Key opinion leaders discuss adequately treating Parkinson disease symptoms with levodopa.
So one of the things that’s also important to talk about when you’re talking about off is whether or not the patient is adequately managed to begin with there is a fear about using too much levodopa early on which then makes patients ration it and not want to use it effectively so they might not be on one of the nicer things about the newer therapies and the
On-demand therapies that are now available is that they’re able to manage their off symptoms after they’ve been adequately managed on levodopa if it’s not adequate enough and then they can do that without perpetuating the fear that they’re using too much levodopa the fear is unfounded in the sense that that’s not the way levodopa works the sooner you use it
You don’t necessarily get used to it or habituate to it or use up its effectiveness but that’s still something that permeates a lot of patients concern about the medication you know if you never have an on you’re never gonna have an off so you have to be adequately treated that your symptoms have improved you are optimally controlled and then when the disease
Progresses you start having these time periods when during the day your symptoms are not optimally controlled and that’s when would be the off time and off periods patients i have right i think it’s fair to point out that you know when you’re talking about what the patients are talking about in the support groups and they you know there’s a lot of stuff out there
On the internet and it’s not just the patients it’s physicians too there’s a true fear of you know levodopa which you know 50 years later is still the most effective treatment for parkinson’s and i think most of us would agree that most patients are you know remain under treated and and so that’s i think one of the big reasons why people are very confused about
Off so some of the pharmacological underpinnings of levodopa therapy are as follows there’s a threshold effect you have to have enough drug circulating at every point in time to get the dopamine created in the brain if you’re below that level nothing happens and unfortunately a patient can’t sense where their blood level of levodopa is they can’t be confident
That despite having taken the medication right on time that it necessarily got absorbed because we know the stomach and the entire gi tract is taking a hit from chronic parkinson’s disease and so it’s wishful thinking that because the drug was taken at least 30 minutes ago it’s going to work for them so that’s where on-demand therapies can help also drugs that
Are better at constant delivery reaching their threshold for effect is another unmet need of therapeutics and perhaps adjunctive therapies as we talked about them will become critical to get more insurance policy that you’re getting the drug to the brain in a constant manner throughout the day and even throughout the night if needed you know peter you bring up
This good point we’ve often thought about off as wearing off and reflecting changes other brain changes with the disease progression with striatal denervation and loss of buffering capacity and this idea that we can’t keep recycling levodopa has been underpinning of the mechanism of how we thought about off but we’ve learned so much more now about non dopaminergic
Means the role of glutamatergic systems and adenosine systems and also the gut because it may not be intuitive to replace an essential neurotransmitter dopamine by swallowing levodopa into where the parkinson’s may begin in the gut
Transcribed from video
Adequately Treating Parkinson Disease With Levodopa By Neurology Live
