The study below has not been conducted in the Philippines but in Mayo Clinic. Nevertheless, its applicability regarding observing the same behavior among patients receiving the same medical treatment for Parkinson's in the Philippine setting has yet to be verified.
The report is that one in six patients receiving therapeutic doses of certain drugs for Parkinson's disease develops new-onset, potentially destructive behaviors, notably compulsive gambling or hypersexuality.
The study extends findings from two Mayo case series published in 2005 that reported a connection between dopamine agonist medications and compulsive gambling or hypersexuality.
Dopamine agonists are a class of drugs that include pramipexole and ropinirole. They are commonly used to treat Parkinson's disease, but low doses also are used for restless legs syndrome. They uniquely stimulate brain limbic circuits, which are thought to be fundamental substrates for emotional, reward and hedonistic behaviors.
"The 2005 case series alerted us that something bad was happening to some unfortunate people. This study was done to assess the likelihood that this effect would happen to the average Parkinson's patient treated with these agents," says J. Michael Bostwick, M.D., Mayo Clinic psychiatrist who spearheaded the new study. It is published in the April issue of Mayo Clinic Proceedings.
The researchers analyzed the medical records of patients with Parkinson's disease residing in counties surrounding Rochester, Minn., who received their primary neurological care at Mayo Clinic in Rochester between 2004 and 2006. This group included 267 patients. Of those, 66 were taking dopamine agonists for their Parkinson's disease. Of those 66, 38 were taking the drugs in therapeutic doses (doses expected to be at least minimally beneficial).
The findings were definitive. Seven patients experiencing new-onset compulsive gambling or hypersexuality were taking dopamine agonists in therapeutic doses. None of the other Parkinson's disease patients developed compulsive gambling habits or hypersexuality, including the 28 patients on subtherapeutic dopamine agonist doses or the other 201 patients not taking dopamine agonists. None of the 178 patients treated only with the standard drug for Parkinson's disease, carbidopa/levodopa, developed these behaviors.
"It is crucial for clinicians prescribing dopamine agonists to apprise patients as well as their spouses or partners about this potential side effect. The onset can be insidious and overlooked until life-altering problems develop," says J. Eric Ahlskog, M.D., Ph.D., Mayo Clinic neurologist who co-authored and treated many of the patients in the 2005 study. "It also is worth noting that the affected patients were all taking therapeutic doses. Very low doses, such as those used to treat restless legs syndrome, carry much less risk."
"For some patients, a reduction in the dose of the dopamine agonist may prove to be sufficient treatment," says Dr. Ahlskog, "although total elimination of the offending drug is often necessary."
Source: Mayo Clinic (2009, April 10). Parkinson's Disease Medication Can Trigger Destructive Behaviors, Study Finds. ScienceDaily. Retrieved January 13, 2010, from http://www.sciencedaily.com¬ /releases/2009/04/090408145346.htm
Showing posts with label dopamine agonists. Show all posts
Showing posts with label dopamine agonists. Show all posts
Monday, January 18, 2010
Sunday, January 17, 2010
Dopamine Medications for Parkinson's Disease
The ‘Gold-standard’ treatment for Parkinson’s Disease (PD) is medication or drug therapy. Virtually all of the available drug therapies act to increase the level of dopamine in the brain. The way in which a given drug accomplishes this feat has a lot to do with the effectiveness of the drug and with potential side-effects of the drug.
Levodopa
Levodopa is the ‘first-line’ medicine for PD. It is a building block in the process that brain cells use to manufacture dopamine. Cells can use this building block to manufacture more dopamine. Levodopa works. It practically normalizes motor symptoms making you feel less stiff, more mobile and more flexible. Unfortunately it does not cure PD and cannot stop the underlying disease process itself.
Levodopa also has side effects. These side effects, however, can usually be eliminated by combining levodopa with other additional drugs. One major side effect of levodopa when used alone is nausea. When there is too much dopamine circulating in the body’s blood stream instead of in the brain, nausea is the result. To prevent this nausea and to enhance the amount of levodopa reaching the brain, levodopa is often given with another drug type called a dopa decarboxylase inhibitor (DDI). A DDI blocks the conversion of levodopa to dopamine in the body’s bloodstream thus allowing more levodopa to reach the brain and preventing nausea.
The most common form of DDI used in most countries is Carbidopa. The combination of levodopa and carbidopa is known by the trade name Sinemet.
