Neurology Lecture Notes Flashcards

Parkinson's disease: overview, pathophysiology, and symptoms

  • Parkinson's disease (PD) is a progressive neurological disorder of the CNS with dopaminergic neuron impairment or death in the brain, leading to imbalanced neurotransmission.

  • Two key abnormal factors:

    • Low dopamine: slows movement, causes bradykinesia, poor motor control, and overall slowed movement.

    • Excess acetylcholine: contributes to rigidity and stiff muscles.

  • Common motor symptoms: tremor (often at rest), rigidity, bradykinesia, shuffling gait, poor motor coordination, postural changes, drooling, masked facies (reduced facial expression).

  • Non-motor features and functional impact: difficulty with activities of daily living (ADLs) such as walking, bathing, feeding; speech changes; emotional masking (reduced facial expression).

  • Video observation (described): predominantly left-sided rest tremor involving hands and feet; tremor most prominent at rest and improves somewhat with action; gait and speech changes observed.

  • Therapeutic goal in PD: restore balance by increasing dopamine and decreasing acetylcholine to improve motor function and ADLs.

  • Conceptual model: treat PD by “the opposite” of the disease mechanism — increase dopamine, decrease acetylcholine.

Pharmacologic strategies in PD: classes and rationale

  • Dopaminergic medications (increase dopamine activity in brain)

  • Anticholinergic medications (decrease acetylcholine activity to rebalance the dopamine–acetylcholine ratio)

  • Enzyme inhibitors to prevent dopamine breakdown (MAO inhibitors, COMT inhibitors) to increase synaptic dopamine

  • Dopaminergic agonists vs. medications that increase endogenous dopamine synthesis

  • Overall goal: relieve dyskinesias, bradykinesia, resting tremor, and rigidity to improve ADLs

Levodopa/carbidopa: cornerstone of therapy

  • Levodopa (precursor to dopamine) converted to dopamine in the brain and increases brain dopamine levels.

  • Carbidopa: peripheral decarboxylase inhibitor; prevents peripheral breakdown of levodopa, allowing more to reach the brain and reducing peripheral side effects.

  • Dosing concept: combination therapy leverages the brain-centrally active dopamine and peripheral protection; over time, wearing-off phenomena can occur as the dose cycle ends and effects wane.

  • Important dosing considerations:

    • Do not rely on high protein meals to optimize absorption; avoid meals high in protein around dosing because protein competes with levodopa for intestinal absorption.

    • Vitamin B6 (pyridoxine)-containing foods can reduce levodopa effectiveness by increasing peripheral decarboxylation; avoid foods high in B6 while on levodopa therapy.

    • Tyramine-containing foods and MAO inhibitors interactions (see MAO inhibitors) can complicate therapy; diet considerations apply especially with MAO-B inhibitors.

  • Wearing-off: loss of medication effect before next dose; can occur randomly and even at high doses; requires monitoring and plan B strategies.

  • Common adverse effects: nausea, vomiting, drowsiness; dyskinesias (exaggerated or involuntary movements), hypotension, tachycardia, hallucinations, and discoloration of sweat and urine.

  • Practical nursing/education points:

    • Take with food to reduce nausea.

    • Monitor for hypotension, dizziness, and syncope; instruct patients to rise slowly when ambulating.

    • Monitor for neuropsychiatric side effects (hallucinations, confusion).

    • Screen for dyskinesias and adjust therapy as needed; monitor for wearing-off and on-off phenomena.

    • Safety: assess driving ability and risk of falls during fluctuating motor control.

  • Important interactions and related drugs:

    • MAO inhibitors (MAO-B selective like selegiline) inhibit dopamine breakdown, augmenting effect but require dietary and drug interaction caution (tyramine-containing foods can precipitate hypertensive crises with non-selective MAO inhibitors).

    • Other dopaminergic agents (see below) can be used in combination or as monotherapy depending on disease stage and tolerability.

