Drug Treatments Of Parkinson's
What is an 'antiparkinson drug'?
An anti-Parkinson drug is any medication that's used to alleviate the symptoms of Parkinsons disease; not to cure Parkinsons disease, but to improve the symptoms. There are several medications that fall into that category - being an anti-Parkinsons drug - and they are increasing in number.
What are 'anticholinergics'?
Anticholinergic medications are sort of what the name suggests. These are medications that block the action of a normally occuring brain chemical called Acetylcholine or anticholinergic or antiacetylcholine. It was determined a long time ago as much by accident, as far as I know, as anything else that these medications are helpful in alleviating the symptoms of Parkinson's Disease. Drugs of this category include things like Artane or Cogentin and these are medications that have been around for a very long time and are actually the type of medications that where used primarily prior to more modern treatment of Parkinson's Disease and the medications that we currently use. These medications are still in use; they may be somewhat problematic with side effects compared to more modern medications, and their effects are modest generally speaking they are not generally regarded as being as good as the medications that have arrived since the identification of a dopamine deficiency in Parkinson's Disease.
What are the side effects to anticholoinergics?
Side effects of anticholoinergic medications can be very troubling. Dry mouth is quite common, blurred vision is another relatively common side effect of these medications. It can also contribute to constipation. They do enter the brain which is their intent, and because of their action being an anticholoinergic, or blocking acetylcholine, it can contribute to some cognitive side effects such as confusion, forgetfulness, or even sometimes hallucinations.
What is 'levodopa'?
The arrival of Levodopa remains one of the triumphs of clinical neuroscience, historically. It was identified in 1959 that people with Parkinson's Disease have a deficiency of dopamine in their brain, and this is a significant factor in the development of the symptoms of Parkinson's Disease - the fact that dopamine is diminished. Now, it's not possible to orally supplement dopamine, because if you take it by mouth, it doesn't get into your brain. That was identified a long time ago. It was figured out that if people give the chemical precursor, the molecule of the brain uses to make dopamine, that will work just as well. Levodopa is exactly that. It's the chemical precursor that the brain uses to synthesize dopamine. People take Levodopa in a tablet form - it's absorbed through their gut, through their intestine, gets into the blood and ultimately does pass into the brain. The brain tissue takes it and synthesizes dopamine from this. The brain cells that remain are working in overdrive, some of the brain cells that have been making dopamine are lost. The ones that remain are working harder to keep that dopamine level up. To encourage that, we give people Levodopa so that the brain cells that are working harder, in overdrive, can have that substrate that they need to make more dopamine. it works quite well.
What are the side effects of levodopa?
The side effects of levodopa can include things like nausea, perhaps drowsiness. Levodopa can also have an impact on things like blood pressure, lowering blood pressure which could contribute to some people having a sense of lightheadedness or dizziness. Levodopa could also contribute to psychiatric side effects, including things like delusional thinking or hallucinations. Years ago, it was described as potentially bringing out an increased interest in sexuality or hypersexuality, in some people. Not commonly so, but occasionally.
What are 'DDIs'?
These are dopa decarboxylase inhibitors. In the United States, this is carbidopa. When levodopa is given by itself, there are enzymes in the blood that rapidly degrade it, requiring larger doses of levodopa which would cause side effects, especially nausea and vomiting, and low blood pressure. To try to reduce the amount of levodopa that people need to take to get it efficiently to the brain, another drug was added to levodopa - carbidopa - which inhibits these enzymes that degrade levodopa. To get the levodopa to the brain where we want it to work, these other enzymes that are in the blood chewing it up are inhibited by this second medication.
What are the side effects of DDIs?
Side effects of these DDI medications, Carbidopa in the United States, are usually non-existent. They're not troubling the people in the doses that were used in the treatment of Parkinsons Disease. At higher doses, they could conceivably cause nausea, but that's unlikely.
What are 'Dopamine Receptor Agonists'?
