Female PharmacistParkinson's disease is degenerative disease that affects the central nervous system of the human body. In fact, it is the second most common neurodegenerative disease in the world.  Truly understanding Parkinson's disease, how it affects those afflicted, and how to treat it is far from simple. The disease is most commonly recognized by how it affects motor function. Named after Dr. James Parkinson, the disease was first described in detail in 1817 and was known as the "shaking palsy".


The first symptoms most people experience with Parkinson's disease are related to movement including shaking, tremors and difficulty walking. As the disease progresses, negative changes in mental and cognitive function can occur. These mental changes can range from impaired speech and memory ability to depression and severe dementia. The causes of the disease have not been precisely determined but it does appear that there could be both genetic and environmental influences. Clinically, the most notable physiologic change in the human body is the depletion of dopamine in the brain due to the death of brain cells responsible for releasing the chemical.


Currently, the best treatment available for Parkinson's disease are drugs to help replace this loss in dopamine as well as non-pharmacologic treatment and therapy to help with the various symptoms. This article will cover both medications for treating this loss in dopamine as well as discuss various therapy methods to help improve the symptoms of Parkinson's Disease.


How To Successfully Treat & Improve Symptoms Of Parkinson's Disease


Exercise Is Important!

  • Studies have shown that exercise may protect brain cells from dying and improve symptoms of muscle stiffness allowing a patient to have better control of movement.
  • Stretching and flexibility exercises can help to relieve stiff muscles, improve flexibility, and make everyday tasks easier .
  • There are many examples of exercise but the key is low intensity and long duration. Multiple scientific studies have shown that there is a significant improvement in gait and mobility in patients that performed low intensity exercise vs. high intensity exercise.
  • Examples of low intensity exercise include marching against a wall, stretching your arms around your body, marching while pumping your arms back.
  • In addition to low intensity exercise, it is very important to combine it with resistance training. Current studies have shown resistance training of the lower body significantly improves motor function in patients. Types of resistance training include leg press, leg curl and leg extensions.
  • Any exercise is better than no exercise!
  • Patients with advances disease should always be monitored and assisted to prevent falls.
Gait Training - Practicing New Ways To Walk
  • Gait training is essentially training yourself and practicing new ways to walk, stand and turn.
  • ​Take large steps when walking and focus on proper heel-toe form.
  • ​Keep the legs at least 10 inches apart​​ while turning or walking as this provides greater support and reduces the risk of falls.
  • Avoid shoes with rubber soles as they can stick to the floor and increase the risk of falls.
  • Walk with a steady rhythm. Believe it or not, walking with the assistance of a metronome has been shown in studies to help those with Parkinson's disease walk over 10% faster than those that walked without a metronome.
Getting To Sleep

  • ​Ask your doctor about adjusting your medication and dosing schedule. This can greatly help daytime sleepiness, nightmares and difficulty falling asleep in the evening.
  • ​Stay awake during the day! Engage in activities and try to avoid napping.
  • ​Exercise early in the day vs. later in the day. Not only does this help promote sleepiness in the evening and allow for a deeper sleep but it can also help reduce stress.
  • ​This may seem obvious, but avoid caffeine for at least 6 hours before bedtime.
  • ​Decrease your fluid intake and make one last trip to the bathroom before deciding to lie down.
  • ​Your bed is a place to sleep and you want your mind to make that association. Do not watch TV in bed or read. Do these activities in different rooms.
  • Sometimes white noise can help. White noise includes fans, noisemakers etc.
How To Deal With "Freezing"

  • ​Think about marching! Studies have shown that simply imagining yourself marching can help activate parts of your brain to get your moving!
  • ​Speaking out loud or even thinking in a rhythm "one-two-three-four" can help you unfreeze.
  • ​Look where you want to go. Many people can unfreeze themselves by aiming at a specific spot on the floor. Give your brain a targeted command. Some patients even use laser pointers to aim at a specific point to aid in unfreezing.
  • In your home, try using floor strips. Lay down a set of parallel floor strips in spots where freezing has been troublesome. Place 2 foot long strips of colored tape about 14-18 inches apart on the floor. These visual markers can help immensely!
​Orthostatic Hypotension - Dizziness Upon Standing Or Stretching

