Adrenergic Pharmacology

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Rapid summary for last-minute revision before your exam.

Adrenergic Pharmacology — Key Facts for FMGE Core concept: Catecholamines (epinephrine, norepinephrine, dopamine) activate alpha and beta adrenergic receptors; non-catecholamines (clonidine, phenylephrine) have different pharmacokinetics High-yield point: Know the difference between alpha-1 (vasoconstriction), alpha-2 (decreased sympathetic outflow), beta-1 (heart), beta-2 (bronchodilation) receptor functions ⚡ Exam tip: Beta-blockers (especially non-selective like propranolol) can cause bronchospasm in asthmatics because they block beta-2 receptors in lungs

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🟡 Standard — Regular Study (2d–2mo)

Standard content for students with a few days to months.

Adrenergic Pharmacology — FMGE Study Guide

Adrenergic Receptors

Alpha Receptors

Alpha-1 receptors (Gq):

• Location: Vascular smooth muscle (skin, splanchnic, renal), iris dilator muscle, bladder trigone/sphincter, piloerector muscles
• Effect: Vasoconstriction (↑BP), mydriasis, bladder sphincter contraction, piloerection
• Blocking agents: Prazosin, terazosin, doxazosin (alpha-1 blockers) - used in hypertension and BPH

Alpha-2 receptors (Gi):

• Location: Presynaptic nerve terminals (autoreceptors), pancreas (inhibits insulin), platelets
• Effect: ↓sympathetic outflow (centrally), ↓insulin release, platelet aggregation
• Agonists: Clonidine (centrally acting antihypertensive), α-methyldopa (pregnancy hypertension)
• Blocking agents: Yohimbine (used for erectile dysfunction - blocks alpha-2)

Beta Receptors

Beta-1 receptors (Gs):

• Location: Heart (SA node, AV node, ventricular muscle)
• Effect: ↑HR (chronotropic), ↑contractility (inotropic), ↑AV conduction (dromotropic), ↑refractory period
• Blocking agents: Metoprolol, atenolol, esmolol - cardioprotective, antihypertensive, anti-anginal, anti-arrhythmic

Beta-2 receptors (Gs):

• Location: Bronchial smooth muscle, vascular smooth muscle (skeletal muscle), uterine smooth muscle, liver
• Effect: Bronchodilation, vasodilation (skeletal muscle), uterine relaxation, glycogenolysis
• Agonists: Albuterol, salmeterol (long-acting) - bronchodilators for asthma
• Blocking agents: Non-selective beta-blockers (propranolol) block beta-2 → bronchoconstriction (contraindicated in asthma)

Beta-3 receptors:

• Location: Adipose tissue, bladder
• Effect: Lipolysis, thermogenesis, bladder relaxation
• Agonists: Mirabegron (for overactive bladder)

Dopamine Receptors

• D1 (vasodilation in renal, mesenteric, coronary beds) - agonists: fenoldopam (hypertensive emergency with renal protection)
• D2 (presynaptic, CNS - antiemetic) - antagonists: metoclopramide, chlorpromazine

Catecholamine Chemistry

Catechol ring: Benzene with two adjacent hydroxyl groups (dihydroxybenzene)

Catecholamines synthesized from tyrosine:

• Tyrosine → L-DOPA → Dopamine → Norepinephrine → Epinephrine
• Enzyme: Tyrosine hydroxylase (rate-limiting), DOPA decarboxylase, dopamine β-hydroxylase, phenylethanolamine-N-methyltransferase (PNMT)

Catecholamines have:

• Rapid onset, short duration (metabolized by COMT and MAO)
• Do NOT cross BBB (polar)
• Inactivated by reuptake (NET, DAT) and metabolism

Non-catecholamines (single hydroxyl or no hydroxyl on benzene):

• Longer duration (not metabolized by COMT)
• Cross BBB (lipophilic) - e.g., phenylephrine, clonidine

Adrenergic Agonists

Direct-Acting Sympathomimetics

Epinephrine:

• Non-selective (α1, α2, β1, β2)
• At low doses: β effects predominate (β2 → vasodilation in skeletal muscle)
• At high doses: α effects predominate (vasoconstriction)
• Uses: Anaphylaxis (drug of choice), cardiac arrest, glaucoma, with local anesthetic (↓bleeding,↑duration)
• Side effects: Tachycardia, hypertension, arrhythmias, anxiety

Norepinephrine:

• α1, α2, β1 (minimal β2)
• Effects: Strong vasoconstriction (↑SVR, ↑BP), reflex bradycardia, ↑cardiac contractility
• Uses: Septic shock (vasopressor), cardiogenic shock
• Side effects: Severe hypertension, tissue necrosis if extravasated

Dopamine:

