Parkinson’s Disease: How Pharmacists Can Make a Difference

Marsha K. Millonig, MBA, RPh President & CEO

Catalyst Enterprises, LCC

Disclosure InformationParkinson’s DiseaseMarsha K. Millonig

I have no financial relationship to disclose.

AND

I may discuss off-label/investigational use in my presentation.

Objectives

• Identify the visual and clinical testing tools used to diagnose PD

• Identify the classes of medications used to treat PD• Understand the pros and cons of each class of

medications and when to use these medications• Understand how concomitant disease states and

medications that could lead to further exacerbation of PD symptoms and how to avoid these situations

• Understand ways that pharmacists can assist PD patients, their caregivers, and physicians to properly manage their condition

What is Parkinson’s Disease?

• Chronic, progressive condition

• Motor symptom disorders• Dysfunction/degeneration

of dopaminergic neurons• Domaminergic neurons in

the substantia nigra control proper coordination and muscle group movement

Pathophysiology

• Lewy body structures also

• Inclusions of α-synuclein

• Disrupts normal neuronal function

Lewy body:Dense Core with Halo

Pathophysiology

• Cell death due to dopaminergic neuron degeneration may be occurring up to 6 years before symptoms appear

• When symptoms appear, about 70% to 80% of the neurons have been lost

• Autonomic, cognitive, other non-motor symptoms usually appear before the motor symptoms

Autonomic Dysfunctions

• Constipation• Dry mouth• Urinary retention/incontinence• Erectile dysfunction/decreased libido• Orthostatic hypertension• Drooling• Heat/cold intolerance

Cognitive Impairments

• Apathy• Anxiety

– Occurs in 20% to 40% patients

• Depression– Occurs in 40% of patients

• Psychosis

Other Non-Motor Symptoms

• Unilateral aches and pains• Fatigue• Restlessness• Paresthesias• Sensation of internal tremor• Continue as the disease

progresses

Causes…

Drawing by Jack Chen, Western University, Adapted from: McNaught K St P et al. Ann Neurol. 2003; Olanow CW, Tatton WG. Annu Rev Neurosci. 1999; Steece-Collier K et al. Proc Natl Acad Sci USA. 2002; Vila, Przedborski. Nat Rev Neurosci. 2003.

UCH-L1 = ubiquitin hydrolase L1

Pathogenic Cascade Failure of UPS

Protein aggregation Mitochondrial dysfunction

Oxidative stress Excitotoxicity

Neuroinflammation

Spreading Apoptosis (cell death)

AgingEnvironment Pesticides

Agricultural toxins Other (?)

Genes PARK 1-10 -synuclein

Nurr-1 Parkin

UCH-L1

UPS = ubiquitin proteosome system

May be Some Protective Factors

Alcoholism

OR = 0.41(0.19-0.89)

Coffee

OR = 0.35(0.16-0.78)

Smoking

OR = 0.69(0.45-1.08)

Ascherio et al. Am J Epidemiol 2004Tanner et al. Neurology 2002

Ragonese et al. Neuroepidemiology 2003

Quik M. Trends Neurosci 2004Wirdefeldt et al. Ann Neurol 2005

From Chen/Fagan 2005.

Scope of the Problem• 1 million Americans• 2nd most common

neurodegenerative disease• Average age of onset: 60

years• 5%-10% cases in people

under 50 years• Slightly more men than

women• Lifetime risk: 1 in 45• Progression: 10-20 years

or more

Cost of the Problem

• $6 billion • Direct and indirect costs• Treatment• Psycho-social care

Does anyone have a family or friend with PD?

Impact

• Reduced quality of life

• Worse than CHF, CVA, back pain, OA, DM, CHD

• Trouble with daily routines

• May trigger frustration, anger, stress

• Higher susceptibility to anxiety and depression

• Personal, family, societal costs

Impact

• Increased medical expenses (physician visits and emergency care)

• Caregiver burden

• Risk of early nursing home placement

Diagnosis

•No definitive imaging techniques or biomarkers•Diagnosis relies on physical and neurological exam•Most common criteria: UK PD Society Brain Bank

From: Chen/Fagan 2005 adapted from Gelb DJ, Oliver E, Gilman S. Arch Neurol 1999; 56:33-39.

