Can you tell me if dopamine works?
What are the the side effects and how can she minimize them? Treatments
Unlike for many other neurodegenerative diseases, there is effective treatment for the symptoms of Parkinson's disease. For most patients, these treatments can provide several years of satisfactory treatment. Unfortunately, no therapy has yet been conclusively shown to slow or reverse the disease. Several candidates have been tested in this regard, and have shown intriguing results. However, these studies will need to be repeated and expanded before these agents can be widely recommended.
Several important factors influence decision-making in treatment of PD. These include:
* Levodopa continues to be the most effective treatment for motor symptoms, and all patients eventually require it.
* Long-term complications of levodopa therapy are a concern, and may influence whether therapy begins with levodopa or a dopamine agonist.
* Non-motor symptoms, especially depression, are increasingly being seen as important targets of therapy.
* Surgical treatment has become a mainstay of late-stage management, although not all patients can afford it or are appropriate candidates.
* Cell transplant therapies are still experimental, and their usefulness is currently lessened by the possibility of unacceptable complications. Additional studies are needed to understand and avoid these complications.
* Non-pharmacological treatments remain an important part of the whole treatment program.
Long-term Complications of Treatment
As PD progresses, it becomes increasingly difficult to adequately control symptoms with medications. The most common problems that arise are motor complications, which include motor fluctuations and dyskinesias.
Motor fluctuations refer to unanticipated loss of effect of a given dose of levodopa鈥攊nstead of a smooth, predictable symptomatic benefit, the patient may lose benefit earlier than usual (termed "wearing off") or may suddenly switch from "on" (symptoms controlled) to "off" (symptoms return). Dyskinesias are involuntary movements that occur when dopamine levels are too high.
Levodopa
Levodopa is converted in the brain into dopamine, the same chemical created by substantia nigra cells and used to control movement. Levodopa was introduced as a PD therapy in the 1960s, and remains the most effective therapy for motor symptoms. It lessens and helps to control all the major motor symptoms of PD, including bradykinesia, which is generally the most disabling feature of the disease.
Carbidopa is included in the standard oral formulation to increase the effectiveness of a dose of levodopa and minimize side effects such as nausea and vomiting.
Levodopa is a type of amino acid. Amino acids, which are contained in certain foods, are the building blocks of proteins. These building blocks are transported into the blood stream through the wall of the intestines. In similar fashion, levodopa must be absorbed into the blood stream through the wall of the intestines. This requires the action of a specific "transporter" or amino acid vehicle in the intestinal lining. Because this transporter can only work so fast, an excessive amount of dietary protein can slow the transport of levodopa into the blood stream. If sufficient amounts of levodopa do not get into the blood stream and ultimately to the brain, then the dose prescribed may not be effective in treating the symptoms of PD. Once levodopa is in the blood stream, it must then cross into the brain, where it becomes active in controlling the symptoms of PD. However, the same "transport phenomenon" occurs when levodopa crosses from the bloodstream into the brain. To avoid the competition of levodopa with other dietary amino acids, patients with more advanced PD may need to time their doses to avoid meals, or reduce the protein content of certain meals.
Adverse effects
Nausea and vomiting are the most common side effects, and are due to accumulation of dopamine in the bloodstream. Orthostatic hypotension (low blood pressure upon standing) also occurs. The risk of hallucinations and paranoia increases over time. Compulsive behavior, including gambling and hypersexuality, is another risk.
Drowsiness is a common adverse effect of levodopa and other dopaminergic therapies, and sudden sleep onset is possible. Patients may not experience any warning signs of sudden sleep onset. It is important to understand this possibility, especially when levodopa therapy begins, when increasing doses, or switching agents.
The most troubling adverse effect from long-term levodopa use is dyskinesias. Dyskinesias are uncontrolled movements, including writhing, twitching, and shaking. Dyskinesias result from the combination of long-term levodopa use and continued neurodegeneration. They typically begin to develop in milder forms after 3 to 5 years of treatment, but are more severe after 5 to 10 years of treatment.
As the disease progresses, the increasing dose of levodopa required for symptom control approaches the dose at which intolerable dyskinesias occur. This limits the continuing usefulness of levodopa. At this point, surgery may be the only effective option. Because of this potential, many physicians recommend starting a younger patient on a dopamine agonist instead of levodopa, which delays the onset of dyskinesias.
Immediate-release levodopa/carbidopa is formulated in doses of 10/100, 25/100, and 25/250 milligram pills. Onset of effect is usually 20 to 40 minutes, and duration of benefit is 2 to 4 hours in more advanced stages of PD.
Dissolving the tablets in orange juice is a possible strategy for speeding the onset of effect. Patients must be sure to consult with their physician before trying this, as the duration of benefit is usually shorter as well.
Continuous infusion of levodopa into the intestine, through a feeding tube, is being studied as of mid-2004. The hope is that continuous infusion may lessen the risk for developing dyskinesias. However, this treatment approach is logistically challenging, and is reserved for only a small subset of patients with severe motor fluctuations or dyskinesias.
Dopamine Agonists
Dopamine agonists are drugs that imitate or mimic the action of levodopa in the brain by directly stimulating dopamine receptors, the same receptors that dopamine itself stimulates. While they are not quite as effective as levodopa, they provide excellent relief of symptoms and delay the onset of motor complications.
A variety of dopamine agonists are available that differ in their duration of action, chemical makeup, method of delivery, and adverse effect profile. The currently available agonists are:
Dopamine Agonists (generic name followed by trade name):
* Apomorphine (Apokyn庐)
* Bromocriptine (Parlodel庐)
* Pergolide (Permax庐)
* Pramipexole (Mirapex庐)
* Ropinirole (Requip庐)
Clinical trials of several of both pramipexole and ropinirole have shown their ability to delay motor complications when used as monotherapy (the only drug given) early in the disease. Agonists tend to produce more edema and psychosis than levodopa, effects which may be more significant than mild dyskinesias, especially in older patients. Hence, in patients who are younger (less than age 70) and otherwise healthy, initiation of dopaminergic therapy with a dopamine agonist may be indicated. Older PD patients (especially those with cognitive problems) are usually treated with levodopa alone.
Adverse Effects
Drowsiness is a common adverse effect of dopamine agonists and levodopa, and sudden sleep onset is possible. Patients may not experience any warning signs of sudden sleep onset. It is important to understand this possibility, which is especially likely at the commencement of therapy, when increasing doses, or switching to a different dopamine agonist.
Other significant adverse effects of dopamine agonists include nausea and vomiting, orthostatic hypotension, edema, and psychosis. My Dad supposedly has it and he takes Stalevo and Dylantin
and the side effects are no worse than shaking anyway.
Dopamine sounds kindof extreme, unless she has quite advanced case of Parkinsons. Dad just has a little shaking, like someone who has low blood sugar. It has never gotten worse supposedly, due to these meds. Currently, the main forms of treatment for Parkinson's is Levodopa plus Carbidopa. Levodopa is converted to dopamine inside the body.
Another drug that is helpful are drugs that mimic dopamine, such as Bromocriptine.
Please consult a doctor about treatments for Parkinson's.
There can be side effects to giving these drugs.
You might want to ask your doctor about L-tyrosine supplement. Ask the doctor if this will help reduce symptoms. |
