Pagedundee.ac.uk

Arlene Coulson,

Neurology Specialist Clinical Pharmacist

MFE Parkinsons disease specialist pharmacist

NHS Tayside

Parkinson’s disease

6 October 2017

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UKCPA Neurosciences MasterclassTreating common neurological conditions in the elderly

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__________________________________________________________________________An essary on the Shaking Palsy (1817)

• “Involuntary tremulous motion, with lessened muscular power, in parts, not in action and even when supported, with a propensity to bend the trunk forward and to pass from a walking to a running pace, the senses and intellect uninjured”

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AN

E S S A Y

ON THE

S H A K I N G P A L S Y.

BY

JAMES PARKINSON.MEMBER OF THE ROYAL SOCIETY OF SURGEONS

LONDON:PRINTED BY WHITTINGHAM AND ROWLAND

FOR SHERWOOD, NELLY, AND JONES,PATERNOSTER ROW

1817.

1. Parkinson, J. An Essay on the Shaking Palsy. 1817. Sherwood, Nelly and Jones. London. Republished: The Classics of Medicine Library. 1986.

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Pathogenesis of Parkinson’s disease

In Parkinson’s disease, dopamine-containing nerve cell bodies within the nigrostriatal and mesocorticolimbic pathways are selectively and progressively destroyed

Figure: Dopaminergic pathways in

human brain (schematic

presentation)

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__________________________________________________________________________Pathology of Parkinson’s disease – neuronal loss

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Loss of dopaminergic neurons from the pars compacta region of the substantia nigra -approx 60% loss of neurons (80% depletion in striatal dopamine) gives PD symptoms

100

Percent of dopamine neurons

Time (Years)

Critical threshold

Normal ageing

PD

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Epidemiology of Parkinson’s disease:Annual incidence by sex & age

Van Den Eeden SK, et al. Am J Epidemiol. 2003;157:1015-1022.

Age in Years

Incid

en

ce

pe

r 10

0,0

00

0-29 30-39 70-7950-59 60-69

200

140

120

100

80

60

40

0

40-49 80+

20

160

180

Male

Overall

Female

Prevalence

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__________________________________________________________________________Parkinson’s disease - Overview

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5% Familial

95% Idiopathic

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__________________________________________________________________________Alpha - synuclein

• Polymeropoulos in 1997 found that mutations in the alpha-synuclein gene can result in PD.

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Alpha synuclein overproduction/toxic species

Cellular dysfunction

Alpha synuclein spread

inflammation

Cell death across many neuronal populations

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Rigidity

Tremor

Bradykinesia

Posturalinstability

Gait disturbances

Diagnosis is essentially clinicalusually easy, except early stages

Clinical symptoms: (20% is motor symptoms)

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Motor symptoms

• Impassive face• Low blink rate/speech volume • Difficulty swallowing• Difficulty starting/stopping• Flexed posture• Shuffling gait /Small steps• Lack of arm swing• Loss of balance• Difficulty with fine movements• Pill-rolling rest tremor

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Autonomic

Sleep related

Clinical symptoms: 80% is non- motor symptoms 30 symptom Questionnaire

Cognitive

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__________________________________________________________________________Autonomic symptoms

• Urinary frequency/urgency• Sleep disturbance

• Constipation/delayed gastric emptying• Excessive sweating• Postural hypotension (30.1% point prevalence in PD1)

• Falls/fracture risk in PD 2 – increase A&E visits, inpatient stay, healthcare costs.

• Management strategies • decrease/stop antihypertensives, anticholinergic

medication, antidepressant medication, dopaminergic medication

• Increase fluid intake• NICE 1st line midodrine (licensed) 2nd line fludrocortisone

1 Velseboer et al. Parkinsonism and related disorders 2011; 17 (10): 724-729.2 Francois et al. Journal of medical economics 2017; 20 (5): 525-532.

