What’s Hot In Pd A Critical Reappraisal Of The Worst Drugs In Parkinsons Disease
What are the worst drugs for Parkinson’s disease patients? Couldn’t a simple list be assembled and disseminated to the Parkinson’s community? Recently Ed Steinmetz, an experienced neurologist in Fort Myers, FL pointed out to me, a list approach published in the;Public Citizen Newsletter;. The approach was to list every drug associated with a single confirmed or unconfirmed symptom of Parkinson’s disease or parkinsonism. Parkinson’s disease is defined as aneurodegenerative;syndrome , whereas parkinsonism encompasses a wider net of drug induced and other potential causes. In parkinsonism, symptoms are similar to Parkinson’s disease, but patients do not have Parkinson’s disease. Patients and family members confronted with a simple “drug list” approach may falsely conclude that most medicines are bad for Parkinson’s disease, and that any medicine may cause parkinsonism. This concept is in general, incorrect.;
Although the approach is well-meaning, it is in need of a major revision, as Parkinson’s disease and parkinsonism are too complex to summarize by simple lists. In this month’s column, I will try to summarize the key information that patients and family members need to know about the “worst pills,” for Parkinson’s disease and parkinsonism.
Tremors Caused By Medications
In addition to drug-induced parkinsonism, which includes rest tremor and is caused by medications that block the dopamine receptor, there are also a wide variety of medications that do not block the dopamine receptor, but can cause other types of tremors, such as postural and action tremors. So if you have these types of tremors, but without the slowness, stiffness and other PD-like symptoms, you could have drug-induced tremor .
A;postural tremor;occurs when a body part is held against gravity. Postural tremors occur for example, when the arms are extended, such as when holding a tray. An action tremor;occurs when a body part is moving. Action tremors occur for example, when the arm is moving toward the mouth to eat.
Drug-induced tremors typically are symmetric or equal on both sides of the body. The medications that can cause tremor include, but are not limited to, lithium, valproic acid, amiodarone, beta-adrenergic agonists, and selective serotonin reuptake inhibitors . Be attentive to whether a tremor starts after any new medication is started. If it does, discuss this with your doctor.
Diagnosis Of Dip And The Role Of Dat Imaging
The clinical diagnostic criteria for DIP are defined as 1) the presence of parkinsonism, 2) no history of parkinsonism before the use of the offending drug, and 3) onset of parkinsonian symptoms during use of the offending drug. Since asymmetrical rest tremors are common in many DIP patients and symptoms persist or progress after cessation of the offending drug, patients clinically diagnosed with DIP may include individuals in the preclinical stage of PD whose symptoms were unmasked by the drug.,,,
DATs are presynaptic proteins in the membrane on terminals of dopaminergic neurons. They take up dopamine from the synaptic cleft projections that extend from the substantia nigra to the striatum. These transporters control dopaminergic transmission by spatial and temporal buffering, rendering the molecule an imaging target in diseases affecting the dopaminergic nigrostriatal pathway. Single-photon-emission computed tomography and positron-emission tomography scans are available using several DAT ligands., SPECT radioligands include 123I-N-3-fluoropropyl-2-carbomethoxy-3-nortropane , 123I-ioflupane, DaTSCAN, and 123I-2-carbomethoxy-3-tropane . PET scans may be superior to SPECT for imaging DATs, in that the lower energy of positrons provides higher resolution, resulting in better image quality with widespread clinical applications. However, most DAT imaging studies, including those in patients with DIP, have utilized SPECT.,-
Can Parkinsons Disease Be Prevented
It is not possible to prevent Parkinsons disease, but some believe that lifelong healthy habits may reduce ones risk of developing the condition. Some medications may also relieve some of its symptoms.
In some PD patients, particularly those who are at the late stage of the disease, surgery may be an option to help improve symptoms.
Some experts also advise doing rpeventive measures such as wearing gloves and other protectvie equipment when applying pesticides as it may help protect you against the disease.
