Parkinson's Disease Flashcards
What is Parkinson’s Disease?
- A chronic, progessive, IRREVERSIBLE, disease that forms a neurological deficit of the extrapyramidal system [In basal ganglia]
- Issues with noncortical voluntary motor control
What are some of the symptoms of Parkinson’s Disease?
- Resting Tremor [pill rolling motion], Rigidity, Slow Movement [Akinesia] Impaired balence, Speech issues…
What is the neuropathological underpinnings of Parkinsons Disease?
- A loss of dopamine releasing neurons in the Substantia Nigra Pars Compacta [darkly pigmented areas]
- Presence of Lewy Bodies in the brain; clump of a-synuclein on nerve cells resulting in the symptoms
What are the Braak Stages?
- Stage 1: Lower Brainstem [Start]
- Stage 2: Raphe
- Stage 3: Substatia Nigra [necessary for PD] [Midbrain]
- Stage 4: Mesocortex/Thalamus
- Stage 5: Neocortex/Prefrontal Cortex
- Stage 6: Entire Cortex
What is the Braak Stages based on?
- Based on the distribution and density of the Lewy Bodies [a-Synuclein] within the brain
What are the two dopamine signaling pathways in neurons?
- DIRECT: D1 receptors [SNpc - Striatum - Gpi/SNpr - Thalamus - cortex]
- INDIRECT: D2 receptors [SNpc - Stiatum - Gpe - STN- Gpi/SNpr -Thalamus - cortex]
What happens then Thalamocortical signaling is interrupted?
- Since both D1 and D2 receptors faver this signaling; it will DECREASE dopamine leading to DECREASED movement [main problem in parkinsons]
What is the way that Anticholinergics are used in Parkinsons Disease?
- Add on therapy for tremors [Caused by an imbalance between Dopamine and cholinergic]
- The decrease in dopamine will increase the cholinergic pathway = tremors
What is L-DOPA?
- A precursor of dopamine and the “GOLD STANDARD” in parkinsons treatment
- Able to enter the CNS [Brain] because of no charge
- SE: Nausea, Vomiting, Hypertension, Psychosis
Why is L-DOPA given with Carbidopa?
- Inhibits DCC from breakdown L-DOPA in the periphery; allowing it to get into the CNS [Brain
- Decrease the side effects
- Dopamine really can’t cross the BBB since its got a net positive charge
What are some of the challeneges associated with L-DOPA therapy?
- On/Off Oscillations: After some times of using L-DOPA the drug effect may begin to fall off unpredictably [give continuos L-DOPA to fix]
- Dyskinesias: Uncontrolled, Involuntary movement with long term use of L-DOPA
- Since L-DOPA needs converted; the body may become unresponsive
What are the dopamine agonsts?
- Apomorphine, Ergolines [Bromocriptine], Non-Eroglines [Ropinirole, Pramipexole, Rotigotine]
What is the function of Apomorphine in parkinsons disease?
- Mixed D1/D2 Agonist [D2 deals with movement] that increases dopamine to the brain
- Used in late stage Parkinsons for rapid relief of the off state
- Non Ergot
- SE: N/V, Hallucinations, ICD, $$$$
What is the funcation of the ergolines [Bromocriptine] in parkinsons disease?
- D2 agonist with some effects in PD
- Helps minimize LD motor fluctuations
- Add on to L-DOPA
- Pergolide and Cabergoline [Strong D2 Agonist] arent used because of Heart Valve Damage
What is the function of the Non-Ergolines [Ropinirole, Pramipexole, Rotigotine] in parkinsons disease?
- D2/D3 agonist with fewer side effects than the ergolines and are used as monotherapies in early-stage PD
- Rotigotine is a transdermal patch
What are the MAO-B inhibitors that are used in parksinsons disease?
- Selegiline, Rasagiline, Safinamide
What is the function of Selegiline and Rasagiline in parkinsons disease?
