Adrenergic Agonists and Antagonists Quiz

Study Notes

Adrenergic Agonists and Antagonists

Adrenergic drugs affect receptors stimulated by norepinephrine or epinephrine.
Some adrenergic drugs directly stimulate adrenergic receptors (adrenoceptors), acting as sympathomimetics.
Other drugs block neurotransmitter action at receptors (sympatholytics).
Other drugs interrupt norepinephrine release from adrenergic neurons.
Adrenergic neurons release norepinephrine as the primary neurotransmitter, found in the CNS and sympathetic nervous system.
In the sympathetic nervous system, two families of adrenergic receptors exist: alpha (α) and beta (β) receptors.
Alpha receptors (α-adrenoceptors):
- Show weak response to synthetic agonist isoproterenol.
- Respond to epinephrine and norepinephrine.
- Potency rank: epinephrine ≥ norepinephrine >> isoproterenol.
- Divided into α1 and α2 receptors:
  - α1 receptors have high affinity for phenylephrine, causing vasoconstriction (especially in skin and abdominal viscera), increased peripheral resistance, and blood pressure.
  - α2 receptors bind selectively to clonidine, causing feedback inhibition of norepinephrine release from stimulated adrenergic neurons, reducing norepinephrine output during high sympathetic activity (resulting in vasodilation).
Beta receptors (β-adrenoceptors):
- Respond to isoproterenol more strongly than epinephrine or norepinephrine (isoproterenol > epinephrine > norepinephrine)
- Divided into β1, β2, and β3 receptors:
  - β1 receptors: Stimulation causes cardiac stimulation (increased myocardial contractility, heart rate, and blood pressure).
  - β2 receptors: Stimulation causes vasodilation, relaxation of skeletal smooth muscle, and bronchodilation.
  - β3 receptors: Involved in lipolysis and bladder function.

Direct-Acting Adrenergic Agonists

Examples include epinephrine, norepinephrine, isoproterenol, and phenylephrine.
Epinephrine: Acts on both α and β receptors.
- Positive inotropic and chronotropic effects, increasing heart contraction and rate, thus increasing cardiac output.
- Activates β1 receptors in the kidneys, releasing renin, which contributes to angiotensin II production (a potent vasoconstrictor).
- Dilates blood vessels to the liver and skeletal muscles (β2 effects).
- Causes bronchodilation (β2 effects) and inhibits histamine release from mast cells.
- Used to treat acute asthma and anaphylactic shock.
Norepinephrine: Primarily affects α receptors in therapeutic doses.
- Increases both systolic and diastolic blood pressure and stimulates cardiac contractility.
- Used to treat shock due to its blood pressure-increasing effects.
Isoproterenol: Synthetic catecholamine stimulating both β1 and β2 receptors.
- Rarely used therapeutically due to non-selectivity.
- Used to treat atrioventricular (AV) block or cardiac arrest.
Dopamine:
- Activates α and β adrenergic receptors; at higher doses, activates α1 receptors and causes vasoconstriction; at lower doses, stimulates β1 cardiac receptors.
- D1 and D2 dopaminergic receptors in peripheral mesenteric and renal vessels, producing vasodilation.
- Drug of choice for cardiogenic and septic shock. Enhances kidney perfusion.
- Used to treat hypotension and severe CHF.
Fenoldopam: Acts as an agonist of peripheral D1 receptors and α2 receptors.
Dobutamine: A β1 receptor agonist.
- Used in acute CHF and to support inotropic action after cardiac surgery.

Indirect-Acting Adrenergic Agonists

Cause norepinephrine release or inhibit its uptake.
Amphetamine: CNS stimulant, used to treat hyperactivity in children, narcolepsy, and appetite control.

Mixed-Action Adrenergic Agonists

Induce norepinephrine release and activate adrenergic receptors.
Ephedrine and pseudoephedrine similar to epinephrine, but less potent.
- Increase systolic and diastolic blood pressure via vasoconstriction, heart stimulation and bronchodilation.
- Used orally to relieve nasal and sinus congestion.

α-Adrenergic Blocking Agents

These drugs block α receptors, causing reflex tachycardia.
Prazosin, terazosin, doxazosin, and tamsulosin: Selective α1 blockers used to treat benign prostatic hyperplasia.

β-Adrenergic Blocking Agents

Nonselective: Propranolol affecting both β1 and β2 receptors.
- Decreases cardiac output, heart rate, contractility.
- Adverse effects may include bronchoconstriction, arrhythmias, impotence, hypoglycemia, lethargy, fatigue, and visual disturbance.
Cardioselective: Block β1 receptors only (e.g., metoprolol, atenolol).
- Used to treat hypertension, angina pectoris, cardiac arrhythmias, myocardial infarction, CHF, hyperthyroidism, glaucoma, and for migraine prophylaxis.
Examples (selective β1 antagonists): acebutolol, atenolol, metoprolol, bisoprolol, betaxolol, nebivolol, and esmolol.
- Note that these selectively blocking agents can lose their selectivity at high dosages.
Yohimbine: A selective alpha-2 blocker, used as a sexual stimulant and for Raynaud's disease.