Parkinson's Disease and Treatment

Parkinson’s Disease Part 1:  What is it and How is it Treated with Pharmaceuticals?

 

Parkinson’s disease is the second most common neurodegenerative disorder following Alzheimer’s disease, although not everyone with Parkinson’s disease-like symptoms will receive a diagnosis of Parkinson’s disease.

 

Essential tremor, a mild tremor originating in the hands, is a condition that has a much slower progression than Parkinson’s disease and is not an indication that patients will eventually develop Parkinson’s disease. Katherine Hepburn, for instance, had essential tremors and voice disturbances throughout much of her later life and until her death at age ninety-two without ever experiencing more severe symptoms of Parkinson’s Disease.

 

Lab work and brain scans do not aid a Parkinson’s diagnosis. The disease develops with the destruction of dopamine-producing neurons in an area of the brain called substantia nigra. Damaging protein deposits (Lewy bodies) build up in the brain and are similar to those found in Alzheimer’s patients. Lewy body dementia is the second most common type of progressive dementia and includes Parkinson’s-like symptoms such as rigidity and tremors so, in reality, Alzheimer’s and Parkinson’s disease overlap as conditions of excessive inflammation in the brain that lead to progressive neurological damage.

 

The location of the damage in the brain determines the specific symptoms of either Parkinson’s or Alzheimer’s disease. Parkinson’s disease is a progressive disease of five stages, including motor and non-motor symptoms. Patients in Stage 1 of the disease experience mild symptoms such as a slight tremor on one side of the body with little impaired movement, a decrease in eye blinking, or a lack of swinging arm movements when walking. As the disease progresses, patients may experience painful muscle rigidity, a loss of smell and taste, constipation, or difficulty moving until patients are unable to care for themselves and experience psychosis and hallucinations. Late-stage Parkinson’s disease is brutal for both patient and caregiver.

 

A small amount of hope may be available through the proper use of cannabis. In the next few editions of this blog, we will discuss pharmacology treatments for Parkinson’s  along with the best way to use cannabis for treating specific Parkinsonian symptoms. Pharmaceutical treatments for Parkinson’s Disease, like all pharmacology for inflammatory neurological conditions, is limited in its effectiveness for easing symptoms and does little to slow disease progression.

 

Pharmaceutical treatment options for Parkinson’s focus on increasing the amount of dopamine within the brain to reduce symptoms because dopamine-producing cells are the ones that are destroyed over time. The gold standard of treatment for Parkinson’s disease is a drug called carbidopa/levodopa (Sinemet), which converts into dopamine once it enters the brain.  Unfortunately, one of the side effects of adding extra dopamine to the brain is to cause excessive, uncontrolled twisting movements called tardive diskinesia.

 

As dopamine is depleted in the brain of a person with Parkinson’s disease, patients experience depression, a lack of pleasure and motivation, fatigue, sleep disturbances, loss of motor control, and impulsive or destructive behaviors. As damage to the brain continues, the joy of life is diminished, and caring for the patient can become increasingly stressful. Although there is a long list of drugs to treat Parkinson’s, their benefits are offset by dangerous side effects and limited benefit potential.

 

 

Pharmaceutical Treatments for Parkinson’s Disease

 

 

Because Parkinson’s disease is the result of the death of a specific set of dopamine-producing neurons, medications that treat the disease all work to increase dopamine levels for as long as there are still neurons left to use it effectively.

 

Sinemet (carbidopa/levodopa) is the most commonly prescribed medication for the treatment of Parkinson’s symptoms. Levodopa is converted into dopamine once it crosses the blood-brain barrier. Although Sinemet works well for symptom control, 30% of patients will suffer side effects that impair motor control within only twenty-four months of initiating therapy.  Excessive movements (dyskinesia) are common with this treatment and can draw unwanted attention to a patient’s condition. High protein meals can interfere with the absorption of levodopa.

 

Another medication category includes COMT inhibitors that block the catechol-O-methyltransferase (COMT) enzyme to prevent the breakdown of levodopa, increasing the amount of dopamine available in the brain. They are useful when treating motor symptoms, but their effectiveness can also diminish over time. COMT inhibitors have a long list of side effects that include behavior and mood changes, hallucinations, fatigue, and upset stomach.

 

A third category of medications includes the dopamine agonists such as ropinirole (Requip), pramipexole (Mirapex), and rotigotine (Neupro).  These drugs mimic the dopamine molecule and bind to the dopamine receptor. Dopamine itself cannot be given as an oral pharmaceutical medication because it is destroyed before reaching the brain (although medications that are precursors to dopamine can cross the blood brain barrier as discussed above). Dopamine agonists can be combined with carbidopa/levodopa to help with movement disorders, but the combination can sometimes work against patients. Side effects include nausea, hallucinations, sleep disorders, and dizziness as well as compulsive behaviors such as excessive gambling. In this way, the drugs act a bit like cocaine by activating dopaminergic control centers for reward and pleasure.  If patients develop compulsive behaviors, the medication should be discontinued.

 

MAO-B inhibitors prevent the breakdown of dopamine by blocking an enzyme called monoamine oxidase. This allows dopamine to hang around in the synaptic cleft for a longer period of time.  The biggest issue with this class of drugs is not the side effects, although they include dizziness, hallucinations, and upset stomach, but rather the long list of severe drug interactions that include everything from the tyramine in hot dogs and bacon, to cough suppressants.

 

Anticholinergic drugs (benztropine and trihexyphenidyl) are not the most effective drugs for treating Parkinson’s disease, but they can be used as a secondary treatments for tremors.  They are not recommended for older patients because they can cause confusion and memory problems. Unfortunately, they have the common side effects of many drugs: dry mouth, urinary retention, and constipation.

 

Amantadine was accidentally found to help with Parkinson’s symptoms.   It works by mimicking dopamine action in the brain, although it was originally used as an antiviral treatment for influenza. It is typically used as an early treatment for Parkison’s and can be helpful with dyskinesias. These drugs will not alter the progression of disease.  They are for symptomatic treatments only.

 

Because Parkinson’s disease symptoms are both seen (motor) and unseen (emotional), finding an effective treatment poses a challenge. Pharmaceutical medications that are initially successful at reducing motor symptoms can cause substantial dyskinesias due to excess levodopa in the brain. As patients continue to use carbidopa/levodopa, it will, unfortunately, become less and less effective as more neurons are killed by the disease. Some patients find that pills only provide relief for up to two hours at a time. In the later stages of Parkinson’s, hallucinations and relentless physical symptoms develop and it is at this time when all Parkinson’s  medications except levodopa (to help with movement) should be discontinued. This is a delicate pharmaceutical balance because high doses of levodopa can also lead to hallucinations. Patients with advanced disease may receive anti-psychotics and supportive care for anxiety, depression, and sleep disturbances. Little reprieve is available through pharmaceutical intervention as patients continue to decline.

 

Author
Dr. Allison Kendrick

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