- [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.