Question

Discuss the drug treatment for Parkinson’s disease (PD), and discuss the current consensus on which agent or agents are recommended for initiating therapy in most patients with PD.

Answer 1

Common Drugs for Parkinson's Disease

Levodopa and carbidopa (Sinemet). Levodopa (also called L-dopa) is the most commonly prescribed medicine for Parkinson’s. It’s also the best at controlling the symptoms of the condition, particularly slow movements and stiff, rigid body parts

Levodopa works when your brain cells change it into dopamine. That’s a chemical the brain uses to send signals that help you move your body. People with Parkinson’s don’t have enough dopamine in their brains to control their movements.

Sinemet is a mix of levodopa and another drug called carbidopa. Carbidopa makes the levodopa work better, so you can take less of it. That prevents man common side effects of levodopa, such as nausea, vomiting, and irregular heart rhythms.

Sinemet has the fewest short-term side effects, compared with other Parkinson’s medications. But it does raise your odds for some long-term problems, such as involuntary movements. An inhalable powder form of levodopa and the tablet istradefylline have been approved for those experiencing OFF periods, OFF periods are when Parkinson's symptoms return during periods between the scheduled dose of levodopa/carbidopa.

People who take levodopa for 3-5 years may eventually have restlessness, confusion, or unusual movements within a few hours of taking the medicine. Changes in the amount or timing of your dose will usually prevent these side effects.

Safinamide (Xadago) is an add-on medicine that may be prescribed when individuals taking levodopa and carbidopa have a breakthrough in Parkinson’s symptoms that were previously under control. Studies show that adding this drug helps individuals experience longer times with reduced or no symptoms. The most common side effects are trouble falling or staying asleep, nausea, falls, and uncontrolled, involuntary movements.

Dopamine agonists. These drugs act like dopamine in the brain. They include pramipexole (Mirapex), rotigotine (Neupro), and ropinirole (Requip).

You can take one of these drugs on its own or along with Sinemet. Most doctors prescribe dopamine agonists first and then add levodopa if your symptoms still aren’t under control.

Dopamine agonists don’t have the same risks of long-term problems as levodopa therapy. So they are often the first choice of treatment for Parkinson's disease.

However, these drugs do raise the chances of some short-term side effects, such as nausea, vomiting, dizziness, light-headedness, confusion, and hallucinations.

Amantadine (Symmetrel) may help people with mild Parkinson's disease.

It works by raising the amount of dopamine that your brain cells can use, which helps you have fewer Parkinson’s symptoms. Recent studies have found that Symmetrel may help ease the involuntary movements that can happen with levodopa therapy. But it may cause side effects, such as confusion and memory problems.

Benztropine (Cogentin) and trihexyphenidyl (Artane). These drugs restore the balance between two brain chemicals, dopamine, and acetylcholine. That eases tremors and muscle stiffness in people with Parkinson's. But these medications can harm memory and thinking capacity, especially in older people. Because of that, doctors rarely prescribe them today.

Selegiline (Eldepryl, Zelapar)) and rasagiline(Azilect). These drugs block the brain chemicals that break down dopamine. That helps your brain have more dopamine to work with.

Some evidence shows that selegiline may slow the progression of Parkinson's disease, especially early on. Common side effects include nausea, dizziness or fainting, and stomach pain.

Studies of animals suggest that rasagiline may also slow the progression of Parkinson's. Side effects include headache, joint pain, indigestion, and depression.

Entacapone (Comtan) and Tolcapone (Tasmar). When you take levodopa, a chemical in your body called COMT makes part of the drug useless. The drugs tolcapone and entacapone block COMT, so the brain can use levodopa more effectively, which ease

Early and correct diagnosis and treatment of Parkinson's disease (PD) are crucial for the patient's well being. At the first visit, it is important to deal with the patient's misconceptions of the disease and its course, to offer sources of information and to suggest exercises. To make a correct initial diagnosis of PD we need to assess the course of the initial levodopa responsiveness. The most frequent challenges in diagnosing PD are the conditions of essential tremor and multiple system atrophy. PD has 3 stages of development: (i) early--from the onset of symptoms to the appearance of motor fluctuations; (ii) middle--from motor fluctuations to the appearance of moderate-to-severe disability; and (iii) advanced--when moderate-to-severe disability is present. The medical treatment of early PD should be started when functional disability appears, which is a different threshold for each patient. For patients below 65 years old, or above 65 years old but with preserved mental function and with no severe comorbidity, initial monotherapy with a dopamine agonist is advisable. This approach appears to delay the appearance and reduce the amount of late motor complications with subsequent levodopa treatment. All dopamine agonists have similar efficacy, which is less than that of levodopa. It is important to consider the adverse effect profile when a choice for initial or adjunctive therapy is made. When levodopa therapy is started as an adjunct in younger patients or as initial monotherapy in older patients, sustained-release levodopa preparations are preferred. They have a longer half-life and possibly stimulate the dopamine receptors more continuously. Anticholinergic drugs are appropriate for younger patients with tremor-dominant PD. Amantadine is mainly used for dyskinesia control. Catechol-O-methyl-transferase inhibitors and neurosurgery are not treatments of choice for early PD but can be very effective for more advanced disease. The presence of presymptomatic markers of PD, such as changes in odour detection, handwriting, speech, movement time of self-initiated motor acts, personality traits, presence of antibodies against dopaminergic neurons, pattern of positron emission tomography results, appearance of mitochondrial DNA mutation profiles, etc., appear to be very important in the light of the emerging neuroprotective therapies. Neuroprotection is aimed at slowing the rate of disease progression. Selegiline has been shown to cause a mild delay in the need for levodopa, possibly suggesting some protection. However, this initial benefit was not sustained in long term studies. Currently, there is no neuroprotective drug for PD.