Parkinson's Flashcards
what is the pathophysiology of parkinsons?
- Chronic, progressive neurodegenerative disease
- Degeneration of dopaminergic neurones in nigro-striatal pathway
- 50-80% loss before symptoms apparent
- Presence of Lewy bodies in neurones leads to cell death
- Changes in GABA glutamate pathway motor symptoms caused
what gets Parkinsons?
• 1 in 500 people in UK • Average age at onset is 60 years – 5-10% “early onset” (30-40s) – Men more commonly affected 3:2 ratio • Complex interaction of factors contributes to increased risk – Genetic factors – Exposure to neurotoxins – Head injury
what are the motor symptoms of parkinsons?
– Tremor, not a fine tremor but always asymmetrical. Usually on one side
– Rigidity – very stiff might not be able to move their arms
– Bradykinesia – slowing of movement. Feet very close together and shuffle when walk
what are the non-motor symptoms?
– Micrographia- this is effect of the way they write
– monotone voice
– Swallowing and speech problems
– Drooling, loss of smell, excessive sweating
– Depression, memory problems and sleep disturbances (REM sleep disorder, can happen years before diagnosis, they act out there dreams)
– Constipation and urinary problems (affects neurones)
– Dizziness and falls
– Dementia
when would you give drug treatments?
- Drug treatments should only be started once motor symptoms affect a patient’s ability to function on a daily basis.
- May be unable to eat or drink by themselves
- Unable to dress themselves
- Drug treatments for motor symptoms aim to increase dopamine levels in the brain, through a variety of mechanisms
what are the types of drug treatments for motor symptoms?
- MAO-B inhibitors
- Dopamine agonists
- Levodopa – gold standard for motor symptoms
- COMT inhibitors
- Amantadine
- Anticholinergics
what is levodopa?
- Most effective treatment - relieves motor symptoms of tremor, bradykinesia, rigidity
- Low dose then titrated up to limit side effects of postural hypotension, nausea, vomiting and psychiatric effects
- Initiate when symptoms interfere with daily activities. Until then, use other first line therapies due to long term problems (decreased efficacy and dyskinesias)
- Usually get 5-10 years of treatment until you start to see a decline, you may chose to use another drug to give them a better 5-10 years later down the year
what is levodopa combined with?
• Levodopa combined with peripheral dopa-decarboxylase inhibitor E.g. Madopar® (co-beneldopa), Sinemet® (co-careldopa), Duodopa®
what are examples of MAO-B inhibitor?
Selegiline and rasagiline
what does MAO-B inhibitor do?
prevents the metabolism of dopamine,increases the dopamine at receptors.
doesn’t change motor symptoms as much so if patient isnt suffering as much these will be first line
what is an example of a dopamine agonist?
- non-ergot - ropinirole, pramipexole, rotigotine
* ergot - pergolide, lisuride, bromocriptine, cabergoline. Not as used due to bad side effects.
when would you give dopamine agonist?
- Useful initial monotherapy - fewer long term problems than levodopa (although less effective for motor symptoms)
- Less effective then L-DOPA, patient preference if they want to use L-DOPA later down the line
what are the side effects of dopamine agonists?
• ergot: lung and cardiac valve fibrosis
– Ergot-derivatives now rarely used
– If patient is on this we need a lot of cardiac and respiratory monitoring
• Nausea and vomiting – very common
• Psychiatric (hallucinations, psychosis) – may be managed by reducing the dose or stopped altogether
• Postural hypotension – this can be caused by disease itself which makes it hard to monitor
• Sudden sleep onset
what is a dopamine dysregulation syndrome/
gambling, hypersexuality, binge eating). They crave L-DOPA, leading to taking more then they need.
what is the later-stage disease?
• As disease progresses, response to treatment declines
• Wearing off
– Plasma drug concentrations fall (trough) – patients experience akinesia and rigidity
– This means in between doses the symptoms will come back and cause issues
• On-off
– When drug concentrations peak, patients can experience motor complications (dyskinesia and dystonia). On-off is fluctuation between
what happens if you fail at first line therpay?
