Autonomic Drugs: BP & Heart-Rate Tracings

Reading a Tracing: The Building Blocks

Three variables. Mean arterial pressure equals cardiac output × systemic vascular resistance. Diastolic pressure tracks SVR, systolic pressure tracks stroke volume and contractility, and pulse pressure (SBP − DBP) widens when contractility rises while resistance falls. Predicting a tracing means asking which receptors a drug stimulates, how that changes SVR and cardiac output, and how the baroreflex answers.

Baroreceptor reflex. A rise in MAP stretches baroreceptors in the carotid sinus (afferents in CN IX) and aortic arch (CN X). The nucleus tractus solitarius then increases vagal output and reduces sympathetic outflow, and ACh on SA node M2 receptors slows the heart. A fall in MAP triggers the reverse, reflex tachycardia.

Predominant tone. At rest the SA node is under parasympathetic (vagal) control, whereas arterioles and veins are under sympathetic control. A ganglionic blocker such as hexamethonium or mecamylamine removes both, so given alone it raises heart rate and lowers blood pressure (orthostatic hypotension), and it abolishes every baroreflex, which exaggerates the response to any pressor.

Signature Tracings of Direct Agonists

Phenylephrine. A pure α1 agonist raises SVR and all three pressures; nothing opposes the baroreflex, so bradycardia is marked. It is used for hypotension during anesthesia and as a nasal decongestant, and its reflex vagal surge was once used to terminate supraventricular tachycardia.

Norepinephrine. Acting on α1 more than β1, with little β2 activity, it raises SBP, DBP, and MAP. Its direct β1 effect would speed the heart, but the reflex vagal response usually wins, so heart rate falls while contractility rises.

Isoproterenol. Equal β1 and β2 agonism dilates skeletal-muscle arterioles and drops DBP and MAP while β1 raises contractility; systolic pressure holds or rises, pulse pressure widens, and heart rate climbs from both direct β1 stimulation and reflex tachycardia.

Epinephrine. β2 receptors respond to lower concentrations than α1, so a low dose behaves like a β agonist: SBP and HR rise, DBP falls, MAP changes little. At high doses α1 vasoconstriction dominates and epinephrine becomes a strong pressor.

Dobutamine. Mainly β1: contractility and cardiac output rise with a modest heart-rate increase and little change in SVR or blood pressure. It is used for low-output cardiogenic shock or decompensated heart failure and for dobutamine stress echocardiography.

Pretreatment Puzzles

α-Blockade. After phentolamine (reversible) or phenoxybenzamine (irreversible), epinephrine's β2 vasodilation is unopposed and its pressor response turns into a depressor response, called epinephrine reversal. Norepinephrine has too little β2 activity to reverse, so its pressor effect is only blunted; phenylephrine's is abolished. Angiotensin II, which acts on AT1 receptors, still raises pressure.

β-Blockade. With β1 and β2 blocked, epinephrine acts only on α1: blood pressure rises more, and reflex bradycardia replaces tachycardia. Clinically, patients on nonselective β-blockers can develop severe hypertension from epinephrine, and their anaphylaxis may resist epinephrine; glucagon raises cardiac cAMP independently of β receptors. The same unopposed-α logic is why α-blockade must precede β-blockade in pheochromocytoma.

Removing the reflex. Atropine blocks the vagal M2 limb, and a ganglionic blocker removes the entire reflex arc. Phenylephrine then raises blood pressure without slowing the heart, and norepinephrine's direct β1 tachycardia appears.

Tracing shortcut: pressure up with heart rate down means α1 dominance plus an intact reflex; DBP down with heart rate up means β2 plus β1; a tracing that flips direction after an α-blocker is epinephrine.

Dopamine, Indirect Agents, and Clinical Traps

Dopamine. "Renal-dose" dopamine does not prevent acute kidney injury. Fenoldopam, a selective D1 agonist, lowers blood pressure while preserving renal perfusion and is used in hypertensive emergencies.

Indirect agents. Tyramine, ephedrine, and amphetamine raise pressure by releasing stored NE. Repeated doses exhaust the releasable pool, so each response is smaller (tachyphylaxis), and pretreatment with reserpine or cocaine abolishes tyramine's effect.

MAO inhibitor plus dietary tyramine (aged cheese, cured meats, tap beer, fermented foods): tyramine escapes first-pass MAO-A in the gut and liver, releases large NE stores, and causes a hypertensive crisis with severe occipital headache and stroke risk; phentolamine is the classic treatment.

Withdrawal rebound. Clonidine, a central α2 agonist whose common side effects are dry mouth and sedation, lowers sympathetic outflow; abrupt withdrawal removes that suppression, producing severe hypertension, tachycardia, anxiety, and sweating; treat by restarting clonidine, because a β-blocker alone risks unopposed α vasoconstriction. Abrupt β-blocker withdrawal exposes receptors that were upregulated during chronic blockade, causing tachycardia, hypertension, and angina or myocardial infarction. Both drugs should be tapered.