Parkinsons

Question 1

What is parkinson’s disease

Answer 1

• progressive neurodegeneration of basal ganglia, and later the brain stem
• loss of 70-80& of neurones within substantia nigra
• corresponding loss of dopamine in the striatum

Question 2

how does parkinson’s effect body chemistry and what are the effects?

Answer 2

1. disorder of extrapyrimidal system involving basal ganglia - maintains posture and muscle tones, regulates voluntary smooth muscle activity
2. loss of dopamine in nigro-striatal
3. relative increase in Ach
4. involuntarty muscle contractions interefere with voluntary movement

Question 3

symptoms of parkinsons

Answer 3

1. tremor
2. rigidity
3. slowness of movement
   and more…

Question 4

3 main dopaminergic pathways

Answer 4

1. motor channel (nigrostriatal pathway)
2. behaviour/emotion (mesocortical pathway)
3. endocrine/secretion (tuberohyophyseal neurons)

Question 5

what causes the motor symptoms in people with parkinsons?

Answer 5

overactivity of neurotransmitter Ach leads to motor symptoms such as tremor, rigidity.

Question 6

What are the aims of drug treatment in parkinsons

Answer 6

Aims to treat symptoms not the cause of the neurodegeneration therefore improving the quality of life by minimizing deterioration and side effects

Question 7

Role of dopaminergic drugs in parkinsons

Answer 7

• increase levels of dopamine in striatum
• deliver a precursor of dopamine thus preventing degredation of dopamine at the neurones
• stimulating dopamine receptors (D2, D3)
• improve bradykinesia and rigidity, less effective at controlling tremor

Question 8

Dopamine replacemnt therapy

Answer 8

because dopamine cannot cross the BBB, a dopamine precursor is used called Levodopa

Question 9

Role of Levodopa in parkinsons

Answer 9

• aleve symptoms of, bradykinesia, involuntary movement
• MOA: Levodopa by various routes crosses the blood brain barrier, is decarboxylated to form dopamine. This supplemental dopamine performs the role that endogenous dopamine cannot due to a decrease of natural concentrations and stimulates dopaminergic receptors
• Adverse effects: nausea, vomitting, hypotension, cardia arythmia, coloured urine, GI bleeding

Question 10

Role of anti-cholonergics in treatment of parkinsons

Answer 10

• Aims to reduce tremour, no effect on slowness of movements
• used in treatment of drug-induced parkinsonian symptoms

Question 11

examples of antimuscuranics in parkinsons

Answer 11

• Orphenadrine, benzhexol, benztropin, procyclidine
• reduce tremor, no offect on slowness of movement
• less effective than levodopa
• side effects: dry mouth, blurred vision, constipation, confusion, hallucimations, euphoria

Question 12

How do the symptoms of parkinsons occur?

Answer 12

Loss of dopamine inhibition alters the output of the basal ganglia circuitry resulting in changed motor control producing the typical parkinson’s symptoms of rigidity, tremor, bradykinesia

Question 13

What is a requirement for levodopa to work?

Answer 13

there must be dopa decarboxylase in remaining striatal neurones

Question 14

Reducing side effects of levodopa

Answer 14

A dopa decarboxylase inhibitor (DDCI) is used to reduce the side effects of levodopa. reducing the amount of dopamine in the periphary reuces adverse affects.
examples include (carbiodopa and beserazide)

Question 15

1st and 2nd line treatment early PD

Answer 15

1st line: Levodopa + DDCI
Oral/transdermal non-ergot dopamine agonist
mono-amine oxidase B inhibitors

2nd line: beta-adrenergic antagonists - postural tremour
Amantadine
anti-cholinergics - severe tremour,rigidity, young

Question 16

Dopamine agonists

Answer 16

• D2 (ergot derived) receptor agonists:
• bromocriptine
• pergolide
• cabergoline
  non ergot:
• Ropinorole - D2 agonist
• pramipexole - D2,D3 agonist
• Apomorphine - D1,D2 agonist (injection)

Question 17

side effects of dopamine agonists

Answer 17

• excessive daytime sleepiness (driving, operating machinery)
• peripheral oedema
• hallucinations
  *

Question 18

side effects - ergot derived dopamine agonists

Answer 18

• Risk of heart valve problems = NO due to moderate/severe cardiac valvulopathy
• seroasal fibrosis
• tests required: ECGs, bloods, echocardiogram, x-ray

Question 19

What does the BBB consist of

Answer 19

specific cellular and etracellular proteins produced and influencing endothelia and pericyte function

Question 20

Levodopa + Carbiodopa

Answer 20

MOA: Levodopa crosses the BBB and gets converted into Dopamine via Dopa-decarboxylase. however dopa-decarboxylase can also inhibit L.dopa before it crosses BBB, therefore Carbiodopa is a dopa decarboxylase inhibitor allowing more levodopa to cross the BBB.

Question 21

COMT-I

Answer 21

Can be given to increase the effects of L.dopa
reduces breakdown of dopamine into 3-omd and 3-mt via COMT enzyme
side effects: hepatotoxicity, nausea, vomitting

Question 22

MAO-B inhibitors

Answer 22

Reduces the breakdown of dopamine into inactive metabolite
Adjunct to L.dopa + carbiodopa

Question 23

What causes Bradykinesia in Parkinson’s

Answer 23

Direct and indirect pathways responsible for increased voluntary/involuntary movement. Loss of dopamine results in loss of stimulation resulting in slowness of movement

Question 24

adverse affects of increased dopamine

Answer 24

nausea, vomitting,hepatotoxicity

Question 25

Amantadine

Answer 25

Dopamine agonist
Increases dopamine release and blocks dopamine reuptake allowing more dopamine to bind to receptor