Neurological System Pharmacology

Guiding Principle

  • Nurses administer medications to target manifestations of conditions.

General Overview of Pharmacology

  • Developmental Framework:

    • Know - therapeutic class, prototype, and mechanism of action

    • Understand - how and where the medication works, leading to the therapeutic and adverse effects.

    • Apply - ABCFOB (Monitoring, Assessment, Administration, Education, Evaluation) - and possibly prevent "happy little accidents."

    • Therapeutic Class: Prototype mechanism of action.

    • Effects: Therapeutic vs. Adverse.

Neurotransmitters

  • Glutamate: Excitatory neurotransmitter.

  • GABA: Inhibitory neurotransmitter in the brain.

  • Glycine: Inhibitory neurotransmitter in the spinal cord.

  • Acetylcholine:

    • Associated with memory and cognition (CNS).

    • Associated with contraction and secretion (the neuromuscular junction in the PNS).

  • Dopamine: Associated with smooth and purposeful muscle movement as well as the reward system.

  • Norepinephrine: Upregulating and stimulating neurotransmitter involved in many body processes, is both excitatory and inhibitory.

Neuromuscular Exemplar: Cerebral Palsy

  • Cerebral Palsy Definition: Permanent, non-progressive neuromuscular disorder caused by injury to brain tissue during development.

  • Patient Needs: Help with muscle spasticity, dystonia, and balance

  • Medication Role:

    • Enhances inhibitory GABA or glycine in the CNS.

    • Limits acetylcholine or calcium activity in the PNS.

  • Patient Explanation: "These medications try to help your body help your muscles relax."

Cerebral Palsy Pharmacology

All drugs to treat cerebral palsy have a downregulating effect

  • Benzodiazepines (e.g., Diazepam)

    • Mechanism: Enhances GABA to provide systemic "brakes."

    • Wanted Effect: Muscle relaxation.

    • Unwanted Effects: Severe sedation, dependency.

    • ABCFOB Risks: Monitor Airway/Breathing; keep Flumazenil ready for overdose.

  • GABA Analogs (e.g., Gabapentin)

    • Mechanism: Mimics GABA to quiet nerve signals.

    • Wanted Effect: Reduced nerve pain/spasms.

    • Unwanted Effects: Dizziness, somnolence.

    • ABCFOB Risks: High fall risk; monitor for organ damage (Renal/Kidney function).

  • Central Skeletal Muscle Relaxants (e.g., Baclofen)

    • Mechanism: Mimics spinal GABA to inhibit muscle contraction.

    • Wanted Effect: Improved range of motion, less pain.

    • Unwanted Effects: Weakness, seizure risk (if stopped abruptly).

    • ABCFOB Risks: If using intrathecal, monitor for organ function or pump failure.

  • Peripheral Skeletal Muscle Relaxants (e.g., Dantrolene)

    • Mechanism: Directly stops calcium release inside the muscle.

    • Wanted Effect: Localized muscle relaxation.

    • Unwanted Effects: Diarrhea, muscle weakness.

    • ABCFOB Risks: Monitor for fall risk; if used intrathecally, check for organ damage (Hepatotoxicity).

  • Neurotoxin (e.g, Onabotulinumtoxin)

    • Mechanism: Blocks acetylcholine release at the nerve ending

    • Wanted Effect: Targeted relaxation of stiff limbs

    • Unwanted Effects: local pain, systemic spread (rare)

    • ABCFOB Risks: Assess airway/breathing (swallow check) and monitor injection site for redness/swelling

  • Anticholinergics (e.g., Trihexyphenidyl)

    • Mechanism: Block acetylcholine to quiet tremors and drooling

    • Wanted Effect: Less drooling/tremors

    • Unwanted Effects: “dry effects” and urinary retention

    • ABCFOB Risks: Organ/brain damage (cognitive impairment and lowered seizure threshold)

General or Unique Considerations for Cerebral Palsy Medications

General Considerations

  • CNS depression and PNS weakening; risk for respiratory issues; fall hazards; all therapeutic effects should focus on decreasing dystonia/spasticity.

Unique Considerations

  • Diazepam: Severe sedation, dependency risk, respiratory caution, and requirement for an antidote.

  • Gabapentin: Monitor renal function.

  • Baclofen: Possibility of premature withdrawal, safety risks, and intrathecal pump malfunctions.

  • Dantrolene: Risk of cardiovascular collapse and hepatotoxicity.

  • Onabotulinumtoxin A: Injection site assessments; peripheral tissue risk; concerns with breathing and swallowing.

  • Trihexyphenidyl: Anticholinergic effects leading to dryness and lowered seizure thresholds; monitor cognitive function.

Neuromuscular Exemplar: Multiple Sclerosis

  • Multiple Sclerosis Definition: Chronic degenerative progressive autoimmune neuromuscular disorder characterized by the immune system attacking the myelin sheath of the CNS.

  • Patient Needs: Help with fatigue, weakness, spasticity, vision problems, and sensory disturbances.

  • Medication Role: Suppress or modulate the immune system to slow the attack on nerve insulation.

  • Patient Explanation: "We need to slow your body’s immune system down to curb its attack on your nerve insulation."

Multiple Sclerosis Pharmacology

  • Class Overview: Medications interfere with immune system function. Important to monitor blood, liver function, and mental health status.

  • Immunomodulator (e.g., Interferon beta-1a/1b)

    • Mechanism: “The shield” - stops immune cells from attacking myelin

    • Wanted Effect: fewer relapses

    • Unwanted Effects: Flu - like symptoms, depression

    • ABCFOB Risks: Monitor LFTS, CBC (low WBC and/or platelets), and skin (Stevens-Johnson syndrome). Mandatory screening for suicide/depression

  • Immunomodulator (e.g., Glatiramer Acetate)

    • Mechanism: “The decoy” - distracts immune cells to attack the drug, not the nerve

    • Wanted Effect: reduces relapse frequency

    • Unwanted Effects: post - injection flushing/chest pain

    • ABCFOB Risks: Assess for post - injection reaction (chest tightness). Monitor for jaundice/liver failure

  • Immunomodulator (e.g., Natalizumab)

    • Mechanism: “The gatekeeper” - blocks immune cells from entering the brain

    • Wanted Effect: high efficacy relapse control

    • Unwanted Effects: fatigue and headache

    • ABCFOB Risks: Black Box - Progressive Multifocal Leukoencephalopathy (PML). Monitor JC virus status and new neuro changes.

  • Immunosuppressant (e.g., Cladribine)

    • Mechanism: “The reset” - depletes specific T and B cells to reboost system

    • Wanted Effect: long-term remission

    • Unwanted Effects: Lymphopenia and infection risk

    • ABCFOB Risks: Monitor CBC for lymphopenia. Teratogenic (dual contraception 6 months after last dose)

  • Immunosuppressant (e.g., Mitoxantrone HCl)

    • Mechanism: “The heavy hitter” - kills overactive immune cells directly

    • Wanted Effect: stops rapid progression

    • Unwanted Effects: heart failure and hair loss

    • ABCFOB Risks: Black Box - Cardiotoxicity (echo/LVEF required before EVERY dose). Lifetime limit of 140 mg/m2

General or Unique Considerations for Multiple Sclerosis Medications

General Considerations

  • Risk for infection; avoid during acute illness; flu-like symptoms are common after start of treatment; injection risks include site irritation and extravasation from IV administration.

Unique Considerations

  • Interferons: Associated with a risk of suicidal ideation.

  • Glatiramer: Risk of liver failure and chest tightness after infusion.

  • Natalizumab: Risk involves PML and potential death from neurological causes.

  • Cladribine: Teratogenic effects necessitate dual birth control measures for 6 months.

  • Mitoxantrone HCl: Risk of cardiotoxicity/heart failure; monitoring ejection fraction before administration is crucial.

Neuromuscular Disorder: Neuropathy

  • Neuropathy Definition: Nerve dysfunction often caused by diabetes mellitus, vitamin B12 deficiency, or chemotherapy agents.

  • Patient Needs: Management of burning pain, stinging sensations, and hypersensitivity to touch.

  • Medication Role: Stabilizing nerve cell membranes or altering neurotransmitter impact in the CNS.

  • Patient Explanation: "We're trying to reduce the intensity of the bad signal or change it to something more tolerable."

