Parkinsons Flashcards
Name 6 treatment options Parkinson’s and examples
- Dopamine precursor: levodopa and carbidopa/benserazide
- dopamine agonists: pramipexole, ropinirole
- increase release endogenous dopamine: amantadine
- inhibit COMT: tolcapone, entacapone
- inhibit mao-b: selegiline, rasagiline
- affect cholinergic system: benzhexol, benztropine
Name 3 long term side effects of dopaminergics
- Motor fluctuations: with Cp drop, “wearing off phenomena”
- Freezing
- dyskinesia: dystonia, akathisia, chorea, myoclonus
First line treatment Parkinson’s?
Levodopa with carbidopa or benserazide: better to improve motor disability Dopamine agonists (ropinirole, pramipexole): better to lessen motor complications
Name 2 drug interactions with selegiline
- High doses: hypertension, especially with tyramine foods
- amantidine (increase release endogenous dopamine) and centrally active antimuscarinic agents: potentiate anti-pd effects
Name a dopamine precursor
Levodopa
Name 2 dopamine agonists
• Pramipexole
• ropinirole
(Bromocriptine, cabergoline, pergolide, apomorphine)
Name an anti-parkinsons drug that stimulate endogenous release dopamine
Amantadine
Therefore not enzyme inhibitor like others.
Name a COMT inhibitor
Entacapone
(tolcapone)
For Parkinson’s
Name a mao-b inhibitor
Selegiline
(Rasagiline)
Parkinson’s
Name 2 anti. Parkinson’s drugs that affect cholinergic system
- Benzhexol
* benztropine
Name indications selegiline
• Parkinson’s mild symptomatic relief prior to initiating methyldopa
Drug interactions with levodopa?
Maoi: hypertension (especially with tyramine)
Name 2 peripheral decarboxylase inhibitors that need to be given with levodopa to prevent metabolism before crossing BBB
- Carbidopa
* benserazide
Name 4 adverse effects levodopa
- Nausea and vomiting ( chemoreceptor trigger zone outside BBB so improve with decarboxylase inhibitor addition)
- psychiatric: schizo like
- CV: arrhythmia, postural hypotension ( improve with decarboxylase inhibitor addition)
- dyskinesias, especially face and limbs
Which medications reduce off time of levodopa? (2)
Entacapone (comt I )
Rasagiline (maob-i)
Indication anticholinergics for Parkinson’s?
First line for Parkinsonism caused by antipsychotics
Which Parkinson’s medication reduce dyskinesia?
Amantadine (stimulate release endogenous dopamine)
Which neurotransmitter is pertinent in Parkinson’s
Dopamine (decrease)
Moa levodopa?
- Dopamine precursor that can cross BBB.
- transported into brain via system L amino acid transporters
- enters nerve terminals in basal ganglia where it’s decarboxylated to form dopamine by dopa decarboxylase
Moa pramipexole?
Dopaminergic (d2) agonist that mimic dopamine
Longer acting than levodopa
Moa selegiline?
- Selective irreversible inhibitor of intraneuronal mao-b
* prevent breakdown dopamine
Moa entacapone?
- Reversible, competitive COMT inhibitor specific for cns
* prevent levodopa break down leading to increase bioavailability at nigrostriatal nerve fibres
Moa amantadine?
- Stimulate release endogenous dopamine!
- other proposed moa: dopamine agonist, monoamine reuptake inhibitor, anticholinergic, NMDA r antag
- also reported to inhibit reuptake dopamine presynaptically and have direct action on dopamine R
Moa benzhexol?
- Anticholinergic or antimuscarinic
- ach inhibit dopamine response
- restore balance between dopaminergic and cholinergic pathways
- reduction tremors
Name 2 long term effects of dopaminergics
- Motor fluctuations (decreased levels): wearing off phenomena ( off time), freezing
- Drug induced dyskinesia (increased levels): dystonia, akathisia, chorea, myoclonus
Which anti-parkinsons drugs offer most favourable long term motor complication profile?
Dopamine 2 receptor agonist: pramipexole, ropinirole
Ropinirole adverse effects? (4)
- Somnolence and sleep episodes
- Nausea
- orthostatic hypotension, syncope
- nightmares and hallucinations
Describe metabolism selegiline and active metabolites (4)
- Single oral dose or transdermal
- extensively metabolised in liver but also intestine via n-dealkylation, carbon hydroxylation, ring hydroxylation.
- active metabolites = amphetamine and methamphetamine
- long half life 39 hours
Name 3 adverse effects selegiline
- Agitation and involuntary movements
- confusion, insomnia, hallucinations
- Nausea
Which 2 factors predict the outcome of deep brain stimulation of subthalamic nucleus for Parkinson’s?
- Intensity to which pt responds to levodopa rx (pre-op) serves as predictor motor improvement. Not helpful for symptoms that don’t respond.
- younger patients with shorter disease duration or shorter motor fluctuations
Name 5 beneficial effects of deep brain stimulation in Parkinson’s
- effective control fluctuating responses to levodopa
- Control dyskinesia that doesn’t improve with med adjustment
- reduce tremor
- reduce rigidity
- improve slowing of movement
Which release formulation is better for levodopa?
At rx initiation, no difference in rate of motor complications seen between extended and immediate release formulations
Half life levodopa-carbidopa combination?
2 hours
Ropinirole drug interaction?
- cyp1a2 metabolise Ropinirole
* cyp1a2 inhibitors eg. ciprofloxacin, flavoxamine, reduce clearance Ropinirole
Which drug has both antiviral and anti Parkinson’s activity?
Amantidine
What percentage levodopa enter brain unaltered?
1-3%
