03: And so family education to learn how to keep the person safe and to make sure that they're doing everything that they can to keep them at their highest functioning level. 03: And it is very exhausting for the family and the caregivers who's taking care of a person who has dementia, who has Alzheimer's disease. 04: And so we want to make sure that we are finding the resources in the community so that the caregiver will also have the support that are needed.
Cholinergic and Adrenergic Neurotransmitter Systems (Nursing)
The patients experience a fatigue on an incredible level. 00: They might have some numbness or some tingling. 00: Well, that should kind of makes sense because they've got problems with the nerves. 00: They may have weakness because they can't control things like they used to be able to. 00: They could be dizzy and have vertigo. 00: They might have issues with their sex acts. 00: They have pain, itching, emotional changes. 00: They be very labile. 00: They might have trouble walking with difficulties. 00: Remember if you have weakness and fatigue and dizziness and vertigo. 00: And then they have a hard time controlling their legs. 00: It might get worse and turn to like spasticity where they really lose control in periods of exacerbation. 00: It can also affect their eyes. 00: They can have problems with their bladder. 00: They may have problems with their bowel. 00: They can have some cognitive changes. 00:
They just may not seem like themselves. 00: It can also include depression. 01: Now, depression may show up as a primary symptom or as a result of what they're dealing with. 01: These are actually a pretty good list of the most common symptoms of MS. 01: But different patients may have different. 01: So, this is where you come in and can really make a difference. 01: When you have a patient that we think might have MS or does have MS, you need to plan extra time in communicating with them. 01: Make sure you appear unrushed. 01: You listen to their symptoms, make sure you document them, and make sure you understand how important it is to them to feel heard and validated. 01: See how vague some of these symptoms are? Sometimes people with MS feel like people are calling them whiners or they're not taking their symptoms seriously. 01: You can quickly establish trust in a therapeutic relationship with a patient struggling with these issues. 01: If you'll slow down, sit down, make eye contact, and ask them questions about what they're experiencing. 02: You'll be amazed at what a difference it makes for that patient. 02: Now, those were the primary symptoms. 02: These are the secondary symptoms. 02:
