parkinson’s disease soheyla mahdavian, pharm.d. assistant professor of pharmacy practice
TRANSCRIPT
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PARKINSON’S DISEASEPARKINSON’S DISEASE
Soheyla Mahdavian, Pharm.D.Assistant Professor of Pharmacy Practice
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DEFINITION
A neurodegenerative disorder of the Central Nervous System. It results from the death of dopaminergic cells in the nigrostriatal, a region of the brain.
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EPIDEMIOLOGY
More common in the elderly over 60 years of age.
5–10% of cases, classified as young onset, begin between the ages of 20 and 50.
More common in men than women.
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RISK FACTORS
Exposure to environmental toxins Herbicides Pesticides
Heavy metal exposure Formed deposits in the substantia nigra
Head trauma (rare) Genetics
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PATIENT CASECC: “My left hand won’t stop twitching.” HPI: DD is a 66-year-old male who recently retired from
Corny Fields Corn Farm. He comes to the clinic today because he has noticed over the past month he’s been having a slight tremor in his hand. He reports the tremor only occurs when he is relaxing. He also mentioned experiencing some fatigue, constipation and an increase in anxiety.
PMH: Asthma, MI, obesitySH: Recently retired, married, and is the caregiver of his
father who has late stage PD, smokes 1 pack/day, currently on a high protein diet for weight loss.
Medications: Advair HFA 250/50, Toprol XL 50mg, Aspirin 81mg
What are the risk factors this patient has?
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PARKINSON’S DISEASE PATHOPHYSIOLOGY
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DOPAMINE TRACTS
Dopamine Tract Origin Function
Nigrostriatal Substantia Nigra Movement
Mesolimbic Midbrain Arousal, memory, stimulus processing, motivational behavior
Mesocortical Midbrain Cognition, social function, communication, response to stress
Tuberofundibular Hypothalamus Regulates prolactin release
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DOPAMINE IN THE BODY
Cognition Voluntary
movement Motivation The brain’s reward
system
Sleep Mood Attention Memory Learning
Dopamine is responsible for many functions in the body, including:
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NORMAL BALANCE OF DOPAMINE AND ACETYLCHOLINE
04/19/23
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IMBALANCE OF DOPAMINE AND ACETYLCHOLINE IN PD
04/19/23
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MOTOR SYMPTOMS• Classic Motor
Symptoms• Resting Tremor• Limb Rigidity• Akinesia or
bradykinesia• Postural Instability
• Other motor symptoms Hypomimia Hypophonia Micrographia Decreased coordination,
dexterity No arm swing when
walking Shuffling gait Dysphagia
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NON-MOTOR SYMPTOMS
Psychiatric issuesDepressionAnxietyCognitive
dysfunctionDementia (late
stages)Sleep Disturbances
Autonomic/sensory disturbancesBladder problemsConstipationSexual dysfunction Impaired smell or
visionPainFatigue
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PATIENT CASECC: “My left hand won’t stop twitching.” HPI: DD is a 66-year-old male who recently retired from
Corny Fields Corn Farm. He comes to the clinic today because he has noticed over the past month he’s been having a slight tremor in his hand. He reports the tremor only occurs when he is relaxing. He also mentioned experiencing some fatigue, constipation and an increase in anxiety.
PMH: Asthma, MISH: Recently retired, married, and is the caregiver of his
father who has late stage PD, smokes 1 pack/day, currently on a high protein diet for weight loss.
Medications: Advair HFA 250/50, Toprol XL 50mg, Aspirin 81mg
Identify the patient’s motor and non-motor symptoms.
