12. PD & MA drugs Flashcards
Describe the synthesis of dopamine, inc. the enzymes involved.
i. L-Tyrosine converted to L-DOPA by tyrosine hydroxylase…
ii. L-DOPA converted to dopamine by DOPA decarboxylase.
Describe the breakdown of dopamine, inc. the enzymes involved.
Dopamine converted to homovanillic acid (via intermediates) by monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT).
A PD P presents with motor symptoms affecting their QoL. Which medication would you recommend?
What if motor symptoms were not affecting their QoL?
Motor symptoms pre-dominant: Levodopa + Carbidopa (+/- other adjuncts if symptoms not controlled).
Motor symptoms not pre-dominant: Levodopa, non-ergot dopamine R agonist OR MAOB inhibitor.
Describe the MOA of levodopa. What must it be used in combination with?
Levodopa = dopamine precursor able to cross the BBB via active transport - taken up by SN neurones and converted to dopamine via DOPA-decarboxylase.
Must be used with carbidopa, a peripheral DOPA-decarboxylase inhibitor (cannot cross BBB), to increase L-DOPA amount reaching brain, decrease dose required and decrease side effects.
Describe the possible ADRs associated with Levodopa.
Low side effects but can include:
- nausea/anorexia (vomiting centres)
- hypotension (central and peripheral) and tachycardia
- psychosis: schizophrenia-like effects, inc. hallucinations, delusions and paranoia
- impulse control disorders
Long-term use:
5. motor complications: on/off, wearing off, dyskinesias, dystonia, freezing
What are the different types of dopamine R agonists and when is each used?
- Non-ergot: used alone when motor symptoms don’t affect QoL, or as adjunct
- Ergot-derived: only used when symptoms not controlled by non-ergot
- Apomorphine (subcutaneous): only for Ps with severe motor fluctuations
How do the side effects of dopamine R agonists compare with those of Levodopa?
- Have less dyskinesias/motor complications.
- But have more:
1. Psychiatric effects, e.g. hallucinations
2. Impulse control disorders, e.g. pathological gambling, hypersexuality, compulsive shopping, desire to increase dosage, punding - And can also cause nausea, hypotension, sedation and confusion.
Which drugs can be used to inhibit the breakdown of L-DOPA/dopamine?
- Monoamine oxidase (MAO) type B inhibitors
- inhibit MAO to increase dopamine
- used alone or as adjunct to L-DOPA - Catechol-O-methyl transferase inhibitors
- inhibit COMT to decrease peripheral metabolism of L-DOPA to 3-O-methyldopa
- used as adjunct to L-DOPA
Why are anti-cholinergics sometimes prescribed in PD?
Loss of dopamine causes relative ACh increase (antagonistic effects) - can help treat tremor (no effect on bradychinesia).
What is the MOA of amantidine?
Possibly:
- enhance endogenous dopamine release
- anti-cholinergic NMDA inhibition
In which situation may surgical management be recommended? What does this involve?
Cases where PD patient is:
- dopamine responsive
- has sig. side effects with L-DOPA
- has no psychiatric illness
Can involve:
- lesions - thalamus for tremor, globus pallidus interna for dyskinesias
- deep brain stimulation - subthalamic nucleus
Which drug would you prescribe a P with MG? What is its MOA?
Acetylcholinesterase inhibitor, e.g. pyridostigmine (oral)
Inhibits acetylcholinesterase… increase ACh amount and duration of action… enhance neuromuscular transmission (skeletal and smooth muscle).
What are the main side effects of pyridostigmine?
Cholinergic side effects:
- miosis
- SLUDGE syndrome
- salivation
- lacrimation
- urinary incontinence
- diarrhoea
- GI upset and hypermotility
- emesis
What can happen in an acetycholinesterase inhibitor overdose?
Cholinergic crisis: over-stimulation of NMJ due to excess ACh… flaccid paralysis (Rs stop responding), respiratory failure and SLUDGE syndrome.
How would you treat a MG P in acute decline/crisis?
IV immunoglobulin against IgG autoantibody to ACh R. 60% respond after 7-10 days.