- both are propargylamines causing the irreversible inhibition of MAO-B [MAO-B will break down dopamine], so these will inhibit MAO-B from breaking down dopamine = INCREASING it
- Mainly monotherapies but can be added on
What is the function of Safinamide in Parkinsons disease?
- reversible inhibition of the MAO-B
- Add on therapy to L-DOPA/Carbidopa
What are the COMT inhibitors used in parkinsons disease?
- Entacapone, Tolcapone, Opicapone
What is the function of the COMT inhibitors?
- They inhibit the methylation of the 3-OH group of DA or L-DOPA by COMT
- Entacapone & Opicapone: decrease metabolism of L-DOPA in PERIPHERY
- Tolcapone: keeps dopamine levels high in the CNS
What are the motors symptoms of Parkinsons disease?
- Tremor, Bradykinesia [slow movement], Rigidity, Parkinsons Gait
What are the non-motor symptoms of Parkinsons disease?
- Anxiety, depression, constipation, insomnia, psychosis, sexual dysfunction
What is the type of assessment used in diagnosing parkinsons disease?
- Unified Parkinson’s Disease Rating Scale [UPDRS]
- Looks as signs/symptoms of parkinsons disease
What are the goals of therapy for Parkinsons disease?
- Manage motor and non-motor symptoms
- Increase QOL
- Preserve daily activities
- Manage adverse drug reactions
What are some of the non-pharmacological treatments used in Parkinsons Disease?
- EXERCISE [always started before actual treatment], Nutritional Counseling, Occupational therapy, Psychotherapy, Speech Therapy
What is the initial treatment for Parkinsons Disease?
- 1st Line: Rule out drug-induced PD [anti-psychotics?]; DOPAMINE PRECURSOR [Gold Standard], Dopamine Agonist, MAO-B inhibitors
- 2nd Line: COMT Inhibitors, Amantadine
What should be the first medication used in the treatment of Parkinsons Disease?
- Levodopa/Carbidopa
- Maybe a Dopamine Agonist
When may a Dopamine Agonist be used as initial treatment?
- if the patient is <60 and is at high risk of dyskinesia [involuntary and uncontrolled movements]
When should you avoid Dopamine Agonist as initial treatment?
- if the patient is >70, history of ICD, cognitive impairment, daytime sleepiness, hallucinations
When would be the best time to start a patient on Levodopa/Carbidopa for Parkinsons Disease?
- when symptoms start affecting their daily life
- Levodopa/Carbidopa > DA > MAOB-I
What is the Dopamine Precursor used in Parkinsons Disease?
- Levodopa/Carbidopa
- First line for PD and the “GOLD STANDARD”
- Add on with Dopamine Agonist or other meds
What are the side effects for Levodopa/Carbidopa in Parkinsons?
- Nausea, Vomiting, LD motor fluctuations, Hallucinations [high dopamine level]
What are some of the clinical pearls for Levodopa/Carbidopa in Parkinsons Disease?
- Increase absorption with empty stomach but food Decrease nausea
- STARTING DOSE: 25/100 LD/CD PO BID-TID
What are some of the long term conplications of using Levodopa/Carbidopa in Parkinsons Disease?
- Levodopa will slowly overtime become more unresponsive and not work as well
What are the Dopamine Agonist used in the treatment of Parkinsons Disease?
- Nonergot and Ergot
What are the Non-Ergot drugs used in Parkinsons Disease?
- Pramipexole, Ropinirole, Rotigotine, Apomorphine
What are the Ergot drugs used in Parkinsons Disease?
- Bromocriptine, Cabergoline
What are the side effects of the Dopamine Agonist [Non-Ergots and Ergots]?
- Nausea. Vomiting, Sudden Sleep, Hallucinations, Impulse Control Disorder, Edema, $$$$
What are the clinical pearls for the Dopamine Agonist?
