00:01 So levetiracetam or Keppra had FDA approval first in 1999. Now it's available as an oral tablet, an oral solution, and it can also be given IV. 00:11 It's a second generation antiepileptic drug. 00:15 Now this used to be in pregnancy category C, but the FDA now uses a narrative summary. 00:22 And we'll have more information available to you on that. 00:25 Let's look at the mechanism and properties of levetiracetam. 00:30 So we're going to do an overview. 00:31 Now you already know it binds to SV2A protein on the synaptic vesicles. 00:36 Remember you found that in the picture. 00:39 Now when this happens it reduces the glutamate release during high frequency neuronal firing. Think seizure. 00:46 Now it has a pretty cool unique efficacy profile in preclinical models. 00:51 That's fantastic. But it also has minimal drug interactions. 00:54 And there's no liver metabolism. 00:57 Now it has 90% bioavailability. 01:00 That's impressive also. 01:02 And it has a 6 to 8 hour half-life . 01:05 So what's the clinical use for this fancy medication? Well, it's a broad spectrum anti-seizure medication. 01:12 So it's effective for focal seizures in both adults and children. 01:16 It's effective for primary generalized tonic clonic seizures. 01:20 It's also effective for juvenile myoclonic epilepsy. 01:25 Now the starting dose is usually 500 to 1000mg a day. 01:28 The maximum dose is 3000mg a day, and that's usually divided into twice a day dosing. Now the advantages. 01:36 Again let's review some more of those. 01:37 There's a favorable side effect profile right. 01:40 The newer medications like serum have a better profile in that they have fewer side effects. 01:46 There's also a wide therapeutic window with this medication that keeps your patient safer. We know we've got a bigger target. 01:54 We're trying to get the medication to a point where it is therapeutic and effective. 01:59 It has excellent pharmacokinetics. 02:01 Remember as 90% bioavailability it has minimal drug interactions. Hallelujah. 02:08 And it's available in both oral and IV forms. 02:11 Now there are some key adverse effects. 02:13 One of the most common is that it can make you kind of sleepy, might make them feel weak, might have some difficulty with their walking. They may seem a little clumsier, and they also may experience dizziness. 02:25 Important that you recognize. 02:27 You educate your patient, and if it's a child, the caregivers know that this medication can cause some behavioral and some mood changes. They might become more irritable. 02:36 They may even show signs of depression. 02:38 They might be more anxious. 02:40 These are all things that you need to report and discuss with the healthcare provider. 02:45 Now, one other fun fact about this it's most of the drug is eliminated unchanged in the urine, about 66%. 02:54 So we talked about the mechanism of action. 02:56 Right. It binds to that synaptic vesicle Protein, which is SV2A you're going to see we repeat that a few times throughout this discussion. So it sticks in your mind. 03:07 We know when it binds to that protein that vesicle protein it's going to modulate that neurotransmitter release. 03:13 That means the neurons aren't quite as excited because once the med is bound to the vesicle protein SV2A, it's going to modulate that release and you'll have less excitability and hopefully less seizures. 03:28 Now, this is a pretty unique mechanism compared to traditional AEDs. 03:33 Now let's pause for just a minute and take a little side trip, because I want to talk about the SV2A the synaptic vesicle protein two A. This is what's called a membrane glycoprotein. 03:44 So hold on. We're going to talk a little bit about this going a little depth. 03:48 So you understand specifically what's going on. 03:51 So a membrane glycoprotein is a protein that's embedded within a cell membrane. And it has one or more sugar molecules we call those oligosaccharides attached to it. 04:02 So a membrane glycoprotein has protein right in the name. 04:07 It's a protein embedded within a cell membrane. 04:10 And it has one or more sugar molecules attached to it. 04:14 Now these proteins play a really important role in cell to cell recognition, adhesion and acting as a receptor for the other molecules because of their unique carbohydrates on their surface. 04:27 So that's what a membrane glycoprotein is. 04:33 SV2A is a membrane glycoprotein. 04:36 Okay. So that's why we went and talked about what a membrane glycoprotein is. 04:41 Now specifically to the SV2A is their structure and their location. So we know that it's a membrane glycoprotein. 04:49 But SV2A is found exclusively in synaptic vesicles of the neurons. 04:54 Now these are present throughout the central nervous system. 04:57 And it is essential for normal neurotransmitter release. 05:02 So this SV2A functions kind of like this regulator of neurotransmitter releases at the synapses. 05:08 Why is this good? Well, the more that we can control this, the less seizure activity the client will experience. 05:14 Now, it also acts as a calcium sensor because SV2A detects calcium levels in the neuron, which is what triggers the process of neurotransmitter release. 05:24 So it functions as a key regulator of neurotransmitter release at the synapses. 05:29 So it's going to regulate the synaptic vesicle fusion. 05:32 Okay. What. Remember it regulates synaptic vesicle fusion. That means it just helps control when and how vesicles containing neurotransmitters merge with cell membranes to release their contents. 05:47 That's why the SV2A s are so important. 05:50 Because, again, it's this key regulator of neurotransmitter release at the synapses. So it controls the rate that the vesicles release the neurotransmitters. It's going to determine how quickly and how frequently vesicles release neurotransmitters into the synapse. 06:06 So it maintains the readily releasable pool of vesicles. 06:10 It ensures there's always a supply of vesicles ready to release neurotransmitters when they're needed. Now the SV2A will also ensure proper timing of neurotransmitter release. It coordinates the precise timing of release so it maintains a proper neural signaling within the brain. 06:28 So these functions all work together of an SV2A because this is what enables precise control of neurotransmission. 06:37 So the SV2A functions again as that key regulator of neurotransmitter release at the synapses. 06:43 That's the most important takeaway for you. 06:47 SV2A functions as a key regulator of neurotransmitter releases at the synapses. 06:53 These functions all work together to enable precise control of neurotransmission between the neurons. Now, I'd like to do a step-by-step explanation of the mechanism of action of levetiracetam. 07:05 So step one there's the initial binding. 07:08 Levetiracetam specifically attaches to the you got it, SV2A protein. We know that's a membrane glycoprotein. 07:16 Now this binding is temporary but it's precise. 07:19 It targets only SV2A. The stronger it binds, the better it works as an anticonvulsant. Step two there's the vesicle modification. 07:29 Now when bound, levetiracetam changes SV2A shape. 07:33 This will affect how it interacts with other proteins and how it handles the synaptic vesicles. Step three there's a neurotransmitter release control. 07:43 The modified SV2A reduces how often vesicles release neurotransmitters, especially during intense brain activity. 07:51 So this is what leads to more controlled neural signaling. 07:55 Now step four. This is the seizure prevention part by reducing the excessive neurotransmitter release Levetiracetam stabilizes neural firing patterns and prevents the synchronized firing that causes seizures. 08:08 So think of it like a brake system. 08:11 Levetiracetam acts as a modulator that prevents excessive neural firing without completely stopping normal brain function. 08:19 So compared to traditional AD mechanisms, levetiracetam has a more specific target. It doesn't have any direct effect on normal neurotransmission. 08:29 It's more of an activity dependent effect. 08:32 And this way it lowers the impact on other neurological functions.
The lecture Levetiracetam: Mechanism of Action by Rhonda Lawes, PhD, RN is from the course Antiseizure Medications (APRN).
Which statement best describes the primary mechanism of action of levetiracetam?
What is the maximum recommended daily dose of levetiracetam?
What is the primary function of the SV2A protein in neurons?
The healthcare provider has prescribed levetiracetam to a patient for seizure management. Which behavioral adverse effects should the provider instruct the patient and family to monitor? Select all that apply.
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