Managing Parkinson's disease with medications
- [Voiceover] So our friend here has recently been diagnosed with Parkinson's disease, and we need to figure out what kind of medications we can give him to help manage the symptoms that he's experiencing. Now you might have noticed there that I said manage instead of treat, and you might reasonably be thinking well wouldn't you want to treat his symptoms, in other words, make them completely go away and not just manage them? Well that would be ideal, but unfortunately we don't currently have any medications that can completely get rid of the symptoms of Parkinson's disease. In other words, we don't currently have a way to stop or reverse the disease progression, the loss of dopamine neurons in the brain that is causing his movement symptoms. So instead, we have to manage his symptoms. We'll have to give him some medications that will minimize how much these symptoms crop up and interfere with his daily living, right? So the management of Parkinson's disease may look quite different for two different people and that's because the disease affects everyone a little bit differently. So we want to make sure that we figure out which movement and non-movement symptoms are really affecting our patient here. Really interfering with his day-to-day tasks so that we can address them properly and not give him any medications that he doesn't need because we don't necessarily want to put everyone on every medication right away if the symptoms aren't really causing too many problems, right? Because there can actually be short and long-term side effects that we might want to minimize or delay. So let's say that our patient here is really struggling with his bradykinesia, his tremor, and his rigidity and he's also finding himself feeling really depressed lately, so we want to manage these symptoms. These are the key symptoms for our guy here. These are the ones that are really decreasing his quality of life, so what kind of medications would help with these movement problems here? Well let's start off by thinking about what's going on inside of our patient that's causing these problems? He's losing dopamine neurons, right? And when you lose dopamine neurons you end up with reduced levels of dopamine in the brain. So what can we do? What can we do to fix this? Well, we can try giving him dopamine to replace the dopamine that he's lost, right? So that seems like a reasonable idea, but there's one sort of caveat there. Dopamine doesn't cross the blood brain barrier. That barrier that keeps unwanted molecules and substances out of our central nervous system. So if we just give our guy here straight up dopamine, the blood brain barrier, it won't let it cross into his brain, so there won't be any increase in dopamine in his brain, which is where we really need to replace it to reduce these movement symptoms. So we need a way around this little conundrum here. So what we can actually do is we can give him a medication that is the precursor to dopamine. So in other words, it will turn into dopamine in the right circumstances. And lucky for us, this precursor is called L-DOPA. So here it is, here is L-DOPA. It can cross the blood brain barrier so that's great. We're in business here. So we give our patient here L-DOPA. Oh, and we also know L-DOPA as levodopa, so you might hear that said as well. And L-DOPA can cross that pesky blood brain barrier and get converted into dopamine. So therefore, it increases dopamine levels in our guy's brain. And just an additional little note about that, it turns out that if we just give L-DOPA, these enzymes that we have that hang around outside of the central nervous system, they actually just go ahead and convert our L-DOPA into dopamine before it even has a chance to get into the brain, so that's kind of a problem, right? That kind of defeats the purpose of giving L-DOPA in the first place. So what we'll do about that, is we'll give him another medication called a peripheral decarboxylase inhibitor and we'll do that at the same time as we give L-DOPA and now this drug, the peripheral decarboxylase inhibitor, it will block those enzymes from turning our L-DOPA into dopamine before it gets into the brain. So good, now L-DOPA is getting into his central nervous system and it's turning into dopamine and this is helping with his movement problems. So L-DOPA is generally considered our most effective medication for dealing with the movement problems in someone like our patient here with idiopathic Parkinson's disease, but there are a few problems that can arise about five to 10 years after someone starts taking L-DOPA. One thing that can happen is something called wearing off. And wearing off is when a dose of L-DOPA it stops lasting as long as it used to, so the patient's symptoms become really bothersome again before it's even time to take the next dose of L-DOPA. So what can we do about this wearing off? Well where does that dopamine go? It's degraded, right? It's being broken down by special enzymes that we have in our brain, so we can try to slow down that degradation of dopamine, that's what we can do. That way it can hang around a bit longer and keep stimulating our dopamine receptors and that can help get out patient here through to their next dose of