  • Notable drug combination example: Levodopa + Carbidopa formulation; conceptually: Levodopa provides dopamine precursor, Carbidopa protects it from peripheral metabolism.

Other dopaminergic medications and strategies
  • Dopamine agonists (mimic dopamine at receptors):

    • Examples: pramipexole, ropinirole. Can be used as monotherapy or in combination with levodopa/carbidopa.

    • Mechanism: directly stimulate dopamine receptors in the brain.

    • Often used earlier in disease or to reduce levodopa requirements.

    • Side effects: similar dopaminergic effects (nausea, dizziness, somnolence, confusion), impulse control issues, and orthostatic hypotension.

  • Amantadine (antiviral with anti-Parkinsonian effects)

    • Mechanism: increases dopamine release and/or inhibits reuptake; modest symptomatic benefit, often used early or adjunctively.

    • Side effects: CNS effects (dizziness, confusion, restlessness), dry mouth, urinary retention; anticholinergic-type effects in some patients.

  • Monoamine oxidase B (MAO-B) inhibitors

    • Example: Selegiline (and other MAO-B inhibitors not named in transcript).

    • Mechanism: inhibit MAO-B enzyme, reducing dopamine breakdown and increasing dopaminergic activity.

    • Practical notes: can cause insomnia if given late in the day; educate about interactions and dietary restrictions related to tyramine-containing foods (less pronounced with selective MAO-B inhibitors, but still relevant in some regimens).

  • Catechol-O-methyltransferase (COMT) inhibitors (enzyme that breaks down dopamine)

    • Rationale: block degradation of levodopa, prolonging its effect and increasing brain dopamine availability.

    • Examples (in general): entacapone, tolcapone. These drugs are typically added to levodopa/carbidopa therapy when wearing-off is problematic.

  • Anticholinergic medications for PD

    • Example: benztropine (cogentin).

    • Role: reduce acetylcholine activity to rebalance dopamine–acetylcholine, mitigating tremor and rigidity.

    • Side effects: classic anticholinergic dry effects (dry mouth, blurred vision, urinary retention, constipation, decreased sweating); CNS depression/drowsiness; confusion or memory issues, particularly in older adults.

    • Contraindications: glaucoma, urinary obstruction (prostatic hypertrophy), myasthenia gravis; caution in elderly.

  • Summary of PD medication strategy

    • Goal: increase dopamine, decrease acetylcholine to restore motor function and ADLs.

    • Common therapy sequences: Levodopa/Carbidopa as cornerstone therapy; introduce dopamine agonists or MAO-B inhibitors to optimize control and possibly reduce Levodopa dose; add COMT inhibitors for wearing-off; add anticholinergics for tremor/rigidity in select patients.

Non-pharmacologic and lifestyle considerations in PD care
  • Nutritional considerations:

    • Avoid high-protein meals around levodopa dosing to maximize absorption.

    • Avoid or limit pyridoxine (Vitamin B6) rich foods when taking levodopa, as B6 can reduce levodopa effectiveness.

    • Common B6-containing foods include whole grains, some greens, bananas, etc. Specific dietary guidance should be tailored.

  • Monitoring and safety

    • Monitor for wearing-off, dyskinesias, orthostatic hypotension, and psychiatric effects.

    • Educate family/caregivers to communicate changes in symptoms and to report new or worsened motor or cognitive symptoms.

  • Education on adverse effects and when to seek care

    • Recognize signs of possible adverse effects (extreme drowsiness, confusion, hallucinations, fainting, severe dyskinesias, uncontrolled movements) and contact healthcare provider.

    • Instruct patients about gradual changes and potential need for dose adjustments.

Seizures and antiepileptic drugs (AEDs)

  • Epilepsy basics

    • Epilepsy is defined by two or more seizures occurring within a period; seizures involve abnormal electrical activity in the brain.

    • Triggers can include fever, head trauma, infections, tumors, stroke; some cases are idiopathic. Some patients receive AEDs for prevention after events like stroke.