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SECONDARY PARKINSONISMUSUALLY REVERSED IF THE CAUSE IS DISCONTINUED AND NO PERMANENT DAMAGE CAUSEDPharmacotoxicity (drug-induced)
Antiemetics (e.g., metoclopramide, prochlorperazine)
Antipsychotics (e.g., phenothiazines, haloperidol, olanzapine, risperidone)
Environmental toxicityCarbon monoxide poisoningManganeseMethanolOrganophosphates
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DIAGNOSIS
No true diagnostic procedure Medical history
Rule out medications causing secondary parkinsonism Rule out family history
Neurological exam Walking and coordination, as well as some simple hand
tasks “Levodopa Test”
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HOW DO WE CORRECT THIS IMBALANCE OF DOPAMINE AND ACETYLCHOLINE IN PD? 04/19/23
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CORRECTING THE PROBLEM
04/19/23
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PHARMACOLOGIC APPROACHES
Dopamine replacement therapy Dopamine releasing therapy Dopamine conservation therapy Blocking acetylcholine Additional therapies
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DOPAMINE REPLACEMENT THERAPY
04/19/23
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DOPAMINE REPLACEMENT THERAPY MOA: Levodopa is
metabolized to dopamine for utilization in the body
Sinemet® (Levodopa/carbidopa)
Parcopa® (Levodopa/carbidopa ODT)
Adverse events Wearing off affects
Dose adjustment Postural hypotension Visual disturbances
Dose adjustment Nausea and/or vomiting
Carbohydrate snack can alleviate
Insomnia Mood Changes Smell and taste
abnormalities Brownish bodily
secretions
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DOPAMINE REPLACEMENT
Brand Name
Generic Name
Formulations
Comments
Sinemet®Sinemet® CR
Parcopa®
Levodopa/Carbidopa
TabletExtended Release TabletODT
Used as last line therapy. May color bodily secretions brown. Nausea and vomiting can be alleviated with carbohydrate snack. High protein diet and pyridoxine reduces efficacy. Carbidopa >75mg per day to be affective.
Stalevo® Levodopa/Carbidopa/Entacaone
Tablet
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KEY POINTS WHEN USING CARBIDOPA/LEVODOPA
• In order for levodopa to be effective, >75 mg of carbidopa should be received with levodopa in a day.
When patients are switched from immediate-release to sustained-release formulation, the dose should be INCREASED and vice-versa.
‘Wearing off’ affects are dose dependant ‘On-off’ affects have no known cause, but it is thought
to be because of several factors: disease progression, end of dosing, and the body’s response to medication.
Apomorphine** (Apokyn) is used for on-off periods in patients with optimized levodopa/carbidopa therapy
Because of oxidative properties, Carbidopa/levodopa should be used as LAST LINE therapy!!
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KEY POINTS WHEN USING CARBIDOPA/LEVODOPA
Protein-based foods should not be administered with levodopa-based therapies.
Vitamin B6 should not be coadministered with levodopa-based products.
High fat meals delay drug absorption. Carbohydrates taken at the same time decrease
nausea and vomiting Drug interactions:
Selegilene, Rasagilene Vitamin B6 High protein/fat meals
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PATIENT CASE DD was first prescribed Sinemet® 25/100 twice
daily. Do you agree with this?
Why or Why not? After about a week of use, he began experiencing
“wearing off affects.” What should we look at before making medication changes?
DD begins to develop a tremor in his right hand. What stage is he in?
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DOPAMINE RELEASING THERAPY
04/19/23
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DOPAMINE AGONISTS
MOA: Stimulates dopamine receptors Bromocriptine (Parlodel) Ropinerole (Requip) Pramipexole (Mirapex) **Apomorphine (Apokyn)- used for on-
off treatment Adverse events:
Dyskinesias Visual disturbances Impulse behaviors Mental disturbances
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DOPAMINE AGONISTSBrand Generic Formulations Comments
Parlodel®
Bromocriptine
Tablet Ergot derived agonist. Not used widely because of pulmonary fibrosis
Apokyn®
Apomorphine
Subcutaneous injection
ONLY USED for “ON-OFF” episodes
Requip®Requip® XL
Ropinerole TabletExtended Release Tablet
Non-ergot derived. substrate of CYP1A2
Mirapex®Mirapex® ER
Pramipexole
TabletExtended Release Tablet
Non-ergot derived.
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KEY POINTS WITH DOPAMINE AGONISTS Is usually FIRST LINE Therapy Adverse reactions:
Ropinerole/Pramipexole Sleep attacks Impulse behaviors (Gambling, shopping)
Vivid dreams Hallucinations
Drug interactions: Inducers/Inhibitors of CYP 1A2 (Ropinerole)
Charbroiled foods Smoking Zafirlukast Zilueton Carbemazepine
MAOIs
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PATIENT CASE
DD was take off Sinemet® and prescribed Requip®
Are there any drug interactions that can occur with this patient?
What side effects should he be aware of? Are there any food restrictions? He continues this medication for 5 years.
