Lecture 31: Parkinsons Disease and Anti-parkinsons drugs C5

Question 1

What are the different types of Parkinsons disease, in what age more present.

Answer 1

Idiopathic Parkinsons is ~80%. No cerebellar signs. Triggers not known. 60yr+ onset

PD+ syndomes: eg. MSA, Spinocerebella Ataxia, Wilsons disease: The cerebellum can be affected as well.

Genetic forms: less than 5%, generally in 40- yr

Question 2

What are some epidemiological risks for Parkinsons

Answer 2

1. Family history- 2x risk.
2. Males higher prevalence
3. Some environmental exposures, pesticides, solvents in woodwork.
4. Animal and dairy product intake

Question 3

What are the 4 cardinal manifestations of PD + 1 more

Answer 3

Cardinal manifestations:

1. Rest tremor
2. Rigidity
3. Bradykinesia
4. Postural instability and gait disturbance
5. Pre-motor and non-motor symptoms

Question 4

How does Parkinsons symptoms present as it progresses

Answer 4

1. Starts presenting symptoms on one side
2. Become more symmetrical as progresses,
3. Remains slightly assymetrical

Question 5

Describe Tremor: (Not all patients have a tremor)

Answer 5

1. Relatively slow, resting tremor. Head tremor is unusual

2. It is there at rest, goes away with movement and comes back with holding posture

Question 6

Describe Rigidity, how is it found

Answer 6

1. Detected using slow passive movements: If mild it can be brought out by coactivation with the other arm: Froments manouvre
2. Displays step-wise increase in tone.

Question 7

Describe Akinesia/ Bradykinesia. How is it found

Answer 7

1. Slowness and poverty of movement with
   fatiguing and decrement of repetitive movement
2. Reduction in amplitude + slowness of movement.
3. Tested through repetitive movements, start from proximal to distal.

eg. touching thumb + finger, hand closing, pro/sup of arms, toe tapping, stamping whole leg.
Also seen in reduced blink frequency

Question 8

Describe 4 Gait and Postural changes seen in PD

Answer 8

1. Dragging one leg, festination - short steps but appear to be hurrying
2. Reduced arm swing, usually assymetric. Forward flexion/ stooping.
3. Freezing of gait: hard to turn around
4. Postural instability and falls: late in course of disease.
   Pull test: pull from behind count number of steps to regain stability. 3+ is abnormal

Question 9

What are some non - motor features of PD

Answer 9

1. Anosmia loss of smell
2. RSBD: rem sleep behaviour disorder: act out dreams
3. Autonomic dysfunction: early on is constipation early, late is postural dizziness
4. Pain, Fatigue, Mood down
5. Late in PD is Cognitive decline reduced attention, concentration, executive dysfunction.

Question 10

What are Lewy bodies as a cause of PD symptoms

Answer 10

Present in the brainstem, basal ganglia and cortex

They are cytoplasmic aggregates of a-synuclein, ubiquitin, neurofilament protein.

Question 11

What is the main treatment of Parkinsons and what is it administered with

Answer 11

Levodopa in tablet form combined with Dopa decarboxylase inhibitor eg. carbidopa/benserazide to prevent enzyme converting it in the blood stream instead of in the CNS

Question 12

What are the adverse effects of Levadopa

Answer 12

• initiation nausea, low bp, can worsen confusion and hallucinations later in the disease.
• can induce dyskinesia with increased frequency and dosage over time

Question 13

What are 4 other oral medications for PD, what do they treat and how. give eg.

Answer 13

1. Dopamine agonists: stimulate dopamine receptors at the PSmem directly eg.ropinirole
2. MAO-B inhibitor: prevent dopamine breakdown at synapse: eg. selegiline: milder drug
3. COMT inhibitors: reduce peripheral metabolism of Ldopa to prolong its effect: good for wearing off symptoms (entacapone, opicapone)

4.Amantadine:
reduce dyskinesia in advanced PD: mild effect on cardinal motor symptoms.

Question 14

How does oral dosing change as PD progresses

Answer 14

As time goes on they need more doses to maintain the same level of effect.

There will be more off periods despite having multiple doses, with unpredictable troughs and highs.

Doses timed to motor symptom

Question 15

What are the 3 advanced therapies for PD for those with motor fluctuations and dyskinesias uncontrolled

Answer 15

1. Subcutaneous continuous infusion pump with dopamine agonist Apomorphine; to offset sudden fluctuations with single injection
2. Deep brain stimulation:
   STN: PD motor symptoms: can reduce medications

GPi: antidyskinesia : allows increase in medication w/out side effects.
- doesn’t stop disease progression, but does increase on time without dyskinesia

3. Duodopa: Levodopa/ carbidopa intestinal gel infusion through PEG tube into duodenum reduces fluctuations related to absorption of LD.
   Can have mechanical and blockage problems