    • Sudden discontinuation of AEDs can precipitate seizures; medications are often continued long-term with gradual taper when appropriate.

  • Common AED categories and representative drugs

    • Hydantoins: Phenytoin (Dilantin)

    • Mechanism: stabilize nerve membranes by blocking sodium influx; reduces neuronal excitability.

    • Pharmacokinetics: well absorbed through GI tract; hepatic metabolism; therapeutic serum level: 10extto20extmcg/mL10 ext{ to } 20 ext{ mcg/mL}.

    • Toxicity signs: nystagmus, ataxia, double vision, sedation, cognitive changes; seizures may worsen if levels become toxic.

    • Additional adverse effects: gingival hyperplasia; skin rash (potential allergy); pretreatment oral hygiene recommended; cardiac arrhythmias or hypotension risk; decreased vitamin D metabolism (bone health risk); potential vitamin K interactions in infants; pregnancy risk (category D); not advisable in pregnancy; avoid abrupt withdrawal; dose adjustments needed in hepatic/renal impairment.

    • Monitoring: regular blood level checks, liver and kidney function tests; monitor for bone health (calcium/vitamin D).

    • Carbamazepine (Tegretol)

    • Class: anticonvulsant, mood stabilizer.

    • Key risk: hematologic suppression (leukopenia, anemia, thrombocytopenia) increasing infection and bleeding risk; hepatic enzyme induction (drug interactions common).

    • Other notes: CNS side effects; potential suppression of pregnancy contraception effectiveness; not ideal for breastfeeding.

    • Valproic acid (valproate)

    • Broad-spectrum AED; reduces electrical activity; used for various seizure types and some bipolar disorder cases.

    • Major risks: hepatotoxicity, thrombocytopenia, pancreatitis; teratogenic risk; monitor liver function tests; risk of pancreatitis and bleeding due to low platelets.

    • Lamotrigine (Lamictal, Lenictal)

    • Mood stabilizer and AED; generally well tolerated but can cause skin rash; risk of serious rash including Stevens–Johnson-like reactions; monitor for rash; dose adjustments needed.

    • Gabapentin (Neurontin)

    • AED with widespread use for neuropathic pain; mechanism not fully understood but acts on GABA-related pathways and reduces neuronal excitability.

    • Side effects: edema, weight gain, mood changes; dizziness, fatigue; may interact with alcohol; renal dosing adjustments may be needed.

    • Pregabalin (Lyrica)

    • Similar to gabapentin; faster absorption; controlled substance (C-5 in many jurisdictions).

    • Indications: neuropathic pain, anxiety, seizures adjunctively; side effects similar to gabapentin; monitor for edema, weight gain, CNS effects.

    • Levetiracetam (Keppra)

    • Broad-spectrum AED; IV option; binds SV2A to modulate neurotransmitter release and reduce excessive neuronal firing.

    • Side effects: CNS effects (dizziness, weakness, agitation); potential for allergic reactions including angioedema; hepatotoxicity possible; monitor for mood changes and suicidality; usually well tolerated.

    • Other agents mentioned briefly

    • Lenictal (lamotrigine) already covered; Keppra (levetiracetam) highlighted; Gabapentin and Pregabalin covered.

  • Clinical considerations for AED management

    • Therapeutic monitoring and dose adjustments based on clinical response and drug levels (especially phenytoin, carbamazepine).

    • Avoid abrupt discontinuation of any AED due to risk of withdrawal seizures; taper under supervision.

    • CNS depression is a common theme across AEDs and is a safety consideration for driving and operating machinery; assess patient status.

    • Pregnancy considerations: several AEDs have teratogenic potential; counsel regarding pregnancy planning and alternative strategies if applicable.

    • Special monitoring: blood dyscrasias with carbamazepine; liver function with valproic acid; blood level monitoring for phenytoin; liver/kidney function for several AEDs.

