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Basic Science
Pharmacology
11 notes available
1 Last Minute Review 2 Neuropharmacology Principles 3 Antiepileptic Drugs 4 Movement Disorder Pharmacology 5 Neuromuscular Pharmacology 6 Headache Pharmacology 7 Pain & Anesthesia Pharmacology 8 Psychopharmacology 9 Stroke & Vascular Pharmacology 10 Immunotherapy & MS Pharmacology 11 Antimicrobials & CNS Infections
Basic Science › Pharmacology

Movement Disorder Pharmacology

Movement Disorder Pharmacology

What You'll Learn

  • Parkinson disease drug classes, mechanisms, and key side effects (levodopa motor complications, dopamine agonist impulse control disorders)
  • Management strategies for levodopa motor fluctuations (wearing off, on-off, dyskinesias) and the role of amantadine for dyskinesia
  • Drug-induced parkinsonism causes (typical antipsychotics, metoclopramide) and safe antipsychotics in PD (quetiapine, clozapine)
  • Drug-induced movement disorders: tardive dyskinesia (VMAT2 inhibitors), akathisia, acute dystonic reactions, and NMS
  • Huntington disease chorea treatment with VMAT2 inhibitors (tetrabenazine, deutetrabenazine)
  • Dystonia pharmacology: botulinum toxin for focal, anticholinergics for generalized, levodopa trial for DRD
  • Essential tremor first-line agents (propranolol, primidone) and spasticity management (baclofen, tizanidine, dantrolene)
  • NMS vs. serotonin syndrome — distinguishing features and management
HighYield Pearls
  • Tolcapone → fulminant hepatic failure: requires LFT monitoring q2–4 weeks × 6 months and informed consent; entacapone & opicapone are NOT hepatotoxic.
  • Dopamine agonist impulse-control disorders: pramipexole (D3) > ropinirole > rotigotine → pathologic gambling, hypersexuality, compulsive shopping, binge eating; ALWAYS screen at every visit.
  • Abrupt baclofen (especially intrathecal pump) withdrawal: fever + altered mental status + rebound spasticity + rhabdomyolysis + seizures → can be FATAL; restart oral bridge + benzodiazepines + cyproheptadine, address pump immediately.
  • Abrupt levodopa withdrawal or DA-blocker overdose: NMS-like / parkinsonism-hyperpyrexia syndrome → never stop L-dopa cold; resume + bromocriptine + dantrolene.
  • Apomorphine SC rescue: an antiemetic may be needed for nausea (trimethobenzamide, the classic pretreatment, is now discontinued/limited in the US); AVOID 5-HT3 antagonists such as ondansetron (severe hypotension) — a classic test vignette.
  • Tetrabenazine box warning: depression & suicidality (Huntington patients already at high risk); deutetrabenazine & valbenazine have less.
  • Botulinum toxin secondary non-response: neutralizing antibodies to onabotulinumtoxinA → switch to rimabotulinumtoxinB (different SNARE target: synaptobrevin instead of SNAP-25).
  • Avoid typical antipsychotics & metoclopramide in PD: pimavanserin is FDA-approved for PD psychosis (5-HT2A inverse agonist, NO D2 block); clozapine has strongest efficacy but needs ANC monitoring; quetiapine commonly used but mixed efficacy — not "safest"; for DLB all antipsychotics need caution (neuroleptic sensitivity + dementia mortality).
  • Anticholinergics (trihexyphenidyl, benztropine) in elderly: confusion, urinary retention, narrow-angle glaucoma, dental caries → AVOID; reserve for young dystonia/tremor.
  • Tofersen for SOD1-ALS: intrathecal antisense oligonucleotide; only ALS gene therapy — know the gene-drug pairing.
🔍 Quick ReferenceMechanism · Adverse effects · Special use / monitoring
Mechanism of action
  • Carbidopa → peripheral aromatic L-amino acid decarboxylase (DDC) inhibitor (does NOT cross BBB; reduces peripheral DA → less nausea/orthostasis)
  • Entacapone / opicapone / tolcapone → COMT inhibitors (prolong levodopa half-life; opicapone once-daily)
  • Selegiline / rasagiline / safinamide → selective MAO-B inhibitors (safinamide also blocks glutamate release)
  • Amantadine → NMDA antagonist + presynaptic DA release + mild anticholinergic
  • Tetrabenazine / deutetrabenazine / valbenazine → VMAT2 inhibitors (deplete presynaptic DA)
  • OnabotulinumtoxinA → cleaves SNAP-25; RimabotulinumtoxinB → cleaves synaptobrevin (VAMP) → block ACh release at NMJ
  • Pimavanserin → 5-HT2A inverse agonist with NO dopamine receptor activity (PD psychosis)
  • Baclofen → GABA-B receptor agonist (spinal & supraspinal)
  • Riluzole → Na-channel blocker + glutamate release inhibitor; Edaravone → free-radical scavenger; Tofersen → SOD1 antisense oligonucleotide
  • Onasemnogene abeparvovec → AAV9 SMN1 gene replacement (SMA); Nusinersen → intrathecal SMN2 splice-modifying ASO; Delandistrogene moxeparvovec → AAV9 micro-dystrophin (DMD)
Adverse effects
  • Livedo reticularis + ankle edema + visual hallucinations → amantadine
  • Impulse-control disorders (gambling, hypersexuality, shopping, binge eating) + sleep attacks → dopamine agonists (pramipexole)
  • Fulminant hepatic failure → tolcapone (entacapone & opicapone spare the liver)
  • Orange / brown urine discoloration → entacapone, opicapone
  • Cardiac valvular fibrosis → ergot DA agonists (pergolide — withdrawn; cabergoline — echo screen)
  • Insomnia + amphetamine-like metabolites → selegiline (rasagiline & safinamide do NOT)
  • Depression / suicidality + parkinsonism → tetrabenazine (boxed warning)
  • Fever + AMS + rebound spasticity + seizures + rhabdomyolysis → abrupt baclofen / intrathecal pump withdrawal
  • Serotonin syndrome with meperidine / tramadol / SSRIs → MAO-B inhibitors (esp. selegiline)
  • Confusion, urinary retention, dental caries, narrow-angle glaucoma in elderly → trihexyphenidyl, benztropine
  • Severe hypotension when combined with apomorphine → ondansetron (avoid — use trimethobenzamide)
Special use / monitoring
  • Only FDA-approved agent for levodopa-induced dyskinesia (EASE-LID) → amantadine ER (Gocovri)
  • Inhaled rescue for OFF episodes → Inbrija (inhaled levodopa); SC / sublingual OFF rescue → apomorphine (Apokyn / Kynmobi)
  • 24-hour continuous SC pump for advanced PD → Vyalev (foslevodopa-foscarbidopa)
  • Huntington chorea & tardive dyskinesia → VMAT2 inhibitors (tetrabenazine, deutetrabenazine, valbenazine)
  • PD psychosis without worsening motor symptoms → pimavanserin (also off-label DLB)
  • Cervical dystonia, blepharospasm, limb dystonia, chronic migraine (PREEMPT) → botulinum toxin (3–4 month duration)
  • Refractory spasticity (MS, SCI, CP) → intrathecal baclofen pump
  • SOD1 familial ALS — intrathecal antisense oligonucleotide → tofersen; modest survival benefit in ALS → riluzole + edaravone
  • Spinal muscular atrophy <2 yrs, one-time IV AAV9 → onasemnogene abeparvovec; intrathecal q4 months → nusinersen
  • Duchenne exon-skipping antisense → eteplirsen (exon 51), golodirsen / viltolarsen (exon 53), casimersen (exon 45)
  • LFT monitoring q2–4 weeks × 6 months → tolcapone; ANC monitoring weekly × 6 months → clozapine (PD psychosis option)
Parkinson Disease Pharmacology