  • Try to avoid suddenly standing up from a sitting down or laying down position. Sudden positional changes greatly increase the likelihood of dizziness. Smaller more frequent meals are recommended.
  • ​Avoid extremely large meals that are consumed quickly. Quickly eating a large volume of food can cause low pressure cause dizziness.
  • Avoid large quantities of alcohol in one sitting.
  • ​Be sure to have adequate fluid intake.
  • ​Avoid low sodium diets as this will likely cause low water in the body.
Difficulty Swallowing & Excessive Salivation

  • ​Typically excessive salivation in Parkinson's patients comes from difficulty swallowing, not excessive production of saliva. Trouble swallowing can be very dangerous and increase the risk of death due to aspiration pneumonia.
  • It's very important to know the symptoms of patients that are having difficulty swallowing, also known as dysphagia. These symptoms include choking or coughing upon food intake, food in mucus when coughing up, gargling sounds when eating and throat discomfort. 
  • Not only is difficulty swallowing simply burdensome for patients, it is a frequent cause of death. Ingestion of foreign material into the lungs can lead to pneumonia.
  • ​In terms of pharmaceutical medications for excess salivation, there are a variety of options including atropine or scopalamine eye drops given under the tongue and a medication known as Glycopyrrolate (Robinul). These medications help to dry up secretions and can be very beneficial.
  • ​If salivation gets to be too much, radiation of the salivary glands is an option.
  • ​Meetings with a speech pathologist can help and patients can undergo intensive swallowing therapy . Studies have shown this to be beneficial.
  • ​Always sit up straight when eating and avoid lying down,
  • Eating soft pureed foods can help avoid choking hazards.
Constipation

  • Due to the loss of motor function, constipation is a common problem in those with Parkinson's disease. Constipation can be a negative impact on quality of life and can also decrease the effectiveness of many different medications.
  • ​Increasing fluid intake can help constipation but it's also important to avoid large volumes of water before bedtime.
  • ​A high fiber diet has shown to be beneficial for constipation. Fiber from fruits and vegetables is best but fiber supplements such as psyllium or methylcellulose can help as well. 
  • ​Exercise has shown to beneficial for treatment of constipation.
  • ​An over the counter product known as Miralax (Polyethylene Glycol) has shown positive benefits is drug trial
Tremors - Movement Disorder

  • Tremors and movement disorders are the main symptom associated with Parkinson's disease. Treatment for these are typically based on medications which is described in detail below.
Medications

  • Sinemet (Carbidopa/Levodopa)
  • ​Comtan (Entacapone)
  • ​MAOB-I (Monoamine Oxidase B Inhibitors) including Eldepryl (Selegiline) and Azilect (Rasagaline)
  • ​Symmetrel (Amantadine)
  • ​Exelon (Rivastigmine)
  • Direct Dopamine Agonists including Mirapex (Pramipexole) and Requip (Ropinirole)​

As we can see from this list, there are a lot of different drug therapies for Parkinson's disease. There isn't truly one medication that is recommended as a first line therapy compared to others. Historically however, Sinemet (Carbidopa/Levodopa) has been one of the first choices for therapy in patients over 70 years old and has been used for over 20 years. Due to some problems with involuntary movements and the unpredictable duration of action of the drug, patients under 70 years typically are started on different medications.

Sinemet
SinemetSinemet contains two different drugs, carbidopa and levodopa. Levodopa is a direct precursor to dopamine (what is lacking in Parkinsons patients). Levodopa is converted in the body to dopamine. In order for the medication to be effective, the dopamine must be available in the brain. Excess dopamine that is the the rest of our bodies can create side effects such as nausea ​and vomiting. Carbidopa is added to the drug to help prevent this. Carbidopa is known as a peripheral dopa decarboxylase inhibitor. It prevents much of the levodopa in our bodies from being converted to dopamine before it reaches the brain. Carbidopa and levodopa are almost always given together in a combination such as in Sinemet.