  • Practical patient education and safety

    • Driving and activities requiring alertness may be impaired; evaluate on an individual basis.

    • Take all AEDs as prescribed; do not stop abruptly; inform about possible withdrawal symptoms and the need for tapering.

    • Alerts and safety reminders: carry medical alert information if taking AEDs; recognize signs of an impending seizure and when to seek help.

    • Lipid and diet considerations: most AEDs interact with other drugs; inform healthcare provider about all medications and supplements.

Anxiolytics, hypnotics, and sleep-related medications

  • Benzodiazepines (anxiolytics and sedatives)

    • Role: reduce anxiety, provide sedation, and can be used as pre-procedure medication to induce relaxation.

    • Mechanism: potentiate GABA activity in the reticular activating system, leading to sedation and anxiolysis; in higher doses can induce hypnosis/sleep.

    • Pharmacokinetics and safety: absorbed well from GI tract; peak ~30 minutes; cross placenta; excreted in urine; caution in pregnancy and breastfeeding (unclear safety). In older adults, lower dosing is preferred due to increased sensitivity and fall risk.

    • Overdose reversal: flumazenil is the antidote for benzodiazepine overdose (note: transcript mentions Narcan in a delayed example, but naloxone (Narcan) reverses opioids, not benzodiazepines).

    • Contraindications and cautions: do not use with respiratory depression or glaucoma; avoid in concomitant alcohol use; avoid in pregnancy/breastfeeding when possible; elderly require conservative dosing.

    • Side effects and risks: CNS depression, confusion, dizziness, amnesia, dependence and withdrawal potential; tolerance can develop.

    • Common suffix cue for inhalation/normally prescribed anxiolytics: many end with -zolam (e.g., diazepam) or -pam (e.g., lorazepam).

  • Non-benzodiazepine sleep medications (Z-drugs)

    • Includes zolpidem (Ambien), zaleplon (Sonata), eszopiclone (Lunesta).

    • Mechanism: enhance GABA activity at GABA-A receptors but are not benzodiazepines; primarily for short-term treatment of insomnia.

    • Highlights: faster onset of sleep; risk of next-day sedation, dizziness, and cognitive effects; primarily for short-term use.

    • Important safety notes: avoid alcohol; elderly patients at higher risk of falls and confusion; do not drive after taking; pregnancy and breastfeeding considerations apply undefined safety.

    • Dosing and administration nuances: zolpidem may be taken with food to slow absorption and reduce morning sedation; avoid abrupt changes in sleep schedule.

  • Acute sedation and anesthesia context

    • Benzodiazepines and non-benzodiazepine sedatives may be used for preoperative anxiety or procedural sedation, with monitoring for respiratory depression.

Neuromuscular blocking agents and perioperative paralysis

  • Purpose and context

    • Used to facilitate anesthesia during surgery, intubation, and certain procedures by inducing skeletal muscle paralysis while the patient remains unconscious under anesthesia.

  • Non-depolarizing (quietly blocking) agents

    • Examples discussed: pancuronium (pan curonium), vecuronium.

    • Mechanism: block acetylcholine receptors at the neuromuscular junction, preventing depolarization and muscle contraction.

    • Clinical use: muscle relaxation for operative conditions; patient remains asleep under anesthesia.

    • Important safety notes: monitor cardiovascular and respiratory status closely; risk of respiratory arrest if ventilation is not managed.

  • Depolarizing (depolarizing) agent

    • Example discussed: succinylcholine.

    • Mechanism: initially depolarizes the receptor leading to transient fasciculations, followed by paralysis due to receptor blockade.

    • Characteristics: rapid onset; short duration, useful for rapid sequence intubation.

    • Side effects and risks: malignant hyperthermia (a life-threatening reaction with high fever and severe rigidity), hyperkalemia, bradycardia, bronchospasm; heightened concern in patients with neuromuscular conditions (e.g., myasthenia gravis) or asthma; significant risk with certain comorbidities.

