Session 11 - Parkinsons Flashcards Preview

Semester 5 - Farmocology > Session 11 - Parkinsons > Flashcards

Flashcards in Session 11 - Parkinsons Deck (56)
1

Give four motor symptoms which characterise parkinson's disease

Tremor
Rigidity
Bradykinesia
Postural Instability

2

Describe the tremor which occurs in parkinsons - What is it caused by?

 Low frequency rest tremor
 Abolished by movement
 Low dopamine and disturbance of other neurotransmitters

3

What two types of rigidity do you find in parkinsons?

Lead pipe rigiditiy/Cog-wheel

4

What type of rigidity do you not find in parkinsons and why?

Clasp knife
Sign of pyramidal disorder, which parkinsons is not.

5

What is rigidity caused by in parknson's

Low dopamine and disturbance of other NTs

6

What is bradykinesia caused by in dopamine

Low dopamine

7

Give 6 non-motor manifestations of parkinson's

o Mood changes
o Pain
o Cognitive change
o Urinary symptoms
o Sleep disorder
o Sweating

8

What are two causes of parkinonism

o Idiopathic Parkinson’s Disease
o Dopamine blocking or depleting drugs
 Particularly antipsychotics

9

How is parkinson's disease taken up?

Pre-synaptically by dopaminergic neurones

10

What are the two main pathologies which come in parkinsons?

Presence of neuronal inclusion called lewy bodies
Loss of dopaminergic neurones from pars compacta of the substantia nigra in the midbrain that project to the striatum of the basal ganglia

11

What are lewy bodies and how do they progress?

 Contain tangles of α-synuclein and ubiquitin
 Gradually become more widespread as the condition progresses, spreading from lower brainstem  Midbrain  Cortex

12

When do parkinson's symptoms occur?

Once there is 50% cell loss

13

Outline the metabolic path of dopamine (before it and after)

L-Tyrosine -> L-Dopa -> Dopamine -> Noradrenaline -> Adrenaline

14

What converts L-dopa to dopamine?

DOPA decarboxylase

15

What is the main pharmacokinetic properterial difference between L-Dopa and Dopamine

L-dopa can.. Wait for it.. Cross the BBB :D :D :D :D !!! :D :D :D !!! :D :D :D :D

16

Name 6 drugs used in Parkinson's treatment

Levodopa (L-DOPA)
o Dopamine receptor agonists
o MAOI Type B inhibitors
o COMT inhibitors
o Anticholinergics
o Amantadine

17

What is the route of admine of L-Dopa?

Oral

18

How much of an L-Dopa dosa reaches the brain

1%

19

What are indications for L-DOPA (1)

Parknsons

20

What is the mechanism of action for L-dopa

 L-DOPA is the immediate precursor of Dopamine and is able to penetrate the blood brain barrier to replenish the dopamine lost in the Neostriatum

21

Name four ADRs for L-dopa

 Nausea and vomiting
 Psychiatric side effects (Schizophrenia-like symptoms)
 Cardiovascular effects (hypotension)
 Dyskinesia

22

What kind of drug is L-dopa usually given with and why?

peripheral DOPA decarboxylase inhibitor (Sinemet, Madopar), reducing necessary dose, side effects and increase the amount of L-DOPA reaching the brain

23

Name a pharamocologically active substance which would increease breakdown of L-dopa

Vitamin B6

24

What is the risk of using monoamine oxidase inhibitors as L-dopa adjuvants

Hypotensive crisis

25

What do anti-psychotics do in parkinsons?

block dopamine receptors and parkinsonism is a side-effect

26

Why do large doses of L-dopa have to be given?

 Extensive peripheral metabolism of L-DOPA means that large doses have to be given to produce therapeutic effects. These large doses are more likely to bring about adverse effects.

27

What inhibits absorption of L-dopa

Large protein meals (compete with amino acids)

28

How is L-dopa metabolised in the body?

 90% inactivated in intestinal wall by MAO and DOPA decarboxylase
 9% converted to dopamine in peripheral tissues
 1% crosses BBB to enter the CNS (competes with amino acids)

29

Give two advantages of L-dopa

Highly efficacious
Low side effects

30

Give two disadvantages of L-dopa

Precursor, needs enzyme conversion
- Long term loss of efficacy and development of involuntary movements

31

Why would you use a dopamine receptor agonist?

