Therapeutics of basal ganglia

Question 1

Where are dopaminergic cells lost from in Parkinsons Disease

Answer 1

Substantia Nigra

Question 2

There is an imbalance between what in Parkinsons disease

Answer 2

Direct and indirect pathways

Question 3

Is the direct pathway more or less active in Parkinson

Answer 3

Less

Question 4

Is the thalamus excited or inhibited in Parkinsons

Answer 4

Inhibited

Question 5

Which 2 structural abnormalities can be seen in Parkinsons

Answer 5

Loss of dopaminergic cells in SN

Presence of neurones of lewy bodies

Question 6

What protein are Lewy bodies enriched with

Answer 6

alpha synuclein

Question 7

What imaging process can be used to monitor dopaminergic nigral cell loss

Answer 7

DaT (dopamine transporter) imaging

Question 8

What can transporter be labelled with in DaT

Answer 8

SPECT ligands

Question 9

What are the features of Parkinsons disease

Answer 9

Frozen facial expression
Flexed posure
Altered gait and postural changes
Difficulty in initiating and stopping movement
Resting tremor
Bradykinesia
Rigidity

Question 10

What is microphagia

Answer 10

Increased tendency to smaller illegible handwriting

Question 11

Name some non motor features of the disease

Answer 11

Olfactory dysfunction
Depression
Psychotic symptoms
Cognitive dysfunction
Dementia
Sleep disturbance
Autonomic dysfunction

Question 12

By how many years may non motor features precede the typical features

Answer 12

12-15 years

Question 13

Name 6 genes involved/ associated with Parkinsons disease

Answer 13

SNCA
LRRK2
GBA
PARK2
PINK1
PARK7

Question 14

What mutation gives the alpha synuclein protein

Answer 14

SNCA

Question 15

Is Parkinson’s incidence and prevalence higher in men or women

Answer 15

Women

Question 16

What does MPTP stand for

Answer 16

methyl-phenyl-tetrahydropyridine

Question 17

What is the compound MPTP transformed into

Answer 17

MPP+

Question 18

What does dysfunction of complex 1 of mitochondrial respiratory chain lead to

Answer 18

Oxidative stress

Question 19

What kind of receptors are G protein coupled receptors

Answer 19

Dopamine receptors

Question 20

What receptors are in the D1 family

Answer 20

D1 and D5

Question 21

What receptors are in the D2 family

Answer 21

D2, D3 and D4

Question 22

Name the 5 categories of drugs commonly used to treat Parkinsons disease

Answer 22

• Dopaminergic compounds
• MAOb inhibitors
• Anticholinergic compounds
• Amantadine
• COMT inhibitors

Question 23

What is L-DOPA

Answer 23

Levodopa is a biosynthetic precursor

Combined with peripherally acting DOPA decarboxylase inhibitors

Question 24

Name 2 peripherally acting DOPA decarboxylase inhibitors

Answer 24

Carbidopa

Benserazide

Question 25

What dopaminergic agonist can be used as a transdermal patch

Answer 25

Ropinirole

Question 26

What dopaminergic agonist can be used as an infusion

Answer 26

Apomorphine

Question 27

How do MAOb inhibitors work

Answer 27

Protect residual dopamine against oxidation

Question 28

Name 2 MAOb inhibitors

Answer 28

Rasagiline | Selegiline

Question 29

Why are anticholinergic compounds used to treat parkinsons

Answer 29

Dopamine loss leads to hyperactivity of cholinergic cells

Question 30

Name 3 anticholinergic compounds

Answer 30

Orphenadrine Procyclidine Trihexyphenidyl

Question 31

How does amantadine work

Answer 31

Inhibits dopamine reuptake | Increases dopamine release

Question 32

What drug are COMT inhibitors used with to enhance its effects

Answer 32

L Dopa

Question 33

Name 2 COMT inhibitors

Answer 33

Entacapone | Tolcapone

Question 34

Name 5 non motor adverse effects of L-DOPA

Answer 34

``` Nausea/ vomiting Postural hypotension Psychosis Impulse control disorders Excessive day-time sleepiness ```

Question 35

Name 3 motor complications of L-DOPA

Answer 35

On-off effect Wearing off Dyskinesia and dystonia

Question 36

Define dystonia

Answer 36

Cramps

Question 37

What 3 things must PD patients have regular access to

Answer 37

Monitoring and alteration of medication Continuating point of contact Reliable source of info

Question 38

What kind of graft can be implanted in PD

Answer 38

Human embryonic mesencephalic graft | Functional and releases dopamine

Question 39

What area of the brain can be stimulated in PD

Answer 39

Subthalamic nucleus

Question 40

Define chorea

Answer 40

Involuntary jerky movements

Question 41

What structural changes occur in huntingtons

Answer 41

Major degeneration of striatal neurons and cortical atrophy

Question 42

What protein is involved in Huntingtons disease and what chromosome is involved

Answer 42

Huntingtin | Chromosome 4

Question 43

Repeats of what are abnormal in Huntingtons

Answer 43

Glutamine/ CAG codon

Question 44

How many repeats of CAG counts as abnormal

Answer 44

36

Question 45

In which pathways is there a loss of medium size spiny neurones

Answer 45

Striato-pallidal | Striato-nigral

Question 46

What mechanisms undely neurodegeneration in Huntingtons

Answer 46

``` Excitotoxicity Loss of neurotrophic factors Accumulation of aggregates of Huntingtin protein Dysregulation transcription Increased oxidative stress Abnormalities in axonal transport ```

Question 47

Symptoms of Huntington's disease

Answer 47

``` Choreic movement Gait abnormalities Lack of coordination Cognitive impairment Psychiatric disturbances Sleep disturbance Weight loss ```

Question 48

What anti depressants can be used in Huntingtons

Answer 48

Imipramine | Amitriptyline

Question 49

What antipsychotic drugs can be used in Huntingtons

Answer 49

Haloperidol | Olanzapine

Question 50

What sort of drug is tetrabenazine

Answer 50

Vesicular amine transporter inhibitor