Download Parkinson`s Disease: How Pharmacists Can

Parkinson’s Disease: How
Pharmacists Can Make a
Difference
Marsha K. Millonig, MBA, RPh
President & CEO
Catalyst Enterprises, LCC
Disclosure Information
Parkinson’s Disease
Marsha 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:
Dense Core with Halo
• Lewy body
structures also
• Inclusions of αsynuclein
• Disrupts normal
neuronal
function
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…
Aging
Genes
 PARK 1-10
 -synuclein
 Nurr-1
 Parkin
 UCH-L1

Pathogenic Cascade
 Failure of UPS
 Protein aggregation
Mitochondrial dysfunction
 Oxidative stress
 Excitotoxicity
 Neuroinflammation

Environment
 Pesticides
Agricultural toxins
 Other (?)
Spreading Apoptosis (cell death)
UCH-L1 = ubiquitin hydrolase L1
UPS = ubiquitin proteosome system
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.
May be Some Protective Factors
Alcoholism
Coffee
Smoking
OR = 0.41
OR = 0.35
OR = 0.69
(0.19-0.89)
(0.16-0.78)
(0.45-1.08)
Ragonese et al.
Neuroepidemiology 2003
From Chen/Fagan 2005.
Ascherio et al. Am J Epidemiol
2004
Tanner et al. Neurology 2002
Quik M. Trends Neurosci 2004
Wirdefeldt et al. Ann Neurol
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
Classic Cardinal Symptom Tetrad
Resting Tremor
Bradykinesia
Rigidity
Postural Instability
From: Chen/Fagan 2005 adapted from Gelb DJ, Oliver E, Gilman S. Arch
Neurol 1999; 56:33-39.
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 test
C. MRI and CT scans
D. All of the above
E. 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 test
C. MRI and CT scans
D. All of the above
E. 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 Staging
Stage 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 scale
C. Hoehn and Yahr system
D. 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 scale
C. Hoehn and Yahr system
D. DSM-IV
Treatment Guidelines
•
•
•
•
•
American Academy of Neurology
www.aan.org
2006
Neurology 2006;66:7:983-995
http://neurology.jwatch.org/cgi/content
/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)
Symptomatic Treatment
Substantia Nigra
Selegiline
Rasagiline
Amantadine
Levodopa
BBB
Dopamine agonists:
apomorphine
bromocriptine
pergolide
pramipexole
ropinirole
GABA
DA
ACh
DDC
COMT
dopamine
levodopa
3-OMD
Carbidopa
Striatum
Trihexiphenidyl
Benztropine
Entacapone
Tolcapone
From Chen/Fagan 2005. Adapted
from www.wemove.org
Therapy: What is the Chief Complaint?
Predominant Symptom
No functional impairment
Mild symptoms
Mild-moderate sxs
Discrete symptoms
Motor fluctuations
Clinical Options
Neuroprotection (?)
Amantadine, MAO-B inhibitor
Dopamine agonist, levodopa
Tremor—antimuscarinic
Dyskinesias – amantadine
Entacapone, apomorphine
Surgery