Parkinson’s Drugs For Block III Flashcards
What is the pathophys of Parkinson’s
caused by an imbalance between dopamine (DA) and acetylcholine (ACh) neurons on innervation of gamma-aminobutyric acid (GABA) receptors
What are the S/s of PArkinsons
Tremor, Rigidity, Dyskenesia, Akenesia, Bradykinesia, Postural/ Gait Disturbance
Clinical presentation Parkinson’s?
Flat affect, reduced blinking, flat face, Depression, Dementia, Psychosis
Which drugs can induce Parkinson’s like S/s
Antipsychotics (i.e. phenothiazines) and Antiemetics
Prochloroperazine (Compazine) (Antiemetic)
Chlorpromazine (Thorazine) (antiemetic)
Trifluoperazine (Stelazine) (1* typical)
Thioridazine (Mellaril) (1* typical)
Haloperidol (Haldol) (1* typical)
Metoclopramide (Reglan) (GI Benzamide)
Which Dopamine agent is best at Tx improving motor disability
Levodopa
Which Dopamine Agent is best at Lessing Motor complications
Dopamine agonists
What are the 1st line monotherapy Tx for Parkinson’s
Dopamine agonists
Bromocriptine (Parlodel)
- Semisynthetic ergot derivate
- Rarely used
Rotigotine (Neupro)
- Non-Ergot
- Transdermal system
What are the ADE of Dopamine Agonists Bromocriptine and Rotigotine
Pleuropulmonary and/or cardiac fibrosis is a concern
-Chest x-ray with abnormal pulmonary exam
Postural hypotension, dizziness
Hallucinations, mental confusion
GI disturbances
Digital vasospasm and leg cramps
What Parkinson’s Drugs are used for RLS
Pramipexole (Mirapex)
Ropinirole (Requip)
(NONERGOT)
What is the clinical use of Pramipexole
Effective as monotherapy for mild parkinsonism and in patients with advanced disease
Allows the dose of levodopa to be reduced and smoothing out response fluctuations in advance disease.
What is the clincal use of Ropinirole
Affective as monotherapy in patients with mild disease
Allows the dose of levodopa to be reduced and smoothing out response fluctuations in advance disease
Parkinson’s pts with advanced disease should get:
With mild disease should get?
Advanced: Pramipexole
Mild: Ropinirole
What is the clinical use of Apomorphine
acute, intermittent treatment of “off” episodes associated with advanced Parkinson disease;
recurring hypomotility, “off” episodes
What is the MOA of Apopmorphine
Dopamine receptor agonist (Short-acting)
Stimulates post-synaptic D2-type receptors
How must apomorphine be titrated
Must be titrated in a setting where BP can be monitored
What should be done if a pt misses a Apomprphine does x 1 wk
If patient does not dose for more than 1 week, reinitiate at 0.2ml dose and increase
What are the ADE of apomorphine
Severe N/V
Ortho hypotension
Hallucinations
Dyskinesia
Somnolence
What is the prophylaxis Tx for N/V with apomorphine
prophylaxis with trimethobenzamide (anti-emetic) 3 days prior to initiating apomorphine and continued for the first month of therapy, if not indefinitely
What are the contraindications of Apomorphine
5-hydroxytryptamine-3 antagonists (5-HT3) antagonists (ondansetron, granesitron, dolasetron, palonosetron) causes severe hypotension and loss of consciousness
IV use (thrombus formation)
Sulfite sensitivity (preservative)
How must apomorphine be admin
Sub Q!
IV use= thrombus formation
What drugs should apomorphine be avoided in
5-hydroxytryptamine-3 antagonists (5-HT3) antagonists (ondansetron, granesitron, dolasetron, palonosetron)
causes severe hypotension and loss of consciousness
What is the MOA of carbidopa
Aromatic L-Amino Acid decarboxylase (AAAD) inhibitor that does not cross the BBB
Prevents some peripheral conversion and metabolism of levodopa to dopamine in the peripheral tissues thereby allowing increased availability of levodopa to cross into the CNS
What is the MOA of Levodopa
Precursor to dopamine that has the ability to cross the BBB
and replenish depleted dopamine in the brain
Converted into dopamine in the periphery
How long does levodopa have effect till it begins to decline
“Honeymoon”: patients normally respond favorably to levodopa for 3-5 years then the effects start to decline
What are the ADE of Carbidopa and Levodopa
Acute Effects (excessive dopamine): nausea, vomiting, postural hypotension, confusion, agitation, hallucinations, cardiac arrhythmias
Dyskinesias (excessive dopamine):
Drug induced abnormal involuntary movements, including dystonia
Treatment: decrease levodopa dose or add an anticholinergic or amantadine as an anti-dyskinetic drug
What is the Tx for dyskinesia induced by levodopa
Treatment: decrease levodopa dose or add an anticholinergic or amantadine as an anti-dyskinetic drug
What is the role of amantadine
Anti-dyskinesia medication
How do we treat the “wearing off” period of Levodopa
“Wearing Off” phenomenon: end of dose deterioration, symptoms return before the next dose
Treatment: add dopamine agonist, adding a MAO-B inhibitor, a COMT inhibitor or increasing the frequency dose of levodopa (shorten the dosing interval)