How Often Do Drugs Induce Parkinsons Disease
Before I begin I wish to state clearly: this is not aimed at blaming patients with Parkinsons disease for becoming ill. The aim of this blog post is to explore and review the extent to which drugs, both illegal and legal, induce Parkinsons disease. Officially this type of Parkinsons is known as drug-induced Parkinsons and the symptoms termed Parkinsonism instead of Parkinsons symptoms. The terminology is not the only variation between drug-induced and organic forms of Parkinsons disease. Drug-induced Parkinsonism is occasionally reversible with the aggressive treatment. In addition drug-induced Parkinsonism features symmetrical symptom manifestation. If both arms shake symmetrically and simultaneously drug-induced Parkinsons is the culprit. These two key differences set drug-induced Parkinsonism apart from organic Parkinsons disease.
Overall the chemicals and prescription drugs associated with Parkinsonism have diverse applications with the only common factor being dopamine. Most is known concerning the ability for anti-psychotic medications to cause Parkinsonism. While eliciting opposite behavioral effects, amphetamine and anti-psychotics both disrupt use of dopamine by the brain with enough potency to cause Parkinsonism. MPTP acts as a toxin that selectively destroys the dopamine system leaving the user with Parkinsonism.
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Drugs That Stimulate Dopamine Receptors
Dopamine receptor agonists were introduced as adjuncts to levodopa therapy to help control the motor fluctuations that occur in patients with Parkinson’s disease. The dopamine agonists available for the treatment of Parkinson’s disease in the United States are bromocriptine ,19 pergolide ,20 pramipexole 21 and ropini-role .22 Side effects, including nausea, dizziness, hallucinations and cognitive effects, tend to occur most commonly during the first few weeks after initiation of a dopamine agonist. Consequently, dopamine agonists must be started at a low dosage level and gradually titrated to therapeutic levels.
In most cases, dopamine receptor agonists should be initiated when patients are still taking a low to medium dosage of levodopa . Patients taking more than 600 mg of levodopa per day have a higher incidence of adverse events from dopamine receptor agonists.
Although dopamine agonists are generally considered useful as adjuncts to levodopa, their introduction in early Parkinson’s disease, even as monotherapy, may reduce motor fluctuations later in the disease. As monotherapy, however, dopamine agonists may not provide adequate improvement. Patients who do not respond to levodopa are unlikely to respond to dopamine agonist monotherapy.
Dopamine Agonists Used in Parkinson’s Disease
|Properties and side effects|
0.125 mg three times daily
0.25 mg three times daily
Upper respiratory Infection
Dopamine Agonists Used in Parkinson’s Disease
Can These Symptoms Be Reversed
In general, Parkinsons-like symptoms should improve;after the medication causing the problem is stopped. Unfortunately, its not a quick fix it could take months.;
In some cases, the drug-induced symptoms might actually reveal a previously unknown chronic condition like actual Parkinsons disease or Lewy body dementia.
Environmental Toxins And Parkinsons Disease
Parkinsons disease is said to be because of the loss of dopamine-releasing nerve cells in a small, central part of the brain called the substantia nigra. The substantia nigra produces dopamine, which helps coordinate movement in our body.
But when nigral nerve cells are impaired, less dopamine is released and motor function is affected. And thats when hallmark Parkinsons symptoms including tremors, difficulty balancing, and slowed movement start to set in.
Several studies have suggested that environmental toxicants including pesticides, herbicides, and other pollutants are linked to an increased risk of developing Parkinsons disease.
Heres how these chemicals are said to play a role in the development of the neurological disorder:
What Is Dopamine Blockade
Dopamine is a chemical in our brain. It helps us to move.
Medication Induced Parkinsonism is caused by medications which block the action of dopamine.
These nefarious medications;do this by blocking the microscopic sites in the brain where dopamine usually attaches itself. There is no death of cells.
On the other hand, in typical Parkinsons disease, there is actual death of cells in the Substantia Nigra .
Therefore, these processes are very different from one another.
In addition, the symptoms produced by Medication Induced Parkinsonism are also somewhat distinct. There is usually no tremor and both sides are equally affected. Medication Induced Parkinsonism can progress very rapidly, whereas Parkinsons disease usually progresses very slowly.
Why is levodopa not useful in Medication-Induced Parkinsonism?
Levodopa gets converted into dopamine in the brain. But then it has nowhere to attach!
Therefore, levodopa is not very useful in medication-induced Parkinsonism.
Who Are At Risk Of Developing Drug Included Parkinsonism
Some patients may be at a higher risk of developing medication-induced Parkinson
ism than others. Some of the risks include-
Women: Women are seen to be two times as much at risk of having drug inducing Parkinsons disease than men.