Bradykinesia Rigidity

Resting Tremor

Postural Instability

Classic Cardinal Symptom Tetrad

Diagnosis•Drug history—some drugs can cause side effects mistaken with early PD

–Dopamine Receptor Blockers–Conventional & Atypical

Antipsychotics (except clozapine)–Metoclopramide–Antiemetics (droperidol,

prochlorperazine, promethazine)–Pimozide (Orap), amoxapine

Diagnosis

•Bradykinesia plus:– Rest tremor or rigidity

•Unilateral onset•Insidious onset•Absence of early falls, dementia•Good response to dopamine

•Unmistakable in advanced disease•Difficult to differentiate in early disease

Scans

• CT or MRIs• Assess damage to s. nigra in later

stages of PD• Rule out tumors, strokes, other

disorders:– Supranuclear Palsy– Shy-Dager Syndrome– Wilson’s Disease

Self-Assessment Question One

A definitive diagnosis of PD includes which of the following:

A. A complete physical and neurological assessment

B. A blood testC. MRI and CT scansD. All of the aboveE. A and C only

Self-Assessment Question One

A definitive diagnosis of PD includes which of the following:

A. A complete physical and neurological assessment

B. A blood testC. MRI and CT scansD. All of the aboveE. A and C only

Things to look for…

– Gait disturbances– Lack of manual dexterity– Reduced arm swing– Postural instability– Rigidity– Tremor

Additional Motor/Non-Motor Features of Parkinson’s

From: Chen et. al. JMCP 15:3:S1-21

PD Classification

• Uses a 5-stage classification system• Called Hoehn and Yahr after creators• UPDRS is another system

– Unified PD Rating Scale that measures mental functioning on a scale from 0 to 199 (total disability)

– Used most in clinical trials

Hoehn & Yahr StagingStage 1: Unilateral disease

Stage 2: Mild bilateral disease; good balance

Stage 3: Mild/moderate bilateral; some postural

instability; still independent

Stage 4: Severe disability; Unable to function

independently

Stage 5: Wheel chair bound

Hoehn MM, Yahr MD. Neurology 1967;17:427-442

Self-Assessment Question Two

What is the most common means used to determine the stage of a person’s PD?

A. Unified Parkinson Disease Rating Scale (UPDRS)

B. Parkinson’s staging scaleC. Hoehn and Yahr systemD. DSM-IV

Self-Assessment Question Two

What is the most common means used to determine the stage of a person’s PD?

A. Unified Parkinson Disease Rating Scale (UPDRS)

B. Parkinson’s staging scaleC. Hoehn and Yahr systemD. DSM-IV

Treatment Guidelines

• American Academy of Neurology• www.aan.org• 2006• Neurology 2006;66:7:983-995• http://neurology.jwatch.org/cgi/con

tent/full/2006/801/1

Recommendations

From: Chen et. al. JMCP 15:3:S1-21

Quality Indicators for PD

From: Chen et. al. JMCP 15:3:S1-21

Treatment Options

• Dopamine precursor• Dopamine agonists• Preservation of dopamine in brain

– COMT inhibitors– MAO-B inhibitors

• Regulation of muscle movement– Anticholinergics

Therapeutic Agents

From: Chen et. al. JMCP 15:3:S1-21

Anticholinergics/Precursors

• Benztropine (Cogentin)• Trihexyphenidyl (Apo-Trihex)• Procyclidine (DSC in US)

• Carbidopa/Levadopa (Sinemet CR)

COMT Inhibitors

• Entacapone (Comtan)

• Tolcapone (Tasmar)

MAO-B Inhibitors

• Rasagiline (Azilect)

• Selegiline (Eldepryl, Emsam, Zelapar)

Dopamine Receptor Agonists

• Apomorphine (Apokyn)• Bromocriptine (Parlodel)• Pramipexole (Mirapex)• Ropinirole (Requip)• Rotigotine (Neupro, recalled in

4/2008)

NMDA Receptor Inhibitor

• Amantadine (Symmetrel)

DAGABA

ACh

Striatum

Substantia Nigra

Levodopa

Amantadine

SelegilineRasagiline

Dopamine agonists: apomorphine bromocriptine pergolide pramipexole ropinirole

TrihexiphenidylBenztropine

BBB

dopamine levodopa 3-OMDDDC COMT

Carbidopa EntacaponeTolcapone

From Chen/Fagan 2005. Adapted from www.wemove.org

Symptomatic Treatment

Therapy: What is the Chief Complaint?

Predominant Symptom Clinical Options

No functional impairment Neuroprotection (?)

Mild symptoms Amantadine, MAO-B inhibitor

Mild-moderate sxs Dopamine agonist, levodopa

Discrete symptoms Tremor—antimuscarinicDyskinesias – amantadine

Motor fluctuations Entacapone, apomorphine

Surgery