parkinson’s disease update - center for health in...
TRANSCRIPT
![Page 1: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/1.jpg)
Parkinson’s Disease Update
Colleen Peach, RN, MSN, FNPMovement Disorders Clinic
Emory University School of MedicineMarch 7, 2015
![Page 2: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/2.jpg)
Parkinson’s Disease
• Progressive, chronic, neurodegenerative disease
• Slow, selective loss of substantia nigra dopaminergic neurons
• Clinical features due to severe loss of striatal dopamine
![Page 3: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/3.jpg)
Lang AE et al. N Engl J Med. 1998;339(15):1044, 1049-50.Olanow CW et al. Neurology. 2001;56(suppl 5):S1.
Epidemiology of Parkinson’s Disease
• About one million affected each year• Second most common neurodegenerative
disease in elderly ( after Alzheimers)• Average age of onset is 60 years• 5% to 10% of PD patients have symptoms
before age 40 (“young-onset PD”)• Prevalence in population >80 years old is 10%
![Page 4: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/4.jpg)
Parkinson’s Disease (cont.)
• Age is single most consistent risk factor• Onset is insidious• Male predominance 3/2• Affects all ethnic and socioeconomic groups• James Parkinson first described “shaking palsy”
in 1817
![Page 5: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/5.jpg)
Fahn S. Ann NY Acad Sci. 2003;991:1‐14.
0 3 8 15 20
Years
OnsetDiagnosis
Therapy
PreclinicalPhase
HoneymoonPeriod
Motor ComplicationPeriod
ResistantSymptoms
Cognitive Decline
‐2 to ‐6
Typical Progression and Clinical Course
![Page 6: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/6.jpg)
Pathophysiology
• PD occurs when neurons in the substantia nigradie or become impaired
• Substantia nigra is located in the midbrain. Dopamine pathways are also connected to the frontal and limbic (emotional) regions of the brain
![Page 7: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/7.jpg)
Pathophysiology (cont.)
• Dopamine is the chemical messenger responsible for transmitting signals between the substantia nigra and the “relay station” of the brain, the corpus striatum, to produce smooth, purposeful muscle activity
• Loss of dopamine in the striatum leaves the patient unable to direct or control their movements in a normal matter
![Page 8: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/8.jpg)
Classification of PD
• Primary, Degenerative form• Idiopathic Parkinsonism
• Secondary • Toxins• Drugs• Trauma, Vascular, and Post-Encephalitic
![Page 9: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/9.jpg)
Classification (cont.)
• Parkinson-Plus Syndromes• Multi-system atrophy (MSA)• Progressive Supranuclear Palsy (PSP)• Cortical-basal Ganglionic Degeneration
(CBGD)• Dementia Syndromes
• Alzheimer’s with PD symptoms• Lewy Body Disease
![Page 10: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/10.jpg)
Potential Causes of PD
Genes -synuclein
Parkin UCH-L1
Susceptibility genes
Environment Pesticides Rural living Other (?)
Apoptosis (cell death)
McNaught K St P et al. Ann Neurol. 2003;53(suppl 3):S73-S86; Olanow CW, Tatton WG. Annu Rev Neurosci. 1999;22:123-124; Steece-Collier K et al. Proc Natl Acad Sci USA. 2002;99:13972-13974.
Pathogenic Mechanisms Protein aggregation
Mitochondrial dysfunction Oxidative stress Inflammation Excitotoxicity
UCH-L1 = ubiquitin hydrolase L1.
![Page 11: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/11.jpg)
Characteristic Motor Symptoms
• Tremor
• Bradykinesia/akinesia
• Rigidity
• Postural instability
![Page 12: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/12.jpg)
PD Symptoms • Micrographia
• Masked Facies/Hypomimia
• Hypophonia
• Decreased Arm Swing
• Shuffling Gait
• Truncal Flexion
• Fatigue
![Page 13: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/13.jpg)
PD Symptoms (cont.)
• Dysphagia
• Sialorrhea
• Decreased Gastric Emptying
• Dry Eyes
• Seborrhea
![Page 14: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/14.jpg)
Non-Motor Symptoms in PD
• Mental Changes• Dementia
• Depression
• Sleep Disturbance• Fragmented Sleep
• REM behavioral sleep disorder
![Page 15: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/15.jpg)
Non-Motor Symptoms in PD
• Dysautonomia• Constipation• Sexual dysfunction• Bladder dysfunction• Sweating• Orthostasis
• Pain• Untreated patients
• Shoulder and back pain• Treated patients
• Off dystonia (foot pain)
![Page 16: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/16.jpg)
Diagnosing PD
• At least 2 of 4 cardinal features:• Rest tremor (4-6 Hz)• Rigidity• Bradykinesia• Postural instability+
• Diagnosis more difficult when tremor absent
• Asymmetric onset
![Page 17: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/17.jpg)
Diagnosing PD (cont.)
