Management and treatment of parkinson s disease
Download
1 / 41

- PowerPoint PPT Presentation


  • 213 Views
  • Updated On :

Management and treatment of Parkinson’s Disease. SAHD Naghme Adab. Reminder- what is PD?. UK Brain bank criteria Bradykinesia/Akinesia is obligatory ( slowness of initiation, reduction in speed and amplitude of repetitive actions) AND at least one of the following Rigidity 4-6Hz tremor

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about '' - wheeler


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript

Reminder what is pd l.jpg
Reminder- what is PD?

  • UK Brain bank criteria

  • Bradykinesia/Akinesia is obligatory

    • ( slowness of initiation, reduction in speed and amplitude of repetitive actions)

      AND at least one of the following

  • Rigidity

  • 4-6Hz tremor

  • Postural instability


Slide3 l.jpg

  • Overall prevalence ≈ 160 / 100 000

  • Incidence rates ≈ 20 / 100 000 / year

  • 2% of people over 80 are affected

    …….therefore in a catchment area of ≈ 1 million people we would expect 1600 patients with PD and 200 new cases per year

  • Mean age at onset 60

  • <5% of PD in under 40s


Case history 1 l.jpg
Case History 1

  • 55 year old man, RH

  • Plumber

  • Tremor, right sided, 9-12 months

  • Difficulty holding spanner, manipulating small objects

  • Difficulty bending/getting up off floor etc

  • Otherwise well, no medication

  • Right sided rest tremor, bradykinesia/rigidity



Case history 2 l.jpg
Case History 2

  • 76 year old female, RH

  • Right sided tremor, walking slow, difficulty dressing, 12-18 months

  • Right sided signs of PD, slow to rise from chair, slow, small steps

  • BP on ACEI, well controlled


Case history 3 l.jpg
Case History 3

  • 68 year old man, RH

  • Left sided tremor for 2 years

  • OK with ADL’s, mobility not affected

  • Tremor embarrassing

  • Retired, not on medication

  • Left sided rest tremor, mild bradykinesia, normal gait


When to start l.jpg
When to Start

  • circumstances

  • risk/benefit ratio

  • usually depends on functional impairment

  • No real evidence for neuroprotection BUT…..


General principles l.jpg
General Principles

  • low and slow

  • titrate to response or SE

  • unlike epilepsy, PD is chronic and progressive

  • most pts will need drugs altered over a period of years


Pathways l.jpg
Pathways

  • The basal ganglia receive huge no of inputs and produce outputs back to cortex and brainstem

  • Part of an information loop that takes info from cortex processes it and feeds it back

  • dopamine is produced by substantia nigra in brain stem

  • modulates output of striatum (caudate + putamen)

  • The main input system is the striatum

  • The main output system is the Globus Pallidum ( Gpi)


Slide12 l.jpg

DIRECT PATHWAY

INDIRECT PATHWAY


Drugs used in management of pd l.jpg
Drugs used in management of PD

  • Classes of PD drugs available

    • PD motor symptoms

    • Dementia, psychosis, non-motor

  • What to use when

    • New diagnosis

    • Adjuvant therapy

    • Complex disease

  • Suggested flow chart for treatment of PD


Classes of drug in pd l.jpg
Classes of drug in PD

  • Levodopa/carbidopa

  • Dopamine agonists

  • MAO-B inhibitors

  • COMT inhibitors

  • Amantadine

  • Continuous dopaminergic stimulation (CDS)

  • Acetylcholinesterase inhibitors


Dopamine metabolism l.jpg
Dopamine metabolism

Phenylalanine hydroxylase

Phenylalanine

Tyrosine

Tyrosine hydroxylase

DOPA

Dopadecarboxylase

Levodopa

COMT

AADC

3-O-methyldopa

Dopamine

COMT

MAO

3-methoxytyramine

3,4-dihydroxyphenylacetic acid

MAO

Homovanillic acid



L dopa l.jpg
L-Dopa

  • always given with a decarboxylase inhibitor

  • sinemet (carbidopa) co-careldopa

  • madopar (benserazide) co-beneldopa

  • Madopar dispersible may have slightly quicker onset of action

  • can be given in slow release prep ( Sinemet CR)- but usually reserved for overnight symptoms