STARTING DOSES:
- Pramipexole IR 0.125mg PO TID; ER 0.375 mg PO daily
- Ropinirole IR 0.25 mg PO TID; ER 2 mg PO daily
- Rotigotine 2 mg PATCH Q24H
- Apomorphine 2 mg SubQ injection
What are the MAO-B Inhibitors used in Parkinsons Disease?
- Rasagiline, Selegiline, Safinamide
What is the MOA of MAO-B Inhibitors in Parkinsons Disease?
- It will prevent the break down of dopamine; increased dopamine will decrease any motor issues
What are the side effects of the MAO-B Inhibitors in parkinsons disease?
- Nausea, Vomiting, Headache, Insomnia [selegiline], Hypo- and Hypertension
What are some of the clinical pearls for the MAO-B Inhibitors in parkinsons disease?
STARTING DOSES:
- Rasagiline 0.5 mg PO Daily
- Selegiline 5 mg PO Daily
- Safinamide 50 mg PO Daily
- Risk of serotonin syndrome
What are the COMT Inhibitors used in Parkinsons disease?
- Entacapone, Opicapone, tolcapone
What is the MOA for the COMT inhibitors for Parkinsons Disease?
- stops the breakdown of dopamine within the brain, increasing the levels of it in and minimizing the affects of Parkinsons
What are the side effects for the COMT inhibitors in parkinsons disease?
- Nausea, Vomiting, Brown/Orang urine color [entacapone], hepatotoxicity [tolcapone]
What are the clinical pearls for the COMT inhibitors in parkinsons disease?
- NOT used in early PD patients with LD/CD
STARTING DOSE - Entacapone 200 mg PO
- Tolcapone 100 mg PO TID
- Opicapone 50 PO QHS
What is the function of Amantadine in parkinsons disease?
- MOA: increase the release and block the reuptake of dopamine within the brain
- RARELY used in monotherapy
What are some of the side effects of Amantadine in parkinsons disases?
- Insomnia, Confusion, Halluciantion, Livedo Reticularis
What are some of the clinical pearls for Amantadine in parkinsons disease?
- reserved for LD/CD peak dose dyskinesias
- STARTING DOSE: 100 mg PO BID
What is the function of the Anticholinergics in Parkinsons disease?
- MOA: blocks the overreactive cholinergic neurons in the brain; this reduces the dopamine/cholinergic imbalance
What are the Anticholinergics in parkinsons disease?
- Benztropine, Trihexyphenidyl
What are some of the side effects for the anticholinergics in parkinsons disease?
- Blurry vision, Urinary retention, Dry mouth, Constipation, Confusion/dementia
What are some clinical pearls for anticholinergics in parkinsons diseases?
STARTING DOSE:
- Benzotropine 05mg PO QHS
- Trihexphenidyl 1 mg PO daily
- Avoid if > 65 yo because of the Anti-muscarinic SE
What medications do you really not want to use in a patient that has parkinsons disease?
- Antipsychotics
What are the pros of using Levodopa/Carbidopa in parkinsons disease?
- GOLD STANDARD
- Cheapo
- bunch of dosages forms
What are some cons of using Levodopa/Carbidopa in parkinsons disease?
- Motor Fluctuations
- Multiple time a day
What are some pros for Dopamine agonists in parkinsons disease?
- Once daily
- Better in young patients
- Limited motor fluctuations
What are some cons for Dopamine Agonists in parkinsons disease?
- $$$
- Less benefit than LD/CD
- MANY adverse effects
Who should take dopamine agonist for Parkinsons disease?
- Age < 60 & high risk of dyskinesias
- AVOID if: >70yo, history of ICD, Cognitive impairment, sleepiness, hallucinations
What are some pro for MAO-B inhibitors in parkinsons disease?
- Well tolerated
- delays motor fluctuations
What ares some cons for MAO-B inhibitors in parkinsons disease?
- Least effective against motor symptoms
- serotonin syndrome?
Who should get MAO-B inhibitors in parkinsons disease?
- Have minor symptoms
- Have higher risk of motor fluctuations
