Movement disorders Flashcards
Movement disorders
Parkinson's (idiopathic IPD and drug-induced) Tremor Huntington's Dz Tics RLS
IPD
1 million in US, usually dx 55-65yo, MC in men
Degeneration of dopaminergic nerons in the nigrostriatal pathway–motor sx not detectable until 70-80% loss. imbalance between dopaminergic and cholinergic pathways. genetic links
Environment: pesticides, well water. inverse correlation with smoking and caffeine
IPD clinical presentation
At least two of the following: limb muscle rigidity, resting tremor, bradykinesia.
r/o drug-induced disorder: antipyschotic agents, metoclopramide, prochlorperazine.
No dx testing
Sx generally worsen.
hypomimia: masking of facial expressions. freezing movements, festinating gait, postural instability
Tx of IPD
Anticholinergic agents: benzotropine; amantadine
increased endogenous dopamine: levodopa, carbidopa
MAO-B inhibitor-selegiline, rasaglinine
dopamine agonists: ergot derivatives, bromocriptine; non-ergots: pramipexole, ropinirole
apomorphine
Anticholinergic agents
Trihexyphenidyl, benztropine
Most effective for tremor in early dz. good for younger pts (<65)
ADRs: anticholingeric sx. (dry)
Amantadine
MOA: unknown, may influence DA synthesis, release or reuptake
Modest benefit for tremor, rigidity, bradykinesia. short lived.
Suppresses levodopa-induced dyskinesia
Dose: 200-300mg/d divided, lower w/ CrCl
SEs: confusion, dizziness, dry mouth, hallucinations
Livedo reticularis: reversible; diffuse skin mottling and often LE edema
Carbidopa/Levodopa
Sinemet
MOA: direct l-dopa supplementation plus inhibition of peripheral conversion of l-dopa to DA by LAAD
Formulations: IR, ODT, CR
Dose: 200-800mg/day IR, 2400mg MDD for CR
Absorption affected by diet. Delays gastric emptying time, take with high protein.
Always be incombo with LAAD inhibitor
Carbidopa/Levodopa effects
Contraindications: narrow angle glaucoma, nonselective MAOIs (hypertensive crisis)
DDI: dopamine antagonists: antiemetics, antipyschotics. Bupropion: increased ADRs. Protease inhibitors (toxicity). Phenytoin, iron–reduce l-dopa efficacy
ADRs: anorexia, n/v, hypotension, arrhythmias, sedation, vivid dreams, hallucinations.
Long-term motor complications: wearing off, drug resistant off periods, rapid fluctuations, dyskinesia
Long term motor complication of Carb/Levo
End of dose wearing off: increasing loss of neuronal DA storage capability, increased dependence on exogenous L dopa. Options: increase l-dopa dosing frequency, change to long-acting, add short acting, add DA agonist, MAO-B inhibit, or COMT inhib
Drug-resistant off periods: d/t delayed gastric emptying of decreased GI absorp. Options: give on empty stomach, crush tab or take ODT, avoid CR.
Rapid flucuations: rapid transition from normal/dyskinetic “on” motor activity to bradykinetic “off” states. Options: add MAOB inhib, COMT inhib, or dopamine agonist
Dyskinesias: abnormal involuntary movements, often with peak dose. Options: smaller, more frequent ldopa doses, CR form, add amantadine, surgery for severe.
MAO-B inhibitors
Monoamine oxidase A metabolizes norepinephrize, serotonin and dopamine
Monoamine oxidase B metabolizes dopamine only
MOA: blocks DA metabolism by MAO-B
Agents: Selelgiline (eldepryl, zelapar); rasagiline (Azilect)
Uses: extends Ldopa duration of action–may provide up to 1 hr of “on” time.
Selegiline
MAO-B inhibi.
ADRs: N, dizziness, HA, insomnia, hallucinations. rare a. fib
Contraindications: meperidine ODT only: methadone, tramadol,,,,
Rasagiline
MAO-B inhibi
First line for managing motor fluctuations; may slow rate of disease progression in early stages.
ADRs: orthostatic hypotension, N/V/C, dyskinesia, HA, depression. Rare GI hemorrhage
CI: cyclobenzaprine, St john’s wart, methadone, tramadol, propoxyphene
COMT inhibitors
MOA: extend effects of l-dopa by inhibiting COMT induced metabolism
Agents: Entacapone-peripheral; Tolcapone: peripheral and central
ADRs: fatal hepatotoxicity (Tolcapone). orange/brown urine, delayed onset diarrhea. Dopaminergic ADRs may require l-dopa dose reduction
DI: nonselective MAOIs
Use: wearing off, rapid flutuations, reduces “off” time
Entacapone first line for motor fluctuations
Tolcapone reserves for non responders
Dopamine agonists
MOA: direct agonistic effects on dopaminergic D2 receptors
Oral: ergot derivatives (bromocriptime), non-ergots (pramipexole*, ropinirole)
Parenteral: apomorphine
Transdermal: rotigotine
Dopamine agonists ADRs
n, confusion, hallucinations, light-headed, LE edema, postural hypotension, sedation.
Serious: compulsive behavior, psychosis, sleep attacks, pleuropulmonary fibrosis (ergots)
Uses: non-ergots–initial monotx. Ldopa adjunct: may allow ldopa dose reduction, improve off periods, reduce motor fluctuations, allow additional coverage when high dose ldopa not tolerated.