Goal: Restore dopaminergic tone in the striatum. Drug selection depends on age, symptom severity, and side-effect profile.

Drug Class Agents Mechanism Key Points
Levodopa/Carbidopa Sinemet, Sinemet CR, Duopa (intestinal gel), Rytary (ER beads), Inbrija (inhaled), Vyalev (foslevodopa-foscarbidopa SC pump) Levodopa → dopamine in CNS; carbidopa blocks peripheral decarboxylation Most effective agent for motor symptoms; motor complications develop over time (wearing off, dyskinesias). Rytary (ER beads with multiple onset peaks for OFF reduction); Inbrija (inhaled levodopa for OFF rescue); Vyalev (foslevodopa-foscarbidopa SC pump, FDA Oct 2024) — 24-hour continuous SC infusion
Dopamine Agonists Pramipexole (D3 > D2), ropinirole (D2/D3), rotigotine (patch), apomorphine SC (Apokyn), Kynmobi (sublingual apomorphine film) for OFF rescue Direct stimulation of D2/D3 receptors Impulse control disorders (gambling, hypersexuality, shopping) — pramipexole has the highest association with ICDs among dopamine agonists due to strong D3 selectivity (frequently tested); hallucinations; somnolence/sleep attacks; leg edema
MAO-B Inhibitors Selegiline, rasagiline, safinamide Inhibit monoamine oxidase B → decrease dopamine breakdown Mild symptomatic benefit; used as monotherapy (early PD) or adjunct; safinamide also modulates glutamate; serotonin syndrome risk with SSRIs/meperidine. Selegiline metabolized to amphetamine/methamphetamine (insomnia at high doses); rasagiline and safinamide do NOT
COMT Inhibitors Entacapone, opicapone, tolcapone Block catechol-O-methyltransferase → prolong levodopa half-life Always used WITH levodopa; tolcapone → hepatotoxicity (requires LFT monitoring); entacapone is safer; Opicapone (Ongentys) — once-daily COMT inhibitor (no hepatotoxicity, unlike tolcapone); orange urine discoloration
Amantadine Amantadine, amantadine ER (Gocovri) NMDA receptor antagonist; also increases dopamine release Only FDA-approved drug for levodopa-induced dyskinesia; livedo reticularis; hallucinations; avoid in renal failure
Anticholinergics Trihexyphenidyl, benztropine Block muscarinic acetylcholine receptors in striatum Most useful for tremor-dominant PD in younger patients; avoid in elderly (confusion, urinary retention, constipation, cognitive impairment)
Adenosine A2A Antagonist Istradefylline Blocks adenosine A2A receptors on indirect pathway neurons Adjunct to levodopa for OFF episodes; does not increase dyskinesia significantly
💎 Board Pearl

Levodopa remains the most effective drug for PD motor symptoms. Carbidopa prevents peripheral conversion to dopamine (reducing nausea/hypotension) but does NOT cross the BBB. ≥75 mg/day carbidopa needed for full peripheral DDC inhibition; standard 25/100 TID just meets threshold (75 mg). Add Lodosyn (extra 25 mg carbidopa) for nausea.

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