Lecture 12 - Parkinson's Disease Drugs Flashcards Preview

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Flashcards in Lecture 12 - Parkinson's Disease Drugs Deck (56)
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1

Parkinson's disease is a _____ disorder

movement

2

When do symptoms usually appear?

60 yrs old

3

List 5 symptoms of Parkinson's

-rhythmic tremor
-leaning forward
-difficulty rising
-muscle rigidity
-shrinkage of handwriting

4

List 4 voluntary motor pathways

-upper motoneurons
-lower motoneurons
-corticospinal pathway
-piramidal tracts

5

List 4 involuntary motor pathways

-extrapiramidal system
-basal ganglia
-reticular system
-vestibular system

6

What is parkinson's caused by?

by the loss of neurons in the substantia nigra and thus, the loss of dopamine innervation of striatum (part of the basal ganglia)

7

When do parkinson's symptoms occur?

when about 70% of nigrostriatal neurons are lost

8

Abnormal signalling leads to ??

impaired mobility

9

Describe the normal path of neurons

GABA neurons are inhibited by dopamine and stimulated by acetylcholine

10

Describe the path of neurons in parkinson's disease

dopaminergic neurons die, leaving a relative excess of ACh

11

Describe the path of neurons in huntington's disease

GABA neurons die as well as some ACh neurons

12

Symptoms amenable to drug therapy

-bradykinesia
-resting tremor
-muscle rigidity
-abnormal posture
-early treatment for 'neuronal sparing'

13

Discuss pharmacologic targets for parkinson's

-increase Da signalling in brain
-Levodopa therapy
-decrease cholinergic activity (striatal muscarinic receptors)
-decrease peripheral dopamine effects at D1/D2 dopamine receptors
-decrease peripheral L-dopa metabolism

14

dopamine receptors are ______

metabrotropic

15

D1 subfamily members

D1
D5

16

Describe D1 subfamily

Gs
Increase cAMP

17

D1 subfamily members

D2
D3
D4

18

Describe D2 subfamily

Gi
Decrease cAMP

19

Striatum has what kind of dopamine receptors

D1
D2

20

What kinds of medication would be used to treat the first appearance of parkinson's

MAO B inhibitors
Levodopa
Dopamine agonists
Amantadine
Anticholinergics

21

Describe the disposition characteristics of L-dopa

-rapid absorption from the small intestine by aromatic amino acid transport system
-crosses BBB
-peak plasma concentration 1-2 hr after ingestion
-plasma half life = 1-3 hrs

22

Bioavailability issues with L-dopa

-metabolism in intestine, blood, and peripheral tissues
-concurrently ingested food (protein, iron)
-only 1% actually enters the brain

23

Therapeutic effects of L-dopa

-reduces rigidity and bradykinesia
-improves motor function and speech
-return of facial expression
-first choice drug for improving motor function

24

Side effects of L-dopa

-nausea and vomiting
-anorexia
-hypotension and cardiac arrhythmias
-dyskinesias (abnormal involuntary movements)
-can have an on-off effect
-behavioural changes
-insomnia, confusion
-psychosis, schizophrenia-like behaviour, hallucinations

25

An adjunct to L-dopa = ?

carbidopa

26

How does carbidopa work?

-inhibits dopa decarboxylase (DDC or aromatic L-amino acid decarboxylase AADC)
-does not cross BBB
-reduces the amount of L-dopa required and thus, reduces the adverse effects of L-dopa

27

Describe standard adjunct therapy for parkinson's

L-dopa + carbidopa = Sinemet
L-dopa + bensarazide = Prolopa

28

Another adjunct to L-dopa = ?

Entacapone

29

Describe Entacapone

-primarily for treating later stage parkinsons' disease
-selective and reversible inhibitor of peripheral COMT
-reduces peripheral metabolism of L-dopa
-does not cross BBB
-this leads to increased conversion of L-dopa to dopamine in the brain

Entacapone - used to treat problems associated with long term therapy of L-dopa (wearing off/ on-off effects)

-can enhance adverse effects of L-dopa, such as dyskinesias, nausea, psychosis and confusion

30

Sinemet + entacapone = ?

stalevo