What is parkinsonism?
Parkinsonism is generally characterized into four symptoms:
- bradykinesia
- muscular rigidity
- resting tremors
- impairment of postural balance.
The primary pathology of the disease is a decrease in dopamine in the basal ganglia. This disease is mostly observed in older persons 40 years and above. Although some authorities might claim a genetic cause, an infection may possibly predispose an individual to parkinsonism. The pathophysiologic basis of the idiopathic disorder may be related to exposure to some unrecognized neurotoxin or to the occurence of oxidation reactions with the generation of free radicals. Simply put, there are still unknown causes why an individual can have parkinsonism but the primary cause readily accepted by authorities is a genetic predisposition.
There are several kinds of Anti-Parkinsonism drugs. These are:
Sinemet® (levodopa 100mg/carbidopa 25mg) causes a reduction in peripheral metabolism of levodopa. SInce levodopa is a precursor of dopamine, a reduction on its metabolism will mean that more precursors will enter the brain. More precursors in the brain will lead to more dopamine production. It is known that dopamine cannot pass the blood-brain barrier and only its precursors can pass from the peripheral blood to the CNS. Basically, the primary management is intravenous (IV) administration of dopamine precursors (levodopa) so that there is an increase in the concentration in the peripheral blood, and carbidopa, which reduces the metabolism of peripheral levodopa, facilitating its production in the CNS.
Dopamine agonists (ergot and non ergot drugs) primarily act on dopamine receptors, more particularly the D3 receptor. They agonize the dopamine effects which results in increased dopamine sensitivity and action of the receptors.
MOA (monoamine oxidase) inhibitors retard the breakdown of dopamine. Selegiline is a selective, irreversible inhibitor of MAO beta at normal doses. High doses of this drug may lead to inhibition of MAO alpha also. Rasagiline is more potent than selegiline in preventing MPTP induced parkinsonism.
COMT inhibitors prolong the action of levodopa by diminished metabolism of L-dopa. They also decrease L-dopa clearance and increase relative bioavailability of L-dopa. It is to be noted that these drugs cannot be used alone. They may be coupled with dopamine precursors and decarboxylases.
Amantidine is an anti-viral agent which potentiates dopaminergic functions by influencing synthesis, release and reuptake of dopamine. It is less potent than L-dopa.
Acetylcholine-blocking agents act primarily on improving tremors and rigidity. They have no effect on bradykinesia. Commonly used drugs are benztropine, biperidine, orphenadrine, procyclidine and trihexyphenidyl.
One might also try neuroprotective therapy such as:
There are several kinds of Anti-Parkinsonism drugs. These are:
- Dopamine precursor/ decarboxylase (e.g. levodopa/carbidopa or Sinemet®)
- MAO beta inhibitors (e.g. rasagiline, selegiline)
- Anti-viral drugs (e.g. amantidine)
- COMT inhibitors (e.g. entacapone, tolcapone)
- Acetylcholine blockers (e.g. biperidine, benztropine)
- Dopamine Agonists
- Ergot (e.g. bromocriptine, pergolide)
- Non Ergot (e.g. pramipexole, ropinirole)
Sinemet® (levodopa 100mg/carbidopa 25mg) causes a reduction in peripheral metabolism of levodopa. SInce levodopa is a precursor of dopamine, a reduction on its metabolism will mean that more precursors will enter the brain. More precursors in the brain will lead to more dopamine production. It is known that dopamine cannot pass the blood-brain barrier and only its precursors can pass from the peripheral blood to the CNS. Basically, the primary management is intravenous (IV) administration of dopamine precursors (levodopa) so that there is an increase in the concentration in the peripheral blood, and carbidopa, which reduces the metabolism of peripheral levodopa, facilitating its production in the CNS.
Dopamine agonists (ergot and non ergot drugs) primarily act on dopamine receptors, more particularly the D3 receptor. They agonize the dopamine effects which results in increased dopamine sensitivity and action of the receptors.
MOA (monoamine oxidase) inhibitors retard the breakdown of dopamine. Selegiline is a selective, irreversible inhibitor of MAO beta at normal doses. High doses of this drug may lead to inhibition of MAO alpha also. Rasagiline is more potent than selegiline in preventing MPTP induced parkinsonism.
COMT inhibitors prolong the action of levodopa by diminished metabolism of L-dopa. They also decrease L-dopa clearance and increase relative bioavailability of L-dopa. It is to be noted that these drugs cannot be used alone. They may be coupled with dopamine precursors and decarboxylases.
Amantidine is an anti-viral agent which potentiates dopaminergic functions by influencing synthesis, release and reuptake of dopamine. It is less potent than L-dopa.
Acetylcholine-blocking agents act primarily on improving tremors and rigidity. They have no effect on bradykinesia. Commonly used drugs are benztropine, biperidine, orphenadrine, procyclidine and trihexyphenidyl.
One might also try neuroprotective therapy such as:
- antioxidants
- anti-apoptotic agents
- glutamate antagonist
- intraparenchymally administered glial-derived neurotrophic factor
- coenzyme Q10
- anti-inflammatory drugs
- symptomatic treatment of mild parkinsonism is best avoided until symptoms develop a significant impact on patient's lifestyle.
- when treatment becomes necessary, a trial of amantidine and/or an antimuscarinic drug may be worthwhile
- with progression of the disease, dopaminergic drugs alone or with low dose of Sinemet can be used
- in severe parkinsonism with complications of levodopa, COMT inhibitor drugs are used
- deep brain stimulation may be helpful in patient who fail response adequately to this measure
- young and with mild disease may use rasagiline or selegiline.
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