  • Malignant hyperthermia: emergency management

    • Signs: severe muscle rigidity, hyperthermia.

    • Immediate actions: provide 100% oxygen, discontinue triggering agent, administer dantrolene (muscle relaxant) and implement cooling measures.

    • Monitoring: continuous vital signs and telemetry; ensure airway and ventilation support.

  • Contraindications and cautions for neuromuscular blockers

    • Not suitable for patients with asthma or myasthenia gravis (these conditions affect neuromuscular transmission and may worsen paralysis).

    • Caution in patients with significant hepatic or cardiac disease due to potential drug effects on heart rate and blood pressure; monitor closely for bradycardia and hypotension.

  • User notes and memory cues

    • The general principle: these drugs blunt acetylcholine signaling at the neuromuscular junction to prevent muscle contraction.

    • Anesthesiologists monitor patients closely; these agents are typically used in controlled surgical environments.

Practical nursing implications and test-preparation takeaways

  • PD-related nursing considerations

    • Recognize the signs of dyskinesia improvement with medication as a therapeutic success.

    • Watch for wearing-off and on-off phenomena; communicate changes promptly to the care team.

    • Educate patients about dietary interactions (protein and B6) with levodopa/carbidopa therapy.

    • Monitor for orthostatic hypotension and fall risk; implement safety measures for gait and mobility.

  • AED-related nursing considerations

    • Monitor for therapeutic levels where applicable (e.g., phenytoin at 10–20 μg/mL).

    • Watch for CNS side effects: dizziness, drowsiness, ataxia, confusion, and potential gait instability.

    • Monitor for hematologic toxicity with carbamazepine (leukopenia, anemia, thrombocytopenia) and for hepatic toxicity with valproic acid.

    • Screen for rash and potential Stevens–Johnson-like reactions with lamotrigine; stop the medication if a rash develops.

    • Avoid abrupt withdrawal of AEDs; plan gradual taper under clinician supervision.

  • Safety and patient education for anxiolytics/hypnotics

    • Advise against driving or operating machinery when taking benzodiazepines or Z-drugs until sedative effects are understood.

    • Emphasize the risk of dependence and withdrawal; taper rather than abrupt stopping.

    • Warn against combining with alcohol or other CNS depressants.

    • For benzodiazepine overdose (uncommon but serious): the recommended reversal agent is flumazenil (not always used in all settings; naloxone reverses opioid overdose).

  • Monitoring and follow-up priorities across therapies

    • Regular assessment of motor function, tremor, rigidity, bradykinesia, gait, and ADLs for PD.

    • Routine labs and monitoring for AED-associated adverse effects (LFTs for valproic acid, CBC for carbamazepine, etc.).

    • Ongoing patient and caregiver education about diet, adherence, and safety.

Quick reference: key numerical values and concepts

  • Levodopa-related dietary/interactions:

    • Avoid high-protein meals around dosing: protein competes with intestinal absorption of levodopa.

    • Avoid vitamin B6 (pyridoxine)-rich foods to prevent peripheral dopamine breakdown and reduce levodopa efficacy.

  • Phenytoin therapeutic level and toxicity threshold:

    • Therapeutic serum level: 10extto20μg/mL10 ext{ to } 20 \mu g/mL

    • Signs of toxicity: nystagmus, ataxia, double vision, sedation, confusion; gait instability.

  • MAO inhibitors (dietary cautions): tyramine-containing foods can precipitate hypertensive crises when combined with non-selective MAO inhibitors; selective MAO-B inhibitors have fewer dietary restrictions but caution still advised.

  • Anticholinergic dry effects (benztropine): dry mouth, blurred vision, urinary retention, constipation; decreased sweating; CNS effects (confusion, memory issues).

  • Malignant hyperthermia (neuromuscular blockers): emergency with severe hyperthermia and rigidity; treated with dantrolene and supportive measures.