Neurological pharmacology

Question 1

What are the different drug classes used in Parkinson’s?

Answer 1

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

Question 2

Why don’t we treat Parkinson’s with dopamine?

Answer 2

Because dopamine cannot cross the blood brain barrier

But L-DOPA can

Question 3

Tell me about L-DOPA.

Answer 3

Oral administration
T1/2=2hrs
It is used in conjunction with a peripheral DOPA decarboxylase inhibitor so L-DOPA doesn’t get metabolised in the peripheral tissues before getting into the CNS

Question 4

What are the advantages and disadvantages of using L-DOPA?

Answer 4

Highly efficacious
Low side effects

BUT
Precursor (needs enzyme conversion)

Long term:

• Loss of efficacy
• Involuntary movements
• Motor complications:
  
  • On/off
  • Wearing off
  • Dyskinesia’s
  • Dystonia
  • Freezing

Question 5

What are some of the ADRs of L-DOPA?

Answer 5

Nausea/anorexia
Hypotension
Psychosis
Tachycardia

Question 6

What are some interactions of L-DOPA?

Answer 6

Pyridoxine (vitamin B6) increases peripheral breakdown of L-DOPA

MAOIs risk hypertensive crisis

Many antipsychotic drugs block dopamine receptors and parkinsonism is a side effect

Question 7

Give some examples of dopamine receptor agonists.

Answer 7

Apomorphine - Ergot derived
Bromocriptine - non ergot
Ropinirole - Subcutaneous

Question 8

What are the advantages and disadvantages of using dopamine receptor agonists?

Answer 8

Direct acting
Less dyskinesia’s/motor complications
Possible neuroprotection

BUT

Less efficacy then L-DOPA
Impulse control disorders
More psychiatric ADRs
Expensive

Question 9

What are some impulse control disorders?

Answer 9

Also called Dopamine Dysregulation Syndrome

Pathological Gambling
Hypersexuality
Compulsive shopping
Desire to increase dosage
Punding (repetitive behaviours and fascinations)

Question 10

What are some of the ADRs of dopamine receptor agonists?

Answer 10

Sedation
Hallucinations
Confusion
Nausea
Hypotension

Question 11

How do monoamine oxidase B inhibitors work?

Answer 11

Monoamine oxidase B metabolises dopamine and predominates in dopamine containing regions in the brain

SO MOAB inhibitors enhance dopamine

Question 12

Give some examples of MOAB inhibitors.

Answer 12

Selegiline

Rasagaline

Question 13

Why are MOABs used?

Answer 13

Can be used alone
Prolong action of L-DOPA
Smooth out motor response
May be neuroprotective

Question 14

Give an example of a COMT inhibitor.

Answer 14

Entacapone

Question 15

How are COMT inhibitors used to treat Parkinson’s?

Answer 15

Catechol-O-methyl Transferase inhibitors
COMT breaks down dopamine
So inhibiting it enhances dopamine
But no therapeutic effect alone
It works by reducing peripheral breakdown of L-DOP to 3-O-methyldopa

So used in combination with L-DOPA and peripheral dopa decarboxylase inhibitor
Has L-DOPA ‘sparing’ effect
Prolongs motor response to L-DOPA

Question 16

How are anticholinergics used to treat Parkinson’s?

Answer 16

Acetyl choline may have antagonistic effects to dopamine

Minor role in treatment of PD

Question 17

What are the advantages and disadvantages of using anticholinergics in treatment of Parkinson’s?

Answer 17

Treat tremor
Not acting via dopamine systems

BUT
No effect of Bradykinesia
ADRs:
- Confusion
- Drowsiness
- Usual antocholinergic ADRs

Question 18

How is amantadine used in the treatment of Parkinson’s?

Answer 18

Mechanism of action is uncertain
(enhanced dopamine release)
(Anticholinergic NMDA inhibition)

Poorly effective
Few side effects
Little effect on tremor

Question 19

What is the therapeutic management of myasthenia gravis?

Answer 19

Acetylcholinesterase inhibitors

Corticosteroids (decreased immune response)
Steroid sparing (Azathioprine)
IV immunoglobulin
Plasmapheresis (removes AChR antibodies and short-term improvement)