Dopamine Agonists are in a sense synthetic dopamine. These are medications that are not converted by brain tissue into dopamine, but they try to mimic that action of dopamine in the brain. They go directly to the receptors for dopamine that are existent in the brain and try to stimulate them, mimicking the action of dopamine. They are reasonably effective in alleviating Parkinsons Disease but they are not quite identical to true natural dopamine. Their efficacy or their ability to alleviate symptoms we think is somewhat slightly inferior to Levodopo or natural dopamine.
What are the side effects of Dopamine Receptor Agonists?
The side effects of Dopamine Agonists can include low blood pressure. It may include nausea, and also drowsiness, and the drowsiness is a concern. I do caution people about this when they start these types of medications. Agonist medications can also create psychiatric side effects including visual hallucinations or delusional thinking - having ideas that are not reality-based.
What are 'COMT inhibitors'?
We spoke about DOPA decarboxylase as an enzyme system in the blood that degrades levodopa. There's a second set of enzymes that also are existent in the blood stream that degrades levodopa. They're called Catecholomethyl transferase, or COMT for short. So, to try to deliver levodopa to the target organ, namely the brain, both of these enzyme systems, the DOPA decarboxylase and the COMT system are inhibited to efficiently deliver levodopa to the brain. COMT inhibitors are also added to levodopa along with carbidopa to block both of these enzyme systems, so that the levodopa is not degraded in the blood before it can get to the brain. This helps get it there more efficiently and also prolongs the action of levodopa once it's ingested.
What are the side effects of COMT inhibitors?
COMT medications may cause side effects by their mechanism of enhancing the effect of Levodopa. By themselves, they're usually pretty well tolerated. They don't cause much in the way of side effects. COMT inhibitors may cause discoloration of urine, making it an orange or amber color, which is of no significance, but if you don't caution people about it, it could be alarming to them if their urine color has changed. Rarely, not often, they cause diarrhea. In about five or ten percent of people who use these medications, they may get diarrhea. One of the COMT inhibitors, specifically tolcapone, has been associated with some nasty liver effects, in a very small number of people. But it did cause liver injury, and in fact, death, in a few patients after it had been more widely used. For that reason, tolcapone is required to have liver function testing accomplished on a monthly basis for six months, and thereafter according to the judgement of the clinician. Also, baseline liver function tests - these are blood tests - prior to starting the medication. In the United States, it's also requested by the FDA that people sign a form acknowledging they're aware of these potential complications of tolcapone, before initiating the medication.
What are MAO inhibitors?
MAO inhibitors are another form of medication that inhibits an enzyme, mostly in the brain (that's the target for inhibition). These are enzymes that degrade dopamine in the brain, and by inhibiting that set of enzymes, the action of dopamine in the brain can be prolonged. MAO inhibition is used as a model therapy with a modest effect on treating the symptoms of Parkinsons disease, by a medication called rasagiline. There are two of them actually - rasagiline and selegiline - and both these medications can be used as a so-called adjunct or added to levodopa, again to try to prolong the effect of somebody taking levodopa, so that they get a longer action, and less of this fluctuation of symptoms during the course of the day.
What are the side effects of MAO inhibitors?
MAO inhibitors in general are well tolerated with very few side effects. Again, they may augment the effect of dopamine in the brain and by doing so bring out dopamine-related side effects, which could include things like dysconesias, these involuntary, squirming movements that the medication, particularly the lividopa, the use could create. There are cautions about the use of MAO inhibitors in conjunction with other medications. There is a caution regarding both of these medications, both rasagiline and salegiline, about using them with anti-depressant medications at the same time, although in my practice I do do this - I just caution people about it. Rasagiline does carry a caution about certain food interactions, these are things like aged cheeses or certain red wines or aged meats. This is really a theoretical concern, and something that has not been observed in clinical practice. Both of these medications, both salegiline and rasagiline, have contraindications of use with certain pain medications at the same time. There are very specific pain medications which are described in the package inserts of both these medications.
