Drugs for Movement Disorders Flashcards
How can rehabilitation be used as a non-pharmacological treatment of PD?
- Focus on gait re-education
- Improvement of balance and flexibility
- Enhancement of aerobic capacity and strength
- Improvement of movement initiation
- Augmentation of functional independence
What can occupational therapy include in treatment of PD?
- Speech and language therapy for those experiencing problems with communicating, swallowing, or saliva
- Strategies to improve the safety and efficacy of swallowing to minimize the risk of aspiration, such as expiratory muscle stress
- Strategies to improve speech and communication, such as attention to effort therapies
What does MAO-A metabolize?
- Norepinephrine and serotonin
What does MAO-B metabolize?
- Phenylethylamine and benzylamine
What metabolizes dopamine and tryptamine?
- Equally by MOA-A and MOA-B
What is the MOA of amantadine?
- Exact mechanism is unknown
- Direct and indirect effects on dopamine neurons
What are the clinical applications of amantadine?
- Drug-induced extrapyramidal symptoms
- Adjunctive therapy for dyskinesias
- Monotherapy for patients with mild motor symptoms
What are some toxicities of amantadine?
- CNS depression
- Impulse control disorders
- Psychosis
- Suicidal ideation and depression
- May cause livedo reticularis –> purplish mottled discoloration of the skin, usually on the legs
What is the MOA of selegiline?
- Potent, irreversible inhibitor of MAO
What are the clinical applications of selegiline?
- Adjunct in the management of PD when levodopa/carbidopa use has on-off phenomenon
- Off label use is PD
What are some toxicities seen with selegiline?
- Antidepressants increased risk of suicidal thoughts and behaviors in pediatric and young adult patients in short term studies
- May cause exacerbation of HTN
- May cause CNS depression
What is the MOA of ropinirole?
- Non-ergot, has high relative in vitro specificity and full intrinsic activity at D2 and D3 DA receptors
What are the clinical applications of ropinirole?
- Treatment of PD
- Can be administered in addition to levodopa/carbidopa and/or to treat levodopa on-off phenomenon
- No efficacy in those who levodopa doesn’t work
What are some toxicities with ropinirole?
- Dyskinesias
- Impulse control disorders/compulsive behaviors
- Increased risk of melanomas
- Orthostatic hypotension
- Psychotic effects
- Somnolence
- N/V, constipation
- Headaches
What is the MOA of tolcapone?
- Selective and reversible inhibitor of COMT –> a major pathway for levodopa degradation when decarboxylase is blocked by carbidopa
What are the clinical applications of tolcapone?
Adjunct to levodopa and carbidopa for the treatment of idiopathic PD in patients with motor fluctuations
What is a big risk of tolcapone?
- Risk of potentially fatal acute fulminant liver failure, only use in PD patients on L-dopa/carbidopa who are experiencing symptom fluctuations and are NOT responding satisfactory to other agents
What are some toxicities of tolcapone?
- Abnormal thinking/behavioral changes
- CNS depression
- Loss of impulse control
- Orthostatic hypotension
- Exacerbation of preexisting dyskinesia
What is the MOA of carbidopa and levodopa?
- Immediate precursor to dopamine
- Crosses BBB
- Carbidopa is a peripheral DOPA decarboxylase inhibitor
What are the clinical applications of carbidopa and levodopa?
- Parkinsonian syndrome
- Restless leg syndrome
What are the toxicities of carbidopa and levodopa?
- GI effects –> anorexia, N/V
- Postural hypotension
- Hypertension and/or cardiac arrhythmias
- Dyskinesias
- Behavioral effects
- Wearing off and on-off phenomena
Why is carbidopa given with levodopa?
- A smaller dose of levodopa can be given but still have the same amount reach the brain
- Carbidopa blocks peripheral DOPA decarboxylase
What are some device aided therapies for movement disorders?
- Deep brain stimulation of the subthalamic nucleus or globus pallidus interna
- Intrajejunal levodopa-carbidopa enteric gel administered through percutaneous gastrostomy
What is the on-off phenomenon in PD?
- Back and forth switch between mobility and immobility in levodopa treated patients
- Typically occurs as an end-of-dose or “wearing off” worsening of motor function
What can help reduce the on-off phenomenon in PD?
- Controlled release form of levodopa
- Shorten the interval between levodopa doses
- Adding a medication –> dopamine agonist, COMT inhibitors, or MAO-B
What is the MOA of benztropine?
- Cholinergic antagonist at muscarinic receptors
- Also blocks histamine receptors
What are the clinical applications of benztropine?
- Monotherapy or combo for PD
- Predominantly for tremor and dystonia in younger people
- Should be avoided in elderly and those with cognitive impairment
- Can be helpful in reducing the amount of saliva to treat excessive drooling
What are some toxicities of benztropine?
- Anti-cholinergic effects
What are the four main drugs class choices for monotherapy of symptomatic PD?
- MAO-B inhibitors
- Amantadine
- Dopamine agonists
- Levodopa
What is given to patients with mild symptoms and want little interference with daily function?
- MAO-B inhibitor –> given once daily
- Amantadine
What is given to patients older than 65 with diminished daily function and quality of life?
- DA agonist or levodopa
What is given to patients younger than 65 with diminished daily function and quality of life?
- Immediate release levodopa –> more effective for improving motor function and quality of life
What can be used to treat sialorrhea in PD?
- Botulinum toxin A injections
What can be used to treat orthostatic hypotension in PD
- Midodrine
- Domperidone
- Fludrocortisone
What can be used to treat REM sleep behavior disorder in PD?
- Melatonin or clonazepam
What can be used to treat depression in PD?
- Start low and go slow
What can be used to treat psychosis in PD?
- Quetiapine and clozapine –> standard treatment
- Maybe rimavanserin
What can be used to treat dementia in PD?
- Rivastigmine or donepezil
- Memantine
What is the biggest focus when treating Huntington disease?
- Treat non-motor symptoms like depression, irritability, paranoia, anxiety, or psychosis
What are some non-pharmacologic treatments for restless leg syndrome?
- Exercise
- Leg massage
- Applied heat
- Avoidance of aggravating drugs and sleep deprivation
What could help symptoms of restless leg syndrome?
- Correction of coexisting iron deficiency anemia
What can be given if there is persistent severe restless leg syndrome despite non-pharmacologic therapy?
- Non-ergot dopamine agonists (ropinirole) –> if comorbid depression or obesity/metabolic syndrome
- Alpha-2-delta calcium channel ligand if there are no comorbidities or comorbid pain, anxiety, or insomnia
What can be given for restless leg syndrome in pregnancy?
- Often managed with nonpharmacologic strategies, iron supplementation
- Pharmacologic therapies to consider if needed include clonazepam and carbidopa-levodopa
What should first be looked at when treating restless leg syndrome?
- Iron stores –> replete iron if <75 ng/mL
What is used when treating an intermittent disability due to tremor?
- Propranolol is first line
What is used when treating a persistent disability due to tremor?
- Propranolol and primidone are first line
- Gabapentin is second line
- Botulinum toxin is used in drug refractory tremor
What is the only drug that seems to have an impact on the survival of ALS?
- Riluzole
What are some treatment options for Wilson disease?
- Low copper diet
- Agents that reduce copper levels –> penicillamine and potassium disulfide
What is the MOA of penicillamine?
- Copper chelating agent that is readily excreted by the kidney
What does potassium disulfide do?
- Reduces intestinal absorption of copper