 Used in combination with L-DOPA in an attempt to reduce it’s late adverse effects, or when it does not control symptoms

32

Give three ADRs for dopamine agonists

 Sedation, hallucination, confusion
 Nausea
 Hypotension
 Psychiatric symptoms

33

What is the most commonly used dopamine receptor agonist?

 Bromocriptine is most used

34

What are the main psychiatric side-effects of dopamine receptor agonists

impulse control disorder – pathological gambling, compulsive shopping - Basically due to shit high dopamine

35

Why is mech of action of monoamine oxidase inhibitor useful in parko?

 Selegiline selectively inhibits the MAOB enzyme in the brain that is normally responsible for the breakdown of dopamine. By inhibiting breakdown, the dose of L-DOPA is prolonged.

36

Give three ADRs of MOA

 Selegiline selectively inhibits the MAOB enzyme in the brain that is normally responsible for the breakdown of dopamine. By inhibiting breakdown, the dose of L-DOPA is prolonged.

37

What is a Catechol-O-methyl Transferase Inhibitors used for

 Adjunct to L-DOPA therapy to reduce end-dose ADRs

38

Give a contra-indication for COMT?

Phaeochromcytoma - Can't break down dat noradrenaline any more! So much adrenaline! Ahh!

39

What is the mechanism of action of COMT

 Inhibits the enzyme COMT, which degrades L-dopa in the periphery. No therapeutic effect alone.
 Potentiates effects of L-dopa

40

Give three ADRs for COMT

 Nausea and Vomiting
 Abdominal pain
 Diarrhoea

41

What is the mech of action of anti-cholinergics in parko

 Antagonists at the muscarinic receptors that mediate striatal cholinergic excitation
 Acetylcholine -> Antagonistic effect on dopamine
 Main action in treatment of Parkinson’s disease is to reduce excessive striatal cholinergic activity

42

What are the main ADRs of anti-cholinergics?

Alzheimers effects!
 CNS effects – Mild memory loss, acute confusional states
 Dry mouth and blurred vision (less common)

43

Give two therapeutic notes for anticholinergics, in respect to withdrawal of therapy

 Termination of anticholinergic treatment should be gradual, as parkinsonism can worsen when these drugs are withdrawn
 Good for treating tremor, however has no effect on bradykinesia

44

What does amatadine do and when is it used?

 Synergistic effect when used in conjunction with L-DOPA
 Stimulates neuronal dopamine release and inhibition of its reuptake
 Additional muscarinic blocking actions

45

Give three ADRs of amantadine

 Anorexia
 Nausea
 Hallucinations

46

How do you reduce side-effects of parkinsons?

Reduce L-dopa dose and add an adjuvant

47

What is surgery used for in parko?

To remove lesions causing tremor and globus pallidus dysfunction

48

What can you do to the subthalamic nucleus to treat parko?

Deep brain stim to relieve symptoms

49

HOw does parko get worse

Over 15 year period
o Dyskinesia – 94% (writhing movement due to L-DOPA treatment)
o Falls – 81%
o Cognitive Decline – 84% (50% have hallucinations)
o Somnolence – 80%
o Swallowing Difficulty – 50%
o Severe Speech Problems – 27%

50

What is myasthenia gravis? (3 main pathological things + bit that causes death)

o An autoimmune destruction of the end-plate ACh receptors
o Loss of junctional folds at the end-plate
o A widening of the synaptic cleft
The crisis point is when it affects respiratory muscles

51

Give three presenting symptoms of myasthenia gravis

o Drooping eyelids
o Fatigability and sudden falling due to reduced ACh release
o Double vision

52

When are symptoms of myasthenia gravis worse?

Effected by general state of health and emotion

53

What is treatment for myasthenia gravis?

o Acetylcholinesterase inhibitors (e.g. Pyridostigmine)
 Prevent breakdown of Ach in synaptic cleft

54

What are side-effects of Acetylcholinesterase inhibitors?

 Can cause muscarinic side effects (parallel those effects seen with excessive release of Ach)
 Miosis
 SSLUDGE Syndrome

55

What is plasmapheresis used for in myasthenia gravis?

o Plasmapheresis
 Removes AchR antibodies and gives short term improvement
Immunosupression for long term treatment

56

What is SSLUDGE syndrome?

Muscarinic side effects
o Salivation
o Sweating
o Lacrimation
o Urinary Incontinence
o Diarrhoea
o GI upset and hypermotility
o Emesis