Pharmacology of the Autonomic Nervous System Study Notes

Functional Organization of the Autonomic Nervous System

The autonomic nervous system (ANS) is divided into two primary systems that regulate involuntary bodily functions: the Sympathetic (Adrenergic) system and the Parasympathetic (Cholinergic) system. The Sympathetic system is associated with the ‐fight‐ response, which prepares the body for stress or physical activity. Its physiological effects include increases in heart rate, respiration rate, and blood flow to the skeletal muscles, while simultaneously decreasing gastrointestinal (GI) function and causing pupillary dilation (mydriasis). Conversely, the Parasympathetic system is described as ‐homeostatic‐ as it focuses on restoring the body to normal levels. It brings the heart rate, respiration rate, and muscle blood flow back to resting levels, returns GI function to normal operations, and constricts the pupils back to their normal size.

Mechanisms of Neural Transmission in the Autonomic Nervous System

Neural signaling in the autonomic nervous system involves a specific sequence of components including the presynaptic nerve, the postsynaptic nerve, and the synaptic cleft. The presynaptic nerve is the nerve that generates the original electrical impulse. The synaptic cleft is the physical space bridged by chemical substances known as neurotransmitters. The postsynaptic nerve is the nerve waiting to receive the impulse on the other side of this gap. The primary neurotransmitters of the autonomic nervous system are Acetyl Choline ($ACh$) and Noradrenaline (also known as norepinephrine). $ACh$ acts as the presynaptic neurotransmitter in both the sympathetic and parasympathetic ganglia. It also serves as the postsynaptic neurotransmitter at most parasympathetic nerve endings and the postsynaptic sympathetic terminals located at sweat glands. Noradrenaline acts as the postsynaptic neurotransmitter for sympathetic nerves, with the specific exception of those leading to sweat glands.

Classification and Localization of Cholinergic Receptors

Cholinergic receptors are divided into two main categories: Muscarinic and Nicotinic. Muscarinic receptors are stimulated by muscarine and $ACh$. These receptors are localized in the cardiac atrial muscle, the cells of the Sinoatrial ($SA$) and Atrioventricular ($AV$) nodes, smooth muscle, exocrine glands, and the central nervous system ($CNS$). They can be pharmacologically blocked by atropine. Nicotinic receptors are stimulated by nicotine and $ACh$ and are localized at neuromuscular junctions, autonomic ganglia, and the $CNS$. These receptors are specifically blocked by tubocurarine and hexamethonium.

Subtypes and Physiological Roles of Adrenergic Receptors

Adrenergic receptors are generally stimulated by epinephrine and are subdivided into Alpha and Beta categories. Alpha-adrenergic receptors include the $\alpha_1$ and $\alpha_2$ subtypes. $\alpha_1$ receptors are postsynaptic and primarily produce excitatory actions. They are localized in the eye, where they cause mydriasis (pupillary dilation); in the blood vessels, where they induce vasoconstriction; and in the sphincters of the gastrointestinal and urinary tracts, where they cause spasms. $\alpha_2$ receptors are presynaptic and serve as a feedback mechanism to decrease sympathetic discharge from the brain and reduce the release of Noradrenaline ($NE$). Beta-adrenergic receptors include $\beta_1$ and $\beta_2$ subtypes. $\beta_1$ receptors are localized in the heart, where they stimulate all cardiac properties; the $CNS$, causing stimulatory effects; and the kidney, where they increase renin release. $\beta_2$ receptors are localized in the bronchi to cause bronchodilation and in the blood vessels of skeletal muscles to cause vasodilation ($VD$). They also play roles in glycogenolysis, tremor production, and increasing insulin secretion.

Comparative Physiological Effects of the Sympathetic and Parasympathetic Systems

The Sympathetic system induces a wide range of organ-specific effects, including the dilation of pupils, inhibition of salivation, relaxation of the bronchi, and acceleration of the heartbeat. It inhibits peristalsis and secretion in the GI tract, stimulates glucose production and release (glycogenolysis), and triggers the secretion of adrenaline and noradrenaline. Additionally, it inhibits bladder contraction and stimulates orgasm. The Parasympathetic system produces contrasting effects, such as constricting pupils, stimulating saliva flow, constricting the bronchi, and slowing the heartbeat. It stimulates peristalsis and secretion, stimulates the release of bile, and causes the bladder to contract.

Classification and Pharmacokinetics of Sympathomimetic Drugs

Autonomic nervous system drugs function by either mimicking neurotransmitters or interfering with their release. Sympathomimetics are categorized into Catecholamines and Non-catecholamines based on their chemical structure and pharmacokinetic properties. Catecholamines, such as Adrenaline, Noradrenaline ($NA$), Dopamine, and Isoprenaline, provide direct stimulation of adrenergic receptors. They are not absorbed orally, have a rapid onset but short duration of action, are easily destroyed by Monoamine Oxidase ($MAO$), and do not cross the blood-brain barrier ($BBB$). Non-catecholamines, including Phenylephrine, Ephedrine, and Amphetamine, work through both direct and indirect stimulation of receptors. Unlike catecholamines, they are absorbed orally, have a slow onset but long duration of action, are not destroyed by $MAO$, and can cross the $BBB$.

Pharmacological Actions and Clinical Indications of Sympathomimetics

Sympathomimetic drugs affect multiple systems. In the cardiovascular system ($CVS$), they stimulate the heart and cause vasodilation in skeletal blood vessels while causing vasoconstriction in cutaneous and splanchnic blood vessels. In the eye, they cause mydriasis and decrease intraocular pressure ($IOP$). In the lungs, they induce bronchodilatation. They also act as a physiological antidote for histamine, making them effective antiallergic agents. Clinical indications include anaphylactic shock (using Adrenaline), acute hypotensive states or shock (using Dobutamine, $NE$, or Phenylephrine), congestive heart failure ($HF$), and cardiac arrest (via intracardiac Adrenaline). They are also used for heart block (Isoprenaline), in combination with local anesthesia (Adrenaline), and for bronchial asthma (Salbutamol or Adrenaline).

Adverse Effects, Contraindications, and Nursing Implications

The use of sympathomimetics can lead to cardiovascular adverse effects such as tachycardia, arrhythmia, angina, hypertension, and ischemia. Central and musculoskeletal side effects include tremors, insomnia, and anxiety. These drugs are contraindicated in patients with hypertension, angina, and thyrotoxicosis. Nursing implications require a thorough assessment of patient history regarding cardiovascular disease, cerebrovascular disease, diabetes mellitus, and hyperthyroidism. Administration protocols dictate that norepinephrine drips must not be mixed with other medications in an $IV$ line. Parenteral drugs must be diluted to prevent tissue irritation or infection, and catecholamines must be protected from light exposure. Nurses must teach patients to monitor their pulse, blood pressure, and urine output for signs of toxicity when using local decongestants. Patients should be informed that Isoprenaline may turn saliva or sputum pink and that any discolored solution, specifically Phenylephrine, must be discarded.