Last time, I discussed the effects of dopamine agonists. Today, I will continue to the discussion on medications.- Levodopa still remains the gold standard in the treatment of PD. But, because dopamine is unable cross the blood brain barrier it must be given in a precursor form that does cross barrier when ingested. However, because Levodopa causes nausea when taken orally it is combined with lodosyn – hence the two numbers in the medication compound of Sinemet for which its name arises from –Sin emet (without emesis).
Yet despite this, one of the biggest problems with intake of dopamine compounds whether is medopar or levodopa is frequent nausea. In my experience, women are more susceptible to this side effect compared to men. Fortunately, for the majority of people with PD who experience nausea find it to be transitory lasting 1-2 weeks and then gradually subsiding.
For those of us, who find the nausea to be more persistent there are a number of ways to deal with this problem.
1. increase the lodosyn portion of medication- it comes in 25mg tablets. Most doctors, including myself, typically prescribe an extra 25 mg to be taken with each dose. Other physicians, however, may choose to give a larger dose once daily (100- 300mg).
2. others may select different compounds with varying delivering systems which have more favorable gi symptoms such as Parcopa which happens to be orally disintegrating thus bypassing the Gut.
3. a third option is use of anti emetics such as zofran or domperidone to minimize side effects.
4. finally, one of the easiest way to combat this problem is to take levodopa with food especially protein based which diminishes absorption to a degree; thus having a lower gastric side effect profile or combining levodopa with comtan, tasmar, or opicapone (COMT inhibitor). This last tactic by the way is extremely effective in reducing and preventing dyskenesias as well as wearing on/off phenomena. one of my favorite drugs is Stalevo which is a combination drug of both levodopa and comtan making things easier and cheaper. The down side of stalevo is that it may cause increased migraines, and headaches most of which are due to increased blood pressure.
All dopamine compounds have risk of causing sedation but not as high as with dopamine agonists- but I suspect that the sedation is directly related to increased blood pressure, which in my experience is more common in women than
Rytary is the intermediate relatively new compound of levodopa which has a bead delivery system which because of its slow delivery there is much less gi problems as well as less other side effects. although, it is typically given two tablets at a time – personally I have found that taking one tablet at a time has decreased the risk of dyskenesias. I absolutely love Rytary because it gave me my life back completely..before Rytary I had stopped enjoying music, and reading ..
Of note: I have personally found that this causes much more constipation and also higher likelihood of high blood pressure.
****Autonomic dysfunction in Parkinson’s as well the medications both dopamine agonists and dopa itself can cause hypertensive urgency this can manifest as chest pain, sob (shortness of breath), headache, and vision problems.I myself experienced this with Rytary. However, this does not mean you must stop medication. I simply had my blood pressure medicine increased. Talk with your physician regarding options.
Parcopa as I mentioned before is another option for treatment and in my opinion underutilized. I love using parcopa because it is orally disintegrating can be used even in patients that are not able to swallow, especally in hospital post surgeries or when asked to be NPO (i.e. no drinking, eating before procedures. Also great when someone has lots of nausea. it is also faster acting than oral but lasts as long as regular sinemet.
Inbrijia Inhaler– the newest medication that is levodopa which it bypasses gi symptoms and also is fast acting – faster than Parcopa, however it is shorter acting. It’s great for on/off – used and targeted as a rescue medicine. Although, it works great it is not very easy to use especially when you are off or on the go because it requires several steps to use. Thus,limiting its use plus it is very expensive. If have cough or sob or asthma may not be able to use.
Apomorphine injection is another terrific medication which is severely under utilized. It works amazingly well – fast acting and safe. Available and covered for many years plus no longer has to be initiated only at doctors office. There are services available 24 hour 7 days a week to help with any questions. Plus the syringes and shots are extremely easy to use. Soon this medicine will be available in a thin film strip (from Sunovion) which will make treatment for “on-off” easier and on the go.
