Adrenergic Drugs (Chapter 18) – Comprehensive Bullet-Point Study Notes

Overview of the Sympathetic Nervous System (SNS) and Adrenergic Drugs

• Adrenergic drugs = agents that stimulate (mimic) the SNS
• Synonyms: adrenergic agonists, sympathomimetics
• SNS + parasympathetic nervous system = autonomic nervous system → maintains homeostasis through a checks-and-balances arrangement
• Primary endogenous catecholamine neurotransmitters (NTs) mimicked: norepinephrine (NE), epinephrine (EPI), dopamine
• Therapeutic pharmacology goal: harness or modulate these NT effects in specific organs/tissues

Adrenergic Receptor Families & Locations

1. Alpha-Adrenergic Receptors

• Sub-types: alpha1 (postsynaptic), alpha2 (presynaptic)
– Alpha1 → located on effector cells (blood vessels, bladder sphincter, uterus, eye, etc.)
– Alpha2 → located on nerve terminals; function = feedback control ↓ NT release
• Typical agonist responses: vasoconstriction; CNS stimulation

2. Beta-Adrenergic Receptors

• Sub-types: beta1 (heart), beta2 (bronchiolar/vascular/visceral smooth muscle)
• Beta1 agonist responses: cardiac stimulation (↑ contractility, HR, AV-conduction)
• Beta2 agonist responses: bronchodilation; uterine & GI relaxation; glycogenolysis; ↑ renin release

3. Dopaminergic Receptors

• Activated only by dopamine
• Stimulation dilates renal, mesenteric, coronary, cerebral vessels → ↑ blood flow

4. Organ-Specific Chart (Receptor → Response)

Cardiovascular
  • Blood vessels: alpha1 → vasoconstrict | beta2 → vasodilation
  • Cardiac muscle: beta1 → ↑ contractility
  • AV node, SA node: beta1 → ↑ HR & conduction
Gastrointestinal
  • Muscle: beta2/alpha → ↓ motility
  • Sphincters: alpha1 → constriction
Genitourinary
  • Bladder sphincter: alpha1 → constriction
  • Penis: alpha1 → ejaculation
  • Uterus: alpha1 → contraction | beta2 → relaxation
Respiratory
  • Bronchial muscle: beta2 → dilation
Endocrine
  • Liver: alpha1/beta2 → glycogenolysis
Ocular
  • Pupil (radial muscle): alpha1 → mydriasis (dilation)

Catecholamines

• Compounds (endogenous or synthetic) capable of sympathomimetic action
• Metabolized by MAO & COMT enzymes
• Endogenous: $\text{EPI},\; \text{NE},\; \text{dopamine}$
• Synthetic: dobutamine, phenylephrine, etc.

Mechanisms of Action

• Direct-acting: drug binds directly to receptor (e.g., EPI)
• Indirect-acting: drug triggers NT release from vesicles → NT activates receptor (e.g., amphetamine-like)
• Mixed-acting: does both (e.g., ephedrine)

Drug Effects by Receptor

Alpha Stimulation

• Vasoconstriction (↑ BP)
• ↓ GI motility
• Bladder sphincter constriction
• Uterine contraction
• Male ejaculation
• Mydriasis

Beta1 Stimulation

• Positive inotropy (↑ force)
• Positive chronotropy (↑ HR)
• Positive dromotropy (↑ AV-node conduction)
• Formula reminder: $\text{CO}=\text{HR}\times\text{SV}$ → ↑ HR or ↑ SV ⇒ ↑ cardiac output

Beta2 Stimulation

• Bronchodilation
• Uterine & GI smooth muscle relaxation
• Hepatic glycogenolysis → ↑ serum glucose
• ↑ renin → long-term BP modulation

Therapeutic Indications

Respiratory (Bronchodilators)

• Acute relief/selective beta2 agonists: albuterol, levalbuterol, metaproterenol, pirbuterol, epinephrine (inhaled), formoterol, salmeterol (chronic prevention)

Nasal Decongestion

• Topical alpha1 agonists constrict arterioles → ↓ nasal blood flow
• Examples: ephedrine, naphazoline, oxymetazoline, phenylephrine, tetrahydrozoline

Ophthalmic

• Conjunctival congestion relief & mydriasis (open-angle glaucoma) via alpha agonists
• Agents: epinephrine, dipivefrin, naphazoline, tetrahydrozoline

Overactive Bladder

• Beta3 agonist mirabegron → detrusor relaxation → ↑ bladder capacity

Cardiovascular / Vasoactive (Pressors & Inotropes)

