pd_sk_06_15
TRANSCRIPT
Parkinson’s Disease
Sunhee Kim TSU COPHS
Pharm.D
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Key Concepts 1. Therapeutic consideration
2. Optimal time to start drug therapy
3. Surgery
4. Pharmacotherapy � Anticholinergic medication � Monotherapy & adjunct therapy
� Motor complication � Drug use complication & treatment
Sources: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 9th ed. http://siberiantimes.com/science/casestudy/news/a-major-breakthrough-in-treating-parkinsons-disease-cannot-reach-patients/ 3
� Increasing age
� Male sex
� Heredity (close relative with disease)
� Toxin exposure (e.g., herbicides, pesticides)
INVERSE CORRELATION WITH CAFFEINE CONSUMPTION AND CIGARETTE SMOKING
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. 4
Risk Factors
§ General Features
§ Motor Symptoms
§ Autonomic and Sensory Symptoms
§ Mental Status Changes
§ Sleep Disturbances
§ Laboratory Tests
§ Other Diagnostic Tests
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 9th ed. 5
Clinical Presentation
S#16
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed.
6
Clinical Presentation: Motor Symptoms
§ Decreased manual dexterity
§ Difficulty arising from seated position
§ Diminished arm swing during ambulation
§ Dysarthria
§ Dysphagia
§ Festinating gait
§ Flexed posture
§ “Freezing” at initiation of movement
§ Hypomimia
§ Hypophonia
§ Micrographia
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. 7
Clinical Presentation: Autonomic and Sensory symptoms
§ Bladder and anal sphincter disturbances
§ Constipation
§ Diaphoresis
§ Fatigue
§ Olfactory disturbance
§ Orthostatic BP changes
§ Pain
§ Paresthesias
§ Paroxysmal vascular flushing
§ Seborrhea
§ Sexual dysfunction
§ Sialorrhea
Clinical Presentation: Mental status changes
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. 8
§ Anxiety
§ Apathy
§ Bradyphrenia
§ Confusion
§ Dementia
§ Depression
§ Sleep disorders
• Diagnostic features § Tremor
§ Rigidity § Akinesia/Bradykinesia
§ Postural instabilty
• Diagnosis § Bradykinesia with any one element (T, R, P) § Higher confidence with B, R, P, and good response to
dopaminergic therapy
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 9th ed. 9
Diagnostic Clinical Presentation
Table 43-1.
� Step 1: Presence of bradykinesia and at least one of the following: resting tremor, rigidity, or postural instability
� Step 2: Exclude other types of parkinsonism or tremor disorders (see Differential diagnosis)
� Step 3: Presence of at least three supportive positive criteria:
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 9th ed. 10
Diagnostic Criteria for PD and Differential Diagnosis
� Asymmetry of motor signs/symptoms
� Unilateral onset
� Progressive disorder
� Resting tremor
� Excellent response to
carbidopa/L-dopa
� L-dopa response for 5 yrs or longer
� Presence of L-dopa dyskinesias
Differential diagnosis
1. Essential tremor
2. Pharmacotoxicity (drug induced) � Antiemetics (e.g., metoclopramide, prochlorperazine)
� Antipsychotics (e.g., phenothiazines, haloperidol, olanzapine, risperidone)
� Other drugs (α-methyldopa, cinnarizine, flunarizine, tetrabenazine)
3. Environmental toxicity (e.g., manganese, organophosphates)
4. Infections (e.g., human immunodeficiency virus, subacute sclerosing panencephalitis)
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 9th ed.