AIDS Patients: People with AIDS are at a higher risk.
Family History: Patients having a family history Parkinsons disease are at a higher risk of having drug induced Parkinsonism.
Elderly: Since elder people are usually on multiple medicines, they are at risk of having drug induced Parkinsonism.
New Neuromodulator For Drug
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Parkinson’s patients may be aided by sonic hedgehog protein pathway stimulation as per a study “Dopaminergic co-transmission with sonic hedgehog inhibits abnormal involuntary movements in models of Parkinson’s disease and L-Dopa induced dyskinesia”, at The Graduate Center, CUNY, and the CUNY School of Medicine, published in the journal Communications Biology. Parkinson’s disease is a progressive neurodegenerative disorder that primarily affects movement due to loss of nerve cells – neurons that produce a chemical messenger in the brain called dopamine .
Lewy bodies, triggered by the misfolding of a protein called alpha-synuclein Drug-Induced Dyskinesia Dopamine replacement therapy result in involuntary movements L-dopa induced dyskinesia . drugs that increased signaling by a protein called sonic hedgehog, or Shh, can inhibit LID. The New Neuromodulator ‘Shh’ has not previously been considered a neurotransmitter . The present study reveals that it does in fact act as a neuromodulator. “In rodent and non-human primate models, the administration of L-dopa together with sonic hedgehog agonists attenuates the expression of LID. We provide novel insight into the underlying mechanisms behind LID formation and provide a potential therapeutic solution,” imbalance between dopamine and Shh after L-dopa treatment is a major cause of LID.
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Drugs That Increase Dopamine Levels
Because dopamine itself does not cross the blood-brain barrier, it is administered as the precursor levodopa in combination with carbidopa . Carbidopa blocks peripheral dopa decarboxylase, the enzyme that converts levodopa to dopamine within the blood-brain barrier. With the levodopa-carbidopa combination, more levodopa reaches the brain and is converted to dopamine.13 This drug combination was named Sinemet because it decreases the side effects caused by peripheral dopamine, especially nausea and vomiting.
Although some newer agents are now prescribed as first-line therapy, levodopa is still considered the most efficacious treatment for Parkinson’s disease. In addition, a response to this agent confirms the diagnosis. Unfortunately, levodopa’s short duration of action necessitates increasingly frequent dosing as the disease progresses. Thus, doses eventually have to be taken as often as every 90 minutes.
The controlled-release formulation of levodopa-carbidopa has to be broken down in the gastrointestinal tract. It can be taken every four to six hours but, because absorption is reduced, higher total daily dosages are usually required.
The side effects of levodopa in either formulation include orthostatic hypotension, nausea, hallucinations and peak-dose dyskinesias. Levodopa therapy should not be used in patients with narrow-angle glaucoma, and caution is advised in giving this drug to patients with malignant melanoma.
Parkinsonism Vs Parkinsons Disease
Parkinsonism refers to a cluster of symptoms that mimic the movement problems caused by Parkinsons disease. Its sometimes referred to as atypical Parkinsons disease, secondary parkinsonism, or Parkinsons plus.
Parkinsons disease is a chronic, neurodegenerative brain disorder. In addition to problems with movement, Parkinsons disease causes non-motor symptoms that arent caused by drug-induced parkinsonism. They include:
Another key difference between drug-induced parkinsonism and Parkinsons disease is symmetry. Drug-induced parkinsonism usually affects both sides of the body equally. Parkinsons disease affects one side of the body more than the other.
Parkinsonism can be caused by medications, repeated head trauma, and environmental toxins. It can also be caused by neurological disorders, including Parkinsons disease. Other neurological conditions that cause parkinsonism include:
- progressive supranuclear palsy
These medications dont cause resting tremors. Rather, they cause:
- Action tremors. These occur in a body part thats moving, not a body part thats resting.
- Postural tremors. These occur when a body part is forced to withstand gravity, such as when arms are outstretched or legs are raised.
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What To Do If Your Senior Has Parkinsons
If you notice Parkinsons-like symptoms in your older adult, the first thing to do is talk with their doctor. The doctor should review their complete medication history and you should let them know about any other symptoms or changes.
Important: Dont make any changes to medications without doctor approval that could cause serious problems.
Not All Drugs In These Classes Will Cause Symptoms Of Parkinsonism
Whats the difference?
