ANS Pharmacology – Sympathetic & Parasympathetic Drugs

Autonomic Nervous System (ANS) – High-Yield Overview

• Two automatic, involuntary branches control most visceral organs, operating largely without conscious thought to maintain homeostasis.

  • Sympathetic (SNS) – “fight or flight” / high & dry

    • Prepares the body for stressful situations: increases heart rate, dilates pupils, inhibits digestion.

  • Parasympathetic (PNS) – “rest & digest” / wet, moist & mucusy

    • Promotes body calming: slows heart rate, constricts pupils, stimulates digestion.

• Core neurotransmitters, essential for chemical signaling within the ANS:

  • SNS ⇒ epinephrine (Epi) & norepinephrine (NE) – primarily at target organs (postganglionic).

  • PNS ⇒ acetylcholine (ACh) – at all ganglia and parasympathetic postganglionic synapses.

Primary Receptor Families

(know location, action, & memory cue)

• Adrenergic (SNS) – Receptors that bind epinephrine and norepinephrine.

  • $\alpha_1$ – Located primarily on Arteries (A for A) and other smooth muscles (e.g., bladder neck, prostate, pupils).

    • Action: Causes vasoconstriction, leading to ↑BP; also causes mydriasis (pupil dilation) due to radial muscle contraction.

  • $\beta_1$ – Predominantly in the 1 heart.

    • Action: Increases heart rate, contractility, and conduction velocity (dromotropy), leading to increased cardiac output.

  • $\beta_2$ – Found in 2 lungs (bronchial smooth muscle), skeletal muscle arteries, uterine muscle, and liver.

    • Action: Causes bronchodilation, vasodilation in skeletal muscle (improving blood flow for muscle activity), uterine relaxation, and promotes hepatic glycogenolysis (↑ blood glucose for energy).

• Cholinergic (PNS) – Receptors that bind acetylcholine.

  • Muscarinic – Primarily located on parasympathetic target organs (e.g., glands, smooth muscles, heart).

    • Think “mucus” because they mediate effects like ↑ secretions (saliva, sweat, GI), ↑ GI/GU motility, and pupil constriction (miosis) through circular muscle contraction.

  • Nicotinic – Located in all autonomic ganglia (both SNS and PNS) and at the Neuromuscular Junction (NMJ) on skeletal muscle.

    • Less direct drug-test focus for autonomic drugs, but crucial for signal transmission to postganglionic neurons and skeletal muscle contraction.

Organ-by-Organ Effect Chart

Mnemonic for SNS activation:

“Can’t see, can’t spit, can’t poop, can’t pee.” (This applies when SNS is dominant or anticholinergic drugs are given).

Drug-Class Map

• Agonist = "stimulate the receptor" – These drugs bind to and activate receptors, mimicking the effect of endogenous neurotransmitters.

  • Adrenergic agonist ⇒ Mimic SNS effects (synonym = sympathomimetic).

  • Cholinergic agonist ⇒ Mimic PNS effects (synonym = parasympathomimetic).

• Antagonist = "block the receptor" – These drugs bind to receptors but do not activate them, preventing endogenous neurotransmitters from binding and thus blocking their effects.

  • Adrenergic antagonist ⇒ Block SNS effects → leading to PNS-type effects.

    • (aka alpha-/beta-blockers)

  • Cholinergic antagonist ⇒ Block PNS effects → leading to SNS-type effects.

    • (aka anticholinergics or parasympatholytics).

Adrenergic Agonist Prototype – Epinephrine

• Receptor profile: Non-selective, meaning it stimulates most adrenergic receptors: $\alpha<em>1$, $\beta</em>1$, $\beta_2$. This broad action contributes to its diverse clinical effects.

• Routes: Can be given IV (for rapid, systemic effect in emergencies like cardiac arrest), IM (for anaphylaxis), SQ (less common for acute emergencies), endotracheal (ET) (alternative route during cardiac arrest if IV/IO is not accessible).

