This is what we're gonna focus on in the particular video series.
Dopamine prodrug that replaces missing dopamine and its friend carbidopa.
Remember, levadopa is not dopamine because we can't get dopamine over that blood-brain barrier
to help our brain but it will increase dopamine synthesis in the striatum.
Okay, let's quickly review that.
Remember, the substantia nigra usually supplies the dopamine
but those neurons end up getting damaged in Parkinson's disease
and they can't supply enough dopamine to the striatum.
The striatum is where those neurons are that control movement
and that's why we have the motor problems in Parkinson's disease.
So, you need an active transport system in the brain, will carry the levodopa across the blood-brain barrier.
Remember that those tight pores is not gonna easily cross
but we have an active transport system that will carry levodopa into the brain.
Now once we can get it across that blood-brain barrier,
the dopamine neurogenic nerve terminals in the striatum uptake the levodopa and convert it to dopamine.
Whoa, stop right there. That is super cool.
Look, we solved the problem of getting dopamine into the brain.
We take a prodrug like levadopa, we use an active transport system to transport it across the blood-brain barrier,
and then the nerve terminals in the striatum uptake the levodopa
and convert it to dopamine. That's a party, alright.
That's cool when they figured out how to make that work.
It was a brilliant and life changing discovery for Parkinson's patients. So, you got it?
Levadopa is not dopamine.
It's an active transport system to cross that tight blood-brain barrier.
When it gets into the brain, the striatum takes up the levodopa and converts it to dopamine.
That is amazing.
Okay now, why add carbidopa?
Alright, well once we talk about this, you're gonna understand it's like French fries and ketchup or Ernie and Bert.
It's just -- they just go better together. Levodopa and carbidopa are better together.
See, carbidopa can't cross the blood-brain barrier but this is the super cool thing that it does.
It slows down the breakdown or the official term is decarboxylation of levodopa in the intestines
and the rest of the tissues.
So, carbidopa, does it cross the blood-brain barrier? No, I say.
Carbidopa doesn't cross the blood-brain barrier
but what it does is it slows down the breakdown of levodopa.
By slowing down the breakdown of levodopa in the intestines
and the peripheral tissues, more of it is gonna make it to where we need it to go.
Cool. So, carbidopa. Does it cross the blood-brain barrier? No. What does it do?
It kinda distracts everything going on in the gut and the intestine
and it makes sure that not as much of the levodopa is broken down or decarboxylated in your gut
and the peripheral tissues that's why more levodopa can make it across the blood-brain barrier.
Remember you need that active transport system to do that.
If I get more levodopa into the brain, then I'm gonna have more dopamine than is available in the brain.
Why? Well, levodopa is converted into dopamine, remember?
So if I have more levodopa, then I'm gonna have eventually more dopamine in the brain.
In fact, when I put levodopa and carbidopa together, I can reduce the dosage of levodopa by a lot being 75%.
So when I said they are better together, I wasn't kidding.
They're incredibly better together.
So we always wanna use the smallest affective dose for any type of disease.
Parkinson's is right up there on that list because we know we're gonna have a wearing off effect with these medications.
So we try to use the smallest most effective dose of these medications
so we can extend the amount of time that they're effective for the patient over the long term.
Now, I know we get really excited about levodopa cuz it is super cool but it also has some challenges
because first of all, the effects of levodopa/carbidopa do diminish over time.
It's most effective for the first two years
and then progressively you're gonna see a decline over three to five years
and the patient may kind of end up where they were
when they first starting receiving the medication with their symptoms.
So it is really effective but usually for just the first two years
and then progressively you're gonna see a decline over the next three to five years.
Now, it seems really mean but patients can actually develop dyskinesias from the medication.
So levodopa that we're taking to treat dyskinesias or difficulty with movement can also cause dyskinesias.
So that really, really seems unfair.
Now there's an important point I want you to remember about dietary protein.
So if you have dietary protein, it competes for transport across the blood-brain barrier.
So, here's the deal: protein gets to cross your brain with an active transport as does levodopa.
So if you take in a big meal of like, you know,
let's say grandpa's eating breakfast and he's gonna have ham and bacon and sausage
and eggs and kick back his levodopa/carbidopa, that's not a good idea
because dietary protein that's in those eggs and ham and sausage -
besides that I haven't even talked about what's happening to his heart -
but all that dietary protein that grandpa takes in with his levodopa/carbidopa
is gonna be in competition for active transport because protein
and levodopa/carbidopa need that active transport to get to the brain to be used.
So, you have got to teach your patients and family not to eat high protein meals
with their levodopa/carbidopa
because this will decrease the effectiveness of the medication in treating Parkinson's disease.
Now you already know why but just humor me, I'm gonna say it again.
Because remember, levodopa/carbidopa is not dopamine.
It has to be transported across the blood-brain barrier with an active transport system.
If that active transport system is all full of grandpa's sausage and egg and all those other protein dietary meals,
not as much levodopa/carbidopa is gonna make it over into the brain to be turned into dopamine.
So grandpa's medications are gonna be even less effective.
Okay so, you can help that by making sure patients know don't eat big protein meals.
You can work with a nutritionist or a dietitian and help them spread their protein out over the day
because they do need protein, we just don't want them to reduce the effectiveness of their medication.