Adrenergic agonists (sympathomimetics) mimic norepinephrine and epinephrine — the "fight or flight" response. The effect depends on which receptor the drug stimulates.

Types of action

• Direct — bind the receptor (epinephrine, norepinephrine, phenylephrine, albuterol)
• Indirect — release stored norepinephrine (amphetamines) or block its reuptake (cocaine)
• Mixed — both (ephedrine, pseudoephedrine)

Catecholamines (epinephrine, norepinephrine, dopamine, dobutamine, isoproterenol) are destroyed quickly by MAO and COMT: they are not effective orally, act within minutes, and wear off within minutes when an infusion stops.

By receptor

• Alpha-1: hypertension, headache, reflex bradycardia, peripheral, renal, and mesenteric ischemia, necrosis if an IV infusion leaks, urinary retention; rebound nasal congestion (rhinitis medicamentosa) when decongestant sprays are used more than about 3 days
• Beta-1: tachycardia, palpitations, dysrhythmias, chest pain and myocardial ischemia (↑oxygen demand)
• Beta-2: tremor, nervousness, tachycardia, hypokalemia, hyperglycemia, lactate rise
• CNS (oral and indirect agents): anxiety, insomnia, restlessness
• Alpha-2 agonists: sedation, dry mouth, bradycardia, hypotension, rebound hypertension on abrupt withdrawal

Epinephrine raises glucose and lactate and can cause chest pain, dysrhythmias, and pallor. These effects are brief and do not justify withholding it in anaphylaxis.

Contraindications and cautions

• Tachydysrhythmias, uncontrolled hypertension, severe coronary artery disease (except epinephrine in anaphylaxis or arrest — no absolute contraindication in those emergencies)
• Uncorrected hypovolemia before vasopressors — correct volume first
• Pheochromocytoma, hyperthyroidism, angle-closure glaucoma (alpha-1 mydriasis)
• Diabetes (beta-2 hyperglycemia), prostate enlargement (alpha-1 retention with decongestants)
• Midodrine: supine hypertension, severe heart disease, acute kidney disease, urinary retention, pheochromocytoma, thyrotoxicosis
• Sulfite sensitivity: some vials contain sulfites — this does not prevent epinephrine use in anaphylaxis

Pregnancy and lactation

• Epinephrine is given for anaphylaxis in pregnancy without hesitation — the mother's circulation protects the fetus
• Oral decongestants are generally avoided in the first trimester and in uncontrolled hypertension; pseudoephedrine can reduce milk supply
• Methyldopa is a long-established option for hypertension in pregnancy

Interactions

• MAO inhibitors (and linezolid) + indirect or mixed agents (pseudoephedrine, ephedrine, amphetamines) → hypertensive crisis; MAOIs and tricyclic antidepressants also exaggerate direct agonists
• Beta blockers: blunt epinephrine; a nonselective beta blocker plus epinephrine can cause severe hypertension with reflex bradycardia (unopposed alpha). Glucagon is given for anaphylaxis that does not respond in clients on beta blockers
• Halogenated inhaled anesthetics sensitize the heart to catecholamine dysrhythmias
• Clonidine + beta blocker: if both are to be stopped, the beta blocker is stopped first (several days) before clonidine is tapered, to limit rebound hypertension
• Mirabegron inhibits CYP2D6 (raises metoprolol, desipramine); avoid with thioridazine
• Stimulants and caffeine add to sympathomimetic effects

Listed in priority order.

1. Emergency drugs — right dose, route, and strength
   • Anaphylaxis: epinephrine IM 1 mg/mL into the mid-outer thigh; never IV push the 1 mg/mL strength. Cardiac arrest: 0.1 mg/mL IV/IO. Labels in the US now show mg/mL, not ratios (1:1,000, 1:10,000)
   • After epinephrine: continuous monitoring of HR, rhythm, BP, SpO₂; prepare a second dose; observe for biphasic reactions
2. IV adrenergic infusions (high-alert)
   • Infusion pump, dedicated line, independent double check; continuous ECG and arterial or frequent BP; titrate to the ordered MAP; wean gradually
   • Check the IV site at least hourly; at the first sign of blanching or swelling: stop, notify, phentolamine per protocol (see Topic 59)
   • Monitor urine output (≥ 0.5 mL/kg/h), mental status, skin perfusion, lactate, glucose, and potassium
3. Oral and inhaled agonists
   • Heart rate and BP before doses; report HR above the ordered limit, chest pain, or palpitations
   • Midodrine: check supine and standing BP; hold and report supine hypertension; give the last dose in the late afternoon
   • Albuterol: monitor potassium with frequent or continuous use; tremor is expected
4. Alpha-2 agonists — BP and HR before doses (hold per parameters, commonly HR < 60/min or SBP < 90 mmHg); sedation and fall risk; never omit doses without a taper plan
5. Methyldopa — baseline and periodic CBC and liver tests

• Epinephrine auto-injector or nasal spray: carry two devices at all times; use at the first sign of a severe allergic reaction (breathing trouble, throat tightness, faintness, widespread hives with vomiting), inject into the outer thigh through clothing if needed, then call emergency services even if symptoms improve. Check expiry dates; store at room temperature
• Decongestants: limit nasal sprays to about 3 days (rebound congestion); avoid oral decongestants with high BP, heart disease, glaucoma, or prostate enlargement unless the prescriber approves; never combine with an MAO inhibitor
• Clonidine or guanfacine: do not stop suddenly — rebound high BP can be dangerous; rise slowly; avoid alcohol and other sedatives; patch users apply to hairless skin on the upper arm or chest and rotate sites
• Midodrine: take during the day while up and about; do not lie flat for long after a dose; report pounding headache, blurred vision, or a pounding heartbeat when lying down
• Mirabegron: have BP checked periodically
• Report chest pain, fast or irregular heartbeat, severe headache, or cold, pale, or painful fingers or toes

• Alpha-1 = vasoconstriction; beta-1 = heart; beta-2 = bronchi (and uterus); alpha-2 = central "brake" on sympathetic outflow
• Anaphylaxis: IM epinephrine 0.01 mg/kg, max 0.5 mg adult, mid-outer thigh — first and immediately
• Never give 1 mg/mL epinephrine IV push; cardiac arrest uses 0.1 mg/mL
• Norepinephrine = first-line septic shock vasopressor; check IV site hourly; phentolamine for extravasation
• Phenylephrine → reflex bradycardia; oral phenylephrine is an ineffective decongestant
• Beta-2 agonists → tremor, tachycardia, hypokalemia, hyperglycemia
• Clonidine: taper — rebound hypertension
• Midodrine: supine hypertension — last dose at least 4 hours before bedtime
• MAOI + pseudoephedrine = hypertensive crisis
• Beta-blocked client with refractory anaphylaxis → glucagon