11
Table 43-1. Cont’d
5. Metabolic disorder (e.g., hypothyroidism, parathyroid abnormalities)
6. Neoplasms, strokes, traumatic lesions involving the nigrostriatal pathways
7. Normal-pressure hydrocephalus
8. Parkinsonism with other neuronal system degenerations a) Corticobasal ganglionic degeneration
b) Dementia with Lewy bodies
c) Multiple-system atrophies
d) Progressive supranuclear palsy
e) Familial (hereditary) parkinsonism (next slide)
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 9th ed. 12
Table 43-1. Cont’d
e) Familial (hereditary) parkinsonism • Autosomal dominant
• α-Synuclein gene mutation (PARK1 and PARK4) • Levodopa responsive dystonia • Leucine-rich repeat kinase 2 (LRRK2) mutation • Rapid-onset dystonia parkinsonism (DYT12) • Spinocerebellar ataxias (SCA2, SCA3)
• Autosomal recessive • Wilson’s disease • Young-onset parkinsonism (DJ-1, parkin, PINK1)
• X-linked recessive • Fragile X tremor/ataxia syndrome (FXTAS) • Lubag (DYT3 or Filipino dystonia parkinsonism)
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 9th ed. 13
Table 43-1. Cont’d
Differential Diagnosis: Essential Tremor cause • Medication
• Corticosteroids • Metoclopramide (S#11) • Valproate • Sympathomimetics • SSRIs, TCAs, theophylline • Thyroid preparations
• Caffeine
• Tobacco
• Chronic alcohol
Source: Michael EE, Mildred DG, Parkinson’s Disease and other movement disorders. In: Brian KA, Robin LC, Michael EE, Joseph BG, Pamala AJ, Wayne AK, Bradley RW, eds. KODA-KIMBLE & YOUNG’S Applied Therapeutics: The Clinical Use of Drugs. 10th ed.
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S#4
Essential tremor and PD � Table 57-9
Source: Michael EE, Mildred DG, Parkinson’s Disease and other movement disorders. In: Brian KA, Robin LC, Michael EE, Joseph BG, Pamala AJ, Wayne AK, Bradley RW, eds. KODA-KIMBLE & YOUNG’S Applied Therapeutics: The Clinical Use of Drugs. 10th ed. 15
Source: http://www.cmecorner.com/programs.asp?audience=&ProductID=1144&partner=medpage
16
Prodromal
Enteric (Gut) Nervous System
Olfactory Bulb Cortical Pathology
Lewy body pathology in the myenteric plexus results in colonic denervation
Olfactory loss occurs bilaterally despite the fact that motor signs are generally asymmetric or unilateral
Cognitive impairment and dementaia eventually affect 80% of patients with PD
Constipation is reported in 60% to 80% patients and may predate motor symptoms by years
Olfactory dysfunction ultimately affects up to 90% of PD patients
Neuropsychiatric symptoms (visual and auditory hallucinations) may present in PD
Table 3. Non-motor symptoms in early PD
• Non-specific symptoms may precede motor symptoms and Tremor by 20 years
• Non-specific symptoms o Hyposmia o Constipation o Fatigue
TREATMENT
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 9th ed. 17
� Goal
1. Improve motor and motor symptoms
2. Preserve ability to perform activities of daily living (ADL)
§ Improve mobility
§ Minimize adverse effect and treatment complication
§ Positive disease modification
§ Improve nonmotor features
General Approach to Treatment
• Nonpharmacologic treatment
• Pharmacologic intervention
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 9th ed. 18
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 9th ed. 19
Fig. 43-4. General approach to the management of early to advanced PD
- AGE - DISEASE SEVERITY - TREMOR CAUSE - SURGERY
• Surgery
• Adjunct to pharmacotherapy
• Preferred modality • Deep-brain stimulation (DBS)
• Targets • Thalamus
• GPi • Subthalamic nucleus
Sources: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 9th ed. http://www.mayoclinic.org/documents/mc5520-06-pdf/doc-20079151
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Nonpharmacologic therapy
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• Physical therapy
• Occupational therapy
• Speech training
• Increased fluid and fiber intake to reduce constipation
• Discontinue concomitant medications that may worsen motor symptoms, memory, falls, or behavioral symptoms
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. 21
Pharmacologic therapy
• Anticholinergic medication
• Amantadine
• Carbidopa/L-dopa
• COMT Inhibitors
• Dopamine Agonists
• MAO-B Inhibitors
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 9th ed. 22
Treatment: General Approach
• Algorithm for management of early and late disease Figure 43-4: Monoamine oxidase-B (MAO-B) inhibitor (e.g., rasagiline) as monotherapy typically first treatment.
