Autonomic Drugs – BCSE Study Guide

Overview and Clinical Importance

The autonomic nervous system (ANS) is a critical regulatory system that controls involuntary physiological processes including heart rate, blood pressure, respiration, digestion, and glandular secretions. Understanding autonomic pharmacology is essential for veterinary practice because these drugs are used daily in sedation, anesthesia, emergency medicine, and treatment of various organ system disorders.

The ANS has two main divisions: the sympathetic nervous system (SNS), which mediates the "fight or flight" response, and the parasympathetic nervous system (PNS), which controls "rest and digest" functions. A balance between these divisions maintains homeostasis, and drugs can be used to modulate this balance therapeutically.

Autonomic Nervous System Fundamentals

Organization and Neurotransmitters

The ANS consists of a two-neuron chain from the central nervous system to target organs. The preganglionic neuron has its cell body in the CNS, while the postganglionic neuron has its cell body in an autonomic ganglion. Understanding the neurotransmitters and receptors at each synapse is fundamental to predicting drug effects.

MEMORY AID - "ALL PREGANGLIONIC NEURONS USE ACETYLCHOLINE": Remember "ALL Ach Before the Ganglia" - both sympathetic AND parasympathetic preganglionic neurons release acetylcholine (ACh) acting on nicotinic receptors. It is only AFTER the ganglion that they differ: parasympathetic postganglionic neurons continue using ACh (on muscarinic receptors), while sympathetic postganglionic neurons switch to norepinephrine (on adrenergic receptors).

Table 1. Comparison of Sympathetic and Parasympathetic Divisions

MEMORY AID - "SLUDGE/DUMBELS" for Muscarinic Effects: Cholinergic (muscarinic) stimulation causes: Salivation, Lacrimation, Urination, Defecation, GI upset, Emesis (SLUDGE). Alternatively: Diarrhea, Urination, Miosis, Bradycardia/Bronchospasm, Emesis, Lacrimation, Salivation (DUMBELS). These mnemonics are essential for identifying cholinergic toxicity and anticholinergic side effects!

Autonomic Receptor Types and Effects

Cholinergic receptors are classified as nicotinic (ion channels) or muscarinic (G-protein coupled). Adrenergic receptors include alpha-1, alpha-2, beta-1, beta-2, and beta-3 subtypes, each with distinct tissue distributions and effects.

Table 2. Cholinergic Receptor Types and Functions

Table 3. Adrenergic Receptor Types and Functions

MEMORY AID - Adrenergic Receptors: "Alpha = Arteries" (?1 causes vasoconstriction). "Beta-1 = 1 Heart" (primarily cardiac effects). "Beta-2 = 2 Lungs" (bronchodilation). Remember: ?2 receptors are on the PREsynaptic terminal and provide negative feedback - like a thermostat turning DOWN the heat. Alpha-2 agonists (dexmedetomidine, xylazine) cause sedation by reducing CNS norepinephrine release.

Cholinergic Agonists

Direct-Acting Cholinergic Agonists

Direct-acting cholinergic agonists (parasympathomimetics) directly stimulate cholinergic receptors. They are classified based on their receptor selectivity (muscarinic vs. nicotinic) and their susceptibility to degradation by acetylcholinesterase.

Table 4. Direct-Acting Cholinergic Agonists

Indirect-Acting Cholinergic Agonists (Anticholinesterases)

Anticholinesterase drugs inhibit the enzyme acetylcholinesterase (AChE), preventing the breakdown of acetylcholine and prolonging its action at cholinergic synapses. This indirectly increases cholinergic activity at both muscarinic and nicotinic sites.

Table 5. Anticholinesterase (Cholinesterase Inhibitor) Drugs

MEMORY AID - "Neo Does NOT cross, Physo DOES": Neostigmine (Neo) does NOT cross the blood-brain barrier and only works peripherally. Physostigmine (Physo) DOES cross the BBB, making it the treatment for CENTRAL anticholinergic toxicity (e.g., delirium from atropine overdose). When giving neostigmine to reverse NMB agents, always co-administer atropine or glycopyrrolate to prevent dangerous bradycardia from peripheral muscarinic stimulation!

Cholinergic Antagonists (Anticholinergics)

Muscarinic Antagonists

Muscarinic antagonists (antimuscarinics, parasympatholytics) competitively block acetylcholine at muscarinic receptors. They produce effects opposite to parasympathetic stimulation: increased heart rate, bronchodilation, decreased secretions, mydriasis, and decreased GI motility.

