Autonomic Nervous System Part 2: Parasympathetic Nervous System

Overview of the Parasympathetic Nervous System (PSNS)

• General Characteristics:

  • Also known as the Cholinergic system.
  • Commonly referred to by the mnemonic "Rest and Digest."
  • Primary functions include the restoration of energy stores and maintaining internal balance (homeostasis).
  • Unlike the sympathetic nervous system, which often has a diffuse effect, the parasympathetic system tends to stimulate a specific body part or system.

• Neurotransmitter:

  • The primary neurotransmitter (NT) is acetylcholine ($ACH$).
  • $ACH$ is used at both the ganglia and the postganglionic nerve endings.

The Vagus Nerve

• Anatomical and Functional Profile:
  • It is the 10th cranial nerve and contains primarily parasympathetic fibers.
  • Branches: It branches to the larynx, pharynx, heart, lungs, blood vessels, and various digestive areas.
  • Parasympathetic Responses:
    • Slows the heart rate.
    • Causes bronchoconstriction.
    • Increases gastrointestinal (GI) activity.
    • Decreases blood pressure.
  • Related Reflexes and Functions: Involved in the gag reflex, sweating, and speaking.
  • Vasovagal Response: Sudden or excessive stimulation of the vagus nerve can lead to a significant drop in heart rate ($HR$) and blood pressure ($BP$). This is referred to as a "vasovagal" response and can result in syncope (fainting).

Parasympathetic Organ Effects and Neurotransmission

• Organ-Specific Responses:

  • Adrenal medulla: Not supplied by parasympathetic nerves.
  • Arteries: Most arteries are not supplied by parasympathetic nerves; however, stimulation can result in a slight decrease in blood pressure through other mechanisms.
  • Heart:
    • Decreases heart rate ($HR$).
    • Decreases Atrioventricular ($AV$) conduction.
    • Causes a slight decrease in contractility.
  • Intestines/GI Tract: Increased motility and increased secretions.
  • Pupil of the eye: Constriction, also known as miosis.
  • Respiratory passages: Causes bronchoconstriction.
  • Urinary bladder: Contraction of the bladder wall.
  • Urinary sphincter: Relaxation, facilitating urination.

• Summary of Effects:

  • Release of $ACH$ (cholinergic).
  • Increased urination and defecation.

Cholinergic Receptor Types

All cholinergic receptors are stimulated by $ACH$. They are categorized into three main types:

• Muscarinic ($M$):

  • Location: Located on cardiac muscle, smooth muscle, and glands.
  • Site: Found at the parasympathetic postganglionic nerve endings.
  • Effects: Decreased $HR$, bronchoconstriction, increased digestion, increased GI secretions, increased urination, and pupillary constriction.

• Nicotinic 1 ($N_n$):

  • Location: Found at the ganglia (synapse area) of both parasympathetic and sympathetic nerves.

• Nicotinic 2 ($N_m$):

  • Location: Somatic nervous system, specifically at the neuromuscular junction of skeletal muscle.
  • Function: Stimulation at this site causes the skeletal muscle to contract (under voluntary control).

Neurotransmission and the Life Cycle of Acetylcholine

• Nerve Structure:

  • Parasympathetic nerves typically have a long preganglionic nerve.
  • The ganglion contains Nicotinic 1 ($N_n$) receptors.
  • $ACH$ is released at the ganglion.
  • The postganglionic nerve endings release $ACH$.
  • The effector organ contains muscarinic receptors.

• Synthesis and Inactivation (Figure 7.1):

  1. Synthesis: Choline is taken up into the nerve ending and combined with $Acetyl-CoA$ to form $ACH$.
  2. Storage: $ACH$ is stored in vesicles within the cholinergic nerve ending.
  3. Release: Upon stimulation, $ACH$ is released into the synaptic cleft.
  4. Binding: $ACH$ stimulates muscarinic receptors ($M$) on internal organs/glands, nicotinic receptors ($N_n$) on autonomic ganglia, or nicotinic receptors ($N_m$) on skeletal muscle.
  5. Inactivation: $ACH$ is inactivated enzymatically by acetylcholinesterase. It is broken down into Choline and Acetate.