• Either rasagiline or DA agonist can be used first in physiologically young patients.
• Levodopa (e.g., carbidopa/levodopa) is preferred initial therapy for patients older, cognitively impaired, or who have moderately severe functional impairment.
• Consider adding catechol-O-methyltransferase (COMT) inhibitor to extend levodopa duration of activity when motor fluctuations develop. Alternatively, consider adding MAO-B inhibitor or DA agonist.
• Amantadine may be added to manage levodopa-induced peak-dose dyskinesias.
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 9th ed. 23
Table 43-2. Drugs Used in PDa
Sources: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 9th ed. 2. Rytary® http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/203312s000lbl.pdf 24
Generic Name Trade Name Starting Doseb (mg/day)
Maintenance Doseb (mg/day)
Dosage Forms (mg)
Anticholinergic drugs
Benztropine Cogentin 0.5–4 1-6 0.5, 1, 2
Trihexyphenidyl Artane 1–2 6-15 2, 5, 2/5mL
Anti-Parkinson’s Agent / Antiviral / Dopamine Agonist (Lexicomp)
Amantadine Symmetrel 100 200–300 100, 50/5 mL
Carbidopa/levodopa products
Carbidopa/levodopa Sinemet 100–300c 300–1,000c 10/100, 25/100, 25/250
Carbidopa/levodopa ODT Parcopa 100–300c 300–1,000c 10/100, 25/100, 25/250
Carbidopa/levodopa CR Sinemet CR 200–400c 400–1,000c 25/100, 50/200
Carbidopa/levodopa/ entacapone
Stalevo 200–600d 600–1,600d 12.5/50/200, 18.75/75/200, 25/100/200, 31.25/125/200, 37.5/150/200, 50/200/200
Carbidopa Lodosyn 25 25–75 25
Carbidopa/levodopa ER Rytary 23.75/95 612.5/2450 23.75/95, 36.25/145, 48.75/195, 61.25/245
Table 43-2. Drugs Used in PDa
Sources: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 9th ed. 25
Generic Name Trade Name Staring Doseb (mg/day)
Maintenance Doseb (mg/day)
Dosage Forms (mg)
COMT inhibitors Entacapone Comtan 200–600 200–1600 200 Tolcapone Tasmar 300 300–600 100, 200 Dopamine agonists Apomorphine Apokyn 1–3 3–12 30/3 mL Bromocriptine Parlodel 2.5-5 15–40 2.5, 5 Pramipexole Mirapex 0.125 1.5–4.5 0.125, 0.25, 0.5, 1, 1.5 Pramipexole ER Mirapex ER 0.375 1.5–4.5 0.375, 0.75, 1.5, 3, 4.5 Ropinirole Requip 0.75 9–24 0.25, 0.5; 1, 2, 3, 4, 5 Ropinirole XL Requip XL 2 8–24 2, 4, 6, 8, 12 Rotigotine Neupro 2 2-8 1,2,3,4,6,8 MAO-B inhibitors Rasagiline Azilect 0.5–1 0.5–1 0.5, 1 Selegiline Eldepryl 5–10 5–10 5 Selegiline ODT Zelapar 1.25 1.25–2.5 1.25, 2.5
Table 43-3 Monitoring of Potential Adverse Reactions to Drug Therapy
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 9th ed.
26
Generic Name Adverse Drug Reaction Monitoring Parameter Comments
Anticholinergic
Benztropine Anticholinergic effects, confusion, sedation
Dry mouth, mental status, constipation, urinary retention
Reduce dosage; avoid in elderly; history of constipation, memory impairment, urinary retention
Trihexyphenidyl See benztropine See benztropine See benztropine
Anti-Parkinson’s / Antiviral / Dopamine Agonist (Lexicomp)
Amantadine Confusion Livedo reticularis
Mental status; renal function Lower extremity examination; ankle edema
Reduce dosage; adjust dose for renal impairment Reversible upon drug discontinuation
L-dopa
Carbidopa/L-dopa Drowsiness Dyskinesias Nausea
Daytime drowsiness Abnormal involuntary movements Nausea
Reduce dose Reduce dose; add amantadine Take with food
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 9th ed.