Table 6. Muscarinic Antagonists (Anticholinergics)

MEMORY AID - Atropine vs. Glycopyrrolate: "Atropine goes to the BRAIN, Glyco stays in the PERIPHERAL LANE." Atropine is a tertiary amine that crosses the BBB causing potential CNS excitement. Glycopyrrolate is a quaternary amine (charged) that cannot cross the BBB - making it preferred when you want peripheral anticholinergic effects without CNS side effects. However, atropine has faster onset and is preferred in emergency situations like CPR.

Adrenergic Agonists (Sympathomimetics)

Adrenergic agonists mimic the effects of sympathetic nervous system activation by stimulating adrenergic receptors. They are classified based on their receptor selectivity (alpha vs. beta, and subtypes) and their mechanism of action (direct receptor binding vs. indirect release of catecholamines).

Catecholamines

Table 7. Catecholamine Adrenergic Agonists

MEMORY AID - Dopamine Dose Effects: "DRB" = Dopamine Receptors at Low, Beta at Medium, Alpha at High. At low doses (1-3 μg/kg/min), dopamine stimulates D1 receptors causing renal vasodilation. At medium doses (3-10 μg/kg/min), ?1 effects predominate (increased cardiac output). At high doses (greater than 10 μg/kg/min), ?1 effects cause vasoconstriction.

Alpha-2 Adrenergic Agonists

Alpha-2 agonists are among the most commonly used sedatives in veterinary medicine. By stimulating presynaptic ?2 receptors in the CNS, they reduce norepinephrine release, producing profound sedation, analgesia, and muscle relaxation. They also stimulate peripheral ?2 receptors causing initial vasoconstriction and reflex bradycardia.

Table 8. Alpha-2 Adrenergic Agonists in Veterinary Medicine

MEMORY AID - Alpha-2 Agonist Effects ("SAD BRAD"): Sedation, Analgesia, Decreased GI motility, BRadycardia, Arrhythmias (AV block), Decreased insulin release. Also remember: ?2 agonists cause initial hypertension (peripheral vasoconstriction) followed by hypotension, and they cause marked ataxia in large animals. These effects can be reversed with ATIPAMEZOLE (the "anti" to ?2 agonists).

Beta Adrenergic Agonists

Table 9. Beta Adrenergic Agonists

Alpha-1 Adrenergic Agonists

Table 10. Alpha-1 Adrenergic Agonists

Adrenergic Antagonists (Sympatholytics)

Alpha Adrenergic Antagonists

Table 11. Alpha Adrenergic Antagonists

MEMORY AID - Alpha-2 Reversal Agents: "AtiPAMEZOLE is the ANTIdote for medeTOMidine/dexmedeTOMidine." Notice the similar endings! For xylazine in large animals, yohimbine or tolazoline may be used, though atipamezole also works. Remember that reversal removes the analgesia too - ensure adequate pain management before reversing!

Beta Adrenergic Antagonists (Beta-Blockers)

Beta-blockers competitively antagonize catecholamines at beta-adrenergic receptors. They are classified as non-selective (block both ?1 and ?2) or cardioselective (preferentially block ?1). They reduce heart rate, contractility, and blood pressure.

Table 12. Beta Adrenergic Antagonists

Neuromuscular Blocking Agents

Neuromuscular blocking agents (NMBAs) act at the nicotinic receptors of the neuromuscular junction (Nm receptors) to cause skeletal muscle paralysis. They are used during anesthesia to facilitate intubation, provide muscle relaxation during surgery, and aid mechanical ventilation. They have NO analgesic or sedative properties - patients must always be adequately anesthetized when NMBAs are used!

Classification of Neuromuscular Blocking Agents

NMBAs are classified into two categories based on their mechanism of action: depolarizing agents (which first stimulate then block the receptor) and non-depolarizing agents (which competitively block the receptor without initial stimulation).

Table 13. Comparison of Depolarizing vs. Non-Depolarizing NMB Agents

MEMORY AID - "Sux SUCKS" for Succinylcholine Side Effects: Salivation, Unusual cardiac effects (bradycardia, arrhythmias), Contractions (fasciculations), K+ elevation (hyperkalemia), Sustained block in pseudocholinesterase deficiency. Also causes malignant hyperthermia in susceptible individuals (especially swine) and has a risk of masseter muscle rigidity.

Table 14. Specific Neuromuscular Blocking Agents

MEMORY AID - Order of Muscle Paralysis and Recovery: Muscles are affected in this order: Small, rapidly contracting muscles (eyes, face) first, then limbs, trunk, intercostals, and DIAPHRAGM last. Recovery occurs in REVERSE order - diaphragm recovers first, eyes last. This is why patients may be able to breathe but still have facial weakness during recovery. Monitor using peripheral nerve stimulator (train-of-four).