​It is very important to understand exactly how to take Sinemet. Below are some things to always keep in mind:

  • ​Never abruptly stop taking Sinemet as this can cause serious side effects
  • ​Never take Sinemet with a high protein meal as it greatly decreases the absorption of the drug
  • ​It is OK to take it with food, just not a high protein meal
  • ​The normal duration of effect is about 5 hours but it may need to be dosed every 2 hours in those with advanced Parkinson's disease
  • ​The maximal effect can take around 3 weeks with some patients not getting maximal effect for up to 6 months!
  • ​Vitamin B6 in doses over 200 mg can cause problems with Sinemet absorption. Vitamin B6 has been shown to actually help many patients with Parkinson's disease but you want to be sure to space out Sinemet and vitamin B6 as much as possible. 
Below are some possible side effects of Sinemet:

  • ​Nausea and vomiting
  • ​Dyskinesia (fidgeting, jerking, twisting or turning)
  • Vivid dreams
  • ​Orthostatic hypotension (significant and quick drop in blood pressure)
  • ​Salivating
  • Sweating​


Sinemet CR

Sinemet CR

Sinemet CR was created to help patients dose less frequently and also help reduce the likelihood of the "On/Off" symptoms that patients can experience with regular Sinemet. There are a few important things to know about Sinemet CR dosing. It is very important not to increase the dose on Sinemet if you are experiencing a wearing off effect and this can actually create more problems. Instead, you should talk to your doctor about increasing the frequency of dosing. 

Lastly, Sinemet CR takes long to absorb than regular Sinemet. Typically you want to take your dose an hour before you are going to need it. So if your last dose of the medications wears off at 8PM, you should take Sinemet CR at 7PM.


Comtan

ComtanComtan (Entacapone) is known as a COMT inhibitor or a catachol-O-methyltransferase inhibitor. COMT is an enzyme in our body that breaks down dopamine. Inhibiting COMT would therefore stop COMT from breaking down dopamine allowing more to be available in the brain.


Comtan has no effect when taken by itself and is always given with another medication such as Sinemet. In fact, there is a drug known as Stalevo that combines levodopa, carbidopa and entacapone all in one tablet. Taking Comtan with Sinemet can extend the effect of that drug by one to two hours. It also doesn't typically increase the side effects of Sinemet as it only increases the overall exposure to the drug and doesn't increase peak concentrations of it. Comtan is usually very well tolerated but can cause the following side effects:

  • Nausea/Vomiting
  • Brown/orange color urine
  • ​Dizziness
  • Constipation


Selegiline & Rasagaline

Selegeline
Both selegiline and rasagaline are known as Monoamine oxidase-B inhibitors (MAO-B Inhibitors). MAO-B breaks down dopamine and taking MAO-B inhibitors can increase the amount of dopamine available to the brain. Multiple studies have shown that starting therapy with MAO-B inhibitors delays the need for other drugs by over 9 months. Studies have also shown that MAO-B inhibitors decrease free radical production and may decrease cell death! In the past before the MAO-B inhibitors were available, there were only MAO-I medications.


There are many different types of MAO enzymes in the body and problems can occur when all of the enzymes are being inhibited. A famous drug interaction occurs with MAOI drugs and foods that contain tyramine such as cheese wine and sausage. Taking MAOI drugs with these things can cause dangerously high blood pressure levels. Fortunately, the new MAO-B inhibitors only affect the "B" type enzymes and the food interactions are not a problem with common dosages of selegiline and rasagaline.​


(Requip) Ropinirole & (Mirapex) Pramipexole

RequipRequip (Ropinirole) & Mirapex ( Pramipexole) are known as direct dopamine agonists and are used to stimulate dopamine production in our own bodies. These drugs are very commonly prescribed as first line medications in Parkinson's patients that are less than 70 years old as multiple studies have shown that these drugs out perform Sinemet in terms of controlling involuntary movements and improving motor function.  In addition to their use in Parkinson's disease, they are also sometimes used in patients with restless leg syndrome. In terms of side effects, these dopamine agonist drugs can cause the following:

  • Sedation
  • ​Nausea
  • Hallucinations
  • Orthostatic hypotension
  • Impulsive feelings
  • Hypersexuality


It's important to know that everything listed in this article, from medications available to at home techniques to reduce the symptoms of Parkinson's disease, are only a few of the many possibilities available to patients and their families. Parkinson's is a debilitating illness that severely impacts countless lives. We hope that this article provided some help and advice. As always,we are available for questions on any subject or therapy you would like to inquire about.