After reading the article on cytokine role in the inflammatory role in Parkinson's disease I researched other causes of Parkinson's and found that in some cases Parkinson's can be drug-induced. Some anti -psychotic medications can contribute to Parkinson's because they lower the dopaminergic activity. A drug called Levadopa is most commonly used to treat Parkinson's but overtime it becomes counter productive due to feedback inhibition. This results in a disease called Levodopa (LD)-induced dyskinesia (LID) one of the most common motor complications in advanced Parkinson's disease.
Reference
Burkhard PR., Grotzch H, Sztajzel R. Levadopa - induced ocular dyskinesia in Parkinson's disease. Eur J Neurol. 2007 Oct 14(10):1124-8.
Subscribe to:
Post Comments (Atom)
9 comments:
Very interesting to think that therapeutics can also result in neurodegeneration, just like inflammation can be both beneficial and damaging, such as in Alzheimer's disease (AD). For example, the inflammatory response in this disease is beneficial in that reactive microglia phagocytose and degrade the beta-amyloid protein (that is responsible for the damaging plaques in AD) and dead cell debris. This reduces the likelihood of further cell loss via cytotoxic release. However, when an uncontrolled inflammatory response is induced, neuronal loss and activation of microglia to secrete neurotoxins (in response to the beta-amyloid present in some degree in all human brains) override the benefits of the inflammatory process. The neurotoxin release by the microglia then plays a leading role in plaque formation, initiating a cycle of neurodegeneration that deteriorates the brain in AD. Both scary and interesting!
If levadopa appears to bring on worse affects of the later stages of parkinsons disease earlier than why is it prescribed as a medication to help be a treatment? Shouldn't doctors not prescribe this treatment if it appears to not help and just bring on worse stages of parkinsons earlier?
This just goes to show how more long term studies should be performed on a drug before it released to the public and prescribed. A great deal of unnecessary complications could be avoided!
L-dopa is actually considered the "cornerstone" of care for Parkinson's patients in that it can pass the blood-brain barrier and then be converted to dopamine, which the brain can then use to replace lost dopamine from missing brain cells. Dopamine itself cannot cross the blood-brain barrier and therefore treatment with a combination of Levodopa and Carbidopa, which delays conversion of L-dopa to dopamine, is common. Like many drugs, I think, in treatment of chronic conditions, usually dosages need to be increased with time, and therefore early diagnosed patients are often treated with alternatives until the need for L-dopa really presents itself. There are also suggestions given like not eating a high protein meal with your L-dopa ingestion, to maximize effectiveness. L-dopa is certainly not a cure, but does change the lives of many people with Parkinson's. There are always side effects, but I think the alternative here is more often worse. It does not stop the disease's progression, exactly why research continues to be so important for the future.
http://www.ninds.nih.gov/disorders/parkinsons_disease/detail_parkinsons_disease.htm#90753159
implant electrodes in various nuclei are also helpful and more is on the horizon in the treatment with them
I've done some research on drug induced Parkinson's myself. I currently care for a patient who has been diagnosed with the disease. I have never heard of it before and was interested in what it was! From what I have learned, I'm pretty sure you might have the concept of "drug induced" Parkinson's confused. Any MD's out there that can correct me if I am wrong??? Dr. Cohen, I'm looking in your direction!
When you speak of "drug induced Parkinson's", I think you are referring the specific phenomenon that certain anti-psychotic medications prescribed to treat conditions other than Parkinson's and medications used to treat nausea (Reglan and Compazine) can induce Parkinson's-like symptoms in people who do not have the disease. The drugs themselves do not contribute to already existing Parkinson’s. In addition, the specific pathology of drug-induced Parkinson’s differs from the permanent Parkinson's disease associated with the neurotoxin MPTP, which results in loss of nerve cells in the substantia nigra of the brain: the drug-induced disorders cause symptoms that mimic those of permanent Parkinson’s but are not associated with a loss of nerve cells in the substantia nigra like permanent Parkinson's disease. Therefore, the disease is essentially reversible if treatment with the causative drugs is withdrawn.
It is true that L-Dopa can lead to the effects mentioned in your post (LID), but this phenomenon is not what causes "drug induced" Parkinson's. It is simply a complication of L-Dopa therapy that exacerbates existing Parkinson’s. Often, drug induced Parkinson’s is misdiagnosed as “permanent” Parkinson’s, particularly in the elderly who are more commonly prescribed the medications that cause the Parkinson’s-like symptoms. This leads to needless treatment with costly and possibly toxic antiparkinsonian medications for a disease that doesn’t truly exist in these patients.
Refs:
1.)http://www.pdcaregiver.org/WhatIsParkinsons.html
2.) A danger in making the diagnosis of Parkinson's disease. Lancet. 1982 May 29; 1(8283): 1212-3.
3.)http://www.thefreelibrary.com/Drug-induced+Parkinson's,+part+2-a017811959
Marybethm, you don't need me here, you have it exactly right about the difference between drug-induced and "normal" Parkinson's.
I guess there has never been a drug without side effects; it is the fundamental fact of pharmacology. One always has to calculate a risk-benefit ratio. Parkinson's has been so much alleviated by l-dopa that it can be considered a wonder drug; but it is not without its complications. It amazes me that you can just give a drug like this to a patient, without having to somehow deliver it just to the areas that need it, and still get a good response without too many complications.
That is very weird how one drug can help some parts of a certain disease while hinder other parts of your body causing more complications. I wonder if patients would stop taking a certain drug if they know that complications will arise. I guess it depends on the severity of the disease and what they are willing to risk in order to stop their pain.
About MPTP:
It is known to be selectively transported, presumably by dopamine transporters, into dopaminergic neurons, where it is oxidized to MPP+, reversibly binds to complex I in the mitochondrial electron transport chain, and thus inhibits electron flow and ATP production, eventually resulting in death of the dopaminergic neurons, and Parkinsons. MPP+ injections have no effect: the charged molecule is not taken into neurons. The really interesting part is that I can use pesticides that inhibit the ETC in the same way (Rotenone) and not get Parkinson's effects; I can also use pesticides that are structurally very similiar to MPP+ (Paraquat), that also inhibit the ETC, and still no Parkinsons. Cell death? Oh, yes. MPTP is just about the only compound that will result in Parkinsons symptoms. Deadly, sure, but still cool.
Post a Comment