Side effects of levodopa l.jpg
Side effects of levodopa

Short-term

  • GI

    • N&V

    • Loss of appetite

  • Cardiovascular

    • Postural hypotension

  • Sleep

    • Somnolence

    • Insomnia

    • Vivid dreams, nightmares

    • Inversion of sleep-wake cycle

  • Psychiatric

    • Confusion

    • Visual hallucinations

    • Delusions, illusions

Long-term

  • Involuntary movements

    • Peak-dose dyskinesia

    • Diphasic dyskinesia

    • Dystonia

  • Response fluctuations

    • Wearing off

    • Unpredictable on/off

  • Psychiatric

    • Confusion

    • Visual hallucinations

    • Delusions, illusions

  • Keep total daily dose of levodopa as low as possible (≤ 600mg)


Mao b inhibitors selegiline l.jpg
MAO-B inhibitors - Selegiline

  • Monotherapy

    - No comparative data with other monotherapies

  • Adjuvant therapy

    - Poor evidence base for use as adjuvant in advanced PD

  • Preparations available

    - Selegiline PO tablets, 2.5mg – 10 mg daily

    - Eldepryl tablets/liquid, 2.5mg – 10 mg daily

    - Zelapar fast-melt tablets, 1.25mg daily

  • Amphetamine metabolites

    - Hallucinations, insomnia, nightmares, vivid dreams

    - Postural hypotension, nausea, confusion

Tend to avoid in the elderly

Use rasagiline instead


Mao b inhibitors rasagiline l.jpg
MAO-B inhibitors - Rasagiline

  • 10-15 fold more potent than selegiline

  • No amphetamine metabolites

  • 1mg daily

  • Monotherapy

  • Adjuvant treatment

    • Reduces off time by 48-56 mins/day

    • Increases on time without dyskinesias

    • Similar in efficacy and tolerability to entacapone

  • Well tolerated

    • Initial ‘flu-like’ symptoms in first 2 weeks

    • Safe with most SSRIs (avoid/use with caution with fluoxetine and fluvoxamine: serotonergic syndrome)


Dopamine agonists l.jpg
Dopamine agonists

  • Ergot-derived DAs

    • Bromocriptine, lisuride, pergolide, cabergoline

    • Cardiac valvulopathy

    • Pulmonary, retroperitoneal, and pericardial fibrotic reactions

  • Non-ergot DAs

    • Ropinirole, pramipexole, rotigotine, apomorphine

  • Monotherapy, adjuvant therapy

  • Mode of delivery

    • Oral, patch, sub-cutaneous

  • Delay onset of motor fluctuations, dyskinesias


Dopamine agonists23 l.jpg
Dopamine agonists

  • Common side effects

    • N&V, loss of appetite

    • Postural hypotension

    • Confusion, hallucinations

    • Somnolence

  • Impulse control disorders



Comt inhibitors l.jpg
COMT inhibitors

  • Must be taken with levodopa

  • Entacapone (200mg with each levodopa dose)

    • On time increased by 1hr 1 min

    • Off time decreased by 41 min

  • Tolcapone (100mg tds)

    • On time increased by 1hr 38 mins

    • Off time decreased by 1 hr 32 mins

  • Stalevo

    • Combines sinemet with entacapone


Comt inhibitors26 l.jpg
COMT inhibitors

  • Side effects

    • Dyskinesia (so ↓ levodopa)

    • Diarrhoea

    • Nausea, somnolence, abdo pain

    • Discoloured urine (body fluids orange)

  • Hepatic toxicity (tolcapone)

    • Only 3 pts died fulminant liver failure

    • Rigorous blood monitoring

    • Stop if AST or ALT exceed upper limit of normal


Antimuscarinics l.jpg
Antimuscarinics

  • Dopamine loss leads to loss of inhibition of cholinergic stimulation

  • may be helpful in tremor

  • SE confusion/cognition, dry mouth/eyes, urinary retention

  • Very rarely used!


Continuous dopaminergic stimulation l.jpg
Continuous dopaminergic stimulation

  • Pulsatility of oral treatments

  • In early disease, remaining dopaminergic neurons can store excess dopamine and act as ‘buffer’ to low dopamine levels

  • As disease progresses, more neurons die and buffer capacity is lost

  • Apomorphine

  • Duodopa

  • Deep brain stimulation


Non motor symptoms in pd l.jpg
Non-motor symptoms in PD

Citalopram

Quetiapine, clozapine

  • Depression, psychosis

  • Dementia

  • Sleep disorders

    • Restless legs syndrome

    • Periodic limb movements of sleep

    • REM sleep behaviour disorder

  • Falls

  • Autonomic disturbance

    • urinary dysfunction

    • weight loss, dysphagia

    • constipation

    • erectile dysfunction

    • orthostatic hypotension

    • excessive sweating

    • sialorrhoea

Acetylcholinesterase inhibitors

clonazepam

Oxybutynin, tolterodine

movicol


Drugs to avoid in pd l.jpg
Drugs to avoid in PD!!

