September Meeting Notes–Dr. Falconer gives us an Introduction to Parkinson’s

Dr. Drew Falconer’s Visit Part 2

Our September speaker was Dr. Drew Falconer, Board Certified Neurologist and Movement Disorder Specialist. He is Co-Director (along with Dr. Rogers) of the Movement Disorders Program at Inova. Dr. Falconer came to tell us about the new inhaler for off periods. To bring us up to speed, he gave us a most informative and educational talk, what I’ll call:

Parkinson’s 101: A Crash Course in Parkinson’s and the Medications to Treat It.

Parkinson’s disease is a complex disorder that affects everything in your body. People too often get overwhelmed in the nebulous world of Parkinson’s disease. “It is just a deficiency in a hormone–dopamine,” Dr. Falconer reassured us. “When dopamine levels drop, vision, walking, balance, skin, bowels (constipation) and other bodily functions are affected. The common source is a chemical deficiency.” Dr. Falconer used diabetes as a corollary. People with diabetes do best when their sugar levels are stabilized throughout the day. In Parkinson’s, the goal is to fix dopamine deficiencies. What makes it hard is that Parkinson’s affects everyone differently, from onset to symptoms to medication response.

Off Periods are when Parkinson’s symptoms return. Off/On Time is a language that has been created to give a name to how your symptoms are doing. On Time occurs when you take your medication, and it kicks in and does what you want it to do, physically and mentally. Off Time occurs when symptoms return. They differ for everyone. Sometimes anxiety and depression can be a sign of Off Time. Some people describe it as “air deflated out of a balloon.” Some people feel withdrawn and have to sit alone; some shuffle when they walk; some experience a harder time thinking or brain fog. Off Time causes motor symptoms, such as shaking/tremor, slowness, stiffness, balance problems, speech difficulties, and difficulty getting out of a chair, as well as non-motor symptoms, including drowsiness/tiredness, confusion, restlessness, pain/aches/muscle cramps, anxiety, and mood changes.

There are Four Major Categories of Parkinson’s Medications used to make us feel better:

Dopamine Agonists have been around since the early 90’s. They stimulate the receptors for dopamine and mimic dopamine (“agonize the receptors”). Ropinerole (Requip), generally taken twice a day, is the oldest and has more side effects than the newer medications. Pramipexole (Mirapex) came out in 2002 and is taken once a day, usually at bedtime. Rotigotine (Neupro patch) bypasses the gut for smooth, predictable dopamine stimulation 24-hours a day. Very early on, some people can get away with just a dopamine agonist. How you sleep, eat, and the demands of your day all affect drug delivery and how you feel.

Carbidopa-Levodopa (C/L) is the second category of Parkinson’s medications. Levodopa is the precursor to produce dopamine. Carbidopa is added to prevent nausea and vomiting (the brand name Sin/emet means ‘without vomiting’), and to keep levodopa as levodopa long enough to get into the brain (where it can convert to dopamine). Dyskinesia is a side effect of levodopa. There are three varieties of C/L:

1. The classic yellow tablet invented in 1968 and available since 1972. Its limitation is the delivery system. Only about 5% of what’s in C/L gets to the brain and it doesn’t last long (3-4 hours), although early in the disease it can last longer. C/L is also affected by food and if you eat protein, that 5% becomes 1%.
2. Early in the 1990’s, they came out with C/L ER (extended release), which Dr. Falconer says is a terrible drug to take during the day. Basically it is a ground up tablet put in a wax matrix that your stomach acid eats away, so gives uneven delivery.
3. Rytary offers a better delivery system as it is time-released. Early into the disease, most people can take every 6-7 hours; later on most people take 4 times-a-day about 5 hours apart.

Entacapone (Comtan) is the third medication category. It works by blocking the substance that breaks down levodopa and makes more of it available to the brain (10-15% availability). It is taken with C/L. Stalevo is a drug that combines entacapone, carbidopa and levodopa, which can add about 30 minutes of peak on time.