L-DOPA without their symptoms coming back to bother them. So we can do this with a few different types of medications. We can use something called a monoamine oxidase B inhibitor, also known as an MAOB inhibitor. So MAOB is an enzyme that hangs around in our brain and it breaks down dopamine, so we don't want that. So we can use an MAOB inhibitor to stop his breakdown and that allows us to keep higher levels of dopamine in the brain, good, so that's one thing that we can do to prevent this wearing off, and another type of medication we can use is called catechol-O-methyltransferase inhibitor. Man, that's a mouthful. But if we break that down, the name actually makes sense. So catechol here stands for catecholamine and dopamine is a type of molecule in the catecholamine group. So is epinephrine and norepinephrine. You might have heard of those as well. So these are all catecholemines and methyltransferase here means that this is an enzyme. Remember that the ace part means that it's an enzyme. This enzyme, what it does, is it transfers a methyl group onto the dopamine and this inactivates the dopamine. So already we know that we're going to have to do something about this because we want our dopamine to stick around for a bit longer. So when we give our patient here a COMT inhibitor, I'll just go ahead and shorten this to COMT, we stop that breakdown, right? So we have more dopamine floating around to bind to the receptors, the dopamine receptors, and to reduce movement symptoms. So another problem that we can see with prolonged use of L-DOPA is too much involuntary movement. Now that's a little unexpected, right? That's kind of the opposite of what we would expect in someone with Parkinson's disease. I mean, Parkinson's disease it messes around with out basal ganglia pathways, so that we end up with a reduction in movement, right? So why are we getting too much movement here? Well we can think of L-DOPA as a pendulum, a pendulum that is trying to swing our patient from reduced movements to being able to move normally, but over time after being on L-DOPA for several years, the pendulum can kind of over shoot and we end up with too much movement and we call this dyskinesia, so that presents an interesting little problem here. Essentially, what we need to think about when we're treating Parkison's disease is that well L-DOPA is our most effective medication, but if we use it for a long time, there's a chance the pendulum will swing the other way so to speak and dyskinetic movements will result. So what do we do? Well sometimes we might delay starting L-DOPA for as long as we reasonably can. So in other words, we'll try to manage our patient's symptoms without resorting to L-DOPA right away or maybe we'll just try to use a little bit of L-DOPA and use another medication as well, at least until later on in the disease when we really, really need L-DOPA. L-DOPA is kind of like the ace up our sleeve, that we want to hang onto until we want to play it and that way we can maybe delay these long-term side effects from happening. So then the question becomes, other than dopamine, what else could we give our patient here that would help him with his movement problems? Well we could give him something that acts like dopamine, right? Something that stimulates his dopamine receptors the same way that dopamine does. So let's do that and these are called dopamine agonists. They play the role of dopamine. Kind of like how a substitute teacher plays the role of the regular teacher and helps teach the class while the regular teacher is away. So when we give him these dopamine agonists, the neurons with dopamine receptors are stimulated just as though dopamine was there doing the job. So you might be wondering, okay well if these dopamine agonists act like dopamine, then why is L-DOPA the most effective medication? Shouldn't these agonists be just as effective? Well while these agonists do act like dopamine, they're not dopamine, right? They're not a perfect fit for the receptor. Just like how the substitute teacher just isn't as good a fit for the class as the regular teacher is. So these agonists, they just aren't as effective as the real thing, but they can be really helpful maybe early on when symptoms aren't too bad, when the disease hasn't progressed too far, or maybe when we're using them together with L-DOPA, so that maybe L-DOPA can be used a little bit less. So those are the main types of medications that we would normally use to manage the movement symptoms of Parkinson's disease, but we also need to manage the other symptoms, right? Like the depression that our patient is experiencing. So one thing that we might want to do before we try to treat his depression or any other symptom that someone with Parkinson's disease might experience, is that we would want to figure out if the symptom is due to the disease itself or if it's a side effect of one of his other medications. If it is the disease itself and the symptom needs medication, then we would just try to find the most suitable medication that we can for managing it. And if instead it's a side effect of a medication that he's already on, then we would try, if we could, to maybe adjust the dose of that medication if possible so that he experiences minimal side effects.