Pharmacology of Movement Disorders

Question 1

What are the three dopaminergic pathways in the CNS?

Answer 1

Mesocortical, mesolimbic and nigrostriatal

Question 2

What type of receptor are dopamine receptors?

Answer 2

G-protein coupled receptors

Question 3

What are the D1 family of dopamine receptors?

Answer 3

D1 and D5

Question 4

What are the D2 family of dopamine receptors?

Answer 4

D2-D4

Question 5

What are Lewy bodies?

Answer 5

Intracellular formations enriched with alpha-synuclein

Question 6

What is the cause of Parkinson’s disease?

Answer 6

Loss of dopaminergic cells of the substantial nigra pars compacta and the presence of Lewy bodies resulting in an imbalance between the direct and indirect basal ganglia pathways

Question 7

How may MPTP be involved in the pathogenesis of Parkinsons disease?

Answer 7

MPTP can be converted into MPP+ which is neurotoxic for dopaminergic neurones and can affect/inhibit mitochondrial complex I leading to increased oxidative stress and further damage to the substantia nigra cells.

Question 8

What are the motor symptoms of Parkinson’s disease?

Answer 8

Resting tremor, bradykinesia, gait and postural changes and rigidity

Question 9

What are the non-motor symptoms of Parkinson’s disease?

Answer 9

Olfactory dysfunction, depression, psychotic symptoms, dementia, sleep disturbance and autonomic dysfunction

Question 10

How may Parkinson’s disease be treated?

Answer 10

L-DOPA, dopaminergic agonists, MAOb, anticholinergics, COMT inhibitors and dopamine agonists

Question 11

How may Parkinsons disease be treated with deep brain stimulation?

Answer 11

Stimulation of the sub thalamic nucleus

Question 12

What are the adverse effects of L-DOPA?

Answer 12

Nausea, vomiting, postural hypotension, psychosis, impulse-control disorders, excessive daytime sleepiness and MOTOR COMPLICATIONS (on-off effect, wearing off and dyskinesia/dystonia)

Question 13

What is rotigotine?

Answer 13

Dopamine agonist that can be given via transdermal patch (and used to treat PD)

Question 14

What are entacapone and tolcapone?

Answer 14

COMT inhibitors which inhibit dopamine metabolism peripherally and are used in combination with L-DOPA to treat PD

Question 15

Why may anticholinergics be used in the treatment of PD?

Answer 15

Dopamine loss leads to hyperactivity of the cholinergic cells

Question 16

What are the clinical signs of Huntington’s disease?

Answer 16

Choreic movement, gait abnormalities, lack of coordination, weight loss, sleep disturbance

Question 17

What is the cause of Huntington’s disease?

Answer 17

Autosomal dominant disease associated with gene coding for Huntingtin on chromosome 4; presents with abnormal normal of glutamine (CAG) repeats causing an aggregation of mutated protein inside cells due to the abnormality

Question 18

What gross changes would you see on an MRI of someone with Huntington’s disease?

Answer 18

Cortical atrophy and striatal degeneration

Question 19

What cellular damage occurs in someone with Huntington’s disease?

Answer 19

Loss of medium size spiny neurones of the striato-pallidal and striate-nigral pathways and there are intranuclear inclusions of Huntington protein

Question 20

What causes the neurodegeneration seen in Huntington’s disease?

Answer 20

Excitotoxicity,, accumulation of mutant Huntingtin aggregates and increased oxidative stress

Question 21

How may Huntington’s disease be treated pharmacologically?

Answer 21

Tetrabenazine (prevents amine transport), antidopaminergics (haloperidol), antidepressants (imipramine and amitriptyline)