TREATMENT OF PARKINSON'S DISEASE
Monday, December 20, 2010 by pbl13 in Labels:


Pharmacological

1)Dopaminergic agents
  •        To restore dopamine levels or acticvity
Eg,Dopamine precursor, Cathecol-O-methyl transferase(COMT)inhibitor, Dopamine agonist, Amantadine, Monoamine oxidase inhibitor

2) Antimuscaranic agents
  • ·         In Parkinson disease,reduced dopamine  levels cause a relative cholinergic activity.Antimuscarinic is used to restore the balance

Dopamine precursor
Levodopa and carbidopa combined (Sinemet®) is the mainstay of Parkinson's therapy. Levodopa is rapidly converted into dopamine by the enzyme dopa decarboxylase (DDC), which is present in the central and peripheral nervous systems. Much of levodopa is metabolized before it reaches the brain.
Carbidopa blocks the metabolism of levodopa in the liver, decreasing nausea and increasing the amount of levodopa that reaches the brain. Levodopa is most effective in treating bradykinesia and rigidity, less effective in reducing tremor, and often ineffective in relieving problems with balance. 

Side effects include nausea, especially early in treatment, low blood pressure (hypotension), and abnormal movements (dyskinesias). Slow dosage adjustment and taking medication with food can reduce these effects and using the lowest effective dose may prevent or delay the appearance of motor dysfunction. Levodopa can become ineffective over time.

Depression, confusion, and visual hallucinations also may occur with these medications, especially in the elderly.

 
Dopamine Agonists
Dopamine agonists mimic dopamine's function in the brain. They are used primarily as adjuncts to levodopa/carbidopa therapy. In some cases, these drugs are used as monotherapy, but they are generally less effective in controlling symptoms. 

Side effects are similar to those produced by levodopa and include nausea, sleepiness, dizziness, and headache.

Dopamine agonists include the following:
  • Bromocriptine (Parlodel®)
  • Pramipexole (Mirapex®)
  • Ropinirole (Requip®)
Amantadine (Symmetryl®) is an antiviral drug with dopamine agonist properties. It increases the release of dopamine and is often used to treat early-stage Parkinson's disease, either alone, with an anticholinergic drug, or with levodopa. Generally, it loses its effectiveness within 3 to 4 months.

Side effects of amantadine include mottling of the skin, edema, confusion, blurred vision, insomnia, and anxiety.

MAO-B Inhibitors 
Dopamine is oxidized by monoamine oxidase B (MAO-B). Rasagiline (Azilect®) and selegiline (Carbex®) inhibit MAO-B, increasing the amount of available dopamine in the brain. MAO-B inhibitors boost the effects of levodopa.

Side effects may include nausea, dizziness, abdominal pain, confusion, hallucinations, and dry mouth. 

 MAO-B inhibitors are contraindicated for patients taking tricyclic antidepressants (e.g., Pamelor®) , SSRIs (e.g., Prozac®), or meperidine (Demerol®) and other opiates. Patients who are taking MAO-B inhibitors must follow their physician's recommendations regarding a number of dietary precautions.

COMT (catechol-O-methyl transferase) Inhibitors 
These medications augment levodopa therapy by inhibiting the COMT enzyme, which breaks down dopamine after it is released in the brain. These drugs are only effective when used with levodopa. 

COMT inhibitors include entacapone (Comtan®) and tolcapone (Tasmar®).
 
Side effects of these medications include vivid dreams, visual hallucinations, nausea, sleep disturbances, daytime drowsiness, headache, and dyskinesias.

Carbidopa, levodopa, and entacapone are combined in Stalevo®, which is available in flexible dosing and indicated for patients who experience a reduced effectiveness of their PD medication.

Common side effects of Stalevo® include dyskinesias and nausea, which may be controlled by altering the dosing schedule. 

