Parkinson's Disease

Mar 29, 2021

By Trevor Shewfelt, Pharmacist at the Dauphin Clinic Pharmacy

The scene begins with the skyline of Chicago. The sky is cloudless above the Sears Tower which is a little off to the left. Center foreground is a completely empty highway. The Star Wars soundtrack is playing. Suddenly a red Ferrari, a 250 GT California to be precise, flies directly overhead. Two valets have taken the car for an epic joy ride. In real life, there is no way the Ferrari would have survived this jump, but this is a John Hughes movie. The car just speeds off towards the City center. I kept thinking about this scene from Ferris Buellers's Day Off as I lined up outside Aspen Insurance last week. Aspen seemed to have the earliest opening time out of the places I could go in Dauphin to sign Eric up for Driver's Education.

Ferris Bueller is a kid for whom everything seems to always go right, no matter what he does. Parkinson's Disease is a condition in which your body's movements don't seem to go right. The reason your body is misbehaving in Parkinson's Disease starts in your head. Deep in your brain is an area called the substantia nigra. One of the functions of the substantia nigra is to relay messages from the brain to the body that plan and control movements. For reasons we don't completely understand, in Parkinson's Disease (PD) some cells in the substantia nigra start to die off. The nerve cells that die off are ones that produce the brain signaling chemical dopamine. When 80% of the dopamine cells in the substantia nigra die off, PD symptoms like tremor, slowness of movement, stiffness and balance problems occur.

Parkinson's Disease is one of the most common neurologic disorders and affects about 1% of individuals over 60. The symptoms of PD vary from person to person. We also say PD is progressive, which means it gets worse over time. However, the rate it gets worse will also vary from person to person. Not everyone who has PD will experience all the symptoms. Some of the more common or "hallmark" symptoms include: tremor at rest, impaired dexterity, expressionless face, rigidity and a sense of imbalance. Patients often compensate by lowering their center of gravity, which results in a stooped posture. Other symptoms that may or may not occur include: freezing or being stuck in place, shuffling gait or dragging of one foot, sleep problems, apathy, depression, lowered voice volume or tremor when speaking, difficulty swallowing, constipation, and cognitive impairment.

Getting a diagnosis of PD is not the end of the world. Many Parkinson's patients enjoy an active lifestyle and a normal life expectancy. Maintaining a healthy lifestyle by eating a balanced diet and staying physically active contributes to overall health and well-being. Parkinson's disease can be managed with self-care, medication, and surgery.

Exercise is as important as medication in the treatment of PD. It helps maintain flexibility and improves balance and range of motion. Patients may want to join a support group and continue enjoyable activities to improve their quality of life. Focus on exercise to maintain strength and flexibility. Maintain a healthy diet. Remove throw rugs and low-lying obstacles from pathways inside and outside your home. Replace clothes that have complicated fasteners with those you can slip on easily, such as sweatpants, sweatshirts, or pants with elastic waistbands. Exaggerate lifting your feet and swinging your arms. With each step, pretend you are stepping over a log. Take extra-small bites of food, chew thoroughly, and swallow carefully. Take a breath before you start to speak, and pause between every few words or even between each word. Instead of writing by hand, use a computer.

When we start adding medications to a PD patient's treatment plan, we usually start with levodopa/carbidopa. As a pharmacist, I find these treatments fascinating. In PD, we don't have enough dopamine in the substantia nigra. But if we just give a person a dopamine pill, it wouldn't cross the blood brain barrier. The blood brain barrier is kinda like a biological force field that keeps most substance out of the brain, especially if they are polar molecules. Most medications are polar molecules, including dopamine, so it is kept out of the brain. So, chemists tinkered with dopamine and changed it into levodopa. Levodopa is non-polar enough to cross the blood brain barrier. In the brain levodopa is changed by enzymes into dopamine so it can help with PD symptoms! Perfect, right? Well, levodopa starts to get converted into dopamine outside the brain too. And, remember dopamine can't cross the blood brain barrier. Plus, dopamine outside the brain can lead to side effects like nausea and vomiting. That is why we add carbidopa. Carbidopa prevents enzymes outside the brain from changing levodopa into dopamine, so more levodopa can pass into the brain where it can do some good.