• “Cardioselective sympathomimetics” support failing heart or shock
• Drugs & brief profiles:
– Dobutamine (beta1 selective inotrope)
– Dopamine (dose-dependent D1 → beta1 → alpha1)
– Epinephrine (non-selective prototypical; ACLS drug)
– Norepinephrine (alpha + beta1; no beta2; strong vasoconstrictor)
– Phenylephrine (pure alpha; IV, ophthalmic, nasal)
– Fenoldopam (peripheral D1 agonist → arteriolar vasodilation; lowers severe HTN)
– Midodrine (oral pro-drug; active desglymidodrine; alpha1 → orthostatic hypotension)

Key Individual Agents

Dobutamine

• Synthetic $\beta_1$ selective; ↑ contractility & stroke volume → ↑ CO
• Continuous IV infusion

Dopamine

• Endogenous catecholamine
• Low dose ((1–3\,\mu g/kg/min)) → D1 dilation (brain, heart, kidney, mesentery)
• Medium dose ((5–10\,\mu g/kg/min)) → $\beta<em>1$ ↑ contractility • High dose ((>10\,\mu g/kg/min)) → $\alpha</em>1$ vasoconstriction

Epinephrine

• Non-selective alpha & beta
• Emergency uses: anaphylaxis, ACLS for cardiac arrest, severe asthma, etc.

Fenoldopam

• Peripheral D1 agonist; short-term IV for severe HTN; ↑ renal blood flow

Midodrine

• Alpha1 pro-drug; oral; for symptomatic orthostatic hypotension
• Don’t dose within 4 h of bedtime (supine HTN risk)

Mirabegron

• Beta3 agonist; ↑ bladder storage; AEs: HTN, UTI, HA, nasopharyngitis, nausea, dizziness

Norepinephrine

• Potent alpha + beta1; no beta2; IV only; shock/hypotension

Phenylephrine

• Pure alpha; IV for BP support, SVT control; topical nasal & ocular decongestant

Contraindications

• Known hypersensitivity
• Severe hypertension

Adverse Effects

Alpha Agonists

• CNS: HA, restlessness, excitement, insomnia, euphoria
• CV: chest pain, vasoconstriction, reflex bradycardia, palpitations, dysrhythmias
• GI: anorexia, dry mouth, N/V, taste changes

Beta Agonists

• CNS: mild tremor, HA, nervousness, dizziness
• CV: tachycardia, palpitations, BP fluctuations
• MSK/GI: sweating, N/V, muscle cramps

Toxicity & Overdose Management

• Excessive CNS stimulation → seizures, intracranial hemorrhage (HTN crisis)
• Very short half-lives → supportively manage until drug wears off
• Rapid-acting sympatholytic (e.g., phentolamine) may be required

Drug-Drug Interactions

• Adrenergic antagonists (cancel effect)
• Anesthetic agents (dysrhythmia risk)
• MAOIs (hypertensive crisis)
• Antihistamines & thyroid preparations (potentiate SNS)
• Combining two adrenergic agonists → severe tachycardia/HTN

Nursing Implications

Assessment

• Screen allergies, asthma, HTN, dysrhythmias, cardiovascular disease
• Baseline renal, hepatic, cardiac function
• Vital signs (lying/sitting/standing), peripheral pulses, skin color/temp/cap refill

IV Administration Principles

• Verify clear solutions; use infusion pump
• Monitor site for infiltration/extravasation (tissue necrosis risk)
• Infuse slowly; continuous ECG monitoring
• For extravasation: stop infusion → consider regional antidote (phentolamine)

Respiratory Patient Education

• Avoid triggers; encourage fluids $\le 3000\,\text{mL/day}$ if not contraindicated
• Teach inhaler/nebulizer technique, rescue vs. maintenance distinction

Nasal Decongestants

• Warn about rebound congestion/ulceration with overuse

Monitoring for Therapeutic Effect

• Cardiovascular goals: ↓ edema, ↑ urine output, normalized VS, warm skin, ↑ LOC
• Respiratory goals: normal RR, clear breath sounds, ↑ air exchange, ↓ cough/dyspnea, improved ABGs, ↑ activity tolerance

Clinical Scenario Questions (Illustrative Examples)

• Inhaler sequencing: Always use bronchodilator first → opens airways → better corticosteroid penetration
• Exercise-induced bronchospasm: Choose short-acting beta2 agonist (albuterol) for acute relief
• Dobutamine IV infiltration: FIRST action = stop infusion (then phentolamine & notify HCP)
• Chest tightness during dobutamine drip: FIRST action = assess VS; diagnostics follow
• Albuterol nebulization in ED: immediate priority = monitor SpO2 & respiratory status

Ethical & Practical Considerations

• Risk–benefit: potent life-saving effects vs. severe adverse CV/CNS events
• Use shortest effective duration; meticulous IV technique prevents tissue damage
• Patient teaching critical to prevent misuse (e.g., overuse of OTC decongestants)