• Almost all patients with idiopathic PD will improve with L-dopa therapy
• Parkinson-Plus syndromes will not improve as dramatically
![Page 18: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/18.jpg)
Diagnosing PD (cont.)
• No abnormalities of routine x-rays, labs, EEG, or EKG
• CT/MRI• PET scan• SPECT scan
![Page 19: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/19.jpg)
Factors to consider when initiating therapy
• 1. Age of patient• 2. Severity of symptoms• 3. Cognitive status• 4. Comorbidities/concomitant meds
Olanow CW et al. Neurology 2001:56 (suppl 5):S1-S88
![Page 20: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/20.jpg)
Treating PD
• Also it is important to ask the patient…..
• What symptoms bother you most?
• How much do these symptoms interfere with daily function and lifestyle?
![Page 21: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/21.jpg)
Management of PD
Diagnostic assessment
Motor symptoms Non-motor Affective Cognitive
Bradykinesia
Rigidity
Gait impairment
Tremor Autonomic dysfunction
Sleep disorders
Skin disorders
Deconditioning
Anxiety
Depression
Apathy
Neuropsychological deficits
Intention deficits
Dementia
Psychosis Delirium, agitation
Disease Progression
![Page 22: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/22.jpg)
Medication Management
• Mainstay of therapy is dopaminergic medication
• Dopamine replacement• Activate dopamine receptors• Stimulation of dopamine release• Inhibit dopamine uptake
![Page 23: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/23.jpg)
Medication Management (cont.)Levodopa (L-dopa)
( Dopamine)Give with carbidopa (reduces
nausea)Carbidopa/Levodopa (Sinemet ®)
Dopamine Agonists(Mimic dopamine)Pramipexole (Mirapex ®)Ropinerole (Requip®)Apomorphine (Apokyn ®)Rotigitine (Neupro patch ®)
COMT-Inhibitors(Slow dopamine breakdown)Entacapone (Comtan®)Tolcapone (Tasmar ®)Stalevo
Anticholinergic Medications(Reduce relative excess acetylcholine)Trihexiphenidyl (Artane®)Benztropine (Cogentin ®)
MAO Inhibitor, OtherSelegiline (Eldepryl ®)Amantadine (Symmetrel®)Zydis Selegiline (Zelapar®)
Rasagiline (Azilect®)
![Page 24: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/24.jpg)
PD Treatment – Mild Disease
• With treatment, pt has good control throughout the day without any clear ups or downs
• Grade 1-2 tremor, bradykinesia, rigidity• No retropulsion• No significant dementia
![Page 25: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/25.jpg)
What is your first choice?
1. No treatment2. Amantadine3. Anticholinergics4. Rasagiline/Selegiline5. DA: Ropinirole/Pramipexole6. Carbidopa/Levodopa IR/CR7. Carbidopa/Levodopa/Entacapone
![Page 26: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/26.jpg)
What is your first choice?
1. No treatment2. Amantadine3. Anticholinergics4. Rasagiline/Selegiline5. DA: Ropinirole/Pramipexole6. Carbidopa/Levodopa IR/CR7. Carbidopa/Levodopa/Entacapone
![Page 27: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/27.jpg)
Amantadine
• Antiviral agent for the Asian flu• Anticholinergic, dopaminergic, and NMDA
blocking effects• Mild-to-moderate benefit• Adverse effects: anticholinergic + livedo
reticularis, pedal edema• Dose: 100 bid to qid
![Page 28: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/28.jpg)
Amantadine
• Provides mild-to-moderate benefit
• Neuropsychiatric adverse effects limit use in older patients or those with dementia
• Antidyskinetic effect: can reduce dyskinesia by about 45%, but benefit lasts less than 8 months
Mendis T et al. Can J Neurol Sci. 1999;26:91.Lang AE et al. N Engl J Med. 1998;339(16):1134.Olanow CW et al. Neurology. 2001;56(suppl 5):S24-S25.Thomas, A et al. JNNP. 2004;75:141-143.
