Parkinsons Disease

Question 1

What is parkinsons characterised by? i.e pathology

Answer 1

1. loss of dopaminergic neurons in the substantia nigra

2. accumulation of lewy bodies made of alpha synuclein

Question 2

What are some speculated causes?

Answer 2

Unknown - pesticides, MPTP exposure, genetics, influenza, head trauma
(MPP+ stops mitochondria from working by binding to complex 1 of respiratory chain and thus cell death as no ATP generated)

Question 3

What is treatment therapy for PD?

Answer 3

Modifying dopamine and potentiation of the DA signal that is lost e.g. Levodopa in the early stages of PD whose motor symptoms impact their QOL

Question 4

When is drug treatment initiated in PD?

Answer 4

When motor symptoms impact on quality of life

Question 5

What is levodopa

Answer 5

Direct precursor to dopamine but can cross the BBB, converted to dopamine in the brain by DDC

Question 6

Why is levodopa given with peripherally acting DDC inhibitors?

Answer 6

Inhibiting metabolism of the DDC in the periphery/intestinal wall. This ensures preservation in the bloodstream to get the brain to be converted, ensures L-Dopa enters brain unchanged for conversion to Dopamine and raises striatal dopamine levels to normalise activity in basal ganglia circuits

Question 7

Give examples of DDC inhibitors

Answer 7

Carbidopa

benserezide

Question 8

What other drug can L-Dopa be given with?

Answer 8

Entacapone - as l-dopa is 5% metabolised by COMT

Question 9

Give symptoms of PD

Answer 9

Bradykinesia 
Shuffling 
Arms and legs rigid 
Tremors 
muscle locking
constipation 
Walk slowly 
Loss of smell before movement symptoms
depression/anxiety

Question 10

What are side effects of levodopa?

Answer 10

Acute = psychosis - too much DA
Chronic = dyskinesia
Gambling (reward)
Hallucinations

Question 11

What chromosomes are mutated in PD

Answer 11

Chromosome 4 which encodes for alpha synuclein gene

Chromosome 12 (LRRK 2)

Question 12

Why do we give levodopa and not dopamine

Answer 12

Levodopa can cross the BBB whereas dopamine cannot, dopamine would not get into the brain whereas levodopa can and then get converted into DA

Question 13

What is sinamet?

Answer 13

Carbidopa and levodopa (co-careldopa)

Question 14

What is madopar

Answer 14

Carbidopa and benseraside (co-beneldopa)

Question 15

What drug in particular increases the risk of gambling?

Answer 15

Pramipexole - DA agonist binding to D1 and D2

Question 16

What drug causes red urine?

Answer 16

levodopa

Question 17

What is silegiline/resegiline?

Answer 17

MAOB inhibitor - because MAOB breaks down dopamine. Can be used alone or on combo

Question 18

Why is it important to stick to the dosing schedule?

Answer 18

May lose symptom control as the dopamine would be lost, and risk neuromalignant syndrome. Need to keep a steady level of dopamine but equally don’t want side effects. Difficult to get dosing e.g. no parkinsons symptoms but no adverse effects

Question 19

What would you do if a person with PD who was receiving treatment, got psychosis?

Answer 19

Decrease dose of L-dopa

or initiate clozapine as it doesn’t block DA in the same way- less DA blockade at D2

Question 20

What are side effects of co-careldopa sinamet? how to reduce these?

Answer 20

Nausea, reduced BP

Reduce - increasing the dose slowly

Question 21

What drug can you NOT use in parkinsons for nausea and vomiting? What can you use?

Answer 21

Metoclopramide (D2 antagonist)

Can use domeridone