Drug-induced parkinsonism usually develops on both sides of the body, while typical Parkinsons disease does not. Also, drug-induced parkinsonism usually does not progress like typical Parkinsons.
Unlike Parkinsons, drug-induced symptoms usually go away after the drug is stopped. It may take several months, though, for the symptoms to completely stop. If the symptoms remain, then it is possible that the drug may have unmaskedunderlying Parkinsons disease.
Who is at risk?
- Female: Women are twice as much at risk as men.
- Elderly: Older people are more likely to be on multiple medications or to have underlying Parkinsons disease.
- Those with a family history of Parkinsons disease.
- People with AIDS.
Pharmacologic Treatment Of Parkinson’s Disease
The goals of treatment are to alleviate symptoms that interfere with the patient’s activities of daily living and to prevent or limit complications as Parkinson’s disease progresses. An additional but still only theoretic goal is to prevent or slow the progression of the disease. If secondary parkinsonism is suspected, treatment should be directed at the identified underlying cause. Treatment for idiopathic Parkinson’s disease should be initiated as soon as the patient’s symptoms begin to interfere with routine activities .
Selected Drugs for the Treatment of Parkinson’s Disease
Dizziness, nausea, hallucinations and others
25/100 mg three times daily
May lead to neuroleptic malignant syndrome
Stimulate dopamine receptors
0.125 mg three times daily
0.25 mg three times daily
Contraindicated with concurrent use of MAO-A drugs
100 mg three times daily
Liver function must be monitored
Drowsiness, dry mouth, blurred vision
25 mg at bedtime
0.5 to 1 mg twice daily
1 to 2 mg twice daily
MAO-B = monoamine oxidase B; MAO-A = monoamine oxidase A; COMT = catechol O-methyltransferase.
*Estimated cost to the pharmacist for a one-month supply at the lowest starting dosage, based on average wholesale prices in Red book. Montvale, N.J.: Medical Economics Data, 1999. Cost to the patient will be higher, depending on prescription filling fee.
Price for 1-mg dose; available in 2-mg and 5-mg tablets.
Serotonin Reuptake Blocking Antidepressants Fluoxetine Sertraline And Paroxetine
Several other medications have been reported to cause drug-induced parkinsonism and to worsen parkinsonism in people with Parkinson disease, including the serotonin reuptake blocking antidepressants fluoxetine, sertraline, and paroxetine. Two calcium channel blockers available in Europe and South America , which are piperazine derivatives, are thought to cause drug-induced parkinsonism by blocking dopamine receptors. Reports of parkinsonism induced by other drugs, such as lithium and amiodarone, are so rare that only after parkinsonism has developed should the possible drug effect be taken into account. Because lithium is not known to block dopamine receptors, another mechanism is likely. Some animal data implicate an effect of lithium on intercellular signalling via G-protein coupled receptors . One antidepressant, amoxapine, has dopamine receptor-blocking properties and, therefore, may induce parkinsonism. Parkinsonism as a transient side effect of alcohol withdrawal has been reported without later development of Parkinson disease, but it is unknown how common this is .
Parkinsonism Falls And Fracture Risk
All forms of parkinsonism, both PD and DIP, have implications for bone health. A 2014 meta-analysis on PD and fracture risk concludes that PD increases the risk of fracture.4
Given that the symptoms of parkinsonism affect balance, motor skills, gait, and the bodys ability to control movement, it is no surprise that people with PD are more likely to experience a fall than people without PD. Here is an excerpt from a 2016 study comparing the incidence of falls and fracture in PD patients:
It is estimated that 60.5% of patients with PD experience at least one fall and 39% have recurrent falls. The high frequency of falls consequently contributes to the increased risk for fractures in PD patients, which has been estimated to be approximately two times the risk in healthy controls. It has been estimated that 76% of falls in PD patients require health care services and 33% result in fractures. Falls and fractures may result in a series of unfavorable outcomes, such as disabilities and death. Furthermore, among PD patients with fractures, the mortality rate is approximately 10.6%.5
All too often, doctors prescribe these drugs without appropriate consideration of this risk. This excerpt from a study on DIP clarifies the danger of accepting a prescription of an unnecessary or inappropriate prescription drug:
Shockingly, the drugs that cause DIP are still being prescribed. This yet one more example further proving that the FDAs drug approval process is useless.