High-yield summary

• These notes cover adrenergic receptor signaling, sympathomimetic types, catecholamine drugs and key non-catecholamine agents.
• Focus is on mechanisms, principal effects, clinical uses and major cautions.

1) Adrenergic receptors — signaling and main actions

Alpha-1 (\(\alpha_1\))

• Signaling: \(G_q \rightarrow \uparrow IP_3/DAG/\mathrm{Ca}^{2+}\).
• Location: Mostly postsynaptic on smooth muscle.
• Key actions: Vasoconstriction (skin/mucosa/splanchnic), pupillary dilator contraction (mydriasis), sphincter contraction (GIT/urinary), hepatic glycogenolysis.

Alpha-2 (\(\alpha_2\))

• Signaling: \(G_i \rightarrow \downarrow cAMP\).
• Location: Presynaptic (autoreceptors), postsynaptic, CNS.
• Key actions: Decreases sympathetic outflow, decreases NE release, reduces insulin, renin, lipolysis; increases platelet aggregation.

Beta-1 (\(\beta_1\))

• Signaling: \(G_s \rightarrow \uparrow cAMP\).
• Cardiac effects: Positive inotropy, chronotropy, dromotropy and increased excitability (all cardiac properties up).
• Other: Increases renin release and lipolysis.

Beta-2 (\(\beta_2\))

• Smooth muscle: Relaxes bronchi, GI wall, detrusor and uterus.
• Vessels: Vasodilation in coronary and skeletal muscle beds.
• Metabolic: Increases glycogenolysis and insulin; increases cellular K+ uptake (can cause hypokalemia and tremor).

Beta-3 (\(\beta_3\))

• Action: Detrusor relaxation (used in overactive bladder).

2) Sympathomimetic fundamentals

Direct vs Indirect agonists

• Direct: Bind receptors directly (e.g., adrenaline, noradrenaline, phenylephrine).
• Indirect: Release stored NE from nerve terminals (e.g., amphetamine, tyramine); cause tachyphylaxis due to depletion of stores.

Catecholamines vs Non-catecholamines

• Catecholamines: Poor oral bioavailability (rapidly metabolized by COMT/MAO); poor BBB penetration → minimal CNS effects.
• Non-catecholamines: More orally available (resistant to COMT) and penetrate BBB → greater CNS effects.

3) Important catecholamine drugs & concepts

Adrenaline (epinephrine)

• Receptor profile: Non-selective: \(\alpha_1,\ \alpha_2,\ \beta_1,\ \beta_2\).
• Therapeutic uses: 1) Anaphylaxis (drug of choice), 2) Cardiac arrest (resuscitation), 3) Acute severe asthma, 4) Local hemostasis/epistaxis, 5) Added to local anesthetics to prolong duration.
• Contraindication in peripheral end-artery sites: Avoid fingers, toes, ears, nose, penis — intense \(\alpha_1\) vasoconstriction may cause ischemia/gangrene.
• Adrenaline (Dale) reversal: If given after an \(\alpha\)-blocker, \(\alpha_1\) vasoconstriction is abolished and \(\beta_2\) vasodilation predominates, producing a paradoxical fall in BP.

Noradrenaline (norepinephrine)

• Profile: Strong \(\alpha_1,\ \alpha_2\) and weak \(\beta_1\); minimal \(\beta_2\).
• Effect: Potent vasoconstrictor, increases BP and reflex bradycardia.

Isoprenaline (isoproterenol)

• Profile: Pure \(\beta_1,\ \beta_2\) agonist; no \(\alpha\) activity.
• Effect: Powerful cardiac stimulation and vasodilation in skeletal muscle beds.

Dopamine — dose-dependent receptor effects

• Low dose: \(\mathbf{2\text{--}5\ \mu g}\) → activates \(D_1\) receptors → renal/mesenteric vasodilation, ↑ urine flow.
• Moderate dose: \(\mathbf{5\text{--}10\ \mu g}\) → activates \(\beta_1\) → ↑ cardiac output.
• High dose: \(\mathbf{>10\ \mu g}\) → activates \(\alpha_1\) → generalized vasoconstriction and ↑ BP.

Dobutamine

• Profile/use: Relatively selective \(\beta_1\) agonist used in acute heart failure/cardiogenic shock to increase contractility with minimal peripheral resistance change.

4) Non-catecholamines & selected drugs

Amphetamine (and methylphenidate class)

• Mechanism: Indirectly causes release of NE and dopamine in CNS and periphery.
• Uses: Narcolepsy, ADHD (methylphenidate), short-term obesity treatment.

"Cheese reaction"

• Cause: Patients on MAO inhibitors ingest tyramine-rich foods (aged cheese, wine) → tyramine not broken down → massive NE release → severe hypertensive crisis.

Phenylephrine

• Profile/use: Selective \(\alpha_1\) agonist used as a nasal decongestant and for mydriasis.
• Common topical side effect: Rebound congestion (rhinitis medicamentosa) after prolonged use (>3–5 days).

Selective \(\beta_2\) agents (examples)

• Ritodrine — tocolysis (suppresses premature labor).
• Isoxsuprine — used in peripheral vascular disease (vasodilation).
• Salbutamol (albuterol) — primary bronchodilator for asthma.

Mirabegron

• Profile/use: Selective \(\beta_3\) agonist for overactive bladder; relaxes detrusor muscle.

5) Clinical cautions & common adverse effects

• Alpha-mediated vasoconstriction: Risk of tissue ischemia if applied locally to end-artery areas; reversible agents preferred.
• Beta-2 stimulation: May cause tremor and hypokalemia due to increased K+ uptake into cells.
• Indirect sympathomimetics: Risk of tachyphylaxis and interactions with MAO inhibitors (severe hypertensive episodes).
• Adrenaline use in uncontrolled hypertension or on \(\alpha\)-blockers: watch for paradoxical BP responses (adrenaline reversal).

6) Quick reference — receptor summary table

7) Memorize these high-yield facts

• Adrenaline = non-selective (\(\alpha\) + \(\beta\)) — use in anaphylaxis and arrest.
• Adrenaline reversal occurs if \(\alpha\) blockade already present.
• Dopamine effects are dose-dependent: \(2\)--\(5\), \(5\)--\(10\), \(>10\ \mu g\) categories.
• Non-catecholamines are orally active and cross BBB; catecholamines do not.