  • Code dose is usually $1\,\text{mg}$ IV push every 3-5 minutes.

• Half-life: Very short (t_{1/2} < 5\,\text{min}). Requires continuous monitoring and often continuous infusion due to rapid metabolism.

• Key uses

  • Anaphylaxis / anaphylactic shock: Potent bronchodilator ($\beta<em>2$) and vasoconstrictor ($\alpha</em>1$), reversing hypotension and bronchospasm.

  • Cardiac arrest (VF/VT/asystole/PEA): Improves coronary and cerebral perfusion via vasoconstriction ($\alpha<em>1$) and increases heart rate/contractility ($\beta</em>1$).

  • Severe status asthmaticus / bronchospasm: Provides powerful bronchodilation when other agents fail.

  • Profound hypotension / cardiogenic shock: Increases systemic vascular resistance ($\alpha<em>1$) and cardiac output ($\beta</em>1$) to raise blood pressure.

• Physiologic goals

  • $\alpha_1$ ⇒ Profound vasoconstriction (increases SVR & BP, redirects blood to vital organs).

  • $\beta_1$ ⇒ Increases HR and myocardial contractility, thereby increasing cardiac output (CO) and improving organ perfusion.

  • $\beta_2$ ⇒ Bronchodilation (relieves respiratory distress) and can also increase blood glucose.

• Adverse effects – Due to its widespread receptor activation:

  • Tachyarrhythmias (e.g., ventricular tachycardia, fibrillation) due to cardiac $\beta_1$ stimulation.

  • Hypertensive crisis due to excessive $\alpha_1$ vasoconstriction.

  • Hyperglycemia due to hepatic glycogenolysis via $\beta_2$ activation.

  • ↓ renal perfusion (due to significant vasoconstriction, potentially leading to acute kidney injury).

  • Extravasation necrosis if IV infiltrates, as it causes severe local vasoconstriction and tissue ischemia.

• Drug interactions

  • Tricyclic Antidepressants (TCA) & Monoamine Oxidase Inhibitors (MAOI) ⇒ Potentiate Epi's effects, leading to exaggerated hypertensive and tachycardic responses due to inhibition of NE reuptake or metabolism.

  • $\beta$-blockers ⇒ Attenuate (reduce) Epi's $\beta$ effects, potentially worsening bronchospasm or bradycardia, as beta-blockers occupy the $\beta$ receptors.

  • Digoxin ⇒ ↑ dysrhythmia risk when used concurrently with epinephrine due to combined effects on cardiac excitability.

• Nursing priorities

  • Continuous ECG & BP monitoring: Essential due to the drug's potent cardiovascular effects and short half-life.

  • Large-bore $18–20\,\text{G}$ IV access: For rapid administration and to minimize risk of extravasation; prefer central line if possible.

  • Monitor urine output: Output < $30\,\text{mL h}^{-1}$ indicates ↓ renal perfusion and potential kidney injury; strict I&O is critical.

  • Treat extravasation with phentolamine: An $\alpha_1$ blocker (antidote) injected locally to reverse vasoconstriction and prevent tissue necrosis.

• Patient teaching (EpiPen) – Crucial for patients with severe allergies.

  • Inject into mid-outer thigh (even through clothing) immediately PRN allergy symptoms. Hold for $5–10\,\text{s}$ to ensure full dose delivery.

  • Call 911 immediately after auto-injector use, even if symptoms improve, as a second reaction (biphasic reaction) can occur.

  • Store in a cool, dark place; discard if solution appears pink/brown/cloudy or contains particulates.

  • Use no more than 2 doses per week without consulting a healthcare provider, to avoid excessive adrenergic stimulation.

Adrenergic Antagonists – Beta Blockers

Classification tip

• Names beginning with A → M (e.g., atenolol, metoprolol) are generally selective $\beta<em>1$ blockers (cardioselective). They primarily block $\beta</em>1$ receptors in the heart, leading to less respiratory side effects.