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__________________________________________________________________________Constipation in Parkinson’s

Lifestyle

• Increase dietary fibre

• Increase fluid intake

• Exercise

• Reduction in gastric motility

• Delayed gastric emptying

• Reduce absorption of Levodopa in small intestine

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Optimise Levodopa

Medication review

• Opiates

• Tricylcic antidepressants

• Antimuscarinics

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__________________________________________________________________________Sleep-related symptoms

• Need to pass urine• Difficulty turning over• Difficulty getting out of bed• Cramps/dystonia• Jerks/restless legs• Vivid dreams/nightmares • Hallucinations

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__________________________________________________________________________Cognitive symptoms

• Depression

• Delirium

• Dementia

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__________________________________________________________________________PD - Clinical features and time course of progression

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(RBS=REM Sleep behaviour disorder, EDS=excessive daytime sleepiness, MCI=mild cognitive impairment), Fig from thelancet August 2015

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Pharmacological Treatment of Motor Symptoms

Levodopa Dopa decarboxylase inhibitor

MAO-B inhibitor

COMT inhibitor

Dopamine agonists

•Ropinirole

•Pramipexole

•Rotigotine

Restore depleted

dopamine

Prolong duration of L-Dopa

Stimulate dopaminergic

receptors

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__________________________________________________________________________Drugs to avoid in Parkinson’s disease

• For hallucinations AVOID: Haloperidol, Chlorpromazine, Fluphenazine,

Perphenazine, Trifluoperazine, Flupenthixol

• Clozapine/Olanzepine is the preferred antipsychotic for psychosis in PD.

• For nausea and vomiting AVOID: Metoclopramide, Prochloperazine, Cyclzine

• If anti-emetic required use domperidone or ondansetron.

• For coughs and colds AVOID: Preparations containing sympathomimetics (such

as pseudoephedrine and ephedrine) with MAO-B inhibitors.

• For dementia caution: Acetylcholinesterase inhibitors can exacerbate tremor

or if withdrawn can induce neuropsychiatric symptoms.

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__________________________________________________________________________The future treatment of Parkinson’s disease

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YOUNGER PATIENTS

TREMOR DOMINANT

NO COGNITIVE DEFICITS

OLDER PATIENTS

GAIT/BALANCE PROBLEMS DOMINANT

COGNITIVE DEFICITS

•DOPAMINE CELL TRANSPLANTS or

•GENES TO MAKE DOPAMINE

•And/or

•GROWTH FATORS TO RESCUE DOPAMINE SYSTEM

•DRUGS TO STOP DISEASE PROCESS

(reduce alpha synuclein production)

•VACCINES/IMMUNE THERAPIES TO

STOP IMMUNE SPREAD

•ANTI-INFLAMMATORIES

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__________________________________________________________________________Current disease modifying therapy trials....

• GLP1 agonists (exenatide)

• Isradipine (calcium channel antagonist)

• Nilotinib (tyrosine kinase inhibitor)

• Sargramsostim (GCSF)

• Ambroxol (modulates lysosomal enzyme glucocerebrosidase )

• Simvastatin

• Desferroxamine (oral iron chelator)

• Nicotine

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__________________________________________________________________________Case Study 1

• March 2015

• Alan is a 76 year old man who lives on his own and was diagnosed with PD.

• Alan presented with poor mobility (previous falls due to balance): mobilises

with a stick (significant loss of arm swinging) and trolley in the house, freezing

on turning, bradykinesia, right sided tremor and constipation.

• His regular medicines: Levothyroxine, tramadol, perindopril, paracetamol,

indapamide.

• Medication review in clinic...... Any initial thoughts?

• Start on co-beneldopa 50/12.5mg titrating regimen up to TDS – 8am, 1pm and

6pm and laxido once daily

• Describe how co-beneldopa works and common side effects. 21

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__________________________________________________________________________Case Study 1

• August 2015

• Alan felt he had terrible GI symptoms 1 hour after taking co-beneldopa.

• Switched to co-careldopa 62.5mg TDS (slowly titrated) with domperidone.

• In clinic he had significant postural hypotension (>30mmgHg systolic ) and poor

balance.

• Medication review – what recommendations would you make?

• January 2016

• Alan felt no change in his mobility and was still needing aids to help walk.

• Titrate ropinirole up to 2mg TDS

• Describe how ropinirole works and discuss side effects22

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Impulsive and compulsive behaviour in Parkinson’s monitoring and information tool

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__________________________________________________________________________Case Study 1

• March 2016

• Alan complained of being very rigid first thing in the morning with difficulty

getting out of bed. No evidence of freezing episodes and no more falls. His

swallowing had improved. Perindopril dose had been reduced by GP – no

significant postural drop bp.

