Drugs for Movement Disorders (Wolff) Flashcards
What are the 2 drugs used for Wilson’s Disease?
Basically low copper diets and agents that reduce serum copper levels
- Penicillamine: Copper chelating agent
- Potassium disulfide: Reduces intestinal absorption of copper
What is the Levodopa combination?
Levodopa + carbidopa
OR
Levodopa + carbidopa + entacapone
Tx for Essential Tremor Algorithm
- Mild tremor, no disability –> No rx therapy
- Intermittent disability –> First line agent: Propranolol (unknown MOA, blockade of beta receptors in muscle spindles) –> second line agent: Benzodiazepine
- Persistent disability due to tremor –> First line agents: Propranolol, Primidone (a barbiturate anticonvulsant), or both –> poor response –> second line agents: Gabapentin –> poor response plus predominant limb tremor or head or voice tremor: Botulinum toxin injections (binds to high affinity presynaptic recognition sites on cholinergic nerve terminals –> decreases ACh release, causing a neuromuscular blocking effect)
Tx of Restless Leg Syndrome Algorithm
- Check iron stores, if serum ferritin < 75 ng/mL –>
- Replete iron –>
- Moderate to severe symptoms 2 or more days per week?
- -> No, then intermittent therapy of Carbidopa-levodopa PRN - –> Yes: Daily rx recommended –> Comorbidities (obesity, depression, gait, respiratory failure, substance abuse)?
- -> yes, then give Dopamine agonist (ex. prampipexole, ropinirole, or rotigotine)
- -> no, then give Alpha 2 delta calcium channel ligand (ex. gabapentin, enacarbil, pregabalin, or gabapentin)
What are the treatments for Restless Leg Syndrome?
- Correct iron deficiency anemia
- Non-ergot dopamine agonist (e.g. ropinirole) if comorbid depression, obesity/metabolic syndrome
- Alpha-2-delta calcium channel ligand (e.g. gabapentin) - no co-morbidities. Hx of impulsive control DO
- For intermittent but disabling sx, use DA agonist or carbidopa-levodopa, benxodiazepines or opioids
if pregnant - nonpharmacologic strategies, iron supplement, clonazepam or carbidopa-levodopa
What are the treatments for Huntington Disease?
No current therapy slows dz progression.
Treat non-motor symptoms
- fluoxetine for depression and irritability
– carbamazepine for depression
– avoid agents with substantial anticholinergic effects since can exacerbate chorea
Where are the Dopaminergic neurons in the brain?
Substantia nigra
Where are the Dopaminergic neurons in the brain?
Substantia nigra
What is the main function of Dopamine in normal movement?
movement happens when the “brake” is released
What is the function of Ach in normal movement?
It stimulates the release of GABA which slows movement
Name of drug with “unknown” exact MOA
amantadine
Name of drug that is a weak, noncompetitive NMDA receptor antagonist
amantadine
What is the main effect of amantadine?
reduces Parkinson disease symptoms
What drug is used for Amyotrophic Lateral Sclerosis (ALS)?
Riluzole
- prolongs survival by a few months
Tx for Essential Tremor Algorithm
- Mild tremor, no disability –> No rx therapy
- Intermittent disability –> First line agent: Propranolol (unknown MOA, blockade of beta receptors in muscle spindles) –> second line agent: Benzodiazepine
- Persistent disability due to tremor –> First line agents: Propranolol, Primidone (a barbiturate anticonvulsant), or both –> poor response –> second line agents: Gabapentin –> poor response plus predominant limb tremor or head or voice tremor: Botulinum toxin injections (binds to high affinity presynaptic recognition sites on cholinergic nerve terminals –> decreases ACh release, causing a neuromuscular blocking effect)
What are the 3 clinical applications of amantadine?
- treatment of drug-induced extra-pyramidal symptoms
- adjunctive therapy for dyskinesias in patients receiving Levodopa
- used as monotherapy for pts with mild motor symptoms
What drug has the following toxicities:
- CNS depression
- impulse control disorders
- psychosis
- suicidal ideation/depression
- causes livedo reticularis (purple discoloration of legs)
amantadine
Tx of Restless Leg Syndrome Algorithm
- Check iron stores, if serum ferritin < 75 ng/mL –>
- Replete iron –>
- Moderate to severe symptoms 2 or more days per week?
- -> No, then intermittent therapy of Carbidopa-levodopa PRN - –> Yes: Daily rx recommended –> Comorbidities (obesity, depression, gait, respiratory failure, substance abuse)?
- -> yes, then give Dopamine agonist (ex. prampipexole, ropinirole, or rotigotine)
- -> no, then give Alpha 2 delta calcium channel ligand (ex. gabapentin, enacarbil, pregabalin, or gabapentin)
What are the treatments for Restless Leg Syndrome?
- Correct iron deficiency anemia
- Non-ergot dopamine agonist (e.g. ropinirole) if comorbid depression, obesity/metabolic syndrome
- Alpha-2-delta calcium channel ligand (e.g. gabapentin) - no co-morbidities. Hx of impulsive control DO
- For intermittent but disabling sx, use DA agonist or carbidopa-levodopa, benxodiazepines or opioids
if pregnant - nonpharmacologic strategies, iron supplement, clonazepam or carbidopa-levodopa
What drug has the following toxicity [black box]:
antidepressants increased risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies
selegiline
What are the 2 main clinical applications of selegiline?