Neuropathy Pharmacology

  • GABA Analog (e.g., Pregabalin)

    • Mechanism: “The muzzle” - modulates Ca+ channels to reduce release of pain-firing glutamate

    • Wanted Effect: reduced burning/zapping pain

    • Unwanted Effects: edema, weight gain, drowsiness

    • ABCFOB Risks: Respiratory depression risk, fall risk, potential renal and skin (Stevens-Johnson syndrome) damage, screen for suicide

  • Sodium Channel Blocker (e.g., Carbamazepine)

    • Mechanism: “The shield” - blocks Na+ channels to stop repetitive firing of pain signals

    • Wanted Effect: relief from trigeminal neuralgia

    • Unwanted Effects: ataxia, blurred vision, dizziness

    • ABCFOB Risks: Black Box - bone marrow suppression (bleeding risk) and Stevens-Johnson syndrome NO GRAPEFUIT JUICE

  • TCA (e.g., Amitriptyline)

    • Mechanism: “The mute button” - blocks reuptake of norepinephrine and serotonin to dull pain signals

    • Wanted Effect: improved sleep and pain relief

    • Unwanted Effects: “dry” effects, sedation

    • ABCFOB Risks: Cardiotoxicity (arrhythmias), fall risk (orthostatic hypertension)

  • SNRI (e.g., Duloxetine)

    • Mechanism: “The volume knob” - boosts serotonin and norepinephrine to calm the brain’s pain perception

    • Wanted Effect: reduced diabetic/chronic pain

    • Unwanted Effects: nausea, sweating, dry mouth

    • ABCFOB Risks: Liver toxicity (LFTs) and skin damage (Stevens-Johnson syndrome), serotonin syndrome, suicide risk, increased bleeding risk with anticoagulants

General or Unique Considerations for Neuropathy Medications

General Considerations

  • Increased fall risk due to CNS depression and potential drying side effects.

Unique Considerations

  • Pregabalin: Can cause lower extremity edema, kidney issues, and Stevens-Johnson syndrome; also carries a suicide risk.

  • Carbamazepine: Associated with drug reactions like SJS, DRESS, bone marrow suppression, and potential for liver impairment; patient counseling on avoiding grapefruit juice is needed.

  • Amitriptyline: Possible heart arrhythmias as a side effect.

  • Duloxetine: Risk of SJS, serotonin syndrome, and bleeding complications.

Neuromuscular Disorders: Parkinson’s Disease

  • Parkinson’s Disease Definition: Progressive neuromuscular disorder resulting from the degeneration of dopamine-producing cells deep in the brain, leading to dopamine deficiency and excessive acetylcholine activity.

  • Patient Needs: Assistance with TRAP (Tremor, Rigidity, Akinesia/bradykinesia, Postural instability) manifestations.

  • Medication Role: Increasing dopamine availability, acting as dopamine mimetics, preventing dopamine breakdown, and reducing acetylcholine effects.

Parkinson's Pharmacology

  • Dopaminergic (e.g., Carbidopa-levodopa)

    • Mechanism: “The oil” - converts to dopamine; carbidopa acts as the “bodyguard.”

    • Wanted Effect: reduced rigidity/bradykinesia

    • Unwanted Effects: nausea and dyskinesia

    • ABCFOB Risks: orthostatic hypotension, glaucoma (intraocular pressure), monitor LFTs, do not administer with a high protein meal

  • MAO-B inhibitor (e.g., selegiline)

    • Mechanism: “the preserver” - tops dopamine breakdown to extend levodopa

    • Wanted Effect: Improved motor control

    • Unwanted Effects: insomnia and oral irritation

    • ABCFOB Risks: Hypertensive crisis (tyramine) and potential serotonin syndrome

  • Dopamine Agonist (e.g., Pramipexole)

    • Mechanism: “The key” - Direct stimulation of dopamine receptors.

    • Wanted Effect: Improvement in TRAP symptoms.

    • Unwanted Effects: Sleep attacks, psychosis, compulsive behaviors.

    • ABCFOB Risks: Sudden sleep episodes and potential fall risks.

  • Anticholinergic (e.g., Benztropine)

    • Mechanism: Blocks acetylcholine to reduce tremors and drooling.

    • Wanted Effect: Decreased tremors and drooling.

    • Unwanted Effects: “I can’t see, I can’t pee, I can’t spit, I can’t shit.”

    • ABCFOB Risks: tachycardia, urinary retention, amd gluacoma risk

General or Unique Considerations for Parkinson’s Medications

General Considerations

  • Increased fall risk due to orthostatic hypotension, bradykinesia, and dyskinesia; Increased psychosis risk and behavioral changes/impulse control problems; Timing is critical; do not stop abruptly.

Unique Considerations

  • Carbidopa-Levodopa: Orthostatic hypotension; dyskinesias; nausea; “on-off” phenomenon; avoid high-protein meals; monitor LFTs and intraocular pressure; hallucination risk; do not abruptly discontinue.

  • Selegiline: Risk of hypertensive crisis with tyramine; serotonin syndrome potential (avoid SSRIs/TCAs/St. John’s Wort); insomnia (administer in morning); monitor blood pressure.

