The basis of autonomic pharmacology reflects the physiology of the sympathetic nervous system (SNS) and the parasympathetic nervous system (PSNS) to regulate involuntary reactions to stresses on multiorgan systems within the body. When a pathologic process is present that affects the homeostasis achieved between the SNS and PSNS in this process, either of these branches can become overactive while the other is excessively inhibited.[1] This break in homeostasis results in various clinical manifestations that can range in severity from simply presenting rhinorrhea symptomology to fatal presentations like cardiovascular collapse.[2] For a wide range of presentations and severity of pathologies, the agents classified in autonomic pharmacology are indicated to re-establish the homeostasis that the human body attempts to produce via the autonomic nervous system (ANS).[3]
Within autonomic pharmacology, there are four specific categories of drugs based on how they affect the ANS:
The clinical indications of medications from each of the four categories are listed below. Important to note is that this is not a complete list due to the vastness of this topic; drugs included are representative of each category.
FDA-labeled indications:
Cholinomimetics/Cholinesterase antagonists[4][5][6][7]:
Anticholinergics[8][9][10][11][12][13][14]:
Adrenoreceptor agonists/Sympathomimetics[15][16][17][18][19][20][21]:
Adrenoreceptor antagonists[22][23][24]:
As with the homeostasis established via processes performed by the SNS and PSNS, drugs from each of the four categories listed above also work inversely of each other. The primary mechanism of action for most of these agents are to serve as either agonists or antagonists of specific receptors within these systems.[2] The receptors with their locations and physiologic actions are listed below.
For adrenoreceptors stimulated by norepinephrine (synapses) and epinephrine (endocrine), involved in SNS processes[25][26]:
For cholinoreceptors stimulated by acetylcholine, most involved in PSNS processes[27]:
For dopamine receptors, most involved in both SNS and PSNS processes[28]:
In terms of the four categories mentioned, each is an agonist and/or antagonist of the receptors listed. Cholinomimetics have agonist activity at muscarinic receptors augmenting PSNS activity to achieve the desired effects of increasing GI motility and decreasing intraocular pressure.[4][5] Whereas the other agents mentioned work directly on receptors as agonists/antagonists, the subcategory of drugs that also achieve similar effects to cholinomimetics is the cholinesterase antagonists. These agents inhibit acetylcholinesterase enzymes within the synaptic cleft to increase the concentration of acetylcholine, resulting in increased PSNS neurotransmission and facilitating skeletal muscle contraction.[7] Inversely, the anticholinergic agents work to inhibit PSNS activity, the main mechanism of action involving antagonism of muscarinic receptors resulting in increased heart rate and conduction velocity and stimulate bronchodilation.[8][9]
Within the SNS system, adrenoreceptor agonists/sympathomimetics work at alpha and beta receptors to potentiate SNS activity to achieve higher cardiac output and fast bronchodilation.[16][18] Inversely, adrenoreceptor antagonists are also active at alpha and beta receptors in decreasing SNS neurotransmission to reduce heart rate, dampen high catecholamine states, and increase urinary smooth muscle relaxation.[24][22][23]
Due to the various effects of the ANS on cardiovascular, pulmonary, gastrointestinal, and genitourinary systems, the general theme of reactions to these medications involves effects on these organ systems. The various reactions to each of the categories of agents include[16][18][24][22][23]:
Based on the adverse reaction profiles of each category, several significant contraindications can be elucidated[34][35][31]:
Toxic profiles of the four categories described are mostly involved in overdose, exhibiting the same effects that are augmented so that the benefits no longer outweigh the risks. The primary reversal strategy for these situations typically is to discontinue the offending agent and treat the resultant symptoms.[1] Several agents of each category have toxic effects which require more specific reversal methods as listed[7][36][37][38]:
Healthcare workers who prescribe agents that work on the autonomic system must be fully aware of the side effects of these agents. Requisite close monitoring of vital signs, including blood pressure, heart rate, respiratory rate, oxygen saturation, and temperature is strongly recommended when attempting to reestablish autonomic homeostasis with ANS agents.[2] Several common conditions which require autonomic pharmacological correction need specific monitoring[39][40][41][42]:
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