![Page 29: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/29.jpg)
Livedo Reticularis
![Page 30: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/30.jpg)
Anticholinergics
• Option for young patients (<60 years) whose predominant symptom is resting tremor
• Available agents:– trihexyphenidyl (Artane)– benztropine (Cogentin)
• Adverse effects often limit use due to:– Memory impairment – Dysphoria– Confusion – Antimuscarinic effects– Hallucinations – Dry mouth– Sedation – Blurred vision
Olanow CW et al. Neurology. 2001;56(suppl 5):S24-S25.
![Page 31: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/31.jpg)
MAO Inhibitors
Selegiline1989
Oral Disintegrating SelegilineRasagiline
2006
![Page 32: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/32.jpg)
Rasagiline
• An irreversible selective MAO-B inhibitor
• Administered orally once per day
• No amphetamine or amphetamine-like metabolites
• FDA approved for the treatment of PD as both initial therapy and adjunctive therapy
![Page 33: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/33.jpg)
Olanow CW et al. Neurology. 2001;56(suppl 5):S6-S7.Parkinson Study Group. Ann Neurol. 1996;39:37-38.
MAO-B Inhibitors• Inhibit monoamine oxidase B enzyme, which
breaks down dopamine following its action in synaptic cleft
• Selegiline is an irreversible MAO-B inhibitor• DATATOP study
• Provided slight symptomatic benefit• delayed the need to begin levodopa therapy by 9
months • Inconclusive evidence in humans that selegiline
slows progression in PD
![Page 34: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/34.jpg)
PD Treatment –Moderate Disease
• Pt feels more kick in with meds, sometimes wears off between doses
• Grade 1-2 tremor, bradykinesia, rigidity• ± Mild dyskinesias• May have retropulsion, but usually
recovers unaided• No significant dementia
![Page 35: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/35.jpg)
What is your first choice?
1. No treatment2. Amantadine3. Anticholinergics4. Rasagiline/Selegiline5. DA: Ropinirole/Pramipexole6. Carbidopa/Levodopa IR/CR7. Carbidopa/Levodopa/Entacapone
![Page 36: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/36.jpg)
What is your first choice?
1. No treatment2. Amantadine3. Anticholinergics4. Rasagiline/Selegiline5. DA: Ropinirole/Pramipexole6. Carbidopa/Levodopa IR/CR7. Carbidopa/Levodopa/Entacapone
![Page 37: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/37.jpg)
Dopamine Agonists
• Ergot-derived dopamine agonists-First generation:• pergolide (Permax ® )
• bromocriptine (Parlodel ® )
• Non–ergot-derived dopamine agonists-Second generation:
• ropinirole HCl (Requip® )
• pramipexole (Mirapex ® )
• apokyn injection
• rotigitine (Neupro patch ® )Olanow CW et al. Neurology. 2001;56(suppl 5):S14.
![Page 38: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/38.jpg)
Dopamine Agonists
• Pramipexole (0.5-1.5 mg po tid)
• Pramipexole ER (up to 4.5 mg/day)• Ropinirole (3-6 mg po tid)
• Ropinirole 24 ER (6-24 mg po qd)
• Apomorphine (0.2-0.6 mL sc prn; Max: 0.6 mL/dose, 5 doses/day, 2 mL/day)
• Adverse effects: hallucinations, nausea, ICD, sleepiness, edema
![Page 39: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/39.jpg)
Levodopa
• Most effective drug for parkinsonian symptoms
• 1970: Carbidopa/Levodopa (Sinemet ) Approved by the FDA . Rapidly became the drug of choice for PD
• Large neutral amino acid; requires active transport across the gut-blood and blood-brain barriers
• Side effects: nausea, postural hypotension, dyskinesias, motor fluctuations
![Page 40: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/40.jpg)
Levodopa (cont.)
• Motor fluctuations• Up to 50% of patients after 5 years of treatment• 70% of patients after 15 years of treatment• End-of-dose “wearing off” phenomenon• Unpredictable “on-off” fluctuations
• Dyskinesias• Peak dose or diphasic
• Neuropsychiatric disturbances• Hallucinations• Confusion
Lang AE et al. N Engl J Med. 1998;339(16):1134-36.
![Page 41: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/41.jpg)
Parcopa(Carbidopa/levodopa Orally
Disintegrating Tablets)
• RapiTab technology dissolves rapidly on the tongue without need for water
• Same strength and dosage schedule as conventional carbidopa/levodopa
• Equivalent benefit and side effects• Rapid access to medication, convenient
![Page 42: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/42.jpg)
Response to Levodopa and Progression of Parkinson’s Disease
Shorter duration motor response
Increased incidence of dyskinesias
Time (h)
Moderate PD
Clin
ical
Effe
ct
Dyskinesia Threshold
ResponseThreshold
Short durationmotor response
“On” time consistently associated with dyskinesias
Long duration motor response
Low incidence of dyskinesias
Time (h)
Early PD
Levodopa
Clin
ical
Effe
ct
2 4 6
Dyskinesia Threshold
Response Threshold
Time (h)
Advanced PD
Clin
ical
Effe
ct
Dyskinesia Threshold
Response Threshold
Olanow CW, Agid Y. http://www.medscape.com/viewprogrm/1847-pnt.