All dopa compounds can have side effects of dyskenesia, hallucinations, sleepiness, etc.
all rights reserved by Maria De Leon (aka. Parkinson’s Diva)
Today, I thought it might be a good time to do some quick review of the PD medications available. As a physician and patient I have can safely say I have tried or been on most medications if not all. So, I will give you my unbiased opinion of my experience as patient and doctor of each medicine. This in hopes of helping you make informed decision about your treatment options as well as recognizing any possible side effects related to them.
Here it goes:
Although, Sinemet is by far one of the oldest and still considered gold standard in treatment of PD, I will discuss last.
First, I will tackle dopamine agonists- which were the first to come out on the market as a novel treatment back in the mid 19190’s binding the dopamine receptors at various locations with greater affinity at some spots than others hence for the differences in each.
Mirapex was the first of this class. It is now available in regular and extended form. i believe this is a great drug and works well for all Pd symptoms and can be used long term with little consequences in most people. However, over time it may loose its affinity (>5 years) but can be reintroduce after a short withdrawal period of about 6 months and have initial full effect. The biggest problem I and my patients experienced with this medication is profound sedation. For most this resolves within a week to two. in others such as myself it can be persistent with best practice recommendation is to find an alternative treatment. In my practice, since this was one of the few choices at the time, I often used in combination with provigil or nuvigil to decrease sedation and improve function. Danger is severe sedation impairing driving which was my problem. Mirapex ER compound in my experience is equally sedating plus at least in me and other people I know caused a dry cough ( akin to bronchitis which also made breathing difficult) that lasted up to a couple hours. this appeared to occur about an hour after intake. The other problem most people worry about is increased sexual drive and OCD behaviors. in my experience, the sexual drive wanes a after a couple of weeks usually and is more common in men than women. as far as the punding and gambling and other aberrant behaviors usually occur after long term treatment with monotherapy. I treated over a thousand PD patients and to this day i am not aware of this issue in any of my patients but all my patients took a cocktail of various medications at lower doses.
Requip regular and extended caused same type of sleepiness and often caused mild visual hallucinations even in young people with no signs of cognitive function.
Neupro 24 hour patch because of its delivery system it provides a constant release of dopamine agonist thus much better equipped at controlling and preventing motor fluctuations. This medication is easily titrated like mirapex to desired dose. Skin irritation is a major component especially as you graduate to larger patches (i.e. higher dose). For most people maintaining a good rotation to avoid same spot for 3 -4 days at least greatly improves this contact dermatitis. Sometimes the use of topical benadryl or cortisone after removal of patch helps decrease the sensitivity. However, if a painful rash develops or not reseeding it must be stopped. One of the biggest differences between this and other two is the initial surge of energy -given you a high like when on steroids or adrenaline rush. thus may keep you up for a couple of nights. this effects usually lasts only a few days. i personally welcomed this effect since it allowed me to do many things. effect simply wears off without causing a crash in the system. thus, unlike the other 2 dopamine agonist, this one does not cause daytime sleepiness. Plus because it bypasses the gut does not cause nausea. although nausea is not a huge component of dopamine agonists in general. All agonists, in particular larger doses of neupro cause increased swelling / fluid retention especially in women and hence increase blood pressure- an important factor to remember. I treat with a mild diruetic which helps decrease fluid and prevent my blood pressure from going up. Interestingly, in my experience, I have seen the opposite effect in men, no real fluid retention but also a propensity to drop Blood pressure thus more prone to have orthostatic hypotensive episodes particularly with higher dosage of neupro patch. again, sometime to watch out for especially if thin and on blood pressure medications or other medicines that cause low blood pressure.
This is all for tonight, tomorrow I will continue with mao inhibitors.
if you have any questions regarding above discussion or any other topic you feel i might have left out please feel free to let me know.
all rights reserved by Maria L. De Leon MD (Parkinsons Diva)