• Dose-dependent effects:
  • Low (<2 μg/kg/min): D1 (renal vasodilation)
  • Medium (2-10): β1 (inotropy, ↑HR)
  • High (>10): α1 (vasoconstriction)
• Uses: Shock, heart failure, renal failure (low dose)
• Side effects: Tachycardia, arrhythmias, metabolites cause nausea

Dobutamine:

• Synthetic catecholamine; β1 > β2 > α1
• Effect: ↑cardiac contractility with less ↑HR and vasoconstriction than dopamine
• Uses: Acute heart failure, cardiogenic shock

Isoproterenol:

• Non-selective β agonist (β1 = β2)
• Effects: ↑HR, ↑contractility, bronchodilation, vasodilation (β2)
• Uses: Bradycardia, heart block, bronchospasm

Phenylephrine:

• Pure α1 agonist (no beta activity)
• Effects: Vasoconstriction → ↑BP, reflex bradycardia, mydriasis
• Uses: Hypotension (vasopressor), nasal decongestant, ophthalmic procedures

Clonidine:

• α2 agonist (centrally acting)
• Effects: ↓sympathetic outflow → ↓BP, sedation, analgesia
• Uses: Hypertension (especially with renal disease), opioid withdrawal, anesthesia adjunct
• Side effects: Rebound hypertension if abruptly stopped

Indirect-Acting Sympathomimetics

Amphetamine, Ephedrine, Pseudoephedrine:

• Enter nerve terminal → displace catecholamines from storage vesicles → release norepinephrine
• Also inhibit MAO and reuptake
• Cross BBB → CNS effects (alertness, euphoria)

Mixed-Acting

Ephedrine:

• Both direct (weak agonist) and indirect (releases NE) effects
• Longer duration than epinephrine
• Crosses BBB
• Used for hypotension during spinal anesthesia, nasal congestion

Adrenergic Antagonists (Blockers)

Alpha Blockers

Non-selective (α1 = α2):

• Phentolamine: Reversible; used for pheochromocytoma (intraoperative), REVERSIBLE (not for chronic use)
• Phenoxybenzamine: Irreversible (covalent binding); used for pheochromocytoma preoperative and inoperable cases

Selective α1 blockers:

• Prazosin, Terazosin, Doxazosin, Tamsulosin (uroselective): Used for hypertension (prazosin not first-line) and BPH (tamsulosin - selective for prostate α1A)
• Side effects: First-dose orthostatic hypotension (start low, go slow); reflex tachycardia

Beta Blockers

Non-selective (β1 = β2):

• Propranolol: Mostlipid-soluble (crosses BBB); used for hypertension, angina, arrhythmia, migraine prophylaxis, thyrotoxicosis, essential tremor
• Nadolol, Timolol: Used for glaucoma (topical - ↓aqueous humor production)

β1-selective (cardioselective):

• Metoprolol, Atenolol, Esmolol (ultra-short IV): Hypertension, angina, MI, arrhythmias
• Bisoprolol: CHF (benefit in heart failure)
• Side effects at high doses: β2 blockade (bronchospasm,掩盖 hypoglycemia symptoms)

With additional properties:

• Carvedilol (α1 + β non-selective): CHF
• Labetalol (α1 + β non-selective): Hypertensive emergency (IV)
• Nebivolol: β1 selective + NO-mediated vasodilation

Combined Alpha + Beta Blockers

• Labetalol: α1 (weak), β1, β2 blockade; IV for hypertensive emergencies
• Carvedilol: α1, β1, β2; CHF

Side Effects of Beta Blockers

• Bronchospasm (β2 block) - contraindicated in asthma/COPD
• Bradycardia (β1 block) - contraindicated in 2nd/3rd degree AV block
• Masking of hypoglycemic symptoms (β2 block) - use selectively in diabetics
• Rebound angina/MI on abrupt discontinuation (upregulated receptors)
• Sexual dysfunction (central effect)
• Weight gain (slight)
• CNS effects (propranolol - nightmares, depression)

Contraindications to Beta Blockers

• Asthma/COPD (non-selective)
• Severe bradycardia, AV block
• Acute heart failure (cardiogenic shock)
• Unstable angina (caution - can worsen)

Sympathetic Drug Lists

Drug	Receptor Profile	Key Use
Epinephrine	α1, α2, β1, β2	Anaphylaxis, cardiac arrest
Norepinephrine	α1, α2, β1	Septic shock
Dopamine	D1, β1, α1 (dose-dependent)	Shock, heart failure
Dobutamine	β1 > β2 > α1	Acute heart failure
Isoproterenol	β1 = β2	Bradycardia
Phenylephrine	α1	Vasopressor, decongestant
Clonidine	α2	Hypertension
Albuterol	β2	Asthma (bronchodilator)
Salmeterol	β2 (long-acting)	Asthma maintenance
Prazosin	α1	BPH, hypertension
Propranolol	β1 = β2	Hypertension, arrhythmia
Metoprolol	β1 selective	Cardiac protection
Carvedilol	α1 + β	Heart failure

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