- dopamine agonist / levodopa monotherapy
- dopamine agonist AND levodopa therapy
- ADD entacapone or rasagiline or antimuscarinic
- Consider apomorphine
what is a COMT inhibitor?
• Catechol-o-methyl transferase inhibitors
- Use in combination with levodopa
- Prevent metabolism of levodopa to 3-O-methyldopa
what is an example of COMT inhibitor?
Entacapone
what does Entacapone do?
allows decreases levels of levodopa dose so this allows a better profile and on-off fluctuations improved
what are the side effects of COMT inhibitors?
dyskinesias, nausea, diarrhoea - may need to tweak the dose to manage some of these
what is amantadine?
glutamate antagonist at NMDA receptor
when do you use amantadine?
- Treats dyskinesias in late disease
* Efficacy decreases after several months – usually around 8 months until you will need to use a more advanced treatment
what are the side effectws of amantadine?
– psychiatric, e.g. confusion, hallucinations
– GI, e.g. N&V
– oedema, skin rash (livedo reticularis) vascular neck like rash
what is tachyphylaxis?
need more drug to have the same effect over time - this means you need to titrate up
what are anticholingerics?
trihexyphenidyl, orphenadrine
when would you use anticholingerics?
- Now only used for tremor
- Usually used in younger patients when tremor is their only symptoms
- Avoid in elderly due to side effects
what are the side effects of anticholingerics?
– anticholinergic, e.g. constipation, urinary retention
– psychiatric, e.g. confusion, delusions
what is duodopa?
• For PD with severe motor fluctuations and dyskinesia
• Intestinal gel
• Administered using pump via PEG tube (invasive)
can be used up to 16 hours a day
what is an example of a dopamine agonist sub cut?
Apomorphine
- bolus or 12 hour infusion
what are the side effects of dopamine agonist subcut?
– Nausea, vomiting (pretreat with domperidone PR for 3/7, to offset this side affect). Vets use this if pet eaten something they shouldn’t.
– yawning, drowsiness
– abscess / nodule formation – necrotic wound so may have to stop treatment
– prolongs QT interval so you need to monitor heart
what is a treatment option for early morning bradykinesia?
– dispersible levodopa taken on wakening – so it works quickly in the morning
– Night-time dose of dopamine agonist or MR levodopa so its still affective in the morning
what is a treatment option for dyskinesia?
– levodopa dose
– add dopamine agonist or COMT inhibitor & levodopa dose
– add amantadine
– Duodopa infusion via PEG
what is the NICE guideline for non-motor symptoms?
• Sialorrhoea (drooling)
– Hyoscine patches
– Sublingual 1% atropine eye drops twice daily (unlicensed this route)
• Restless legs syndrome
– Ropinirole, pramipexole
• REM sleep behaviour disorder
– Clonazepam 500mcg at night or Melatonin
• Depression
– SSRI (with care), these can worsen symptoms so need to use in lower doses and monitor
• Constipation
– As per BNF
• Psychosis
– Review PD meds
– Quetiapine or clozapine. Clozapine is better but you need to register for the patient monitoring service so usually used 2nd line
– Not typical antipsychotics due to the exacerbation of motor symptoms
• Dementia
– Rivastigmine
• Sexual dysfunction
– PDE inhibitors e.g. sildenafil
what is the role of a pharmacist?
- Monitor for interactions, e.g. iron reduces the absorption of levodopa
- Compliance aids and timing devices – phones apps that can remind you to take these drugs
- Management of adverse effects
- Alternatives in swallowing difficulty
what are future treatment options?
• Deep brain stimulation
– Of subthalamic nucleus (STN) or globus pallidus interna (GPi) – NICE guidance
– For motor complications refractory to drugs
– Foetal cell implants
• New delivery systems, e.g. transdermal
• Antidyskinetic agents, e.g. glutamate antagonists