  • Pramipexole: Sudden sleep attacks; impulse control disorders (gambling, hypersexuality, binge eating); hallucinations/psychosis; orthostatic hypotension and fall risk; taper gradually.

  • Benztropine: Anticholinergic effects (blurred vision, dry mouth, constipation, urinary retention); tachycardia; confusion/delirium in older adults; glaucoma risk; heat intolerance; monitor urinary output and cognitive status.

Seizure Disorders

  • Definition: Seizure disorders involve excessive CNS excitability, leading to sequenced neuron output with involuntary behavioral or physical manifestations (focal, generalized, or both).

  • Patient Needs: Control, reduce the frequency of, and/or stop the recurrence of episodes.

  • Medication Role: Address neurotransmitter imbalances (GABA, glutamate) or stabilize cell membrane ion channels (sodium, calcium).

  • Important Terms: Threshold, aura, tonic, clonic, ictal.

Seizure Pharmacology

  • Sodium Channel Inhibitor (e.g., Phenytoin)

    • Mechanism: “The gatekeeper” - Limits seizure propagation by modulating voltage-gated sodium channels.

    • Wanted Effect: Cessation of seizures.

    • Unwanted Effects: Gingival hyperplasia, nystagmus, ataxia, and slurred speech.

    • ABCFOB Risks: administer via IV, ne percipitates, separate from tube feeds by 2 hours, monitor for suicide risk, increase dental care

  • Sodium Channel Inhibitor (e.g., Carbamazepine)

    • Mechanism: “The shield” - blocks sodium channels to decrease synaptic transmission in the CNS

    • Wanted Effect: relief from trigeminal Neuralgia and seizures

    • Unwanted Effects: blurred vision and urinary retention

    • ABCFOB Risks: Black Box - bone marrow suppression (bleeding risk) and Stevens-Johnson syndrome NO GRAPEFUIT JUICE

  • Sodium Channel Inhibitor (e.g., Oxcarbazepine)

    • Mechanism: “The Neural Blocker” - specifically blocks Na+ channels in the neural membranes

    • Wanted Effect: reduced seizure incidence

    • Unwanted Effects: hyponatremia, hypothyroidism, acne, diplopia

    • ABCFOB Risks: Monitor ECG (heart block); monitor for severe low sodium; use barrier form of contraception (inactivates hormonal contraceptive); suicide risk

  • GABA Analog (e.g., Pregabalin)

    • Mechanism: “The Muzzle” - Inhibits neurotransmitter release by binding to calcium channels.

    • Wanted Effect: Decreased focal seizures

    • Unwanted Effects: Weight gain, peripheral edema, somnolence.

    • ABCFOB Risks: High risk for respiratory depression; monitor PR interval; Monitor plateletes and creatine kinase.

  • GABA Augmenting Agent (e.g., Valproic acid)

    • Mechanism: “The Volume Booster” - Increases GABA levels to suppress electrical activity

    • Wanted Effect: suppressed seizure activity

    • Unwanted Effects: alopecia, weight gain, tremors, peripheral edema

    • ABCFOB Risks: Toxicity in the liver and pancreas; thrombocytopenia; do not administer with milk or carbonated drinks

  • Benzodiazepine (e.g., Lorazepam)

    • Mechanism: “The fire extinguisher” - GABA receptor agonist; shuts down firing immediately

    • Wanted Effect: Immediate stop for status epilepticus.

    • Unwanted Effects: Profound sedation, weakness, and confusion

    • ABCFOB Risks: respiratory depression (apnea); hypotension/cardiac arrest; misuse potential; never stop abruptly

Attention / Neurocognitive Disorders

  • Conditions: Attention Deficit Hyperactivity Disorder (ADHD), Major Neurocognitive Disorder (dementia).

  • Patient Needs: Assistance with inattention, deficits in development, negative behaviors, cognition, awareness, focus, and memory.

  • Medication Role: Increase availability or activity of norepinephrine, dopamine, and acetylcholine through various mechanisms (preventing reuptake, increasing availability, targeting receptors).

ADHD Pharmacology

  • CNS Stimulants (e.g., Methylphenidate [Ritalin], Dextroamphetamine-amphetamine [Adderall])

    • Mechanism: Increases norepinephrine and dopamine, enhancing focus and reducing hyperactivity.

    • Wanted Effect: Improved focus; reduced hyperactivity; better impulse control.

    • ABCFOB Risks: Tachycardia, hypertension, anorexia; growth suppression concerns.