Levodopa 2 4 6 Levodopa 2 4 6
Clin
ical
Effe
ct
Clin
ical
Effe
ct
![Page 43: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/43.jpg)
PD Treatment – Severe Disease
• Motor fluctuations• Dyskinesias• Sometimes no “on” response• Retropulsion• ± Cognitive dysfunction, hallucinations
![Page 44: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/44.jpg)
What is your first choice?
1. No treatment2. Amantadine3. Anticholinergics4. Rasagiline/Selegiline5. DA: Ropinirole/Pramipexole6. Carbidopa/Levodopa IR/CR7. Carbidopa/Levodopa/Entacapone
![Page 45: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/45.jpg)
What is your first choice?
1. No treatment2. Amantadine3. Anticholinergics4. Rasagiline/Selegiline5. DA: Ropinirole/Pramipexole6. Carbidopa/Levodopa IR/CR7. Carbidopa/Levodopa/Entacapone
![Page 46: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/46.jpg)
What is your first choice?
1. No treatment2. Amantadine3. Anticholinergics4. Rasagiline/Selegiline5. DA: Ropinirole/Pramipexole6. Carbidopa/Levodopa IR/CR7. Carbidopa/Levodopa/Entacapone8. DEEP BRAIN STIMULATION
![Page 47: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/47.jpg)
Apomorphine (Apokyn®)
• The only injectable DA available
• Apomorphine sc has been shown in controlled clinical trials to effectively abort OFF episodes in patients already on maximal oral therapies
• Apomorphine is a highly potent DA
Dewey RB Jr, et al. Arch Neurol. 2001;58:1385-1392.
![Page 48: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/48.jpg)
Rescue TherapyApomorphine
• Subcutaneous injection• Fast acting: 7.5-10 min• Short duration of action: 40-120 min• Consistent response: rare dose failures• Similar response to levodopa• Pretreatment with antiemetic
(trimethobenzamide)• Long term, consistent effect
![Page 49: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/49.jpg)
Olanow CW et al. Neurology. 2001;56(suppl 5):S21-S22.Tasmar® (tolcapone) Prescribing Information. Roche Laboratories, Inc. 1998.
COMT Inhibitors
• Only used in combination with levodopa• Inhibit levodopa catabolism/extend duration of
levodopa effect• Indicated for treatment of patients with PD
experiencing end-of-dose “wearing off” with levodopa
• COMT inhibitors available:– entacapone (Comtan) – tolcapone (Tasmar) – may cause hepatic toxicity– Stalevo
![Page 50: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/50.jpg)
Surgical Options
• Surgical Treatments
• Pallidotomy/Thalamotomy
• Deep brain stimulation
![Page 51: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/51.jpg)
Deep Brain Stimulation
![Page 52: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/52.jpg)
Other Areas
• Constipation• Urinary Symptoms• Orthostatic Hypotension• Male Impotence• Depression
![Page 53: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/53.jpg)
Treatment
• Other• Diet• Hydration• Exercise• Stress Management• Counseling• Education
![Page 54: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/54.jpg)
Research
• Neuroprotective Studies• Symptomatic Relief• Alternative Therapy
• Exercise• Dietary Supplement• Spiritual/Prayer
• Surgical Studies• Stem cells• RPE
![Page 55: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/55.jpg)
Research (cont.)
• New Drugs • DUOPA ( carbidopa/levodopa) enteral
suspension indicated for the treatment of motor fluctuations in advanced PD
• Droxidopa for orthostatic hypotension• Rytary a combination of short acting and
long acting levodopa
![Page 56: Parkinson’s Disease Update - Center for Health in Agingaging.emory.edu/documents/PeachUpdatesPD.pdf · • Slow, selective loss of substantia nigra dopaminergic neurons • Clinical](https://reader033.vdocument.in/reader033/viewer/2022052001/601382c05db7584791257636/html5/thumbnails/56.jpg)
Websites
• American Parkinson’s Disease Association• www.apdaparkinson.org
• National Parkinson Foundation• www.parkinson.org
• Michael J. Fox website• MichaelJFox.org
• For community resources• www.healingwell.com