Drug Management of Parkinson’s Disease

“Abbreviations” and “Major Drugs”

The most common drugs include L-Dopa (Levo-dopa), dopamine receptor agonists. Anticholinergic agents, more central acting than atropine, are used to correct the disbalance of cholinergic pathways that are involved with Parkinson’s syndrome… anticipate that if a pt is on an anticholinergic drug, expect severe xerostomia and other effects of muscarinic receptor blockade. Selegiline is a MAO-B inhibitor, it works on the enzyme that breaks down catecholamines, to decrease dopamine breakdown. Secondarily, selegiline may be involved in the pathway to the production of oxidative substances which are thought to play a role in basal cell destruction.


Pts with Parkinson’s will present with a slow, shuffling motion (bradykinesia) and also may have muscle rigidity in their upper torso. Also, the primary symptom is tremor. Usually, Parkinson’s pts will be somewhat controlled, their tremor will be reduced to an acceptable level, so their quality of life isn’t too bad.


The cause of Parkinson’s dz lies in a defect in the brainstem nuclei, especially the substantia nigra (which has dopamine producing cells essential for muscle control). In Parkinson’s dz, there is a loss of these dopamine producing cells. The future management of Parkinson’s dz probably lies in stem cell research. Whatever assaults the basal cell ganglia causes Parkinson’s dz, we haven’t figured out the exact cause yet, but it is not a genetic disorder. Whenever the basal cell ganglia are assaulted, the acetylcholine producing neurons become prominent, making acetylcholine. It is a very rich pathway, and because there are a lot of cholinergic pathways in the motor cortex, you get stimulation of muscles from the acetylcholine. So anti-cholinergic drugs are used to treat Parkinson’s.


Therapeutic Overview

The cause of Parkinson’s is idiopathic (unknown). From the point of view of managing the pt, you’d like to enhance dopamine production but we can’t do it if the neurons aren’t making it. So we have to put back dopamine into the pt. Dopamine isn’t stable if we give it orally, so we give a precursor, Levodopa. Levodopa can be given orally, gets into systemic circulation, and eventually gets to the brain where it is converted to dopamine and acts on dopamine receptors. Dopamine receptors in the brain have a multitude of functions. If you can block muscarinic receptor you can neutralize the emergence of the acetylcholine pathway.



One of the things that results from the activation of monoamine oxidase B is the production of iron metabolites with peroxide in the formation of hydroxyl radicals. Current theories about the cause of aging say that it is due to oxidative stress; the body is producing more peroxides or hydroxyl radicals, which retards or destroys cell function. So the idea that MAO inhibitors may play a role here is a lot of speculation.



When you see drug names you should recognize the class that its in (not responsible for structures). Levodopa is very prominent… although tolerance is low, you’ve got to take a high dose and there is often a wearing off of efficacy, so sometimes a pt will have to switch drug classes for a while and then come back to L-dopa. L-dopa has a short half-life. Carbidopa (a decarboxylase inhibitor) is often co-prescribed to enhance L-dopa’s blood levels (because L-dopa is metabolized by decarboxylase); the two are combined in a single drug called Sinemet. Carbidopa by itself has no efficacy, it must be used as an adjunct. Anticholinergics (ie. trihexyphenidyl) are atropine-like in action. Amantadine is a surprising drug to see here. It was originally designed to fight the flu virus, but was not very effective and not accepted by the medical community, and died a slow death. However, Parkinson’s pts who took amantadine for the flue noticed decreased symptoms of Parkinson’s. Amantadine will never be encountered, even though its mentioned in textbooks, because its very very weak. Selegiline is a MAO-B inhibitor.



The drugs that are being used are all orally effective, but look at the difference in ½ life. So L-dopa, which is the mainstay, has a very short half-life; it must be repeatedly dosed. The anti-cholinergic drugs have a very long ½ life, but xerostomia is quite severe.



Depending on which subtype of dopamine receptor is in which location, activation or blockade will cause different neurological effects. If you have a deficiency of dopamine being released, if the receptor is still intact and you have a dopamine agonist you may get the same response. That’s why dopamine agonists are alternatives.



The neuroprotective effects of selegiline can prevent the progressive neuro-degeneration of what we thought was a drug-induced toxicity. A lot of people speculate that the underlying cause of damage leading to Parkinson’s is the formation of peroxide hydroxyl radicals. So if you can prevent that conversion using an MAO-B inhibitor, that would be good. So people took that theory a little further, and many physicians will tell their pts to supplement their diets with anti-oxidase supplements. The evidence there is a little weak, and many times in controlled studies, supplements have no effect.



“Clinical Problems”

L-dopa has limited effectiveness after 3-5 yrs of treatment. There is fluctuation in response to L-dopa. There is some disorder of movement, called dyskinesia. Some pts show significant psychotic problems. With the anti-cholinergic drugs there are bizarre changes that can occur when you’re dealing with the CNS, including confusion, and memory impairment.


“Oxidative stress and Parkinson’s Disease”

If a pt has the early symptoms of Parkinson’s dz and you put the pt on high doses of an anti-oxidant like vitamin E, think alpha tocopherol or ascorbic acid (vitamin C), selenium, or beta-carotine, would that prevent and retard the development of Parkinson’s dz? If these anti-oxidants are used its usually as an adjunct in the hopes that it will modify the progression.


“Trade Names”

Pts will often refer to brand names. Sinemet is the number 1 prescribed drug, which combines carbidopa and L-dopa. Benztropine has brand name Cogentin. Artane is trihexyphenidyl. Be alert, your pts may be on these drugs.

Category: Pharmacology Notes