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DOPAMINE CONSERVATION THERAPY
04/19/23
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COMT INHIBITORS MOA: Inhibits catechol-O-methyltransferase Tolcapone (Tasmar®) Entacapone (Comtan®) Entacapone/Carbidopa/Levodopa (Stalevo®) Adverse events:
HypotensionDiarrheaOrange colored urine Sleep disturbances
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COMT INHIBITORS
Brand Generic Formulations
Comments
Tasmar® Tolcapone Tablet Associated with hepatotoxicity, has BOTH peripheral and central effect, orange-brown urine, used with levodopa/carbidopa products, use reserved for those not responsive to entacapone.
Comtan®
Entacapone Tablet NOT associated with hepatotoxicity, ONLY peripheral effect, orange-brown urine, used with levodopa/carbidopa products
Stalevo® Levodopa/Carbidopa/Entacapone
Tablet See side effects/comments associated with all three agents
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MONOAMINE OXIDASE INHIBITORS
MOA: Inhibits MAOSelegiline (Eldepryl®)Rasagilene (Azilect®)Adverse events:
- Hypertensive crisis (food restrictions)- Orthostatic hypotension- Insomnia- Hallucinations
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MAOIS
Brand Generic Formulation Comments
Eldepryl®Zelapar®
Selegilene TabletODT Tablet
Selective for MAO-B, but inhibits MAO-A at higher doses
Azilect® Rasagilene Tablet Selective for MAO-B, more potent than Selegilene, preferred over selegilene. CYP1A2 Substrate
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KEY POINTS FOR MAOIS
• Eat in moderation Tyramine containing foods Cheeses Wines Sour cream Yogurt Caffeine Salami/Cold cuts Sauerkraut Fermented or aged foods
• Drug interactions: Other MAOIs COMT Inhibitors CYP1A2 inhibitors/inducers
(Rasagilene) Charbroiled foods Smoking St. John’s wort Zafirlukast Zilueton Carbamazepine
Fluvoxamine* Psuedoephedrine
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PATIENT CASE
BB is given Azilect® later. After looking at his profile, identify
everything he should be aware of?
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Anticholinergics MOA: Antagonizes acetylcholine receptors to block
acetylcholine to restore the balance between acetylcholine and dopamine.
Benztropine (Cogentin®) Trihexyphenidyl (Artane®) NOT a good option for patients>65 years old!! Adverse events:
Anti-SLUDSedationConfusionIncreases IOP
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ANTICHOLINERGICS
Brand Generic Formulations Comments
Cogentin® Benztropine TabletIntramuscular InjectionIV
Because of side effects, NOT the best choice for patients >65yo
Artane® Trihexyphenidyl
TabletSolution
Same as above
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KEY POINTS WITH ANTICHOLINERGICS
NOT a first choice for tremors in PD, but can be used to treat medication induced tremors
NOT the best choice in elderly patients Other medications with anticholinergic
properties used for PD Diphenhydramine (Benadryl®)
Can DD be given these medications for his tremors?
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ANTIVIRALS
Brand Generic Formulations
Comments
Symmetrel®
Amantadine
TabletOral Solution
Not used much. Can cause: Visual disturbances, Sleep disturbances, Anti-SLUD affects, GI disturbances, Hypotension, Caution in patients with seizures or heart failure
MOA: Unknown, but thought to potentiate dopaminergic function
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PATIENT CASE
DD has been taking Stalevo® and Amantadine for two years. He begins developing these ‘freezing’ attacks, or ‘On-Off periods.’ How can this be managed?
DD develops the inability to stand alone, or walk without assistance. What stage has he progressed to?
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CRITICAL THINKING QUESTIONS What role does dopamine play in the symptoms of Parkinson’s Disease? Besides movement issues, happens when there is too little dopamine? What role does dopamine play in the common side effects of the
medications? Does dopamine cross the blood brain barrier? Why would the levodopa/carbidopa products be last line treatment? Which enzymes break down dopamine? Which medications should we be aware of that have drug-food interactions? What is the difference between ‘wearing off’ affects and ‘on-off’ periods? How are the above treated? Which medications for PD should we really not use in elderly patients? Why? What is the rule for changing from IR Sinemet® to Sinemet® CR? What role does pyridoxine play with these medications? Please review the formulations of the Parkinson’s Disease treatment options. What other diseases/disorders can these medications treat? Which medications can cause Parkinson’s disease LIKE symptoms?
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QUESTIONS
Soheyla Mahdavian, Pharm.D.Assistant Professor of Pharmacy Practice Office #347 850-599-8186