Monoamine Oxidase B (MAO-B) Inhibitors are the fourth medication category. They are specific for the channels in your brain where dopamine is and work by going into those channels and blocking what is breaking down dopamine so that the dopamine you are producing lasts longer. Early on, this medication might be all you need. MAO-B inhibitors block the breakdown of natural dopamine that your body produces as well as what you are taking (C/L or dopamine agonist). Medications generally prescribed are Rasagiline (Azilect) and the more recently FDA approved Safinamide (Xadago). Selegiline is an older MAO-B inhibitor that can cause weird side effects. It also doesn’t work as well as Azilect and Xadago.

Amantadine (Osmolex) is an old flu drug, At high doses, it stimulates receptors and can produce weird side effects. At lower doses, it calms dyskinesias (although they don’t know how it works).

Dr. Falconer said there is no blood test to measure dopamine levels and, even if there were, levels fluctuate too much during the day. He drew the chart below to illustrate the therapeutic range for the desired level of dopamine in your blood–that middle range between the two (top and bottom) red lines (“Dopa”). Above that line (up arrow) we are overstimulated (although he did add some people have to be up there to feel better). Too much dopamine can produce dyskinesia, hallucinations, and hypomania. Too little, you will have Parkinson’s symptoms.

The curvy blue line in Dr. Falconer’s illustration shows the up-and-down uneven delivery  of immediate release carbidopa levodopa (C/L). The dotted blue line from the top of the first curve shows how MAO-B inhibitors extend On Time by keeping dopamine blood levels in that middle range longer. However, the longer you have Parkinson’s, the smaller that therapeutic range becomes. The window gets smaller and the duration gets shorter.

Everything that has come out in the past 20 years has been to fix the up-and-down delivery and stabilize dopamine levels. To deal with fluctuations, options are:

1. A dopamine agonist to keep your dopamine from dropping to as low a level.
2. An MAO-B inhibitor: Azilect or Xadago to extend On Time.
3. Rytary, which came out in 2015 and releases C/L at timed intervals: immediately, at 2 hours, and at 4 hours. Dr. Falconer’s second illustration (below) shows why you need more Rytary than C/L. The blue curve indicates the delivery and time of immediate release C/L. Turn it on its side; the red curve indicates the longer and more even delivery of Rytary. It can add 4 to 5 to 6 hours of On Time a day. Approximately 25/100 C/L = 200-300 mg Rytary. 

The new medical way of thinking is to treat Parkinson’s med-wise right away. The theory of Rytary is it imparts less risk of fluctuations and dyskinesia over time. At least three studies have shown, if treated from the beginning, at 10 years you will be doing better than if you had used no medication. If you don’t treat, the body is stressed at low dopamine levels.

Rytary still has to go through the intestine, into the blood, and into the brain. To deal with Off Times, there are now quicker delivery systems. Apokyn, a potent dopamine agonist, has been one option. It works in 10 minutes and lasts about an hour. Its potency can cause hallucinations in people over age 75 to 80, and can cause blood pressure to bottom out.

The newly available Inbrija offers levodopa, the same precursor to making dopamine, in an inhaler. Since it goes from lungs to bloodstream to brain, bypassing the gut, it does not compete with protein so you need a lower dose of levodopa as about 1/3 more gets into the brain. It works in 10 minutes and offers significant relief at 30 minutes, with the best relief at 60 minutes. Dr. Falconer recommends to start to use it before you are totally in the pits, when you first start to feel yourself dipping. It has been approved as an ‘as needed’ medication for standard off periods up to 5 times a day. There are some potential side effects. You are inhaling a powder, so coughing and sputum tinged brown or red can occur, along with the usual levodopa side effects such as day time sleepiness, dyskinesia, hallucinations, and impulse control disorders, among others, all best discussed with your doctor.

You cannot talk about new medications without also talking about insurance. Dr. Falconer said there are over 400 medical insurance plans in Virginia. His office works their best to get patients coverage under their plan and has successfully worked with Medicare too (which has covered Rytary and Inbrija).