Parkinson's disease

Question 1

what does madopar contain? what is its mechanism of action?

Answer 1

L-DOPA + benserazide
L-dopa is a precursor of dopamine and directly compensates for dopamine deficit in Parkinson’s disease.
benserazide is a peripherally acting dopa decarboxylase inhibitor which increases availability of L-DOPA in the brain and reduces its peripheral conversion into dopamine which can cause side effects such as nausea and vomiting.

Question 2

which gene causes a rare case of autosomal dominant familial Parkinson’s and how?

Answer 2

mutations in SNCA gene - this gene encodes for alpha synuclein proteins. mutated alpha-synuclein aggregate to form Lewy bodies - pathology of Parkinson’s

Question 3

What are the roles of basal ganglia?

Answer 3

1. regulate intensity if slow movement
2. inhibit counteracting and unnecessary movements
3. switching motor programs

Question 4

where does the corpus striatum receive its input from?

Answer 4

1. corticostriatal projection - glutaminergic (excitatory)

2. nigrostriatal projections from the substatia nigra pars compacts (dopaminergic)

Question 5

what is the role of the direct pathway?

Answer 5

initiation of volitional movement

Question 6

what is the role of indirect pathway?

Answer 6

antagonising the actions of direct pathway.

Question 7

when is the indirect pathway active?

Answer 7

when at rest or undergoing repetitive movements.

Question 8

what is the effect of dopamine on striatal neurons?

Answer 8

1. acts on D1 receptors to depolarise neurons of direct pathway
2. acts on D2 neurons to hyperpolarise neurons of indirect pathway
3. overall, it increases the action of direct pathway and allows change of motor program

Question 9

List four cardinal symptoms of Parkinson’s disease

Answer 9

1. resting tremor
2. bradykinesia
3. rigidity
4. postural instability and gait disturbances

Question 10

list some non-motor symptoms of Parkinson’s disease

Answer 10

1. anosmia
2. depression
3. psychotic symptoms
4. cognitive dysfunction + dementia
5. sleep disturbances
6. autonomic dysfunction: urinary urgency, hypotension, contipation

Question 11

what is the mechanism of action of Selegiline?

Answer 11

MAO-B inhibitor - reduces breakdown of dopamine

Question 12

what are the side effects of selegiline?

Answer 12

nausea, hallucinations, confusion, depression, loss of balance, insomnia, increased involuntary movements, agitation, slow or irregular heart rate, delusions, hypertension, new or increased angina pectoris, and syncope

Question 13

what is the mechanism of action of amantidine?

Answer 13

increase dopamine release and inhibits its reuptake

Question 14

what are the adverse effects of L-DOPA?

Answer 14

1. on-off effect
2. end-of-dose deterioration
3. peak dose dyskinesia and wearing off dystonia
4. psychosis - action on mesolimbic dopaminergic pathway
5. nausea and vomiting
6. excessive sleepiness

Question 15

what are some non-pharmacological approaches to treating Parkinson’s disease?

Answer 15

1. pallidotomy or thalamotomy

2. deep brain stimulation