Adrenergic Pharmacology covers adrenergic pharmacology for INI CET (AIIMS PG).
Catecholamine Synthesis: Tyrosine → (tyrosine hydroxylase) → L-DOPA → (DOPA decarboxylase) → Dopamine → (DβH — dopamine β-hydroxylase) → Norepinephrine → (PNMT — phenylethanolamine-N-methyltransferase) → Epinephrine
Storage and Release:
- NE stored in dense-core vesicles (with ATP, chromogranin)
- Epi stored in adrenal medulla (and some CNS)
- Release: Ca²⁺-dependent exocytosis (like ACh)
Adrenergic Receptors:
| Receptor | Location | Effect | Agonist | Antagonist |
|---|---|---|---|---|
| α₁ | Vascular smooth muscle, GU (bladder neck, prostate) | Vasoconstriction, GU contraction | Phenylephrine | Prazosin, Terazosin |
| α₂ | Presynaptic nerve terminals, CNS | Inhibits NE release (autoreceptor), vasodilation (CNS) | Clonidine (centrally acting) | Yohimbine |
| β₁ | Heart | ↑HR (chronotropy), ↑conduction (dromotropy), ↑contractility (inotropy) | — | Metoprolol, Atenolol |
| β₂ | Bronchial smooth muscle, vascular smooth muscle, uterus | Bronchodilation, vasodilation (skeletal muscle), uterine relaxation | Salbutamol, Formoterol | Butoxamine |
| β₃ | Adipose tissue | Lipolysis | — | — |
| D₁ | Renal, mesenteric vasculature | Vasodilation | Fenoldopam | — |
Indirect-Acting Sympathomimetics:
- Amphetamine: Enters nerve terminal → displaces NE from vesicles → releases NE (and inhibits reuptake, inhibits MAO)
- Tyramine: Present in aged foods (cheese, wine) → displaces NE (dangerous with MAO inhibitors → hypertensive crisis)
- Cocaine: Blocks NE reuptake transporter (NET) → ↑ synaptic NE
- Reserpine: Depletes vesicular NE stores (irreversible — long duration)
Clinical Uses of Adrenergic Drugs:
- Epinephrine: Anaphylaxis (first-line), cardiac arrest, with local anesthetic (vasoconstriction), glaucoma
- Noradrenaline: Septic shock (vasopressor — α₁ > β₁ → vasoconstriction)
- Dopamine: Shock (low dose: D₁ → renal vasodilation; high dose: α₁ → vasoconstriction)
- Dobutamine: Acute heart failure (β₁ > α₁ → ↑ contractility, slight vasodilation)
- Phenylephrine: Nasal decongestant, mydriasis, hypotension in anesthesia
- Clonidine: Hypertension (centrally acting α₂ agonist → ↓ sympathetic outflow), withdrawal syndromes
β-Blockers (β-antagonists — crucial for INI CET (AIIMS PG)):
- Non-selective (β₁ + β₂): Propranolol (also blocks 5-HT receptor), Nadolol, Timolol (used in glaucoma)
- β₁-selective: Metoprolol, Atenolol, Bisoprolol (preferable in asthma/COPD — less β₂ blockade)
- α + β blocker: Carvedilol (antioxidant properties), Labetalol (used in hypertensive emergencies in pregnancy)
- Side effects of β-blockers: Bradycardia, bronchoconstriction (contraindicated in asthma), masking of hypoglycemic symptoms (caution in diabetics), hypotension, fatigue, depression (CNS penetration), erectile dysfunction
- Contraindications: Asthma (β₂ blockade → bronchoconstriction), severe bradycardia, AV block, acute heart failure
⚡ Exam Tip for INI CET (AIIMS PG): β₂ agonists (salbutamol) cause hypokalemia (shift K⁺ into cells) — important during severe asthma attacks (check K⁺ levels). β₂ receptors couple to Gs → ↑cAMP → activates Na⁺/K⁺-ATPase → hypokalemia.