  • Anything that blocks dopamine

  • Anti-emetics

    • Prochlorperazine

    • Metoclopramide, cyclizine

  • Antipsychotics

    • Chlorpromazine, promazine

    • Fluphenazine, perphenazine, prochlorperazine, and trifluoperazine

    • Haloperidol

Domperidone is the anti-emetic of choice in PD

Use atypicals if needed egquetiapine


Summary l.jpg
Summary

  • Initiate treatment with

    • Levodopa

    • Dopamine agonist

    • Rasagiline

  • Add other oral treatments as required

    • Fluctuations, dyskinesias

    • Neuropsychiatric problems

    • Falls, postural instability

    • Speech/swallowing problems

  • Consider

    • Manipulating dosages (limit to fractionation!!)

    • Manipulating timings

    • Enzyme inhibition (MAO-B and COMT inhibitors)

  • When PD becomes advanced consider

    • Apomorphine, Duodopa, DBS


Case history 132 l.jpg
Case History 1

  • 55 year old man, RH

  • Plumber

  • Tremor, right sided, 9-12 months

  • Difficulty holding spanner, manipulating small objects

  • Difficulty bending/getting up off floor etc

  • Otherwise well, no medication

  • Right sided rest tremor, bradykinesia/rigidity


Case history 233 l.jpg
Case History 2

  • 76 year old female, RH

  • Right sided tremor, walking slow, difficulty dressing, 12-18 months

  • Right sided signs of PD, slow to rise from chair, slow, small steps

  • BP on ACEI, well controlled


Case history 334 l.jpg
Case History 3

  • 68 year old man, RH

  • Left sided tremor for 2 years

  • OK with ADL’s, mobility not affected

  • Tremor embarrassing

  • Retired, not on medication

  • Left sided rest tremor, mild bradykinesia, normal gait


Slide35 l.jpg


Case history 4 l.jpg
Case History 4

  • 71 year old

  • 1997 diagnosed with PD, right sided tremor, bradykinesia/rigidity-all mild

  • L-dopa started after 10 months as symptoms worsened, problems with stairs

  • Started on sinemet 62.5mg od then incresed to tds over 1 week.

  • No response after 2 weeks

  • What next?


Slide37 l.jpg

  • Dose incresed to 125mg tds with good response

  • Stable over 2 years then mobility worsened and patient getting slow and stiff before next drug dose

  • What next?

  • 1999 Increase sinemet to qds

  • (OR add entacapone)

  • Over next 3 years, dose increased to sinemet 250, 125, 250, 125 plus sinemet CR nocte

  • 2002- fluctuations in response- drugs not always helping him switch on, extra movements an hour after taking his medications, switched off prior to his next dose

  • What next?


Slide38 l.jpg

  • Sinemet decreased to 125 qds plus CR nocte

  • Entacapone added

  • No improvement, slightly worse over 6 months

  • What next?

  • Ropinirole added

  • Dose slowly increased over 8 months

  • 2004 (79 yrs old), hallucinations, mild cognitive decline

  • Ropinirole decreased, symptoms worsened

  • Quetiapine added

  • Sinemet levels maintained


Guidelines for drug management of pd l.jpg

Dopamine agonist

Disease progression

Guidelines for drug management of PD

Significant functional disability

MAO-B inhibitor

Levodopa (max 600mg/day)

Add levodopa (max 600mg/day)

Motor complications develop

Add DA or entacapone

Add entacapone or DA

Switch to tolcapone if entacapone fails

Add MAO-B inhibitor if not already given

Add amantadine for dyskinesia

Severe motor complications

Consider apomorphine, Duodopa, DBS


Prescribe on kardex l.jpg
Prescribe on Kardex

  • Sinemet to 125 qds

  • Sinemet CR nocte

  • Add the Entacapone

  • Instead of ropinirole prescribe pramipexole

  • Prescribe a suitable anti-emetic

  • Prescribe a suitable anti-depressant


References l.jpg
References

  • Parkinson’s disease in Practice. Carl Clarke.2nd edition 2007.


ad