Other side effects include the following:
  • Abdominal pain
  • Constipation
  • Diarrhea
  • Discolored urine
  • Dizziness
  • Fatigue
  • Hallucinations
  • Hyperkinesias

Anticholinergics 
Anticholinergics reduce the relative overactivity of the neurotransmitter acetylcholine to balance the diminished dopamine activity. This class of drugs is most effective in the control of tremor, and they are used as adjuncts to levodopa.

These drugs include the following:

  • Benztropine mesylate (Cogentine®)
  • Biperiden (Akineton®)
  • Diphenhydramine (Benadryl®)
  • Trihyxyphenidyl (Artane®)
Side effects associated with anticholinergic drugs include dry mouth, blurred vision, constipation, and urinary retention. In higher doses, these medications may impair memory.

Non-pharmalogical

Deep brain stimulation.

In deep brain stimulation, surgeons implant electrodes into a specific area of your brain. The electrodes are connected to a generator that sends electrical pulses to your brain and may help control your Parkinson's disease symptoms. Surgery may involve risks, and your surgeon will work with you to determine if surgery is the most appropriate treatment for you.

Physical therapy

Goals of physical therapy include maintaining or increasing activity levels, decreasing rigidity and bradykinesia, optimizing gait, and improving balance and motor coordination. Features of the PT program may include:
  • Regular exercise, such as walking (1+ miles/day), swimming, golf, or dancing, depending on the patient's preferences and abilities
  • Stretching and strengthening
  • Exaggerated or patterned movements, such as high stepping and weight shifting
  • Mobility aids, orthotics (such as braces or splints)
  • Training in transfer techniques
  • Training in techniques to improve posture and walking
Occupational therapy

Goals of occupational therapy include maximizing fine motor coordination, especially of the upper extremities, reducing energy expenditure, increasing safety and independence, and improved efficiency of activities of daily living. Features of the OT program may include:
  • Use of orthoses and adaptive equipment
  • Home and workplace modification, improving accessibility, and removing obstructions
  • Adaptation and simplification of utensils, toileting articles, beds, etc
Speech and swallowing

Low voice volume (hypophonia) often occurs in PD. Several PD-specific voice training programs have been developed, which share an emphasis on consciously increasing voice volume as a key strategy. Other features may include modification of speech patterns such as use of shorter sentences, breathing exercises, and range-of-motion exercises for the muscles of speech.
Drooling (sialorrhea) can be a common feature of advanced PD. The origin of the problem is not in increased saliva production, but reduced spontaneity of swallowing. Awareness of the problem, and consciously swallowing more often, may be effective. If not, treatments may include a small dose of an anticholinergic medication under the tongue, or injection of botulinum toxin into the salivary glands to temporarily paralyze them. Both of these reduce saliva production.
Management of swallowing difficulties may include instruction to take smaller bites, to completely empty the mouth before taking the next bite, and eating softer foods.

Sexuality

Sexual dysfunction affects a large proportion of patients with PD and their spouses. Difficulties include erectile dysfunction in males, vaginal dryness, and loss of libido. Hypersexuality from levodopa and dopamine agonists also occurs. Many PD patients are reluctant to talk about these issues with their doctor, and may not connect the symptom to the disease at all. There are useful treatments, both medical and nonmedical, for many of these problems. Patients should always have a thorough urological or gynecological evaluation to rule out non-PD related problems. Sildenafil (Viagra®) has been shown to be safe and effective in men in PD to treat erectile dysfunction.

Driving

PD patients tend to do worse than controls on tests of driving safety, because of increased reaction times and movement times caused by PD. Vehicular control skills are generally well preserved, but attention to safety landmarks declines. Decline in performance seems to be related to a worsening of motor abilities. Patients tend not to be good judges of their loss of driving safety, and family members may need to intervene. A good way to determine driving capability is to have the patient undergo a driving examination at a rehabilitation facility.

Constipation

A good bowel regimen can greatly reduce constipation. Increased fluid intake, a diet rich in vegetables and fruits, use of stool softeners, and increased dietary and supplemental fiber are just some interventions that can help. Working with one's physician and/or a gastroenterologist is the approach to take.

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