Even though it has been around for quite a while, levodopa/carbidopa is still the most effective choice for PD symptoms. However, PD symptoms tend to get worse over time. As symptoms get worse, the dose of levodopa/carbidopa will get increased. The doctor may consider adding other medications like pramiprexole. Pramiprexole mimics the effects of dopamine in the brain so we call it a dopamine agonist. Adding pramiprexole can also reduce some of the potential side effects of levodopa/carbidopa. One type of side effect of levodopa is called dyskinesias. Dyskinesias are an involuntary, erratic writhing movements of the face, arms, legs and trunk caused by muscle spasms. If dyskinesias occur, the doctor can reduce the levodopa/carbidopa dose and add on a different medication like pramiprexole. After a time on levodopa/carbidopa, patients may notice that each dose wears off before the next dose can be taken (the wearing-off effect) or erratic fluctuations in dose effect (the on-off effect). We can counter-act wearing-off and on-off by changing when the levodopa/carbidopa is given or by adding a different medication like pramiprexole.

There are fascinating surgical options for PD as well. The surgery is called Deep Brain Stimulation. It doesn't destroy any brain tissues and it is reversible. It involves putting tiny electrodes deep into the brain. When these electrodes are turned on they can greatly improve or eliminate the symptoms of PD. Because this treatment involves, well brain surgery, it is not the simplest treatment option. It is generally reserved for severe PD for which mediations aren't working anymore.

It turned out Eric and I were lucky. From what I've heard, many people didn't get their kid into Driver's Ed this time around. I hope another class for driving instruction gets added to satisfy all the pent-up demand. As for Eric, I'm sure he will be a very safe driver. I'm sure he will listen well to everything the driving instructor tells him. I'm sure he won't be like Cameron in Ferris Bueller's Day Off. Cameron discovers he can't roll back the odometer on his dad's Ferrari by running it in reverse on a car jack. In frustration, Cam kicks the front bumper repeatedly. Unsurprisingly, the Ferrari eventually falls off the jack and speeds backward through the back wall of the garage and over a cliff. Cam then says how he dad always loved that car more than him and now his dad would have to talk to Cam. These movie flash backs better not be premonitions.

As always if you have any questions or concerns about these or other products, ask your pharmacist.

The information in this article is intended as a helpful guide only. It is not intended to be used as a substitute for professional advice. If you have any questions about your medications and what is right for you see your doctor, pharmacist or other health care professional.

Parkinson Canada - https://www.parkinson.ca/

Ferris Bueller's Day Off Car Jump Scene - www.youtube.com/watch?v=_fQDnDKhcaM

Ferris Bueller's Day Off Car Destruction Scene - www.youtube.com/watch?v=FVqqVlW1a34&t=23s

There are several types of medications used to manage Parkinson's. These medications may be used alone or in combination with each other, depending if your symptoms are mild or advanced.

Conserve dopamine in the brain by blocking the breakdown action of MAO-B. These drugs are selegiline (Eldepryl, Zelapar) and rasagiline (Azilect), which are also neuroprotective and can slow disease progression.

Block the action of the neurotransmitter glutamate, which allows for an increase in dopamine release. This drug is amantadine (Symmetrel).

Introduce agents that mimic dopamine and bind to the receptors in the neuron's synapse. These drugs include pramipexole (Mirapex), and ropinirole (Requip), and apomorphine (Apokyn).

Replace missing dopamine in the brain. The drug levodopa helps with movement problems of tremor, stiffness, slowness, and walking. Levodopa is combined with carbidopa (Sinemet) to reduce nausea side effects and to ensure that levodopa is converted to dopamine in the brain and not in the intestine or blood.

Optimize delivery of Levodopa to the brain by blocking COMT, which breaks down dopamine in the digestive system, allowing a steady supply of Levadopa to reach the bloodstream. These drugs include tolcapone (Tasmar) and entacapone (Comtan).

Reduce activity of the neurotransmitter acetylcholine. These drugs reduce tremor and include trihexyphenidyl (Artane) and benztropine (Cogentin).

Body movement is very complicated. The dopamine in the substantia nigra is only a very small link in the chain. We think the idea to move starts in the motor cortex, goes through the striatum and the striatum and substantia nigra work together to send signals back and forth from the brain to the spinal cord. Then the basal ganglia and cerebellum ensure the movement is carried out in a smooth and fluid manner. When a part of the chain gets damaged, like the substantia nigra other parts of the system try to compensate. Unfortunately, when other part of the system compensate that can lead to over and under stimulation of other brain parts. This is why we get both shut down of motion and rigidity in some parts of the body and tremor in others.

 


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