• No neuropsychiatric side effects. Constipation improved with regular Laxido

• Add co-beneldopa 62.5mg dispersible when waking and increase co-careldopa

125mg 8am, 12 noon and 6pm (titrate up weekly)

• August 2016

• Gradual decline in function and mobility

• Increase co-careldopa 187.5mg 8am, 12 noon and 6pm (titrate slowly) 24

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__________________________________________________________________________Case Study 1

• December 2016

• Alan feeling very slow in the mornings with co-careldopa wearing off before lunch

time.

• What are the other treatment options?

• Add entacapone to morning dose of co-careldopa.

• Take co-careldopa on empty stomach.

• February 2017

• Alan was taking entacapone at wrong time... Taking it at 10am instead of 8am with Co-

careldopa.

• Compliance issues – daughter helps with medicines and requesting Venalink.

• Checked pill timer to remind patient to take medicines at correct times25

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__________________________________________________________________________Case Study 1

• May 2017

• Venalink started but co-careldopa not included (all other medicines are).. “ I

get too many boxes of Sinemet, I find it difficult to open it and I am not sure

if I am taking it when I should”

• D/W community pharmacist who initially reported couldn’t put co-careldopa

in Venalink (due to 7 day stability data)... Negotiated not to make 4 weeks of

Venalink in advance for this man.

• Checked pill timer to remind patient to take medicines at correct times.

• Referral to Pharmacy technicians in Early Intervention Team for compliance

assessment at home. 27

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__________________________________________________________________________Case Study 1

• June 2017

• Compliance improved.....

• Visual hallucinations developed.... “I see spiders in my bowl of porridge” “I

see dark shadows of a person and when I look there is nobody there”

• Vivid dreams.... “I wake up scared thinking somebody is in my house”

• Distressing both patient and daughter....

• What drug would you recommend to reduce/stop?

• Gradually reduce ropinirole to stop...

• Follow up at home.... close communication with PD team. 28

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__________________________________________________________________________Case Study 1

• Future risks

• Severe motor fluctuations with poor levodopa response.

• Over using levodopa.... Dopamine dysregulation syndrome (community

pharmacist useful)

• Neuropsychiatric – hallucinations, impulsive compulsive behaviours,

hypersexuality, gambling ...

• Compliance of medicines...

• Independence diminishing...

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__________________________________________________________________________Case Study 2

• Margaret is a 82 year old lady

• Margaret lives on her own and is fairly independent.

• Diagnosed with Parkinson’s disease 5 years ago

• She is taking co-beneldopa 125mg 8am, 1pm and 5pm except when she plays

golf she will take it earlier at 11am instead of 1pm.

• More recently, Margarets mobility has slowed down.. finding it more difficult

to get out of bed or rise from a chair.

• She is no longer capable of playing a full round of golf which frustrates her.

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__________________________________________________________________________Case Study 2

• List of current medicines: Bendroflumethiazide, Bisoprolol, Simvastatin,

Metoclopramide, Paracetamol, Codeine, Salbutamol inhaler

• Medication review in clinic – what medication changes would you suggest?

• Titrate ropinirole up to 2mg TDS.... Describe how it works and side effects....

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__________________________________________________________________________Case Study 2

• January 2017

• Attends clinic and would be falling asleep in and out of the conversation... Her

daughter reported this to be a new problem.

• Patient concern “when I am sitting on my chair I am worried when I am

holding a cup of tea in case it falls.”

• What do you think this could be and how would you manage it?

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• Ropinirole: excessive daytime sleepiness and sudden onset of sleep

• Caution when driving or operating machinery

• Stopped ropinirole and any other sedatives... and increased co-careldopa....

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__________________________________________________________________________Case Study 3

• Jim is 68 and has had Parkinson’s for 4 years. Bradykinesia and rigidity have

been his main symptoms. Lives with his wife and he remains relatively

independent.

• In recent months life has become more frustrating and his Ropinirole is less

effective.

• Jim’s problems include

• Hand function has deteriorated - needs help with aspects of personal care• Increased difficulty initiating gait - shuffles often & trips easily• Can’t turn over in bed -needs legs lifted onto the bed• early morning toe cramp (Dystonia)• Prominent stooped posture• Some drooling

• Co-beneldopa started and titrated to 125mg TDS and MR at night. 35

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__________________________________________________________________________Case Study 3 – Jim’s journey 3 years on

• 3 years on and Jim is struggling because his wife died suddenly 2 months ago....

