- [voiceover] so our friendhere 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 symptomsthat he's experiencing. now you might have noticedthere that i said manage instead of treat, and youmight reasonably be thinking well wouldn't you wantto treat his symptoms, in other words, makethem completely go away and not just manage them?
well that would beideal, but unfortunately we don't currently have any medications that can completelyget rid of the symptoms of parkinson's disease. in other words, we don'tcurrently have a way to stop or reverse thedisease progression, the loss of dopamine neurons in the brain that is causing his movement symptoms. so instead, we have tomanage his symptoms.
we'll have to give him some medications that will minimize howmuch these symptoms crop up and interfere with hisdaily living, right? so the management of parkinson's disease may look quite differentfor two different people and that's because thedisease 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 withhis day-to-day tasks so that we can address them properly and not give him anymedications that he doesn't need because we don't necessarilywant 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 patienthere is really struggling with his bradykinesia, histremor, and his rigidity and he's also finding himself feeling really depressed lately, so we want to manage these symptoms. these are the keysymptoms for our guy here. these are the ones thatare really decreasing
his quality of life, sowhat kind of medications would help with thesemovement problems here? well let's start off bythinking about what's going on inside of our patient that'scausing these problems? he's losing dopamine neurons, right? and when you lose dopamine neurons you end up with reduced levelsof 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 dopaminethat he's lost, right? so that seems like a reasonable idea, but there's one sort of caveat there. dopamine doesn't crossthe blood brain barrier. that barrier that keeps unwanted molecules and substances out of ourcentral nervous system. so if we just give our guyhere straight up dopamine, the blood brain barrier,it won't let it cross
into his brain, so therewon't be any increase in dopamine in his brain,which is where we really need to replace it to reducethese movement symptoms. so we need a way aroundthis little conundrum here. so what we can actually do iswe can give him a medication that is the precursor to dopamine. so in other words, itwill turn into dopamine in the right circumstances. and lucky for us, thisprecursor 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 thatpesky blood brain barrier and get converted into dopamine.
so therefore, it increases dopamine levels in our guy's brain. and just an additionallittle note about that, it turns out that if we just give l-dopa, these enzymes that wehave that hang around outside of the central nervous system, they actually just go aheadand convert our l-dopa into dopamine before it even has a chance to get into the brain, sothat's kind of a problem, right?
that kind of defeats thepurpose of giving l-dopa in the first place. so what we'll do about that, is we'll give him another medication called a peripheraldecarboxylase 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 enzymesfrom turning our l-dopa
into dopamine beforeit 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 withhis 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 fewproblems that can arise about five to 10 years aftersomeone starts taking l-dopa. one thing that can happen issomething called wearing off. and wearing off is when a doseof 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 totake 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 slowdown that degradation of dopamine, that's what we can do. that way it can hang around a bit longer and keep stimulatingour dopamine receptors and that can help get out patient here
through to their next dose of l-dopa without their symptomscoming back to bother them. so we can do this with a fewdifferent types of medications. we can use something called amonoamine oxidase b inhibitor, also known as an maob inhibitor. so maob is an enzyme thathangs around in our brain and it breaks down dopamine,so we don't want that. so we can use an maobinhibitor to stop his breakdown and that allows us to keephigher levels of dopamine
in the brain, good, so that'sone thing that we can do to prevent this wearing off, and another type of medication we can use is called catechol-o-methyltransferaseinhibitor. 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 partmeans that it's an enzyme. this enzyme, what it does, isit transfers a methyl group onto the dopamine and thisinactivates the dopamine. so already we know that we're going
to have to do something about this because we want ourdopamine to stick around for a bit longer. so when we give our patienthere a comt inhibitor, i'll just go ahead andshorten 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 oppositeof what we would expect in someone with parkinson's disease. i mean, parkinson'sdisease it messes around with out basal ganglia pathways, so that we end up with areduction in movement, right?
so why are we gettingtoo much movement here? well we can think of l-dopa as a pendulum, a pendulum that is tryingto 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 interestinglittle problem here. essentially, what we need to think about when we're treating parkison's disease is that well l-dopa is ourmost effective medication, but if we use it for a long time, there's a chance the pendulumwill swing the other way so to speak and dyskineticmovements will result. so what do we do? well sometimes we mightdelay 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 touse 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 likethe ace up our sleeve,
that we want to hang ontountil we want to play it and that way we can maybe delay these long-term sideeffects from happening. so then the questionbecomes, other than dopamine, what else could we give our patient here that would help him withhis movement problems? well we could give him something that acts like dopamine, right? something that stimulateshis dopamine receptors
the same way that dopamine does. so let's do that and theseare 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 himthese dopamine agonists, the neurons with dopaminereceptors are stimulated
just as though dopaminewas there doing the job. so you might be wondering, okay well if these dopamineagonists act like dopamine, then why is l-dopa themost effective medication? shouldn't these agonistsbe just as effective? well while these agonistsdo act like dopamine, they're not dopamine, right? they're not a perfectfit 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, theyjust aren't as effective as the real thing, butthey can be really helpful maybe early on whensymptoms aren't too bad, when the disease hasn'tprogressed too far, or maybe when we're usingthem together with l-dopa, so that maybe l-dopa canbe used a little bit less. so those are the main types of medications
that we would normally use to manage the movement symptomsof parkinson's disease, but we also need to managethe other symptoms, right? like the depression thatour 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 dueto the disease itself or if it's a side effect ofone of his other medications. if it is the disease itself and the symptom needs medication, then we would just try to findthe most suitable medication that we can for managing it. and if instead it's a sideeffect of a medication that he's already on, thenwe would try, if we could, to maybe adjust the dose ofthat medication if possible
so that he experiencesminimal side effects.