  • SNRI - Non-Stimulant (e.g., Atomoxetine [Strattera], Viloxazine [Qelbree])

    • Mechanism: Selectively boosts norepinephrine availability to improve concentration without “the high”.

    • Wanted Effect: Improved focus; low abuse potential.

    • ABCFOB Risks: Hepatotoxicity, increased heart rate/blood pressure; suicidal ideation; increased HR and Blood pressure

  • Alpha-2 Agonist (e.g., Guanfacine [intuniv], Clonidine [Kapvay])

    • Mechanism: Activates the alpha-2 receptors and calms the sympathetic “fight or flight’ response in the brain

    • Wanted Effect: Reduced aggression and hyperactivity, often used as an adjunct to stimulants

    • ABCFOB Risks: Severe hypotension and bradycardia; profound sedation; dry mouth and constipation

  • Atypical Antidepressant (e.g., Bupropion [Wellbutrin])

    • Mechanism: Inhibits reuptake of norepinephrine and dopamine

    • Wanted Effect: Improved mood and focus; used off-label for ADHD when stimulants are contraindicated

    • ABCFOB Risks: Seizure risk; weight loss/anorexia; insomnia and agitation

Major Neurocognitive Disorder (Dementia) Pharmacology:

  • Cholinesterase Inhibitor (e.g., Donepezil)

    • Mechanism: Inhibits acetylcholine breakdown, increasing activation at synapses.

    • Wanted Effect: Slows cognitive decline, maintains functional ability temporarily.

    • ABCFOB Risks: Bradycardia, dizziness, high fall risk; monitoring for cholinergic crisis is critical.

  • NMDA Receptor Antagonist (e.g., Memantine)

    • Mechanism: Prevents overstimulation of NMDA receptors to reduce neuronal burnout.

    • Wanted Effect: Slows functional decline in moderate-to-severe Alzheimer's.

    • ABCFOB Risks: Risk for nephrotoxicity; requires dose modifications in renal impairment.

  • Monoclonal Antibody (e.g., Lecanemab)

    • Mechanism: Clears amyloid plaques in the brain.

    • Wanted Effect: Slowed clinical decline in early-stage Alzheimer's.

    • Unwanted Effects: Risk of ARIA (brain swelling) and microhemorrhages (requires regular MRI)

Neurosensory Disorders

  • Conditions: Vertigo (e.g., Meniere’s Disease, BPPV), Wet Age-Related Macular Degeneration.

  • Patient Needs: Prevention or cessation of vertigo episodes; address vision loss in AMD.

  • Medication Role: Reduce inflammation, manage infection triggers; in AMD, prevent vascular growth with injections.

Vertigo Pharmacology:

  • Antihistamine (e.g., Meclizine)

    • Mechanism: Acts as an H1 receptor blocker; inhibits vestibular pathways in the brain to dampen the sensation of motion and spining

    • Wanted Effect: Reduced vertigo, nausea, and vomiting associated with movement or inner ear disorders

    • ABCFOB Risks: Tachycardia; Anticholinergic toxicity (urinary retention and dry mouth); Profound sedation; increased fall/injury risk; impairs mental alertness

  • Corticosteroid (e.g., Prednisone)

    • Mechanism: Reduces inflammation by decreasing immune response and capillary permeability to decrease inner ear swelling

    • Wanted Effects: reduced ear fullness, improved hearing, and decreased vertigo

    • ABCFOB Risks: Hypertension and edema; hyperglycemia (monitor blood glucose); behavioral changes

  • Diuretic (e.g., hydrochlorothiazide)

    • Mechanism: Inhibits sodium reabsorption, reducing total fluid volume and endolymphatic pressure.

    • Wanted Effects: Decreased frequency and severity of vertigo attacks

    • ABCFOB Risks: Orthostatic hypotension; hypokalemia; dizziness

Macular Degeneration Pharmacology:

  • Anti-VEGF (e.g., Ranibizumab)

    • Mechanism: blocks the signal for “leaky” new blood vessel growth in the retina

    • Wanted Effects: Stabilization or improvement of vision; reduced renal edema/leakage

    • ABCFOB Risks: monitor for thromboembolic events and severe internal eye infection.

  • Anti-VEGF (e.g., Aflibercept)

    • Mechanism: binds and inhibits VEGF to prevent unexpected vessel growth in the eye

    • Wanted Effects: Preserves vision and reduces retinal swelling

    • ABCFOB Risks: Increased intraocular pressure and injection site infections are concerns.