• Names beginning with N → Z (e.g., nadolol, propranolol) are typically non-selective $\beta<em>{1+2}$ blockers. They block both cardiac $\beta</em>1$ and pulmonary/vascular $\beta_2$ receptors, increasing the risk of bronchospasm in susceptible patients.

Prototype – Atenolol

• Selectivity: Primarily targets $\beta_1$ receptors only (cardioselective) at typical doses. This means it has little/no pulmonary effect, making it generally safer in patients with asthma or COPD, though caution is still advised.

• Indications: Widely used for hypertension (HTN), stable angina pectoris, post-MI (to reduce cardiac workload and prevent remodeling), chronic heart failure (reduces morbidity/mortality in stable patients), and certain tachydysrhythmias.

• Mechanism:

  • ↓ HR & ↓ contractility: By blocking $\beta_1$ receptors in the heart, it reduces myocardial oxygen demand.

  • Suppress $RAAS$ (Renin-Angiotensin-Aldosterone System): Inhibits renin release from the kidneys, which ultimately leads to ↓BP.

• Side effects:

  • Bradycardia & hypotension: Direct consequences of cardiac $\beta_1$ blockade.

  • Fatigue & depression: Common CNS effects, potentially due to reduced cardiac output or direct CNS effects.

  • Impotence: A common, underreported side effect that can affect adherence.

  • Masking of hypoglycemia: Blocks adrenergic symptoms (tachycardia, tremors) that warn diabetic patients of low blood sugar, leading to hypoglycemic unawareness.

• Contra-/Caution:

  • Heart rate < $60$ bpm, 2°/3° AV block (can worsen conduction abnormalities).

  • Acute decompensated heart failure (can depress myocardial function).

  • Severe depression (can exacerbate symptoms).

  • Use carefully in diabetes due to the risk of hypoglycemic unawareness.

• Nursing:

  • Check HR/BP prior to administration: Hold for HR < 60 bpm or SBP < 100 mmHg per parameters.

  • Monitor glucose levels carefully in diabetics.

  • Taper over $1–2\,\text{wks}$: Abrupt withdrawal can cause rebound hypertension, angina, or MI due to hypersensitivity of adrenergic receptors.

Alpha Blockers (brief)

• Drugs typically end in “-sin” (e.g., prazosin, terazosin, doxazosin).

• Mechanism: Block peripheral $\alpha_1$ receptors on blood vessels, leading to vasodilation and a subsequent ↓BP.

• Additional use: Also relax smooth muscle in the prostate and bladder neck, making them useful for improving urine flow in Benign Prostatic Hyperplasia (BPH).

• Key side effect: Orthostatic hypotension (first-dose effect), so advise patients to take the first dose at bedtime.

Cholinergic Agonists

Prototype – Bethanechol

• Receptor: Selectively targets muscarinic receptors.

• Primary use: Treatment of urinary retention (non-obstructive, e.g., post-operative, post-partum, or neurogenic bladder). It works by directly contracting the detrusor muscle of the bladder and relaxing the trigone and sphincter, facilitating voiding.

• Secondary actions (undesirable effects due to systemic muscarinic stimulation): Increased GI motility and secretions, bronchoconstriction, miosis, increased salivation, sweating.

• Adverse effects: Hypotension (vasodilation), bradycardia, bronchospasm (especially in asthma/COPD patients), excessive salivation, abdominal cramps, diarrhea.

• Contraindications: Asthma/COPD (risk of severe bronchospasm), bradycardia, peptic ulcer disease (PUD, due to increased gastric acid), GI/GU obstruction (can cause rupture if flow is blocked).

• Antidote for overdose: Atropine $0.6–1\,\text{mg}$ IV (a muscarinic antagonist) to reverse severe cholinergic effects.

Prototype – Pilocarpine

• Dosage form: Primarily used as ophthalmic drops.

