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03-04-2018, 03:30 AM | #1 | ||
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Senior Member
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Aim
I think PwP should be able to explain why their drug regimen is what it is. This is a starting point to discussing ways of optimizing our drug regimens. I feel this approach gives us a better chance of having an improved QOL than waiting passively for new drugs to arrive on the market. Context Let's start with a description of my needs. I am 62 years old and 12 years post diagnosis. Unmedicated I can function (so there is still some endogenous dopamine production going on), but I am very slow. The exception is walking, which is near normal. Putting on clothes is very difficult. There is a bad hand tremor on my left side, and a moderate hand tremor on my right side. As the disease progresses, I am picking up more and more non-motor symptoms: constipation is the worst, others include seborrhea, drooling, quite voice, urinary urgency. I am OK at swallowing. I have a small amount of memory loss. My posture has both stoop and lean, leading to bad back ache when I walk more than 5 miles. The medication does a fairly good job at reducing the symptoms of my PD, but never to the extent that I appear "normal". The regimen is less effective at reducing the non-motor symptoms. I assume my drug regimen is for symptomatic relief only. It does not affect the progression of the disease. The cost of the drugs has never been an influencing factor on choosing the regimen. I am in the UK. The NHS provides all the drugs that up to now I have wished to use for free. (In England drugs are free if you are over 60, below 60 you need to buy a "season ticket" for £104/year.) As my disease progresses specialist treatments such as DBS and pumps may be unofficially rationed and not be available when I want them. But, we're not there yet. Regimen Let's go on with an explanation of my drug regimen: - 5 x 75mg Stalevo (nominally taken at 0700, 1000, 1300, 1600, 1900); - 8mg ropinirole (0700); - 1mg rasagiline (0700). In addition to drugs my therapy includes 5 miles of walking per day (though I've only managed about half that through the winter) and gadgets to warn of stoop and lean. Graphing the regimen As posted before, I have written an app that estimates levodopa equivalent plasma, LEP, levels minute by minute. See: Parkinson's Disease Measurement: PwP, surveys, trials, analysis If you input my regimen into the app, you get this output. plasmaLevelsGraph.PNG Analysing the regimen I use "levodopa" as a short hand for levodopa/carbidopa. The model I use for my drug regimen is based on these assumptions: - For each drug you can find its conversion factor to get its levodopa equivalent dose, LED (e.g. 1mg ropinirole is equivalent to about 20mg of levodopa in L/C). - You need also to take into account drugs' phamacokinetic properties (e.g. the half-life of levodopa is about 90 minutes, while controlled release ropinirole has a half-life of about 480 minutes). A drug with a long half-life has a flatter LEP curve over time. - Taking into account the conversion factor, the graph of each of the constituents of the regimen is additive (e.g. 8mg ropinirole and 100mg of levodopa, gives a total levodopa equivalent dose of 260mg). - You can plot your estimated LEP levels minute by minute. - At each time there is a threshold below which there is little benefit from your drugs (you are "off"). - At each time there is a threshold above which there is dyskinesia. - Between these two thresholds you are "on". The strategy is to keep plasma levels in the "on" region, with the aim to keep the LEP levels below the dyskinesia threshold. The area under the curve between the LEP plot and the dyskinesia threshold needs to be minimised. This can be done by using a longlasting, high half-life drug to provide a foundation and a shorter acting drug to tip you over the "on" threshold. The demands placed on dopamine will vary from day to day according to exercise, constipation, stress and diet. Consequently, a regimen with fixed doses at fixed times is likely to be sub-optimal. Instead I dynamically dose. That is, rather than take the doses at a fixed time each day I use my body to tell me when I should take my drugs. This takes into account the lag from taking the dose to feeling its effects (about 1 hour for me now), so as to get the benefit as required. The problem, as I see it, with using extended release levodopa is that the pharmacokinetics are not guaranteed. This is due to variations in the time required to release the pill's contents. This is affected by stomach acidity, gastric emptying etc.. Once you take a dose you are committed to its consequences over, perhaps the next 8 hours, without having a guarantee as to what they are and when they come. Finally, I limit my agonist dosage because of fears of developing compulsive behaviour. What next? I am not claiming that my regimen will work for you. Rather, I am suggesting that analysing your drug regimen is useful. I would be interested to hear from other PwP about why they have the regimen that they do. John
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Born 1955. Diagnosed PD 2005. Meds 2010-Nov 2016: Stalevo(75 mg) x 4, ropinirole xl 16 mg, rasagiline 1 mg Current meds: Stalevo(75 mg) x 5, ropinirole xl 8 mg, rasagiline 1 mg |
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