Manegment of parkinson’s disease.

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Transcript Manegment of parkinson’s disease.

Parkinson's disease (PD)
• second most common age-related neurodegenerative disorder
• clinical symptoms,
motor symptoms
Nonmotor symptoms
Nonmotor Symptoms in Parkinson's disease
The Dark Side of the Moon
Nonmotor Symptoms P.D
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Depression
Anxiety
Psychosis
Dementia
FATIGUE
Sleep Dysfunction
Autonomic Dysfunction
Sensory Dysfunction
Depression
• Common ( 7 to 76%)
• may represent the first manifestation of PD
• comparison with patients without PD:
anxiety
pessimism
irrationality
suicidal ideation
•
higher frequency of MDD in patients with akinetic-rigid subtype
when compared with a tremor-dominant
• It is still controversial whether Depression has been associated with a
worse motor progression
Treatment
• There is no clear consensus regarding the use of antidepressants for
the treatment of depression in patients with PD
• the antidepressant effect of PD therapy has to be evaluated
before adding specific antidepressive therapy
• Dopamine agonists
reduce depression in PD
Pramipexole
demonstrated to have the same efficacy of SSRI in MDd
beneficial effect on mood and motivational symptoms in PD patients
without depression
Ropinirole
reduce depression
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MAO)-B inhibitors
weak antidepressant properties
TCAs
effective in treating depression
not well tolerated due to anticholinergic side effects
SSRI
effective in treating depression
potentially serotonin syndrome
aggravating motor symptoms
recent studies evidenced that SSRIs only rarely aggravate motor
symptoms in PD, and that sertraline may be the least
mirtazapine (presynaptic α2-antagonist)
effective in treating depression
demonstrated in reducing Parkinsonian tremor
drug selection should be based on potential
advantages versus potential side effects.
Anxiety
• affects nearly 40% of patients with PD
• The most common anxiety disorders in PD are panic attacks
(especially during off-periods)
• Benzodiazepines should be used cautiously because they may
increase adverse effects
• Buspirone, with dopaminergic effects, is well tolerate 10 – 40 mg
Psychosis
• The most common type of psychotic symptoms in PD are
hallucinations (visual )and delusions (paranoid)
• Hallucinations in treated PD patients is 15–40%
• Delusions occur in up to 10% of patients.
• when the hallucinations occur early in the course of the disease,
especially without any dopaminergic treatment, a diagnosis of levy
body disease should be considered.
treatment
• Excluding general causes of hallucination/confusion(fever & metabolic
dysfunction & drug)
• Reducing the dose or the number of antiparkinsonian drug
anticholinergic drugs
amantadine
(COMT) inhibitors
dopamine agonists
Levodopa
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Atypical antipsychotics
• Cholinesterase inhibitors
• Atypical antipsychotics
Clozapine and quetiapine do not appear to worsen parkinsonism as do other atypical
, and the typical neuroleptics
clozapine is the only atypical antipsychotic fully recommended for
the treatment of psychosis in PD.
because of the side effect of agranulocytosis, which requires frequent blood
testing
Quetiapine represents the most commonly used antipsychotic
treatment in PD patients.
• Cholinesterase inhibitors
rivastigmine, the only cholinesterase inhibitor that is US
FDA-approved for the treatment of dementia in PD,
demonstrated an improvement in neuropsychiatric
symptoms in PD patients with dementia
Dementia
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higher risk of developing dementia 30 -40%
• mean duration of PD before diagnosis of dementia is 10 years
• subtle cognitive deficits can be identified in the early stages
• Risk factors for PD–D include:
age
visual hallucinations
severe motor symptoms : rigidity
postural instability
gait disturbances
Management of dementia in PD
• systematic assessment
• Anticholinergics, amantadine and benzodiazepines
should be avoided because of their relationship with a reduction in
cognitive performances.
• Dopamine agonists should be used cautiously
• Cholinesterase inhibitors
• Cholinesterase inhibitors
donepezil and rivastigmine have been demonstrated to
significantly improve cognitive impairment
memantine, can improvement of cognitive symptoms,
even if its triggering effect on psychosis may limit the use
in clinical practice.
FATIGUE
• Fatigue is a common problem in patients with Parkinson disease
• Treatment of fatigue in PD begins with an attempt to identify the
cause. Excessive daytime sleepiness and depression are both the most
common and the most treatable identifiable causes.
