Exam 4 Remediation – ANS & Related Agents

Module 7 – Autonomic Nervous System (ANS) Drugs

• Focus: management of cholinergic excess, muscarinic agonists / antagonists, urinary agents, central α₂-agonist, and an anti-parasitic.
• Acronyms / mnemonics used throughout:
  • DUMBELLS → classic signs of cholinergic toxicity (Diarrhea, Urination, Miosis, Bronchospasm/Bradycardia, Emesis, Lacrimation, Lethargy, Salivation).
  • DDUCCT → cluster of anticholinergic adverse effects (Dry mouth/Dry eyes, Urinary retention, Constipation, Confusion, Tachycardia).
  • "Clonidi-NE" → drug lowers NE (norepinephrine) through α₂ stimulation.
  • “Permethrin – p-arasite per-ishes” – parasite mnemonic.

Organophosphate (OP) / Cholinergic Crisis – Pharmacologic Rescue

• Pathophysiology
  • OP insecticides & nerve agents → irreversible AChE inhibition → ↑ ACh at muscarinic & nicotinic sites → DUMBELLS.
• First-line drug therapy
  • Atropine (high-dose, repeated) – muscarinic blockade.
  • Pralidoxime (2-PAM) – reactivates AChE if "aging" hasn’t occurred; treats nicotinic symptoms (fasciculations, weakness, paralysis).
  • Benzodiazepines (e.g., diazepam) for seizure prophylaxis.
• “DUMBELLS PROBLEM NEEDS A DUCT MEDICINE” – faculty reminder that a muscarinic antagonist (Atropine) & an AChE re-activator (Pralidoxime) are required.

Atropine (prototype anticholinergic / antimuscarinic)

• Therapeutic class: Antiarrhythmic, antidote.
• Mechanism: Competitive muscarinic receptor antagonist.
• Key indications
  • OP poisoning & other muscarinic agonist overdoses.
  • Mushroom poisoning (muscarine-containing species).
  • Nerve-gas exposure.
  • Symptomatic bradycardia (ACLS).
  • Pre-operative & palliative reduction of secretions.
• Contraindications
  • Acute angle-closure glaucoma.
  • Recent MI or uncompensated HF.
  • GI atony / ileus, severe ulcerative colitis.
  • Severe COPD (thickened secretions).
  • Down syndrome – exaggerated sensitivity.
• Adverse effects (DDUCCT cluster)
  • Mucosal & skin drying.
  • Constipation, urinary retention.
  • Tachycardia, ventricular fibrillation.
  • Photophobia, blurred vision, delirium → coma.
• “Atropine fever”
  • If given as anesthetic pre-med; blocks sweating → impaired heat dissipation → hyperthermia.
• Structural cousins: Scopolamine (greater CNS sedation, motion-sickness patch).

Global Anticholinergic Effects (Mnemonic Recap)

• Blind – mydriasis ⇒ photophobia, blurred vision.
• Mad – confusion, hallucinations, delirium.
• Hot – ↓ sweating ⇒ hyperthermia.
• Dry – mouth, eyes, skin, secretions.
• Red – cutaneous vasodilation, flushing.
• DD UC CT (Dry eyes / Dry mouth, Urinary retention, Constipation, Confusion, Tachycardia).

Direct-Acting Muscarinic Agonists

Bethanechol

• Therapeutic class: Urinary stimulants.
• MOA: Direct muscarinic receptor stimulation → ↑ detrusor tone & bladder pressure → voiding.
• Indications: Post-op urinary retention, neurogenic/atonic bladder.
• Contraindications
  • Mechanical urinary or GI obstruction.
  • Peptic ulcer disease (↑ HCl).
  • Asthma (bronchospasm risk).
  • Heart failure / hypotension.
• Adverse effects (opposite of anticholinergics; think DUMBELLS)
  • Bradycardia, hypotension.
  • Bronchoconstriction, ↑ secretions / sweating.
  • Abd cramping, diarrhea, GI upset.
  • Lacrimation, miosis, tearing.
• Related agents: Pilocarpine (glaucoma, xerostomia), Carbachol (ophthalmic).

Urinary Antispasmodics / Anticholinergics

Oxybutynin

• Therapeutic class: Urinary antispasmodic.
• MOA: Muscarinic receptor inhibition in bladder wall → relaxes detrusor → ↑ capacity & ↓ urgency.
• Indication: Overactive bladder (OAB) with urge incontinence.
• Contraindications
  • Angle-closure glaucoma.
  • Myasthenia gravis (exacerbates weakness).
  • Paralytic ileus.
  • Urinary / GI obstruction or retention.
• Adverse effects (DDUCCT): dry mouth/eyes, constipation, tachycardia, blurred vision, photophobia.
• Specials
  • Caution in pediatric & geriatric pts (CNS & cognitive effects).
  • Dose adjust / monitor in renal or hepatic impairment.

Central α₂-Adrenergic Agonist

Clonidine

• Therapeutic class: Antihypertensive.
• MOA: Stimulates central α₂ receptors → \downarrow sympathetic outflow → ↓ NE release (“Clonidi-NE”).
• Indications
  • Primary hypertension (especially resistant cases).
  • ADHD (extended-release).
  • Alcohol / narcotic withdrawal symptom control.
• Contraindications: Concurrent anticoagulant therapy, active bleeding disorders, systemic lupus erythematosus (SLE) – risk of hematologic ADRs.
• Adverse effects
  • Rebound hypertension if abruptly stopped (taper gradually).
  • Sedation, drowsiness, dry mouth.
• Monitoring: Baseline & periodic BP; teach to rise slowly (orthostasis).

Antiparasitic – Ectoparasite Therapy

Permethrin

• Therapeutic class: Topical antiparasitic.
• MOA: Penetrates parasite nervous system → sodium-channel blockade → paralysis & death in 1–2 days.
• Indications
  • Pediculosis capitis/corporis (lice).
  • Scabies (Sarcoptes scabiei).
• Contraindications: Inflamed / raw skin, breastfeeding (apply after feed or pump-and-dump).
• Adverse effects: Local pruritus, rash, transient burning/tingling.
• Administration pearls
  • Lice: Apply to clean, damp hair for 10 min; rinse; comb nits with fine comb.
  • Scabies: Apply from neck down (avoid eyes/mouth); leave the FULL prescribed time; itching may persist up to 3 weeks post-treatment (dead mite antigens).
  • Reinforce laundering of clothes/bedding, vacuum furniture, treat close contacts.

Integrative / Test-Taking Connections

• Cholinergic vs Anticholinergic Spectrum: Bethanechol (agonist) and Oxybutynin/Atropine (antagonists) produce opposite physiology; contrast their contraindications & ADRs for NCLEX exam stems.
• Heat Regulation: Atropine & Oxybutynin block sweating → monitor temperature, especially in pediatric & surgical pts.
• Withdrawal / Rebound Phenomena: Clonidine abrupt cessation → hypertensive crisis; Atropine infusion stoppage too soon in OP poisoning → symptoms recur.
• OP Exposure Scenarios: Know triad treatment:
  \text{Atropine} + \text{Pralidoxime (2-PAM)} + \text{Diazepam}
• Ethical / Public Health Note: Permethrin resistance emerging; stress correct application & environmental decontamination to prevent community spread.