• Indication: Treatment of glaucoma (both open-angle and acute angle-closure). It reduces intraocular pressure (IOP).

• Mechanism: Causes miosis (pupil constriction) by contracting the iris sphincter muscle. This action mechanically opens the trabecular meshwork (Schlemm’s canal), which facilitates increased outflow of aqueous humor, thereby decreasing IOP.

• Local effects: Transient blurred vision and brow ache are common initially; systemic cholinergic effects are rare with ophthalmic use but can occur with high doses or systemic absorption.

Cholinergic Antagonists (Anticholinergics)

Prototype – Atropine

• Actions: Blocks muscarinic receptors throughout the body, thereby inhibiting PNS effects.

  • ↑HR (vagolytic effect): Blocks the vagal (parasympathetic) input to the heart, leading to increased heart rate.

  • ↓secretions: Reduces saliva, sweat, bronchial secretions.

  • Bronchodilation: Relaxes bronchial smooth muscle.

  • Mydriasis & cycloplegia: Dilates pupils and paralyzes the ciliary muscle, preventing accommodation.

• Clinical uses

  • Symptomatic bradycardia: First-line drug to increase heart rate in hemodynamically unstable bradycardia.

  • Pre-op to dry secretions / prevent aspiration: Reduces respiratory and salivary secretions before surgery, especially in situations where aspiration risk is high.

  • Ophthalmic mydriasis for eye exam: To facilitate fundoscopic examination.

  • ANTIDOTE for muscarinic agonist or organophosphate toxicity: Reverses symptoms of cholinergic overdose (e.g., from nerve gas, insecticides, or drugs like Bethanechol, which cause excessive salivation, bradycardia, etc.).

• Side effects (dose-dependent and related to PNS blockade): Dry mouth (xerostomia), blurred vision (cycloplegia), urinary retention, constipation, tachycardia, and at high doses, CNS effects like delirium, hallucinations, and confusion (especially in the elderly).

• Contraindications: Narrow-angle glaucoma (can precipitate acute attacks by further dilating pupils), benign prostatic hyperplasia (BPH, risk of urinary retention), paralytic ileus (can worsen bowel obstruction), tachyarrhythmias (as it increases HR).

Tolterodine

• Indication: Used to treat overactive bladder (OAB) and urge incontinence, characterized by sudden, strong urges to urinate.

• Effect: Selectively blocks muscarinic receptors in the bladder detrusor muscle, leading to ↓ detrusor contractions. This reduces urinary frequency and urgency, thereby mitigating incontinence episodes.

• Tip: “Tolterodine Tartrate = TT → ‘Tinkle Tamer’ ” for memory.

Benztropine

• Indication: Chiefly used in Parkinson’s disease (to reduce tremor and rigidity) and for treating drug-induced extrapyramidal symptoms (EPS) caused by antipsychotics (e.g., dystonia, parkinsonism, akathisia).

• Mechanism: Acts as a central muscarinic receptor antagonist, helping to restore the dopamine (DA)/acetylcholine (ACh) balance in the basal ganglia. In Parkinson's, excess ACh contributes to symptoms when DA is deficient; blocking ACh reduces these effects.

Shared Anticholinergic Teaching

• Treat dry mouth (xerostomia): “Dry = Try” – use ice chips, sugar-free candy/gum, frequent oral care, and artificial saliva products.

• Manage constipation: Increase dietary fiber and fluid intake; monitor I&O and stool patterns.

• Avoid overheating: Anticholinergics cause anhidrosis (decreased sweating), impairing the body's ability to cool itself, leading to hyperthermia risk.

• Use sunglasses: Mydriasis (pupil dilation) causes photophobia (light sensitivity).

Nursing Process Summary (All Agents)

• Assessment

  • Vital Signs (VS): Baseline HR, BP, respiratory rate, temperature.

