Therapy Flashcards
What is therapy aimed at? and what are the therapies?
The loss of dopamine neurons in PD means that therapy is aimed at restoring function of the transmitter by either replenishing dopamine or by mimicking receptor effects of dopamine.
L-DOPA, dopamine receptor agonist, muscarinic antagonists, amantadine, transplants
Why is this not easy?
There are 5 dopamine pathways in the CNS as well as having peripheral actions so augmenting dopamine function can produced side effects elsewhere.
Why use L-DOPA?
L-DOPA is precursor molecule of dopamine. Unlike dopamine, it can cross the blood-brain barrier where it can then be converted to dopamine by DOPA-decarboxylase.
Why can’t we use dopamine directly?
Can’t cross the blood-brain barrier.
Is L-DOPA effective?
It improve akinesia and rigidity effectively. However, it only works best in the less elderly for the first 18 months, maintained for 2-3 years and then see a gradual decline (probably due to more neuronal death).
What are the CNS side effects of L-DOPA?
Production of dopamine in the brain leads to CNS side effects.
- Dyskinesia
- Psychotic effects
- Reduce prolactin release
- On-off effects between akinesia and dyskinesia
What are the peripheral side effects of L-DOPA?
Production of dopamine in the periphery leads to:
- Hypotension
- Nausea - due to CTZ lacking blood brain barrier
How can we prevent peripheral formation of dopamine?
Use adjuvants
What adjuvants can be used with L-DOPA?
- DOPA decarboxylase inhibitors - carbidopa and benserazide
- Monoamine oxidase inhibitors - selegiline reduces breakdown of dopamine in CNS
Give examples of dopamine receptor agonists
- Bromocriptine - D2 receptor agonist (can be used in oldest patients when L-DOPA no longer effective)
- Apomorphine - D1 and D2 agonist
- Domperidone - D2 antagonist
How do dopamine receptor agonists work?
Mimic the effect of dopamine by binding to same receptors, activating dopaminergic pathways.
Are dopamine receptor agonists effecive?
Should be as they don’t rely on dopamine neurons, they just use post-synaptic receptors.
What are muscarinic antagonists
Correct the relative cholinergic excess that occurs as result of dopamine deficiency to reduce tremor.
Give examples of muscarinic antagonists.
Atropine and benztropine
What is amantadine?
Anti-viral drug, weakly effective but increases dopamine by poorly understood mechanism involving NMDA.