27
Generic Name
Adverse Drug Reaction
Monitoring Parameter Comments
COMT inhibitors
Entacapone Augmenta*on of L-‐dopa side effects; also diarrhea
See carbidopa/L-dopa; also bowel movements
Reduce dose of L-‐dopa; an*diarrheal agents
Tolcapone See entacapone; also liver toxicity
See carbidopa/L-dopa; also ALT/AST
See carbidopa/L-‐dopa; also at start of therapy and for every dose increase, ALT and AST levels at baseline and every 2-‐4 wks for the first 6 months of therapy; aHerward monitor based on clinical judgment
Table 43-3. cont’d
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 9th ed. 28
Generic Name Adverse Drug Reaction Monitoring Parameter Comments
Dopamine agonists
Apomorphine Drowsiness Nausea Orthostatic hypotension
Mental status Nausea Blood pressure, dizziness upon standing
Reduce dose Premedicate with trimethobenzamide Reduce dose
Bromocriptine
Confusion Drowsiness Hallucinations/delusions Nausea Orthostatic hypotension Pulmonary fibrosis
Mental status Mental status Mental status Nausea Blood pressure, dizziness upon standing
Chest radiograph
Reduce dose Reduce dose Reduce dose Titrate dose upward slowly; take with food Reduce dose Chest radiograph at baseline and once yearly
Pramipexole
Confusion Drowsiness Hallucinations/delusions Impulsivity Nausea Orthostatic hypotension
Mental status Mental status Mental status Behavior Nausea Blood pressure, dizziness upon standing
Reduce dose Reduce dose Reduce dose Reduce dose Titrate dose upward slowly; take with food Reduce dose
Ropinirole See pramipexole See pramipexole See pramipexole
Table 43-3. cont’d
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 9th ed. 29
Generic Name Adverse Drug Reaction Monitoring Parameter Comments
MAO-B inhibitors Rasagiline Nausea Nausea Take with food
Selegiline
Confusion Insomnia Hallucinations Orthostatic hypotension
Mental status Mental status Mental status Blood pressure, dizziness upon standing
Reduce dose Administer dose earlier in day Reduce dose Reduce dose
Table 43-3. cont’d
Anticholinergics o Can be used as monotherapy or in combination with other drugs.
o May improve tremor and dystonia but rarely have substantial benefit for bradykinesia or other symptoms.
Side effects More serious reactions
• Dry mouth • Blurred vision • Constipation • Urinary retention
• Forgetfulness • Confusion • Sedation • Depression • Anxiety
o Use with caution in patients with preexisting cognitive deficits and in elderly.
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. 30
Amantadine o Modest benefit for tremor, rigidity, and bradykinesia; may also decrease
dyskinesia at high doses (400 mg/day).
Adverse effects Renal dysfunction
• Sedation • Vivid dreams • Dry mouth • Depression • Hallucinations • Anxiety • Dizziness • Psychosis • Confusion • Livedo reticularis common but
reversible
• 100 mg/day with CLcr 30–50 mL/min (0.5–0.84 mL/s)
• 100 mg every other day for CLcr 15–29 mL/min (0.25–0.49 mL/s)
• 200 mg every 7 days for CLcr <15 mL/min(0.25 mL/s) and patients on hemodialysis
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. 31
Carbidopa and carbidopa/levodopa o Levodopa is most effective drug and ultimately required by all
patients.
o May be started at diagnosis or withheld until symptoms compromise social, occupational, or psychological well-being.
o Carbidopa increases CNS penetration of levodopa and decreases adverse effects from peripheral levodopa metabolism to DA:
Ø Nausea, Vomiting, Cardiac arrhythmias, Postural hypotension, Vivid dreams
o Initially, levodopa 300 mg/day (in divided doses) plus carbidopa (75 mg/day in divided doses) often provides adequate benefit.
o Sweat, urine, saliva appears in dark in color (i.e., red, brown, or balck) => not a harmful side effect
o Contraindication; concurrent use with nonselective MAOIs or use within the last 14 days
Sources: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. Lexicomp: http://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/7167 32
Catechol-O-Methyltransferase Inhibitors o Use only in combination with carbidopa/levodopa to prevent peripheral
conversion of levodopa to DA
o Increase “on” time by 1–2 hrs and decrease levodopa dosage requirements.
o Avoid concomitant use of nonselective MAO inhibitors to prevent inhibition of normal catecholamine metabolism.
o May cause brown-orange urine discoloration.
