This page has moved. Click here to view.
Parkinson’s disease is a very common illness, affecting two people per thousand population. There’s a slight tendency towards Caucasians to be more affected than non-Caucasians. The onset is usually in the seventh decade. The average age of onset is 67 years. It may also present initially in people in their 70’s and 80’s and even 90’s. Parkinson’s disease is a chronic disease, and, since the advent of Sinemet, it usually does not shorten life expectancy Parkinson's disease, Parkinson disease, Parkinsons disease, Parkinsen's disease
The four cardinal symptoms of Parkinson’s disease are: resting tremor - the patient does not absolutely have to have a tremor to make a diagnosis of Parkinson’s disease, but it sure helps. And if you don’t have a tremor it’s a red flag that what you are dealing with is not idiopathic Parkinson’s disease. Muscular rigidity, particularly a ratchety type rigidity and the joint that best demonstrates this is the wrist rather than the elbow. One of the ways to really bring out rigidity is to
The neuropathology of Parkinson’s disease is this Lewy body formation. These are intracytoplasmic eosinophilic deposits that are toxic to cells and cause them to die. There’s progressive neuronal loss and dopamine depletion. This is a presynaptic neuron problem. The presynaptic neurons are the ones that are affected with Parkinson’s disease and nobody knows why people develop Parkinson’s disease. Nobody knows why people develop idiopathic Parkinson’s disease. The
I’m going to go through a little bit of the classification of parkinsonism and there’s a distinction between parkinsonism and idiopathic Parkinson’s disease, but the most important form of parkinsonism is actually idiopathic Parkinson’s disease. I’ll spend the majority of this 45 minutes talking about idiopathic Parkinson’s disease, but there are some secondary causes of parkinsonism, drug- induced; the neuroleptics. Reglan, reserpine, Aldomet. Post traumatic; the best example of this is Mohammed Ali. Vascular Parkinson’s disease; people who have lacunar infarctions in the region of the basal ganglia. It happens commonly, don’t respond well to medicines though. You wouldn’t expect that they would respond to medicines because it’s not only the presynaptic neuron that is destroyed, it’s the postsynaptic receptor neurons that are destroyed with vascular lesions. Hydrocephalic parkinsonism; this is rare. Toxin induced parkinsonism is rare too. Excess copper can do it. There was an MTPT toxin. It was a designer meperidine that was popular in the 70’s and when the drug abusers injected this, this agent was
In addition to Parkinson’s disease, there are a number of Parkinson’s disease-like conditions that look like Parkinson’s disease and invariably were initially diagnosed as having Parkinson’s disease, but they later to go on and declare themselves as one of these Parkinson’s plus syndromes, sometimes called "a multi-systems degeneration’s." The most common is Shy-Drager’s syndrome where a person has a few characteristics. Many characteristics they share with Parkinson’s disease, however they don’t respond very well to Sinemet, they don’t typically have a tremor and they have disabling orthostatic hypotension. This is
The next most common would be progressive supranuclear palsy. These people are invariably diagnosed with Parkinson’s disease but at some point, usually in the first few years, they begin to develop extraocular gaze palsy. This extraocular gaze palsy is the pathologic …it’s not pathologic, it’s a clinical hallmark of PSP.
Drugs that cause parkinsonism; I’ve mentioned all these a few times today. Again, the four cardinal symptoms: tremor, rigidity, bradykinesia, postural instability and response to levodopa. We’ve talked about those four cardinal symptoms and levodopa helps all those things. There are a number of secondary symptoms of Parkinson’s disease that you at least ought to be aware of. I’d like to kind of whip through them fairly fast because I want to spend the majority of the time that I have remaining talking about how to treat Parkinson’s disease. First is seborrhea. Almost everybody with Parkinson’s disease has seborrheic dermatitis. Why? I
General guidelines for the treatment of Parkinson’s disease are: symptomatic treatment really depends on functional status and quality of life. Now you are going to treat a 60-year-old man with Parkinson’s disease probably different than you are going to treat a 85-year-old man with Parkinson’s disease. The 60-year-old man who works and needs to be high functioning many many hours a day is a little different from the 85-year-old guy who is a little slow and has a little bit of tremor, but functionally does everything that he wants to do in life. It’s unwise to try to attempt to eradicate all the signs of parkinsonism and sometimes you just can’t get that tremor to go away. That’s okay. If you keep hammering away trying to get that tremor to go away, you are liable to induce some kind of drug-induced - usually levodopa - induced side effect. Tailor the drug to the patient’s specific symptoms. Now this is most relevant early on in Parkinson’s disease where you might want to save levodopa for when it’s more necessary. You might want to use drugs like the anticholinergic agents for patients in their 60’s because they are pretty effective for tremor. Or amantadine for patients in their 60’s for tremor. Tremor is often the most bothersome symptom in a younger parkinsonian patient because it’s this constant reminder that they’ve got this illness. It seems to me that 80-year-olds don’t care about that so much as they