• True fatigue unassociated with sleepiness or depression is more
difficult to treat
• Suboptimally treated bradykinesia sometimes presents as subjective
fatigue
• Medications used for empiric treatment of fatigue, such as
amantadine and stimulants, such as methylphenidate
Sleep Dysfunction
• Sleep dysfunction 75 to 98% in the PD population
Disorders of sleep initiation and maintenance
Excessive daytime sleepiness (EDS)
Sleep attack (SA)
Rapid eye movements behavior disorder (RBD )
Disorders of sleep initiation and maintenance
• Sleep fragmentation, the most common manifestation
• characterized by reduction in the stages III/IV or REM sleep
• could be due to :
motor manifestations of PD, such as o dystonia and cramp
bladder dysfunction, such as nocturia.
Restless-legs syndrome (RLS)
Sleep apnea
Treatment should include
• good sleep hygiene
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Improved control of motor symptoms of PD
• Treatment of RLS (dopaminergic agents)
• Hypnotic agents is not first line for potential side effects, specifically
confusion and daytime sleepiness.
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There are no controlled data on any specific hypnotic agent in PD
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• Ramelteon, a new hypnotic agent approved for sleep initiation
insomnia, which is a ligand of melatonin receptors, may be useful in
PD ( 8 mg orally once a day, 30 minutes prior to bedtime)
Excessive daytime sleepiness (EDS)
• very common among patients with PD, up to 50%
• Factors that contribute to EDS is
motor disability,
nocturnal sleep impairment
depression and dementia,
• higher prevalence of somnolence in patients treated with
dopamine agonists
• modafinil has not been effective for treating drowsiness in
patients with PD.
Sleep attack (SA)
• sleepiness that occurs without warning
• Patients may be unaware of prodromal sleepiness
• dopaminergic drugs provoke excessive daytime sedation
Rapid eye movements behavior disorder (RBD )
• prevalence in PD patients ranges between 33 and 60%
• male > female this male predominance are not yet known
• treated with
clonazepam in small doses (0.25–1 mg)
dopaminergic agents (DA , levodopa)
donepezil
Melatonin was reported to be effective at doses of 3–12 mg.
Autonomic Dysfunction
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Cardiovascular Dysfunction
Gastrointestinal Symptoms
Urinary & Sexual Dysfunction
Hyperhydrosis
Cardiovascular Dysfunction
• PD patients have higher BP at the off-stage than at on-stage
• patients with the on–off type of motor fluctuation have higher resting
heart rate, greater orthostatic BP
• Early diagnosis and symptomatic treatment of orthostatic hypotension
can greatly improve quality of life and, improve cardiovascular
mortality
Treatment
• reduction of dopamine agonists is often necessary
• Domperidone, a peripheral dopamine-blocking agent
• reduction of antihypertensive drug
• increase BP
α-adrenergic agents such as midodrine
salt-retaining mineralcorticoids (e.g., fludrocortisone).
Pyridostigmine was reported to be effective in neurogenic orthostatic hypotension
but has not been specifically tested in PD.[
Nonpharmacological
elevation of the head of the bed by 10–30°,
increase in salt and fluid intake and the use of waist-high
compression stockings.
Gastrointestinal Symptoms
• Constipation
exercise, dietary modifications, increases in fluid intake and
ultimately use of laxatives (Psyllium, bisacodyl)
coexistent abdominopelvic dyssynergia could be worsened by the use of laxatives
recalcitrant constipation
neostigmine, symbiotic yogurt containing components, botulinum toxin injections
and sacral nerve stimulation.
Dysphagia
the risk of food inhalation
no evidence of increased survival in patients receiving enteral
tube feeding.
• Nausea
often due to dopamine replacement therapy
adjustment of the timing of levodopa therapy in relation to food
and the use of domperidone.
Hypersalivation
reduced ability to swallow rather than overproduction of saliva
Anticholinergics and injection of botulinum toxin into the
salivary glands are therapeutic option
Urinary & Sexual Dysfunction
• Patients usually develop detrusor muscle hyperactivity
• Oxybutynin and tolterodine memory loss and constipation, must be
taken into consideration
• Sexual dysfunction:
male erectile dysfunction .60% of PD
• Sildenafil citrate has been found to be safe and effective
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Hyperhydrosis
• related to hypothalamic dysfunction
• Treatment options for hyperhydrosis are
limited.Propranolol has been helpful in
some cases.