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. 33
Entacapone Tolcapone
Give 200 mg with each dose of carbidopa/l-dopa up to 8 times a day. Manage dopaminergic adverse effects by reducing carbidopa/levodopa dose. No evidence of hepatotoxicity.
100 mg 3 times daily starting and recommended dose as adjunct to carbidopa/levodopa. Reserve for patients with fluctuations unresponsive to other therapies because of potential for fatal liver toxicity.
DA Agonists o Adjunctive therapy in patients with deteriorating, fluctuating, or limited response to
levodopa due to inability to tolerate higher doses.
o Decrease frequency of “off” periods and provide levodopa sparing effect.
o Preferred in younger patients because of less risk of developing motor complications with monotherapy than from levodopa.
o More likely to cause psychosis and orthostatic hypotension in older patients than carbidopa/levodopa.
Side effects: Less common side effects: § Nausea
§ Confusion
§ Hallucinations
§ Lightheadedness
§ Lower extremity edema
§ Postural hypotension
§ Sedation
§ Vivid dreams
§ Compulsive behaviors
§ Psychosis
§ Sleep attacks
§ May worsen dyskinesias when added to levodopa.
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. 34
o Pramipexole 0.125 mg 3 times daily initial dose, increased every
5–7 days as tolerated to maximum of 1.5 mg 3 times a day.
o Ropinirole 0.25 mg 3 times daily initial dose, increased by 0.25 mg 3 times daily every week to maximum of 24 mg/day.
o Apomorphine given as SC “rescue” injection for patients with advanced disease and intermittent “off” episodes despite optimized therapy.
§ Triggers “on” response within 20 minutes.
§ Duration of effect: up to 100 minutes.
§ Most patients require 0.06 mg/kg SC.
§ Premedicate with antiemetic trimethobenzamide
§ Contraindicated with serotonin-3-receptor blockers (e.g., ondansetron).
o Bromocriptine not commonly used because of increased risk of pulmonary fibrosis and reduced efficacy.
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. 35
Monoamine Oxidase B Inhibitors
Selegiline Rasagiline
Blocks DA breakdown and can extend levodopa duration up to 1 hr; may permit reduction of levodopa dose by as much as one half.
Increases peak levodopa effects and can worsen dyskinesias or psychiatric symptoms.
Adverse effects: • Insomnia
• Jitteriness
Oral disintegrating tablet may provide improved response and fewer side effects.
Also enhances levodopa effects.
Modest beneficial effect as monotherapy.
Early initiation associated with better long-term outcomes.
First-line agent for motor fluctuations; may provide 1 hr of extra “on” time during the day.
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. 36
Personalized pharmacotherapy • No pharmacogenomics parameters utilized to guide PD
pharmacotherapy
• Mild functional impairment
• Dopamine agonist monotherapy
• Required therapy in time
• Consider in motor fluctuations
• Management of L-dopa induced peak dose dyskinesias
• Surgery
• Treatment plan
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 9th ed. 37
Evaluation of therapeutic outcomes
• Pharmaceutical care improves outcomes
§ Monitoring parameters
• Appropriate expectations
§ Patient & caregiver
• Periodic review of medication
• Assessment
• Recommendation
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 9th ed. 38
1. Monitor medication administration times.
2. Monitor to ensure that the patient and/or caregivers understand the prescribed medication regimen.
3. Monitor and inquire specifically about dose-by-dose effects of medication, including response to doses of medication and the presence of dyskinesias, wearing-off effects, dizziness, nausea, or visual hallucinations.