Start low and increase slowly. Titrate one drug at a time. Anti-parkinsonian drugs should not be stopped abruptly. You might encounter patients with Parkinson’s disease and you look at them and you think, "Well, maybe they don’t have Parkinson’s disease. My gosh, they don’t have any tremor at all" and it might just be because of how well their medicines have them under control. It used to be very popular to do drug holidays. Maybe even put people in the hospital, take away all their medicines and try to up-regulate their receptor and then give them the medicines back, and then they’d have a super-physiologic response. It ended up
All right, levodopa. Levodopa is rapidly converted to dopamine in the periphery by dopamine decarboxylase. Now two things happen when that happens. Number one is you get sick. Dopamine causes nausea. Number two dopamine does not cross the blood/brain barrier. So it can’t get in to do you any good. When carbidopa was discovered, it was found that this dopamine decarboxylase inhibitor allowed levodopa to be absorbed into the systemic circulation and cross the blood/brain barrier where it could do some good. You need 75 mg to 100 mg of carbidopa to inhibit the full daily supply of dopamine decarboxylase. This is important because some of the - especially starting out early, when you start people out on the medicine - sometimes it’s hard to get in 75 mg carbidopa. The preparations come in 10/100 tablets, which should never be used. There’s no reason to ever use a 10/100 tablet. There’s not enough carbidopa in that tablet. They come in 25/100 tablets also. Now if you have a 25/100 tablets and you give three of those tablets a day you are up there to 75 mg of carbidopa. So low dose Sinemet is somewhere between 100 and 500 mg a day. Medium dose is between 600 and 1,000 and high dose is anywhere from
Sinemet. A combination of carbidopa and levodopa. Onset of action is in a half hour. The peak effect is in two hours and the duration of effect is three to four. It’s pretty convenient to dose this three times a day, four times a day. It competes with dietary amino acids for absorption. So if you give it with a meal you’ll have less nausea but you’ll have less absorption. So one of the ways that I usually do this, to start people off, is I give them half of a dose of 25/100 with a meal. And then
Side effects. They occur in 90% of people after ten years of levodopa therapy. Many of these levodopa complications are, first: this wearing-off phenomenon or higher doses are required for previously attained levels of control. You invariably have to keep increasing peoples Sinemet. There are some other strategies like using a dopamine agonist to augment people’s Sinemet but usually you end up, for great control, you end up increasing people’s Sinemet. Now when you do that - especially the longer people have had Parkinson’s disease - they develop what is known as "peak dose dyskinesia?. And to a lesser extent, "peak dose dystonia." The dyskinesia - remember, levodopa is the movement enabling drug. If you get a high concentration all of a sudden of that stuff in the brain, people can
Now further on down the road when this becomes worse of a problem, what you might be able to do is have a pallidotomy and that will enable you to push the Sinemet and the dopamine agonist. Pallidotomies are - I’m really impressed with this - are incredibly benign … no, I shouldn’t say that. They are not that terribly
Another complication of long term levodopa therapy is confusion and hallucinations. After all, dopamine is the hallucination neurotransmitter. You are adding that to a persons brain. Sinemet CR has some advantages. One of the disadvantages, however, is cost. There is no generic available for Sinemet CR. The cost is twice that of Sinemet. Parkinson’s disease is not a cheap disease to have. A lot of these medicines are very costly. I would not use Sinemet CR unless you have a clear reason to. One of those clear reasons would be things like peak dose dyskinesia, wearing off phenomenon, those sort of things. Particularly the wearing off
Dopamine agonists. Although these are not as effective as levodopa in relieving Parkinson’s disease symptoms, they do offer some advantages. Some real and some theoretic. One is that they don’t have to be converted by dopamine by a failing presynaptic nigra striatal system. They are ready to go as soon as they are
Big big cost differences between these. Bromocriptine, which has been around for a long long time is still very expensive: 10 mg t.i.d. of bromocriptine is $350 a month. There is also some evidence to indicate that this is less efficacious than some of the newer ones. So there’s no reason to use bromocriptine anymore. You’ve got better drugs out there, and less expensive drugs. Pergolide was next. It’s a very expensive drug. Doesn’t really offer much advantage. Wouldn’t use it.
So, in summary, with Parkinson’s disease, I think that all primary care physicians who care for elderly people need to be able to recognize parkinsonism. If you don’t want to treat it, fine but just recognize it so that you can see the functional impairments that people are having and get them some treatment somewhere else. Be aware of potential iatrogenic parkinsonism. It happens. I see several cases of this a year. The latest big offender has been Reglan and the reason why that’s been the latest big offender is because of the bad press that Propulsid has gotten, because of some drug interactions and Reglan is making a little bit of a