PD pharma Flashcards
Principles of treatment?
- Low and slow
- Chronic and progressive - treatment will change over time
- Titrate to response and side effects
Treatment of PD - what areas need to be treated
- Motor symptoms
- Dementia
- Psychosis
- NON-motor
- New, adjuvant and complex disease - different principles
7 Classes of drugs used
- Dopamine compounds
- DA agonists
- MAO-B inhibitors
- COMT inhibitors - catechol-o-methyl transferase (degrades dopamine)
- Amantadine - anti-viral/anti-muscarinic - very rarely used
- Continuous dopamine stimulation (CDS)
- Anticholinesterase inhibitors - in PD dementia; e.g. Rivastigmine, Donepezil, Memantine (NMDA antagonist)
Give some examples of L-dopa. What is it always prescribed with?
- Sinemet, Madopar
- Always prescribed with decarboxylase inhibitor - prevents peripheral conversion to dopamine, meaning more is converted in brain
- carbidopa –> Sinemet = Co-careldopa
- Benserazide –> Madopar = Co-beneldopa
- Slow release prep for overnight symptoms
- Most effective for bradykinesia and rigidity, not great for tremor
- Benefit wears off over time - consider starting as late as possible
What are the side-effects of Levo-dopa? Think short and long term, and by organ systems
Short Term
- GI - N&V, loss appetite
- CV - postural hypotension
- Sleep - somnolence, reversal of sleep pattern, vivid dreams
Long term
- Involuntary movements -peak dose, diphasic, dystonia
- Response fluctuations - on/off unpredictable
- End-of-dose effect - benefit wearing off earlier and earlier
Psychiatric
- Confusion
- Hallucinations
- Delusions/illusions
Examples of MAO-B inhibitors?
What benefits do they provide?
What are SE?
- Selegiline, Rasagiline (much more potent)
- Adjuvant therapy to reduce off time and increase on time (without dyskinesia)
- Rasagiline better tolerated
- risk of halucinations, insomnia, nightmares, vivid dreams
- postural hypotension, nausea, confusion
Examples of Dopamine agonists?
What benefits do they provide?
What are SE - common to levodopa…?
- Ergot derived e.g. bromocriptine, cabergoline, pergolide
- Non-ergot - ropinirole (mirapexin), rotigotine
- As monotherapy or adjuvant therapy
- Delay onset of motor fluctuations, dyskinesias
Nausea, vomiting, loss of appetitie, postural hypotension, somnolence, confusion, Impulse control disorders
Reduced motor Cx compared to L-Dopa
Risk of Fibrotic reactions
Examples of COMt inhibitors?
What benefits do they provide?
What are SE - common to levodopa…?
- Entacapone, Tolcapone, Stalevo (sinemet + entacapone)
- Must be taken with levodopa; reduce on/off effects. Reduce conversion of L-dopa and dopamine into non-useful substrates (3-0 and homo-valinic acid)
- Dyskinesia, NVSOmnolence, Hepatotoxicity - regular LFTs
Examples of Continuous Dopamine Stimulation? features of the 3 main?
- Apomorphine, Duodopa, Deep brain stimulation
- Apomorphine must be given with domperidone; continuous pump or rescue injections
- Duodopa - intrajejunal infusion
- Both are very expensive /year
- DBS - of subthalamic nucleus; good if severe tremor/dyskinesia/fialure of medical - not neuroprotective, so disaese still progresses; no effect on axial e.g. postural hypotension
What are the main non-motor symptoms in PD and how can they be managed? 5
- Depression/psychosis - citalopram, quetiapine
- Dementia - AChesterase inhibitors
- Sleep disorder - ? BZD
- Falls
- Autonomic disturbance - urinary (oxybutynin), constipation (movicol), excessive sweating, impotenc and more
What drugs must be avoided in PD?
Anything that blocks dopamine!!
Anti-emetics e.g. prochlorperazine, metoclopramide, cyclizine
Antipsychotics - haloperidol, chlorpromazine
Initiate with…
Other oral treatments as required…
Consider…
When motor complications develop?
Advanced with severe motor complications?
Don’t forget…
- Levodopa, dopamine agonist, rasagiline
- e.g. fluctuation, dyskinesia, falls, speech/swallow problems
- Manipulating dosage and timing; enzyme inhibition
- Add entacapone/tolcapone and MAO-B if not already given, maybe amantadine for dyskinesia
- Apomorphine, Duodopa, DBS
- MDT - SALT, PD nurse, Physio, OT etc.