Benserazide (Prolopa of Madopar) is the DDI used in Canada and Europe.
In most countries carbidopa/levodopa dosage levels are designated as a fraction: the numerator is the amount of carbidopa in each tablet, and the denominator the amount of levodopa. For example, a combination of 25/100 is composed of 25 milligrams of carbidopa and 100 milligrams of levodopa. Carbidopa/levodopa is also available in a controlled-release formulation known as Sinemet CR. The controlled-release formulations of Sinemet allow for a slower release-time of levodopa into the bloodstream, which helps to smooth out end-of-dose wearing-off fluctuations as well as nighttime sleep disturbances.
Other Dopamine Drugs
Although levodopa effectively treats the symptoms of the disease, the disease nevertheless still progresses and gets worse over time. The disease damages brain cells, neurons, that manufacture dopamine or that convert levodopa to dopamine. As the disease progresses it gets more and more difficult to stimulate the brain production of dopamine. We therefore need alternative ways of keeping brain dopamine levels high enough to support normal motor functioning.
Since dopamine production cells are damaged by the disease we must target other cells that may not produce dopamine but act to use existing dopamine more effectively. Two classes of drugs can do this: drugs that directly stimulate cells that use dopamine--the ‘dopamine agonists’ and drugs that inhibit the breakdown of dopamine in the body and thus increase the levels available to the brain--the ‘COMT and MAO inhibitors’.
Dopamine Agonists
There are several dopamine agonists- Bromocriptine (Parlodel), pergolide (Permax), pramipexole (Mirapex) and ropinirole (Requip). Less widely used agonists include lisuride and cabergoline. All of these agonist drugs mimic the effects of dopamine at selected dopamine ‘receptors’. Receptors are cells that enhance the effects of dopamine in the brain.
There are five types of dopamine receptors in the brain, called D1, D2, D3, D4, and D5. The D2 receptor is most important for the motor symptoms of PD so all of the dopamine agonist drugs stimulate D2. Pramipexole and ropinirole, in addition, stimulate D3 receptors. Because the D3 receptor is involved in mood, personality and emotion, pramipexole and ropinirole may affect mood as well as motor symptoms.
All the dopamine agonist drugs can produce side effects like dizziness, low blood pressure, and psychiatric disturbances so they must be started as a very low dosage, and only gradually increased.
COMT Inhibitors and MAO Inhibitors
The COMT (catechol-O-methyltransferase) inhibitors and MAO-B (monoamine oxidase type B) inhibitors work to block the breakdown and inactivation of dopamine in the body and brain. If COMT is blocked or inhibited, for example, more levodopa can reach the brain’s motor control system. The most common COMT inhibitors are tolcapone (Tasmar) and entacapone (Comtan). COMT inhibitors are particularly helpful for people with motor fluctuations.
But they have side effects. Five to ten percent of patients taking a COMT inhibitor develop diarrhea. This usually means the drug must be stopped. Two to three percent of people taking tolcapone develop serious liver problems requiring close monitoring of liver function when on the drug or cessation of use of the drug entirely. Entacapone does not have these liver toxicity problems.
The MAO-B inhibitors, such as selegiline (Eldepryl) and rasagiline (Azilect), prevent the enzyme MAO-B from breaking down dopamine in the brain itself.
Selegiline is used primarily to prevent or smooth out end of dose motor fluctuations. Its effects are very mild. Selegiline was once believed to act as a neuroprotective drug preventing further damage to dopamine neurons in the brain. It turns out that this neuroprotective effect of selegiline is small or non-existent.
Rasagiline (Azilect), on the other hand, looks to be more promising with respect to its potential neuroprotective effects-though the jury is still out on this crucial effect of the drug. Rasagiline is mostly used in early and moderate Parkinson’s to reduce motor fluctuations. More evidence on rasagiline’s effectiveness and safety is needed.
Source:http://www.nlm.nih.gov/medlineplus/druginfo/meds/a601068.html
Levodopa
Levodopa is the ‘first-line’ medicine for PD. It is a building block in the process that brain cells use to manufacture dopamine. Cells can use this building block to manufacture more dopamine. Levodopa works. It practically normalizes motor symptoms making you feel less stiff, more mobile and more flexible. Unfortunately it does not cure PD and cannot stop the underlying disease process itself.