How do we treat the “on- OFF” phenomenon of Levodopa
unpredictable return of symptoms without respect to the dosing interval
Severity changes ranging from akinesia (off periods) to mobility with dyskinesias (on periods)
Treatment: add dopamine agonist, adding a MAO-B inhibitor, a COMT inhibitor or redistributing dietary protein (high-protein diet reduces levodopa absorption; must keep steady intake)
What effect does a high protein diet have on Levodopa
Reduces absorption
What pts should not receive L-dopa
Contraindications:
- psychotic illness
- narrow-angle glaucoma
- use of non-selective MAOI’s
Precautions:
Peptic Ulcer Disease (PUD)
Malignant Melanomas: levodopa is a precursor of skin melanin and conceivably may activate malignant melanoma
What is the association of L-Dopa and skin cancer
levodopa is a precursor of skin melanin and conceivably may activate malignant melanoma
What is the clinical use of MAO-B inhibitors
Symptomatic control of (mild to moderate) Parkinson Disease
Adjunct therapy for patients with Parkinson’s Disease and motor fluctuations
Pts on Selegiline and Rasagiline should avoid what medications
Patients on MAO-B Inhibitors should avoid medications that increase the risk of Serotonin Syndrome
What is the MOA of selegiline
Irreversibly inhibits the metabolism of dopamine by MAO-B that results in increased dopamine levels in the brain
Does Selegiline effect MAO-A ?
Does not inhibit MAO-A
(degrades: norepinephrine and serotonin)
much lower risk for hypertensive crisis
Loses selectivity at doses > 10mg/day
When should the last dose of selegiline be taken to avoid insomina
Last dose should be early afternoon to prevent insomnia
What is the clinical use for Selegiline
Used in conjunction with levodopa
Mild Disease: may be used alone to try and delay the need for levodopa in early Parkinson’s disease (effects have not been robust)
What drug can be used as monotherapy in order to delay the use of L-dopa
Selegiline
What is Selegiline metabolized to
Amphetamine, can cause insomnia
What is the MOA of Rasagiline
MOA-B non selective inhibitor
Which is more potent, Selegiline or Rasagiline
Rasagiline 5x more potent
Because Selegiline and Rasagiline are MAO-b inhibitors what foods should be avoided
avoid tyramine containing foods
ex; aged cheeses, air-dried or cured meats, tap/draft beers, etc
What is the MOA of a COMT inhibitor
prevents the breakdown of dopamine,
more levodopa available to cross blood-brain barrier
What is the clincal indications for COMT-I
Manage motor fluctuations (“wearing-off” effect)
Adjunct to levodopa/carbidopa in patients with response fluctuations or who have failed or can not use other therapies
What is the urine ADE of COMT-I
Entacapone causes orange discolored urine
Since COMT-I increase the concentration of dopamine, what are the ADE
Increase Dopamine: diarrhea, dyskinesias, nausea, anorexia and hallucinations
When should tolcapone (MAO-I) be used
After Entacapone has failed
Hepatotoxic: get liver function tests (LFTs) at baseline and on a regular basis
Written informed consent is advised by manufacturer for patients who have failed Entacapone
What is the major ADE of tolcapone
Liver toxicity
How should Entacapone be used (MAO-I)
Must use with carbidopa/levodopa
Does not cross BBB
What is the combination of Carbidopa/l-dopa/Entacapone called
Stalevo
How are anticholinergics used in the Tx of Parkinson’s
Mechanism of Action: block the excitatory neurotransmitter acetylcholine to try and restore balance with dopamine
Clinical Use:
- Most effective on tremors and rigidity
- DOC for drug-induced (anti-psychotics) parkinsonism
- Does not relieve symptoms of tardive dyskinesia
Since Benzotropine and Trihexyphenidyl are anticholinergics, what are their ADE
dry mouth, blurred vision, dry eyes, constipation, urinary retention, confusion, and arrhythmias
What are the DOC for drug induced Parkinson’s
Benzotropine or Trihexyphenidyl
What is the clincal use of Amantadine
Posses symptomatic benefits and may reduce dyskinesias caused by levodopa or dopamine agonists
Not as effective on bradykinesia, rigidity, tremor and dyskinesia as anticholinergics
What is the major ADE of Amantadine
Livedo reticularis (RASH)
How do you tx parkinson drug induced hallucination
Stop medications that may contribute to psychosis in the following order: -anticholinergics, -amantadine, -selegiline, -dopamine agonists, levodopa/carbidopa
Avoid typical antipsychotics, risperidone, and olanzapine; worsens Parkinson symptoms
How do you Tx the cognitive disorders of drug induced Parkinson’s
Discontinue/reduce Parkinson disease medications as tolerated
If antipsychotics are needed treat with newer neuroleptics:
Quetiapine (Seroquel)
Clozapine (Clozaril): probably best but unacceptable side effects (agranulocytosis)
