parkinsonism

Introduction:

Parkinson's disease (PD) is a slowly progressive neurological disorder that affects movement, muscle control, and balance. Parkinson� ' s disease is part of a group of conditions called motor system disorders, which are associated with the loss of dopamine-producing brain cells. These dopamine-associated motor disorders are referred to as parkinsonism.

Parkinson's disease (PD) is a slowly progressive neurological disorder that affects movement, muscle control, and balance. Parkinson� ' s disease is part of a group of conditions called motor system disorders, which are associated with the loss of dopamine-producing brain cells. These dopamine-associated motor disorders are referred to as parkinsonisms.

Parkinson's Disease and Dopamine Loss

Parkinson's disease occurs from the following process in the brain:

• PD develops as cells are destroyed in certain parts of the brain stem, particularly the crescent-shaped cell mass known as the substantia nigra.

Parkinson's disease is a slowly progressive disorder that affects movement, muscle control, and balance. Part of the disease process develops as cells are destroyed in certain parts of the brain stem, particularly the crescent-shaped cell mass known as the substantia nigra. Nerve cells in the substantia nigra send out fibers to tissue located in both sides of the brain. There the cells release essential neurotransmitters that help control movement and coordination.

• Nerve cells in the substantia nigra send out fibers to the corpus stratia, gray and white bands of tissue located in both sides of the brain.
• There the cells release dopamine, an essential neurotransmitter (a chemical messenger in the brain). Loss of dopamine in the corpus stratia is the primary defect in Parkinson's disease.

Dopamine deficiency is the hallmark feature in PD. It is one of three major neurotransmitters known as catecholamines, which help the body respond to stress and prepare it for the fight-or-flight response. Loss of dopamine negatively affects the nerves and muscles controlling movement and coordination, resulting in the major symptoms characteristic of Parkinson's disease. Dopamine also appears to be important for efficient information processing, and deficiencies may also be responsible for problems in memory and concentration that occur in many patients.

For Restless Legs Syndrome see the Restless legs syndrome section.
Most patients require lifelong drug therapy to control Parkinson's disease (PD). The only established pharmacological treatment for the geriatric population is medication that can transiently reverse signs and symptoms associated with PD. Treatment should be individualized, based on symptom severity and degree of functional or cognitive impairment. During both initial therapy and dose escalation, elderly patients must be monitored for orthostatic hypotension. The lowest effective dose should be used and dose titration should be done slowly in order to minimize adverse effects. Drugs marked with an (*) are preferred for treating the elderly.

Dopamine (eg, levodopa/carbidopa): These drugs are the mainstay therapy and preferred treatment for PD in the elderly, especially if dementia is present. Levodopa, alone or in combination with carbidopa, helps improve bradykinesia, hypokinesia, and rigidity of PD. More common side effects may include confusion, hallucinations, nausea, and uncontrollable twitching or jerking. Additional monitoring and caution with levodopa are necessary as the elderly may be more sensitive to CNS effects. It is particularly important to monitor for orthostatic hypotension, in elderly patients who are also taking antihypertensive medications and those with which transient hypotensive episodes would be poorly tolerated (eg, cardiovascular or cerebrovascular disease). Neuroleptic malignant syndrome may develop when withdrawing treatment or during significant dosage reduction.

Dopamine agonists (eg, ergot derivatives: bromocriptine, pergolide; non-ergot derivatives: apomorphine, pramipexole*, ropinirole*):

 A dopamine agonist is used as an adjunct to L-dopa when patients have deteriorating response and experience fluctuations or limited clinical response with L-dopa secondary to an inability to tolerate higher doses. A dopamine agonist increases the frequency of "off" periods and provides an L-dopa-sparing effect. They may also be considered as first line therapy for the elderly patient who has normal physical and cognitive function. Pramipexole and ropinirole are the only dopamine agonists approved for monotherapy.

 Nausea is the most frequent reported GI side effect, occurring in >50% of patients. Cardiovascular effects occur infrequently, with the exception of postural hypotension, which should be carefully monitored in the geriatric population and during dose escalations. CNS effects (eg, hallucinations, confusion) are commonly seen in the elderly. Non-ergot derivatives also carry a warning of daytime sleep attacks. Use caution with the administration of other CNS depressants (eg, benzodiazepines, antipsychotics, antidepressants) due to the additive CNS effects of sedation and potentiation of sleep attacks. Dose adjustment in renal impairment is necessary for pramipexole. 

Catechol O-methyl transferase (COMT) inhibitors (eg, tolcapone*, entacapone*): 

COMT inhibitors are used as an adjunct to L-dopa to prevent the peripheral conversion of L-dopa to 3-O-methyldopa, a process which has been shown to increase the effects of L-dopa and decrease "off" time and L-dopa requirements. Their use with nonselective MAOIs is not recommended. Brown-orange discoloration of urine has been reported with use of entacapone. Side effects associated wth the use of COMT inhibitors include dizziness, orthostasis, and diarrhea. Fatal liver injury has occurred with tolcapone; discontinue if liver enzymes are greater than the upper limit of normal or signs and symptoms of hepatic failure occur. 

Anticholinergics (eg, benztropine, trihexyphenidyl):

 Anticholinergic drugs can be used as monotherapy or in conjunction with L-dopa or other antiparkinsonian drugs. These drugs are effective against tremors and dystonic features but are usually ineffective against bradykinesia or other PD disabilities. However, not all patients with tremor will respond to anticholinergics. Serious adverse reactions include forgetfulness, sedation, depression, and anxiety. Elderly patients frequently develop an increased sensitivity to anticholinergic adverse effects and require strict dosage regulation. The side effects of constipation and urinary retention may be worsened in patients who are also taking opioids or who have BPH. 

Dopamine reuptake inhibitor (eg, amantadine): 

A dopamine reuptake inhibitor is effective for mild PD, especially for symptoms of dyskinesia. Elderly patients may be prone to confusional side effects; therefore using divided daily doses may be recommended. The occurrence of insomnia may be reduced with the administration of the second dose early in the afternoon. Abrupt discontinuation of therapy may precipitate a parkinsonian crisis. Anticholinergics may potentiate the CNS effects of amantadine. Dose adjustment in renal impairment is required.

Monoamine oxidase (MAO) type B inhibitor (selegiline): 

When an MAO type B inhibitor is used as an adjunct to L-dopa, it increases the peak effects of L-dopa and may permit the reduction of L-dopa dosage to half the previous optimal dose by blocking the breakdown of dopamine. Selegiline may worsen preexisting dyskinesia or psychiatric symptoms, such as delusions and hallucinations, which may be problematic in the geriatric population. 

Doses greater than 10 mg/day have been associated with loss of MAOI selectivity and may lead to severe hypertensive crisis. Adverse reactions include insomnia and jitteriness. Avoid use in elderly patients who are on concomitant selective serotonin reuptake inhibitors and tricyclic antidepressants. Dose adjustment is required in the elderly.