4. Monitor and inquire about concerns that caregivers may have about the patient, such as presence of abnormal behaviors, dyskinesias, falls, hallucinations, memory problems, mood changes, and sleep disorders
5. Monitor for nonadherence and, if present, inquire for possible reasons (e.g., dosing convenience, financial issues, and adverse effects) and offer suggestions
6. Monitor for presence of drugs that can exacerbate idiopathic Parkinson’s disease motor features (e.g., D2 receptor blockers), and evaluate whether the presence of anticholinergic agent is causing cognitive impairment
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 9th ed. 39
Table 43-6. Monitoring PD Therapy
Periodic Review of Medication
� STARTing and STOPPing Medications in the Elderly
� STOPP/START criteria for potentially inappropriate prescribing in older people: version 2
� START - Screening tool to alert to right treatment � STOPP - Screening tool of older people's prescriptions
40 Sources: http://www.ngna.org/_resources/documentation/chapter/carolina_mountain/STARTandSTOPP.pdf http://ageing.oxfordjournals.org/content/early/2014/10/16/ageing.afu145.full
Monitoring
• Ask patients and caregivers to record medication administration times and duration of “on” and “off” periods.
• Monitor symptoms, side effects, and activities of daily living.
• Liver function monitoring required for patients taking tolcapone.
o Discontinue therapy if liver function tests above upper limit of normal or if signs/symptoms suggest hepatic injury.
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. 41
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 9th ed. 42
Effect Possible Treatments
End-of-dose “wearing off” (motor fluctuation)
Increase frequency of carbidopa/L-dopa doses; add either COMT inhibitor or MAO-B inhibitor or DA agonist
“Delayed on” or “no on” response Give carbidopa/L-dopa on empty stomach; use carbidopa/L-dopa ODT; avoid carbidopa/L-dopa CR; use apomorphine subcutaneous
Start hesitation (“freezing”)
Increase carbidopa/L-dopa dose; add a dopamine agonist or MAO-B inhibitor; utilize physical therapy along with assistive walking devices or sensory cues (e.g., rhythmic commands, stepping over objects)
Peak-dose dyskinesia Provide smaller doses of carbidopa/L-dopa; add amantadine
Table 43-4 Common Motor Complications and Possible Initial Treatments
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 9th ed.
43
1. General measures such as evaluating for electrolyte disturbance (especially hypercalcemia or hyponatremia), hypoxemia, or infection (especially encephalitis, sepsis, or urinary tract infection)
2. Simplify the antiparkinsonian regimen as much as possible by discontinuing or reducing the dosage of medications with the highest risk-to-benefit ratio firsta
a. Discontinue anticholinergics, including other nonparkinsonian medications with anticholinergic activity such as antihistamines or tricyclic antidepressants
b. Taper and discontinue amantadine c. Discontinue monoamine oxidase-B inhibitor d. Taper and discontinue dopamine agonist e. Consider reduction of L-dopa (especially evening doses) and
discontinuation of catechol-O-methyltransferase inhibitors
3. Consider atypical antipsychotic medication if disruptive hallucinosis or psychosis persists
a. Quetiapine 12.5–25 mg at bedtime; gradually increase by 25 mg each week if necessary, until hallucinosis or psychosis improved or
b. Clozapine 12.5–50 mg at bedtime; gradually increase by 25 mg each week if necessary until hallucinosis or psychosis improved (requires frequent monitoring for leukopenia)
Table 43-5 Stepwise Approach to Management of Drug-Induced Hallucinosis and Psychosis in PD
• Course unpredictable but disease progresses over time.
• Secondary complications (e.g., pneumonia, fall-related injuries, choking) can be fatal.
• With appropriate treatment, most patients have long, productive lives for years after diagnosis.
