Drug Treatments of Movement Disorders Flashcards Preview

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Flashcards in Drug Treatments of Movement Disorders Deck (50):
1

What are the main features of neurodegenerative disorders? (3)

-Loss of neurons
-Progressive
-Irreversible (cannot regenerate neurons)

2

When was Parkinson’s first described, and what were the main features?

1817.
-‘shaking palsy
-akinetic-rigid syndrome
-extrapyramidal disorder

3

How does Parkinson’s progress?

Slowly; usually die within 10-15 years.
-death usually due to bronchopneumonia / sepsis

4

What is remission, and how common is it in Parkinson’s?

Disappearance of signs.
-rare, and only lasts for seconds/minutes

5

What are the main symptoms of Parkinson’s? (6)

-Tremor (4-7Hz)
-Rigidity (increased tone)
-Slurred speech
-Akinesia
-Decreased blinking
-Postural changes (stoop, shuffling)

6

What are the unusual ways to describe some of the symptoms of Parkinson’s?

TREMOR – ‘pill rolling’
RIGIDITY - ‘lead piping limbs’
DECREASED BLINKING – ‘serpentine stare’
POSTURAL CHANGES – ‘telegraph pole falls’

7

What is akinesia?

Difficulty initiating voluntary movements.

8

What is the general pathology of Parkinson’s?

-Loss of neruones in substantia nigra
-Lewy body accumulation (eosinophilic proteins in cells)
-Loss of nigro-subtantia inhibitory-excitatory pathway

9

What type of neurones are affected by Parkinson’s?

Dopaminergic neurones.

10

What causes Parkinson’s?

Unknown cause.
-idiopathic

11

What disorders are associated with Parkinson’s? (3)

-Drug-induced (iatrogenic)
-MPTP-induced (amphetamine-related)
-Post-encephalitic

12

What are the 2 pathways affected by Parkinson’s?

Indirect and direct.
-both involve dopamine (D1/D2)

13

What is the direct pathway?

D1-mediated.
-signals from striatum

14

What is the indirect pathway?

D2-mediated.
-signals from striatum

15

What is the abbreviation of dopamine?

DA.

16

What are the general mechanisms of Parkinson’s treatment? (2)

-Increase DA activity
-Decrease Ach activity

17

How is DA activity increased? (4)

-Replace DA
-Decrease DA breakdown
-Increase DA release
-DA agonists

18

What drug is used to replace DA?

L-DOPA.

19

What drugs are used to decrease DA breakdown? (2)

-MAO inhibitors
-COMT inhibitors

20

What drug is used to increase DA release?

Amantidine.

21

What drugs are used as DA agonists? (2)

-Bromocriptine
-Pergolide

22

What class of drugs decrease Ach activity?

Antimuscarinics.
-benzhexol, orphenadrine

23

What is the 1st line treatment for Parkinson’s?

-L-DOPA
-MAO / COMT inhibitors

24

How does L-DOPA increase dopamine levels?

L-DOPA is a precursor for dopamine.
-DOPA decarboxylase converts it

25

How does L-DOPA act?

-L-DOPA crosses the BBB >> neurones.
-converted to DA in neurones and glia

26

What is the main problem with L-DOPA?

Metabolised in the periphery >> only 1% reaches brain.
-90% in intestine

27

What is given with L-DOPA to prevent it being broken down, and how does it work?

Carbidopa.
-inhibits DOPA decarboxylase
-doesn’t pass BBB

28

What are the main side effects of L-DOPA?

-‘On-off’ effect (worsening symptoms)
-Nausea / anorexia
-Dysknesias
-Tachycardia
-Hypotension
-Insomnia

29

What happens to the side effects of L-DOPA with time?

Increased side effects with time.
-partly due to increased dose

30

How do MAO inhibitors reduce DA breakdown?

Mono-amine oxidase (MAO) breaks down DA to homovanillinic acid.
-inhibitors prevent this

31

What is a commonly used MAO inhibitor?

Selegiline.

32

How does Selegiline act?

-MAOb inhibitor (CNS specific)
-Increase DA in brain
-Effective alone in early stages, ineffective later on

33

Where are MAOa and MAOb located?

MAOa – periphery
MAOb – CNS

34

How do COMT inhibitors reduce DA breakdown?

COMT breaks down L-DOPA (>>3-O-methyl DOPA) and DA (>>homovanillinic acid)
-inhibitors prevent this

35

What are COMT inhibitors used for?

Patients with on-off symptoms.

36

What COMT inhibitor was withdrawn due to adverse effects?

Tolcapone.

37

How does amatidine act and when is it used?

Increases DA release.
-useful in early stages, but not generally used

38

What are bromocriptine and peroglide?

Dopamine agonists.
-usually given towards end of disorder

39

What are the selectivities of bromocriptine and peroglide?

Bromocriptine – D1 and D2.
Peroglide – D2 selective.

40

What is the action of antimuscarinics?

Block muscarinic receptors.
-most effective on tremor and drooling
-used only in young with severe tremor

41

How can surgery be used to treat Parkinson’s? (3)

-Lesions
-Implantable stimuli
-Grafts

42

What lesions can be used to treat Parkinson’s?

-Motor thalamus (thalamotomy)
-Globus pallidus (pallidotomy)
-Subthalamus (subthalamotomy)

43

Why are lesions used in Parkinson's?

Can reduce motor symptoms; usually last resort.

44

How does Huntington’s progress?

Gradual onset.
-death within 10-20 years

45

What is the typical age of onset of Huntington’s?

30-50 years.
-younger >> more severe

46

What are the main symptoms of Huntington’s? (2)

-Fidgeting / restlessness >> chorea
-Irritability / moodiness >> dementia

47

What is chorea?

Jerky, involuntary movements.

48

What is the general pathology of Huntington’s?

Selective cell loss in cerebral cortex and corpus striatum.
-medium spiny neurones containing GABA and encephalin = 1st affected
-altered NT levels

49

What causes Huntington’s?

HEREDITARY – autosomal dominant
-gene defect on chromosome 4 (4p16.3)
-CAG repeate (polyglutamine)

50

How is Huntington’s treated?

No cure.
-can control movement disorder: D2 antagonists, DA depletion