Transcript Advances in Managing Parkinson`s Disease

PARKINSON’S DISEASE
Soheyla Mahdavian, Pharm.D.
Assistant Professor of Pharmacy Practice
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.
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.

RISK FACTORS

Exposure to environmental toxins
Herbicides
 Pesticides


Heavy metal exposure

Formed deposits in the substantia nigra
Head trauma (rare)
 Genetics

PATIENT CASE
CC: “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, obesity
SH: 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?
PARKINSON’S DISEASE
PATHOPHYSIOLOGY
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
DOPAMINE IN THE BODY
Dopamine is responsible for many functions in the body,
including:
Cognition
 Voluntary movement
 Motivation
 The brain’s reward
system

Sleep
 Mood
 Attention
 Memory
 Learning

NORMAL BALANCE OF DOPAMINE AND ACETYLCHOLINE
4/8/2016
IMBALANCE OF DOPAMINE AND
ACETYLCHOLINE IN PD
4/8/2016
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
NON-MOTOR SYMPTOMS
 Autonomic/sensory
disturbances
Bladder problems
 Constipation
 Sexual dysfunction
 Impaired smell or
vision
 Pain
 Fatigue

 Psychiatric





issues
Depression
Anxiety
Cognitive
dysfunction
Dementia (late
stages)
Sleep Disturbances
PATIENT CASE
CC: “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
SH: 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.
SECONDARY PARKINSONISM
USUALLY REVERSED IF THE CAUSE IS
DISCONTINUED AND NO PERMANENT DAMAGE
CAUSED
 Pharmacotoxicity


Antiemetics (e.g., metoclopramide,
prochlorperazine)
Antipsychotics (e.g., phenothiazines,
haloperidol, olanzapine, risperidone)
 Environmental




(drug-induced)
toxicity
Carbon monoxide poisoning
Manganese
Methanol
Organophosphates
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”
4/8/2016
HOW DO WE CORRECT THIS
IMBALANCE OF DOPAMINE AND
ACETYLCHOLINE IN PD?
CORRECTING THE PROBLEM
4/8/2016
PHARMACOLOGIC APPROACHES
 Dopamine
replacement therapy
 Dopamine releasing therapy
 Dopamine conservation therapy
 Blocking acetylcholine
 Additional therapies
DOPAMINE REPLACEMENT THERAPY
4/8/2016
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

DOPAMINE REPLACEMENT
Brand
Name
Generic
Name
Sinemet®
Sinemet®
CR
Levodopa/Ca Tablet
rbidopa
Extended
Release
Tablet
ODT
Parcopa®
Stalevo®
Formulation Comments
s
Levodopa/Car Tablet
bidopa/Entac
aone
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.
KEY POINTS WHEN USING CARBIDOPA/LEVODOPA
•

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
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!!
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
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?

DOPAMINE RELEASING THERAPY
4/8/2016
DOPAMINE AGONISTS
 MOA:
Stimulates dopamine receptors
 Bromocriptine (Parlodel)
 Ropinerole (Requip)
 Pramipexole (Mirapex)
 **Apomorphine (Apokyn)- used for onoff treatment
 Adverse events:
Dyskinesias
 Visual disturbances
 Impulse behaviors
 Mental disturbances

DOPAMINE AGONISTS
Brand
Generic
Formulations
Parlodel
®
Bromocriptin Tablet
e
Comments
Ergot derived agonist.
Not used widely
because of
pulmonary fibrosis
Apokyn® Apomorphin Subcutaneous
e
injection
ONLY USED for “ONOFF” episodes
Requip®
Requip®
XL
Ropinerole
Non-ergot derived.
substrate of CYP1A2
Mirapex
®
Mirapex
® ER
Pramipexole Tablet
Extended Release
Tablet
Tablet
Extended Release
Tablet
Non-ergot derived.
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
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.

DOPAMINE CONSERVATION THERAPY
4/8/2016

COMT INHIBITORS
MOA: Inhibits catechol-O-methyltransferase
 Tolcapone (Tasmar®)
 Entacapone (Comtan®)
 Entacapone/Carbidopa/Levodopa (Stalevo®)
 Adverse events:

Hypotension
 Diarrhea
 Orange colored urine
 Sleep disturbances

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®
See side effects/comments
associated with all three agents
Levodopa/C Tablet
arbidopa/En
tacapone
MONOAMINE OXIDASE INHIBITORS
 MOA:
Inhibits MAO
 Selegiline (Eldepryl®)
 Rasagilene (Azilect®)
 Adverse events:
Hypertensive crisis (food restrictions)
- Orthostatic hypotension
- Insomnia
- Hallucinations
-
MAOIS
Brand
Generic
Formulation
Comments
Eldepryl®
Zelapar®
Selegilene
Tablet
ODT 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
KEY POINTS FOR MAOIS
•
Eat in moderation
Tyramine containing foods

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




•
Drug interactions:

Cheeses
Wines
Sour cream
Yogurt
Caffeine
Salami/Cold cuts
Sauerkraut
Fermented or aged foods

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Other MAOIs
COMT Inhibitors
CYP1A2 inhibitors/inducers
(Rasagilene)
Charbroiled foods
Smoking
St. John’s wort
Zafirlukast
Zilueton
Carbamazepine
Fluvoxamine*
 Psuedoephedrine

PATIENT CASE
BB is given Azilect® later.
 After looking at his profile, identify everything
he should be aware of?


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-SLUD
Sedation
Confusion
Increases IOP
ANTICHOLINERGICS
Brand
Generic
Formulations
Comments
Cogentin®
Benztropine
Tablet
Intramuscular
Injection
IV
Because of
side effects,
NOT the best
choice for
patients >65yo
Artane®
Trihexyphenidyl Tablet
Solution
Same as
above
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?
ANTIVIRALS
MOA: Unknown, but thought to potentiate
dopaminergic function
Brand
Generic
Symmetrel® Amantadi
ne
Formulations
Comments
Tablet
Oral Solution
Not used much. Can cause:
Visual disturbances, Sleep
disturbances, Anti-SLUD affects,
GI disturbances, Hypotension,
Caution in patients with seizures
or heart failure
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?

CRITICAL THINKING QUESTIONS
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
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
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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?
QUESTIONS
Soheyla Mahdavian, Pharm.D.
Assistant Professor of Pharmacy Practice
 Office #347
 850-599-8186