- adjunct in the management of PD when levodopa/carbidopa use during the on-off phenomenon
- early PD
What drug has the following toxicity [black box]:
antidepressants increased risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies
selegiline
What are the treatments for Huntington Disease?
No current therapy slows dz progression.
Treat non-motor symptoms
- fluoxetine for depression and irritability
– carbamazepine for depression
– avoid agents with substantial anticholinergic effects since can exacerbate chorea
Name of drug that is another MAO-B selective irreversible inhibitor, has greater potency, and has similar efficacy and adverse effects to the OG drug
rasagiline
Name of drug that is another MAO-B selective REVERSIBLE inhibitor
safinamide
What is the main MOA of ropinirole
increases DA-mediated effects in the CNS by binding to D2 and D3 DA receptors
What is the 2 main clinical application of ropinirole?
- treatment of Parkinson disease
2. can be administered in addition to levodopa/carbidopa
What drug has the following toxicities:
- dyskinesias
- impulse control disorders/compulsive behaviors
- inc. risk for melanoma
- orthostatic hypotension
- psychotic effects
- somnolence
- N/V, constipation
- headaches
ropinirole
Which drug is a D2 agonist, has low risk for hypotension and somnolence but has an inc. risk for hallucinations when compared to ropinirole
pramipexole
Which drug is a D2 agonist and is supplied as a 24 hr transdermal patch
rotigotine
Which drug is a DA agonist and is given sublingual or subQ injection; it’s used to quickly treat “off” episodes
apomorphine
Which drug is an early DA agonist and alkaloid derivative
bromocriptine
Treatments for non motor features of Parkinson Disease
- Sialorrhea?
- Orthostatic hypotension?
- REM sleep behavior disorder?
- Depression?
- Psychosis?
- Dementia?
- Sialorrhea? Botulinum toxin A injections
- Orthostatic hypotension? Alpha- adrenergic agonist midodrine, peripheral D2 antagonist domperidone, and mineralocorticoid fludrocortisone
- REM sleep behavior disorder? Melatonin or Clonazepam
- Depression - general depression tx
- Psychosis? atypical antipsychotics quetiapine and clozapine are standard treatment; recently joined by pimavanserin, a selective serotonin 5- hydroxytryptamine 2A (5-HT2a) inverse agonist
- Dementia? cholinesterase inhibitors such as rivastigmine or donepezil and/or NMDA-antagonist memantine
Treating Parkinson Disease tx rationale
- Mild signs/symptoms?
- Modest antiparkinson effects?
- Most potent antiparkinson therapy?
- Mild symptoms/little interference with daily function?
- Diminished daily function and quality of life?
- Mild signs/symptoms? No therapy needed.
- Modest antiparkinson effects? amantadine and MAO-B inhibitors
- Most potent antiparkinson therapy? levodopa
- Mild symptoms/little interference with daily function? prefer MAO-B inhibitor… modest effects, but generally well tolerated and are given once daily
– amantadine… alternative, modest effects, useful if predominant tremor - Diminished daily function and quality of life? If under 65 y/o use either DA agonist (1x day dose) or levodopa. If over 65 y/o, use immediate-release levodopa and switch to controlled release tablets for fewer daytime doses
What are the clinical applications for benztropine (anticholinergic drug for parkinsonism)?
- predominantly for tremor and dystonia in younger people
* can also be helpful in reducing the amount of saliva to treat excessive drooling
When should benztropine be avoided?
- should be avoided in elderly
* should be avoided in those with cognitive impairment
What is the other anticholinergic drug besides benzotropine?
Trihexyphenidyl
Which drug is causes this [black box] toxicity:
risk of potentially fatal acute fulminant liver failure, only use in Parkinson dz patients on L-dopa/carbidopa who are experiencing symptom fluctuations and are not responding satisfactorily to other agents
tolcapone
what is the drug that is a selective and reversible inhibitor of COMT
tolcapone
What is the main effect of tolcapone
COMT inhibition–> more sustained plasma levels of levodopa and enhanced central DA activity
What is the main clinical application of tolcapone
adjunct to levodopa and carbidopa for tx of signs and symptoms of idiopathic Parkinson dz
What are the toxicities associated with carbidopa (decarboxylase inhibitor) + levodopa?
• gastrointestinal effects… levodopa w/o carbidopa –> anorexia, nausea, and vomiting in ~ 80% of patients (activates chemoreceptor trigger in brainstem outside of BBB); ↓ to ~20% by addition of carbidopa
• postural hypotension, often diminishes with continuing treatment
• hypertension and/or cardiac arrhythmias if large doses or used with nonselective monoamine oxidase inhibitors or sympathomimetics
• dyskinesias… occur in ~80% of patients
• typically choreoathetosis (movement of
intermediate speed of the face and distal extremities); dose-related, but individual variation in the dose required
• behavioral effects including depression, anxiety, agitation, insomnia, somnolence, confusion, delusions, hallucinations, nightmares, euphoria, other changes in mood or personality
• can be treated with atypical antipsychotic agents (clozapine, olanzapine, quetiapine, risperidone)
• wearing-off and on-off phenomena
What drug can also be given with carbidopa + levodopa?
Entacapone (a COMT inhibitor that does not cross BBB)
What is another COMT inhibitor that cannot cross the BBB, acts in periphery to block levodopa degradation, less toxic for the liver… used to treat “off” symptoms
entacapone
