L21 Parkinson's treatments Flashcards
What are the main treatment options for Parkinson’s?
- symptomatic treatment: Pharmacological/ deep brain stimulation
- non-motor management: speech therapy, physiotherapy
What is the cause of Parkinson’s disease?
Death of neurones in substantia nigra leads to dopamine depletioni in the stratium
Classes of drug in treating Parkinson’s (6)
- Dopaminergic agents
- Catechol-O-methyl transferase inhibitor (COMT)
- Monoamine oxidase-B (MAO-B) inhibitors
- Anticholinergics
- Amantadine
- Memantine and other glutamate receptor antagonists/ agonists
*Usually a combination of drugs are required to manage the symptoms
L-DOPA
- Dopaminergic agents
- requires active transport across the gut-blood and blood-brain barrier due to it’s large
- L-DOPA requires DOPA decarboxylase to be converted into Dopamine
- L-DOPA is always given with a decarboxylase inhibitor so prevent conversion into dopamine before entering brain ( the decarboxylase cant cross blood-brain barrier)
What are the side effects caused by L-DOPA?
- results of excessive dopaminergic stimulation, i.e. dyskinesias
- and choreiform, ballistic movements
Direct dopamine receptor agonists
- e.g. pramipexole, ropinirole, rotigotine, bromocriptine
- does not require metabolic conversion
- longer half life than L-DOPA
- may delay motor fluctuations and dyskinesias associated withL-DOPA
- Side Effects: due to activation of other peripheral dopamine receptors
- Nausea, vomiting ( activation of Chemical zone triggering center)
- dizziness, headache, drowsiness, postural hypotension
Selegiline, rasagiline
- irreversible MAO-B inhibitor
- could have neroprotection
- side effects: insomia, nausea, hallucinations and potential interactions with tricyclics and SSRI anti-depressants
= low tyramine diet necessary( low level of marmite and cheese)
Entacapone, Tolcapone
- COMT inhibitors
Triphexphenidyl, benztropine, ethopropazine
- Anticholinergics
- Dopamine usually has inhibitory effects on cholinergics neurones so with a dopaminergic depletion, anticolinergics can be used to replace dopamine’s effects
- effective mainly for tremor
*Side Effects: anti-cholingeric effects, e.g. dry mouth, sedation, confusion
Amantadine
- Initially used as an anti-viral agent
* Side effects: autonomic, psychiatric
Memantine
- NMDA receptor antagonist
- used to treat cognitive defects in Alzheimer’s disease
Surgery- deep brain stimulation
- usually only used when drugs are no longer effective
Cell transplants
- replace the lost neuronal cells by using genetically engineered cells
What is Huntington Disease?
- Polyglutamine (CAG) expansion repeats which is toxic to neurones
- leads to spinobulbar muscular atrophy, detatorubral-pallidoluysian atrophy and spinocerebellar ataxias
Progression of Huntington’s Disease
- Onset correlates with CAG repeat length
- BUT rate of progression does not
Tetrabenazine
- used for treating chorea caused by Huntington’s
Clonazepam
- used to treat rigidity caused by Huntington’s
Possible pharmaceutical targets for Huntington’s
1) protease inhibition- to avoid fragments of DNA to get translated
2) Aggregation inhibition and autophagy-to avoid fragments from accumulating
