L1.2 Parkinson's and Huntington's Disease

Question 1

In relation to Parkinson’s Disease, what does TRAP stand for?

Answer 1

TRAP: Tremour at rest, Rigidity of limbs, Akinesia, Postural problems (leading to loss of balance)

Question 2

what are the motor skill symptoms and non-motor skill symptoms for PD?

Answer 2

Motor skill symptoms: bradykinesia (mask-like face, decreased blinking, degrading fine motor skills), vocal symptoms, rigidity and postural instability, tremors, walking or gait difficulties, dystonia (repetitive muscle movements that makes body parts twist)
Non-motor skill symptoms: mental/behavioural issues, sense of smell, sweating and melanoma, gastrointestinal issues (urinary issues, weight loss, sexual concerns), pain

Question 3

What causes PD?

Answer 3

• PD is due to the selective loss of dopaminergic neurons in the substantia nigra pars compacta of the brain
• The substantia nigra is the major origin of dopaminergic innervation of the striatum, mainly responsible for posture regulation and muscle tone

Question 4

what are the PD effects on voluntary movement?

Answer 4

Increased indirect pathway and increased inhibitory effects = decreases the outcome of the direct pathway = inhibition of voluntary movement

Question 5

Describe the impact of PD on dopamine and acetylcholine.

Answer 5

DAergic neurons from substantia nigra normally inhibit the GABAergic output from the striatum, while cholinergic neurons are excitatory. In PD, the loss of DA neurons leads to overactivity of the ACh component, with activiation of GABA release and muscle rigidity.

Question 6

what are anticholinergic drugs?

Answer 6

anticholinergic drugs reduce the effects of acetylcholine and restore the balance of dopamine by blocking the brain receptors for acetylcholine.

Question 7

what are dopamine-boosting drugs?

Answer 7

these drugs increase dopamine activity and restore the natural balance with acetycholine.

Question 8

what drug can be converted into dopamine?

Answer 8

levodopa (L-DOPA), a precursor of dopamine, is the major initial drug used. It can cross the blood-brain barrier (dopamine cannot cross the blood-brain barrier but a precursor of dopamine can), and is presumed to be taken up by dopaminergic neurons which then convert it to dopamine for use in synapses. This would increase amounts of dopamine available.

Question 9

what drugs can inhibit the metabolism of dopamine?

Answer 9

• Rasagiline, a selective MAO-B inhibitor, may slow the normal degradation of dopamine in the brain and preserve it for recycling into vesicles
• use of sustained release preparations of L-DOPA or addition of COMT inhibitors, such as entacapone, may counteract fluctuations of L-DOPA
• due to gliosis, more MAO-B found in the brains of patients with PD; MAO-B activity levels are doubled in the substantia nigra in PD and correlate with the percentage of dopaminergic cell loss

Question 10

the effectiveness of _______ lasts for only about 2 years because its central conversion to dopamine gradually diminishes, owing to progressive degeneration of the dopaminergic neurons

Answer 10

the effectiveness of LEVODOPA lasts for only about 2 years because its central conversion to dopamine gradually diminishes, owing to progressive degeneration of the dopaminergic neurons

Question 11

the therapeutic benefits of levodopa are maximised by giving it in combination with peripheral dopa decarboxylase inhibitor (e.g. ______) or a selective monoamine oxidase-B (MAO-B) inhibitor (e.g. _____) or a catechol-O-methyltransferase (COMT) inhibitor

Answer 11

the therapeutic benefits of levodopa are maximised by giving it in combination with peripheral dopa decarboxylase inhibitor (e.g. CARBIDOPA) or a selective monoamine oxidase-B (MAO-B) inhibitor (e.g. SELEGILINE) or a catechol-O-methyltransferase (COMT) inhibitor

Question 12

other treatments of PD

• bromocriptine= ?
• amantadine= ?
• anticholinergic drugs (e.g. trihexyphenidyl hydrochloride and benztropine mesylate)

Answer 12

other treatments of PD

• bromocriptine= a dopamine agonist
• amantadine= increases dopamine release
• anticholinergic drugs (e.g. trihexyphenidyl hydrochloride and benztropine mesylate)

Question 13

what are some adverse effects of levodopa?

Answer 13

involuntary movement, ‘on-off effects’, nausea, hypotension, some cardiac arrhythmias

Question 14

describe a surgical treatment of PD

Answer 14

• Brain stimulation technology may benefit patients with advanced, levodopa-resistant Parkinson’s disease. The subthalamic nucleus (STN) or the globus pallidus interna (GPi) are targeted to suppress some of the disabling symptoms of Parkinson’s disease
• DBS works by stimulating the area that influences motor control
• The system delivers electrical pulses that affect brain cell activity, blocking selected brain areas to alleviate movement problems
• This it NOT a cure for Parkinson’s- it reduces the adverse effects of L-DOPA treatment as the disease progresses

Question 15

define huntington’s disease

Answer 15

= HD is a disease of cell loss in the basal ganglia
Instead of slowing down movements, the hallmark symptoms are uncontrolled writhing of the muscles in the face, trunk and neck. While the body’s movement is distorted continuously, there is also progressive dementia.

Question 16

what is happening with the neurons in HD?

Answer 16

In post-mortem brains, there is a 75% reduction in activity of glutamic acid decarboxylase, an enzyme responsible for synthesis of GABA. It is though that with GABA concentrations declining in the brain, dopaminergic circuits are allowed to operate without the usual “brake”.

Question 17

in HD what happens to the GABAergic neurons

Answer 17

Normal: DAergic neurons from substantia nigra usually inhibits GABAergic output from the striatum, while cholinergic neurons are excitatory.
HD: GABAergic neurons degenerate. Inhibitory regulation is lost, with net excitation as the result, leading to uncontrolled motor activity.

Question 18

what are the drug treatments of motor symptoms of HD

Answer 18

Chorea can be suppressed by using drugs which deplete dopamine and other neurotransmitters; such as tetrabenazine. Antagonists to dopamine receptors may also be used in patients, such as haloperidol, which improves motor function and psychosis associated with HD.
Physical side effects of these drugs (drowsiness and less ability to move) can be worse than the chorea. As the disease progresses, natural dopamine levels fall, leading to loss of chorea and increase in rigidity and slowness.