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. 44
Prognosis
Clinical Pearl
• As PD progress, the timing of medication needs to coincide with symptoms
• Evaluate the onset and duration of each dose and make modification accordingly
• Symptoms may worsen when patients are forced to receive medications at predetermined dosing times such as those used in hospitals and nursing homes
=>Let the patient’s symptoms guide the dosing times
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 9th ed. 45
Summary • Clinical Presentation
• Diagnostic criteria
• Pharmacotherapy goals, drug therapy, nondrug therapy, and monitoring parameters
• Based on patient’s perception of the severity of symptoms and effect on quality of life, recommendation should be given
Source: Chen JJ, Nelson MV, Swope DM. Parkinson’s Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 9th ed. 46
Video In-class video
https://www.youtube.com/watch?v=BNzIaABFAMc
https://m.youtube.com/watch?v=aYRCexa5FCk
https://www.youtube.com/watch?v=IHDFQfmkKlg
Above resources listed in reference slide (last pg) 47
Case Study • After completing this case study, the reader should
be able to:
• Recognize motor and non-motor symptoms of PD • Develop an optimal pharmacotherapeutic plan for a patient
with PD as he or she progress through different stages of the disease
• Recommend alterations in therapy for a patient experiencing adverse drug effects, drug-drug interactions, and drug-food interactions.
• Educate patients with PD about the disease, its drug therapy and non-pharmacologic treatments.
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1. DiPiro CV, Schwinghammer TL. DiPiro C.V., Schwinghammer T.L. DiPiro, Cecily V., and Terry L. Schwinghammer.P. In: DiPiro CV, Schwinghammer TL. DiPiro C.V., Schwinghammer T.L. Eds. Cecily V. DiPiro, and Terry L. Schwinghammer.eds. Quick Answers: Pharmacy. New York, NY: McGraw-Hill; 2013. http://tsuhhelweb.tsu.edu:2919/content.aspx?bookid=576&Sectionid=42515526. Accessed May 31, 2015.
2. Chen JJ, Swope DM. Chen J.J., Swope D.M. Chen, Jack J., and David M. Swope. Chapter 43. Parkinson's Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. DiPiro J.T., Talbert R.L., Yee G.C., Matzke G.R., Wells B.G., Posey L Eds. Joseph T. DiPiro, et al.eds. Pharmacotherapy: A Pathophysiologic Approach, 9e. New York, NY: McGraw-Hill; 2014. http://tsuhhelweb.tsu.edu:2919/content.aspx?bookid=689&Sectionid=45310493. Accessed May 31, 2015.
3. LangAE, Connolly BS. Pharmacological Treatment of Parkinson Disease: A Review. JAMA. 2014;311;1670-1683.
4. http://siberiantimes.com/science/casestudy/news/a-major-breakthrough-in-treating-parkinsons-disease-cannot-reach-patients/
5. http://www.everydayhealth.com/parkinsons-disease-pictures/famous-people-with-parkinsons-disease.aspx
6. http://www.salon.com/2014/08/12/rip_robin_williams_an_eccentric_electric_performer_who_fought_his_demons_onscreen/
7. APhA Complete Review for Pharmacy pg 842
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References
8. http://www.cmecorner.com/programs.asp?audience=&ProductID=1144&partner=medpage
9. http://www.nabp.net/system/rich/rich_files/rich_files/000/000/902/original/naplex-mpje-bulletin-04022015.pdf
10. http://www.studygs.net/texred2.htm
11. https://www.youtube.com/watch?v=BNzIaABFAMc
12. https://m.youtube.com/watch?v=aYRCexa5FCk
13. https://www.youtube.com/watch?v=IHDFQfmkKlg
14. http://en.hdyo.org/you/questions
15. Lees AJ, Hardy J, Revesz T. Parkinson's disease. Lancet 2009;373(9680):2055–2066. [PubMed: 19524782]
16. Chen JJ, Swope DM. Pharmacotherapy for Parkinson's disease. Pharmacotherapy 2007;27(12 Pt 2):161S–173S. [PubMed: 18041936] [[XSLOpenURL/ 18041936]]
17. http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/203312s000lbl.pdf
18. Source: http://ageing.oxfordjournals.org/content/early/2014/10/16/ageing.afu145.full
19. http://www.mayoclinic.org/documents/mc5520-06-pdf/doc-20079151
20. ASHP PharmPrep, Psychiatric and Neurology, 27. Parkinsons Disease (1), 28. Parkinsons Disease (2)
21. Lexicomp: http://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/7167
22. http://www.ngna.org/_resources/documentation/chapter/carolina_mountain/STARTandSTOPP.pdf
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References Cont’d
Questions?
Source: http://en.hdyo.org/you/questions 51