ANS Drug Effects and Parasympathomimetics

• Terminology:

  • Parasympathomimetic effects: Drugs that mimic the parasympathetic system (cholinergic agonists, cholinergics).
  • Parasympatholytic effects: Drugs that work against the parasympathetic system (cholinergic antagonists, anticholinergics).

• Direct-Acting Cholinergic Agonists:

  • Mechanism of Action (MOA): Directly stimulate or bind to muscarinic receptors in the parasympathetic division. They mimic the actions of $ACH$.
  • Physiological Effects: Cause miosis, decrease the amount of fluid in the eye (decreasing intraocular pressure), and prevent constipation or urinary retention.
  • Clinical Uses: Glaucoma, post-cataract surgery, urinary retention, and intestinal stasis.
  • Specific Drug Examples: Bethanechol.

• Indirect-Acting Cholinergic Agonists:

  • Mechanism of Action (MOA): Inhibit the enzyme acetylcholinesterase, preventing the destruction of $ACH$ in the synapse. This allows for a buildup of $ACH$ at all cholinergic sites (muscarinic, $N_n$, and $N_m$).
  • Clinical Uses: Urinary retention, intestinal stasis/ileus, and treatment for Myasthenia Gravis.
  • Myasthenia Gravis Definition: An autoimmune disease where antibodies attack the $N_m$ ($N_2$) receptors, causing skeletal muscle weakness and paralysis.
  • Anesthesia Reversal: Can reverse respiratory paralysis caused by certain anesthetic drugs.

• Antidote for Cholinergic Poisoning: Atropine.

Cholinergic Side Effects and Patient Teaching

• SLUDGE Mnemonic (Partially detailed in transcript):

  • S: (Salivation)
  • L: Lacrimation (tearing)
  • U: Urinary incontinence
  • D: (Diarrhea/Diaphoresis)
  • G: (GI upset)
  • E: Emesis (vomiting)

• Other Side Effects: Nausea, blurred vision, bradycardia, muscular tremors, hypotension, and bronchoconstriction.

Anticholinergics (Parasympatholytics)

• Mechanism of Action (MOA):

  • Bind to cholinergic receptors to act as blocking drugs (antagonism).
  • Decrease vagus nerve activity.

• Physiological Effects:

  • Increases heart rate ($HR$).
  • Causes mydriasis (pupillary dilation).
  • Decreases GI secretions and motility (slows digestion).
  • Decreases urination.
  • Causes bronchodilation.

• Patient Teaching and Side Effects:

  • Dry mouth, visual disturbances, urinary retention, constipation, tachycardia, and general drying effects.

• Drug Examples: Atropine (Atropine Sulfate Inj., USP, $1\,mg/mL$ for IM, IV, or SC use).

• Antidote for Anticholinergic Overdose: Physostigmine (which exhibits cholinergic activity).

Sweat Glands and Autonomic Control

• Eccrine Glands:

  • Location: Non-hairy areas, secreting through skin pores.
  • Control: Sympathetic cholinergic control.
  • Receptors: Muscarinic receptors stimulated by $ACH$.
  • Function: Regulate body temperature at all times.

• Apocrine Glands:

  • Location: Hairy areas, secreting through hair follicles and then skin.
  • Control: Sympathetic adrenergic control.
  • Receptors: Alpha-1 ($\alpha_1$) receptors stimulated by Epinephrine ($EPI$) and Norepinephrine ($NE$).
  • Function: Used to cool down when expending energy.

Parkinson’s Disease and Drug Therapy

• Pathophysiology:

  • Characterized by decreased levels of dopamine ($DA$).
  • Low $DA$ leads to excessive $ACH$ activity.

• Symptoms: Excessive motor activity, tremors, muscle rigidity, bradykinesia (slow movement), and difficulty with posture and balance.

• Drug Therapy Objectives:

  • Increase levels of $DA$.
  • Decrease the metabolism of $DA$.
  • Stimulate dopamine receptors.
  • Anticholinergics: Used to block excessive $ACH$ to reduce symptoms of tremor and rigidity.