Neuro - Parkinson's & MG

Question 1

Describe the pathogenesis of idiopathic Parkinson’s disease

Answer 1

Loss of dopaminergic neurones in the substantia nigra
Results in reduced dopamine

Symptoms only start at loss of 50% loss of neurones

Question 2

Describe the use of levodopa in the treatment of Parkinson’s

Answer 2

Crosses the BBB => taken up by dopaminergic neurones in substantia nigra
Converted to dopamine

Question 3

Why should L-DOPA be given with a DOPA decarboxylase inhibitor?

Answer 3

Prevents peripheral conversion of L-DOPA to dopamine

Reduces required dose
Reduces side effects
Increases L-DOPA reaching the brain

Question 4

What are some side effects of L-DOPA?

Answer 4

Nausea 
Anorexia 
Hypotension 
Psychosis - schizophrenia like effects
Tachycardia

Question 5

Why should Vit B6 not be taken with L-DOPA?

Answer 5

Increases peripheral breakdown

Question 6

What happens with long term use of L-DOPA?

Answer 6

Loss of efficacy due to loss of dopaminergic neurones
Sudden loss of effect of drug

Causes dyskinesia and dystonia

Question 7

What are some dopamine receptor agonists?

Answer 7

Non-Ergot:
Ropinirole, pramipexole

Patch:
Rotigotine

Subcutaneous:
Apomorphine- only used w/ se ere motor fluctuations

Question 8

What are some advantages of dopamine receptor agonists used for IPD?

Answer 8

Direct acting
Less dyskinesia and motor complications
Possible neuroprotection

Question 9

What are some disadvantages of dopamine receptor agonists used for IPD?

Answer 9

Less efficacious than L-DOPA
Impulse control disorders
Psychiatric side effects
Expensive

Question 10

What are some Sx of impulse control disorder?

Answer 10

Pathological gambling 
Hypersexuality 
Compulsive shopping 
Desire to increase dose 
Punding

Question 11

What are some side effects of dopamine receptor agonists?

Answer 11

Sedation 
Hallucinations 
Confusion 
Nausea 
Hypotension

Question 12

What are some examples of monoamine oxidase B inhibitors?

Answer 12

Selegiline

Rasagaline

Question 13

What is the MOA of monoamine oxidase B inhibitors?

Answer 13

Inhibits metabolism of dopamine therefore enhance effect of dopamine

Can be used alone
Also prolongs action of L-DOPA => used when pt has wearing off effects

Might be neuroprotective

Question 14

What is the MOA of COMT inhibitors used for IPD?

Answer 14

Reduces peripheral breakdown of L-DOPA to 3-O-methyldopa

Must be given in combination with L-DOPA

Question 15

What is the MOA of anticholinergics in IPD?

Answer 15

ACh might have an antagonistic effect on dopamine
Minor role - doesn’t affect bradykinesia & rigidity

Side effects:
Confusion, drowsiness

Question 16

Describe the pathogenesis of Myasthenia Gravis

Answer 16

Autoimmune disease

Type II hypersensitivity reaction => antibodies bind to ACh receptors therefore block binding of ACh => reduced response

Question 17

What drugs can exacerbate Myasthenia Gravis?

Answer 17

Aminoglycosides
β-blockers, CCB, ACE-inhibitors
Succinylcholine
Magnesium

Affect transmission at the neuromuscular junction

Question 18

Describe the therapeutic management of Myasthenia Gravis

Answer 18

Acetylcholinesterase inhibitors 
Corticosteroids 
Steroid sparing 
IV immunoglobulin 
Plasmapheresis

Question 19

What is the use of acetylcholinesterase inhibitors in Myasthenia Gravis?

Answer 19

Enhances neuromuscular transmission by preventing breakdown of ACh
Therefore more likely to interact with receptors

Question 20

What are some examples of acetylcholinesterase inhibitors?

Answer 20

Pyridostigmine

Neostigmine

Question 21

What are some side effects of anti-muscarinics?

Answer 21

Sludge syndrome

Salivation 
Sweating 
Lacrimation 
Urinary incontinence 
Diarrhoea 
GI upset & hypermobility 
Emesis