Autonomic Pharmacology MCQ

The autonomic nervous system runs in two opposing arms: sympathetic (fight or flight) and parasympathetic (rest and digest). Sympathetic signaling uses norepinephrine and epinephrine acting at alpha and beta adrenergic receptors; parasympathetic signaling uses acetylcholine acting at muscarinic and nicotinic receptors. Almost every dental drug interaction the INBDE tests runs through this system, from epinephrine in local anesthetic, to beta-blockers in the medical history, to pilocarpine for xerostomia, to atropine in an emergency. The single highest-yield interaction is epinephrine plus a non-selective beta-blocker, which produces a hypertensive response with reflex bradycardia.

Sympathomimetics: Alpha and Beta Agonists

• Epinephrine activates alpha-1, alpha-2, beta-1, and beta-2 receptors, with the dominant effect depending on dose: lower doses favor beta effects, higher doses favor alpha vasoconstriction.
• Norepinephrine activates alpha-1, alpha-2, and beta-1, with little beta-2; it produces vasoconstriction and increased mean arterial pressure with a reflex slowing of heart rate.
• Phenylephrine is a pure alpha-1 agonist (nasal decongestant, pressor in shock); isoproterenol is a non-selective beta agonist (beta-1 and beta-2), and dobutamine is mostly beta-1 (used for cardiac inotropic support).
• Albuterol is a selective beta-2 agonist used for asthma and bronchospasm; at high doses it loses selectivity and causes tachycardia and tremor.

Sympatholytics: Alpha and Beta Blockers

• Alpha-1 blockers (prazosin, terazosin, doxazosin, tamsulosin) cause vasodilation and lower blood pressure; tamsulosin is used for benign prostatic hyperplasia and can cause orthostatic hypotension and floppy iris syndrome.
• Beta-blockers are split into non-selective (propranolol, nadolol, timolol) and cardioselective (metoprolol, atenolol, bisoprolol, esmolol); cardioselective agents preferentially block beta-1 at the usual dose.
• Beta-blockers reduce heart rate and blood pressure and are used for hypertension, post-MI care, heart failure, and arrhythmias; they can blunt the warning signs of hypoglycemia and cause bronchospasm (non-selective in asthma).
• The dental drug interaction: a non-selective beta-blocker plus epinephrine produces unopposed alpha-1 vasoconstriction with reflex bradycardia, sometimes with severe hypertension; cardioselective agents are far less likely to do this at usual doses.

Parasympathomimetics: Direct Cholinergics and AChEIs

• Direct cholinergic agonists (pilocarpine, cevimeline, bethanechol) activate muscarinic receptors; pilocarpine and cevimeline are used in dentistry for xerostomia from Sjögren syndrome or head and neck radiation.
• Indirect cholinergics (acetylcholinesterase inhibitors, AChEIs) increase synaptic acetylcholine by blocking its breakdown; examples include donepezil and rivastigmine for Alzheimer disease, neostigmine and pyridostigmine for myasthenia gravis, and physostigmine (crosses the blood-brain barrier).
• Cholinergic toxicity (cholinergic crisis) is remembered by the mnemonic DUMBBELS (diarrhea, urination, miosis, bronchorrhea/bronchoconstriction, bradycardia, emesis, lacrimation, salivation) or SLUDGE (salivation, lacrimation, urination, defecation, GI distress, emesis).
• Acute cholinergic toxicity from organophosphates or carbamates is treated with atropine (blocks muscarinic effects) and, for organophosphates within hours, pralidoxime (regenerates acetylcholinesterase).

Parasympatholytics: Atropine, Glycopyrrolate, Scopolamine

• Muscarinic antagonists block parasympathetic effects, producing the classic anticholinergic picture (dry as a bone, red as a beet, hot as a hare, blind as a bat, mad as a hatter).
• Atropine is used in bradycardia and as part of the antidote for organophosphate poisoning; glycopyrrolate has similar peripheral effects without the central effects (does not cross the blood-brain barrier).
• Scopolamine is used for motion sickness (transdermal patch) and has classic anticholinergic side effects including memory impairment in the elderly.
• Side effects across the class include dry mouth (a particular dental concern), urinary retention, tachycardia, constipation, mydriasis, blurred vision, and confusion in the elderly.

Autonomic Drugs in the Dental Patient

• Almost every dental drug interaction the INBDE tests runs through the autonomic nervous system, and the medication history is the way to find them.
• Alpha-2 agonists (clonidine, dexmedetomidine) decrease sympathetic outflow centrally; abrupt clonidine withdrawal causes rebound hypertension.
• Cocaine and amphetamines are sympathomimetic and contraindicate routine epinephrine use because the effects stack toward hypertensive crisis and arrhythmia; meth use also drives severe rampant caries ('meth mouth').
• Tricyclic antidepressants and MAO inhibitors can potentiate sympathomimetics; cap epinephrine in these patients and use a vasoconstrictor-free local anesthetic when there is doubt.