She was his main carer... Jim’s wife used to manage his medication for him, and

since she died, he is finding it really difficult to remember when to take his

tablets. He often gets mixed up. This has had a major impact on his Parkinson’s

disease and he has been admitted to hospital as not able to cope at home.

• Complex medication regimen is as follows:

• Selegiline 10mg on waking

• Ropinirole 2mg three times daily

• Co-beneldopa 125mg and Entacapone FIVE times daily – 7am, 10am, 1pm, 3pm, 6pm

• Co-beneldopa 125mg CR at bedtime

• Laxido one sachet daily

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__________________________________________________________________________Case Study 3 – Jim’s journey 3 years on

Challenge: Support for patients with complex medication regimes who are being discharged home from hospital

At home when Jim misses his medicine, he slows right down until he is barely able to move, and becomes very anxious and upset. He has fallen a few times, which has really affected his confidence, so he doesn’t like going out of the house anymore. If he gets his night-time medication wrong, he is completely unable to sleep. He is finding it hard to manage his groceries and cooking for himself and is losing weight.

Jim has a son who lives in London with his family. He has good friends living nearby. He is adamant that he wants to stay in his house and is scared of telling anyone what is happening in case he is unable to be discharged home.

What support is there for Jim to manage his condition and medication and enable him to be discharge home?

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__________________________________________________________________________The role of the Pharmacist within the MDT...

• Full medication review

• Co-produce medication changes with the patient and/or carer.

• Educate the patient/carer about their medicines

• Assess patient/carer compliance.

• Assess response to treatment and side effects.

• Use teach back.

• Electronic communication of medication changes to GP via clinical portal.

• Commence pharmaceutical care plan and share across the boundaries with

Community pharmacist/locality pharmacist and pharmacy technicians. 39

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__________________________________________________________________________Recent data collection from clinic patients...

• In a snap shot of 84 patients over 14 clinics, there was a total of 65

medication interventions.

• Increase dose or change in schedule (38%)

• Polypharmacy – add/stop medicine (23%)

• Medication timing issues (11%)

• Compliance issues (9%)

• Difficulty opening medicines (8%)

• Medication supply issues (4%)

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__________________________________________________________________________Consultant feedback.....

1. I can spend less time explaining medications so that gives me time to really delve into other problems.

2. I am assured that medicine side effects are explained

3. I am assured that even if I am caught up with other problems, we will meet the standards of monitoring dopamine dysregulation

4. I am assured that suggested medicine changes will be carried out in a timely fashion

5. Any potential interactions that I have not noticed are flagged up

6. Pharmacists print out ecs medicine list which helps to speed up consultation

7. Pharmacists highlight any potential problems with medicine not being requested on repeat prescription suggesting non-concordance. This helps with discussion, potential support to aid concordance

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Parkinson’s disease pharmaceutical care needs from the patients perspective.....

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__________________________________________________________________________Medication timings....

• Help to remember to take medicines at specific times of the day. Especially if

out of the house or their usual routine.

• Core requirement: label with times of day! In clinic, we supply pill timers and

programme them to go off at medication times. Or advice on using

alarm/voice activated on mobile phone.

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__________________________________________________________________________Difficult opening medication packaging....

• Supplied foil cutters to patients or discussed with community

pharmacy to use non-child lock bottle top.

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__________________________________________________________________________Patient ‘own’ self improvements

Family support was key for most patients→ “Daughter makes up weekly box” “Husband reminds me” → “My wife puts medicines in a cup each day.

→ “My wife picks up my prescription from the pharmacy”

In addition:→ Timing medication with meals.

→ “Take my medicines as soon as I get out of bed and then at meal times”

→ “Combine meal times with my medicines”

→ Using posters throughout house→ “I have charts and posters around the house in visible areas”

→ Keep medicines visible→ “Sit medicines out on coffee table so I can see them”

→ “I leave my weekly pill box out so it is easy to see and check if I have missed any”

→ “Take after meal times and leave them on trolley beside where I sit in the living room”

→ Out and about from the house/usual routine→ I have a daily pill box and try to take my medicines with meals. I sometimes get distracted if my routine

changes and I go out. I sometimes forget in these circumstances”

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