Levodopa also has side effects. These side effects, however, can usually be eliminated by combining levodopa with other additional drugs. One major side effect of levodopa when used alone is nausea. When there is too much dopamine circulating in the body’s blood stream instead of in the brain, nausea is the result. To prevent this nausea and to enhance the amount of levodopa reaching the brain, levodopa is often given with another drug type called a dopa decarboxylase inhibitor (DDI). A DDI blocks the conversion of levodopa to dopamine in the body’s bloodstream thus allowing more levodopa to reach the brain and preventing nausea.
The most common form of DDI used in most countries is Carbidopa. The combination of levodopa and carbidopa is known by the trade name Sinemet.
Benserazide (Prolopa of Madopar) is the DDI used in Canada and Europe.
In most countries carbidopa/levodopa dosage levels are designated as a fraction: the numerator is the amount of carbidopa in each tablet, and the denominator the amount of levodopa. For example, a combination of 25/100 is composed of 25 milligrams of carbidopa and 100 milligrams of levodopa. Carbidopa/levodopa is also available in a controlled-release formulation known as Sinemet CR. The controlled-release formulations of Sinemet allow for a slower release-time of levodopa into the bloodstream, which helps to smooth out end-of-dose wearing-off fluctuations as well as nighttime sleep disturbances.
Other Dopamine Drugs
Although levodopa effectively treats the symptoms of the disease, the disease nevertheless still progresses and gets worse over time. The disease damages brain cells, neurons, that manufacture dopamine or that convert levodopa to dopamine. As the disease progresses it gets more and more difficult to stimulate the brain production of dopamine. We therefore need alternative ways of keeping brain dopamine levels high enough to support normal motor functioning.
Since dopamine production cells are damaged by the disease we must target other cells that may not produce dopamine but act to use existing dopamine more effectively. Two classes of drugs can do this: drugs that directly stimulate cells that use dopamine--the ‘dopamine agonists’ and drugs that inhibit the breakdown of dopamine in the body and thus increase the levels available to the brain--the ‘COMT and MAO inhibitors’.
Dopamine Agonists
There are several dopamine agonists- Bromocriptine (Parlodel), pergolide (Permax), pramipexole (Mirapex) and ropinirole (Requip). Less widely used agonists include lisuride and cabergoline. All of these agonist drugs mimic the effects of dopamine at selected dopamine ‘receptors’. Receptors are cells that enhance the effects of dopamine in the brain.
There are five types of dopamine receptors in the brain, called D1, D2, D3, D4, and D5. The D2 receptor is most important for the motor symptoms of PD so all of the dopamine agonist drugs stimulate D2. Pramipexole and ropinirole, in addition, stimulate D3 receptors. Because the D3 receptor is involved in mood, personality and emotion, pramipexole and ropinirole may affect mood as well as motor symptoms.
All the dopamine agonist drugs can produce side effects like dizziness, low blood pressure, and psychiatric disturbances so they must be started as a very low dosage, and only gradually increased.
COMT Inhibitors and MAO Inhibitors
The COMT (catechol-O-methyltransferase) inhibitors and MAO-B (monoamine oxidase type B) inhibitors work to block the breakdown and inactivation of dopamine in the body and brain. If COMT is blocked or inhibited, for example, more levodopa can reach the brain’s motor control system. The most common COMT inhibitors are tolcapone (Tasmar) and entacapone (Comtan). COMT inhibitors are particularly helpful for people with motor fluctuations.
But they have side effects. Five to ten percent of patients taking a COMT inhibitor develop diarrhea. This usually means the drug must be stopped. Two to three percent of people taking tolcapone develop serious liver problems requiring close monitoring of liver function when on the drug or cessation of use of the drug entirely. Entacapone does not have these liver toxicity problems.
The MAO-B inhibitors, such as selegiline (Eldepryl) and rasagiline (Azilect), prevent the enzyme MAO-B from breaking down dopamine in the brain itself.
Selegiline is used primarily to prevent or smooth out end of dose motor fluctuations. Its effects are very mild. Selegiline was once believed to act as a neuroprotective drug preventing further damage to dopamine neurons in the brain. It turns out that this neuroprotective effect of selegiline is small or non-existent.
Rasagiline (Azilect), on the other hand, looks to be more promising with respect to its potential neuroprotective effects-though the jury is still out on this crucial effect of the drug. Rasagiline is mostly used in early and moderate Parkinson’s to reduce motor fluctuations. More evidence on rasagiline’s effectiveness and safety is needed.
Source:http://www.nlm.nih.gov/medlineplus/druginfo/meds/a601068.html
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