Pathophysiology of Parkinson’s Disease:

Pathophysiology of Parkinson’s Disease – The Parkinson’s disease (PD) were first described by James Parkinson in 1817 in his Essay on the Shaking Palsy. These include:

  • Tremor (usually most noticeable when the limb is at rest)
  • Bradykinesia (slowness of movement)
  • Rigidity (stiffness of movement)
  • Postural instability (imbalance when standing or walking)

The Pathophysiology condition of Parkinson’s Disease can be diagnosis is based on evidence of at least two out of three specific signs and symptoms: tremor, slowed mobility (bradykinesia) and/or stiffness (rigidity).

Parkinson’s disease is not only a disorder of motor symptoms. It is now well known that non-motor symptoms also can be prominent and even disabling in PD. Non- motor symptoms include changes in mood, memory, blood pressure, bowel and bladder function, sleep, fatigue, weight and sensation. Some symptoms have features of both (i.e., mixed motor and non-motor symptoms).

Symptoms in Parkinson’s Disease:

MOTOR SYMPTOMS

•     Bradykinesia (slowness of movement)

•     Rigidity (stiffness of movement)

•     Tremor (involuntary shaking of the hands, feet, arms, legs, jaw or tongue; usually more prominent at rest)

•     Postural instability (tendency to fall)

NON-MOTOR SYMPTOMS

•     Mood changes (depression, anxiety, irritability)

•     Cognitive changes (memory problems, personality changes, psychosis/hallucinations)

•     Orthostatic hypotension (lightheadedness and low blood pressure when standing)

•     Constipation and early satiety (a feeling of fullness after eating small amounts)

•     Hyperhidrosis (excessive sweating)

•     Seborrhea (oily skin)

•     Urinary urgency and incontinence

•     Sexual dysfunction

•     Loss of sense of smell

•     Sleep disorders

•     Insomnia, excessive daytime sleepiness (EDS), rapid eye movement behavioral disorder (RBD) or active dreaming, dream enactment, involuntary movements and vocalizations during sleep, restless leg syndrome (RLS)/periodic limb movement disorder (PLMD)

•     Fatigue

•     Sensory problems (pain, tightness, tingling, burning)

MIXED MOTOR AND NON-MOTOR SYMPTOMS

•     Drooling due to slowed swallowing (sialorrhea)

•     Speech and swallowing problems

Pathology of Parkinson’s Disease:

Parkinson’s disease is a result of the loss of Dopmergic neurons that produce a chemical called dopamine.

The motor symptoms come from the slow and progressive degeneration and death of these neurons in an area of the brain called the substantia nigra, which is in the brain stem.

One reason these brain cells begin to die may be due to genetic abnormalities. The earliest symptoms of PD usually don’t appear for several years after the onset of neurodegeneration because there is plenty of dopamine left in reserve to compensate for the declining supply.

We now also know that the non- motor features of PD arise from the loss of neurons in areas of the brain outside of the substantia nigra and involve chemicals other than dopamine, particularly acetylcholine.

In 2011, a computerized brain scan utilizing a radio-isotope that labels the molecule transporting dopamine into the cell (DaTscan) first became available in the United States.

A DaTscan may be used to assist with the clinical diagnosis of pathophysiology of parkinsons disease and other parkinsonian syndromes when the patient’s presenting symptoms are not straightforward.

Treatment of Parkinson’s Disease:

The following medications used to treat Parkinson’s disease are discussed in this chapter:

  • Levodopa
  • Dopamine agonists
  • MAO-B inhibitors
  • COMT-inhibitors
  • Amantadine
  • Anticholinergics
Levodopa
Carbidopa/ levodopa immediate-release (Sinemet) 10/100,

25/100,

25/250

150–1000 mg of levodopa total daily dose (divided 3-4 times) Low blood pressure, nausea, confusion, dyskinesia Monotherapy or combination therapy for slowness, stiffness and tremor
Carbidopa/ levodopa orally disintegrating (Parcopa) 10/100,

25/100,

25/250

150–1000 mg of levodopa total daily dose (divided 3-4 times) Same as above Same as above, plus need for dissolvable medication in mouth especially if swallowing is impaired
Carbidopa/ levodopa extended-release (Sinemet CR) 25/100,

50/200

150–1000 mg of levodopa in divided doses, depending on daily need Same as above Monotherapy or combination therapy for slowness, stiffness and tremor
Dopamine Agonists
Ropinirole (Requip) 0.25, 0.5, 1, 2,

3, 4, 5

9–24 mg total daily dose (divided 3–4 times) Low blood pressure, nausea, leg swelling and discoloration, confusion, sleep attacks, compulsive behaviors Monotherapy or combination therapy for slowness, stiffness and tremor
MAO-B Inhibitors
Selegiline (l-deprenyl, Eldepryl) 5 5 mg once or twice a day Nausea, dry mouth, light-headedness, constipation; may worsen dyskinesia; possible rare interaction with

anti-depressants and other drug classes

Monotherapy for slowness, stiffness and tremor; adjunct therapy for motor fluctuations
Rasagiline (Azilect) 0.5, 1.0 1 mg once/day Same as above Same as above
Selegiline HCL orally disintegrating (Zelapar) 1.25, 2.5 1.25–2.5 mg

once/day

Same as above Same as above, plus need for dissolvable medication in mouth (absorbed in mouth)
COMT-Inhibitors
Entacapone (Comtan) 200 200 mg 4–8 times daily (with each levodopa dose) Diarrhea, discolored urine, plus enhancing side effects of levodopa, especially dyskinesia and confusion Combination therapy with levodopa

for motor fluctuations

(not pharmacologically active by itself)

Tolcapone (Tasmar) 100, 200 100 mg up to 3 times daily Same as above plus increased risk of liver inflammation Same as above (second-line due to side effects)
Other Antiparkinson Medications
Amantadine (Symmetrel) 100 mg capsules; 50mg/5ml syrup 100 mg 2–3 times daily Nausea, confusion, leg discoloration (livido reticularis), mild anti-cholinergic effects (see below) Monotherapy for slowness, stiffness, and tremor; combination therapy with levodopa for levodopa-induced motor fluctuations; especially helpful for suppressing dyskinesia
Anticholinergics
Trihexyphenidyl (formerly Artane) 2, 5 mg tablets; 2 mg/5 ml elixir 1–2 mg 2 or

3 times daily

Confusion, memory issues, hallucinations, dry mouth, blurry vision, urinary retention Monotherapy or combination therapy, predominantly for tremor in younger people; should be avoided in elderly

The management of PD has traditionally centred on drug ther- apy with levodopa viewed as the ’gold standard’ treatment (Rascol 2002). However, even with optimal medical management, pa- tients with PD still experience a deterioration of body function, daily activities and participation (Nijkrake 2007).

For this reason there has been increasing support for the inclusion of rehabilita- tion therapies as an adjuvant to pharmacological and neurosurgi- cal treatment (Gage 2004; Nijkrake 2007) and a call for the move towards multidisciplinary management of this multidimensional condition (Robertson 2003; Rubenis 2007).

Physio- therapy for PD focuses on transfers, posture, upper limb function, balance (and falls), gait, physical capacity and (in)activity utilising cueing strategies, cognitive movement strategies and exercise to optimise the patient’s independence, safety and wellbeing, thereby enhancing quality of life (Keus 2004; Keus 2007).

Regular exercise, physical therapy, occupational therapy, speech therapy, holistic practices, nutritional consultation, support groups, education, psychological counseling, intelligent use of assistive devices and caregiver relief are all important aspects of the best treatment plan.

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