  • Focused System Exam: Assess lung sounds (for bronchospasm/dilation), GU pattern (urine output, voiding difficulties), neurological status (alertness, orientation, for CNS effects).

  • Medication & Allergy History: Identify concurrent use of OTC decongestants, antihistamines, or other drugs that impact ANS, as these can alter drug effects or increase side effect risk.

  • Baseline Labs: Glucose (especially for beta-blockers, Epi), renal/hepatic function (for drug elimination), ECG when indicated (for drugs affecting cardiac rhythm/conduction).

• Interventions

  • Continual monitoring: For desired therapeutic responses (e.g., improved BP, reduced HR) versus adverse responses (e.g., dysrhythmias, severe hypotension, urinary retention).

  • IV precautions: For vesicants like catecholamines, use large-gauge IVs or central lines. Have antidote for extravasation (phentolamine for adrenergic agents) readily available.

  • Fall precautions: Implement due to orthostatic hypotension risk, especially with alpha-blockers.

  • Accurate I&O: Crucial for drugs affecting bladder function (cholinergic agonists/antagonists) or renal perfusion (adrenergic agents).

  • Titrate/Withhold per parameters: E.g., hold a beta-blocker if HR < $60$ bpm or SBP < $100$ mmHg; adjust vasopressors to maintain target BP.

• Teaching

  • Purpose & expected effects: Clearly explain “what to report” (serious side effects) vs. “what is normal” (common, mild side effects).

  • Self-monitor pulse/BP: Teach patients how to check their own pulse and BP, especially if on cardiac medications; diabetics on $\beta$-blockers must rigorously monitor glucose.

  • Do not abruptly stop beta-blockers: Emphasize the risk of rebound hypertension, angina, or MI.

  • Proper technique return-demo: For inhalers, eye-drops, or EpiPen, ensure the patient/caregiver can demonstrate correct usage.

  • OTC & herb interactions: Educate on potential interactions (e.g., decongestants, cold medicines, grapefruit with certain drugs like tolterodine).

• Evaluation

  • Outcome assessment: Did BP/HR/IOP/urine output move toward the therapeutic goal? Are symptoms alleviated?

  • Safety: Are side effects tolerable? Is patient safety (e.g., no falls, no severe adverse reactions) maintained?

Quick Memory Toolbox

• High & Dry vs Wet & Mucus: SNS (Sympathetic) dries you out (e.g., dry mouth, decreased GI motility); PNS (Parasympathetic) wets you down (e.g., increased salivation, increased GI motility).

• "Can’t see, can’t pee, can’t spit, can’t poop": Classic anticholinergic toxicity profile (e.g., from atropine overdose), summarizing blurred vision (cant see), urinary retention, dry mouth, and constipation.

• Alpha = Arteries ($\alpha_1$ primarily causes vasoconstriction); Beta-1 = 1 Heart (affects heart rate/contractility); Beta-2 = 2 Lungs (causes bronchodilation).

• A-M / N-Z Beta Blocker Rule: Early alphabet (A-M) generally indicates cardioselective ($\beta<em>1$) beta-blockers; later alphabet (N-Z) generally indicates non-selective ($\beta</em>{1+2}$) beta-blockers.

Practice Q & A (self-check)

1. Pt in asthma attack needs bronchial opening.
   
   • Target receptor ⇒ $\beta_2$
   
   • Drug class ⇒ adrenergic agonist (e.g., albuterol)

2. Stimulating $\alpha_1$ causes?
   
   • Vasoconstriction ⇒ ↑BP & mydriasis

3. Block muscarinic receptors in GI?
   
   • ↓ motility, dry mouth, constipation = anticholinergic profile

4. Best class for symptomatic bradycardia?
   
   • Cholinergic antagonist (Atropine) or adrenergic agonist ($\beta_1$) depending on context

Ethical / Practical Considerations

• Overuse of OTC sympathomimetics: Many cold/allergy medications (e.g., pseudoephedrine, phenylephrine) contain adrenergic agonists that