Autonomic Nervous System (Pharmacology, Receptors, and Physiology)

The autonomic nervous system (ANS) regulates involuntary bodily functions and is crucial for maintaining homeostasis. Understanding the ANS involves knowing its various receptors, which play a significant role in how drugs interact with this system. This video emphasizes pharmacology related to the ANS while providing essential background on receptor types and general physiology necessary for mastering drug interactions.

The autonomic nervous system consists of two main components: the sympathetic and parasympathetic nervous systems. The sympathetic system, known for its 'fight or flight' response, activates during extreme stress to prepare the body for action, while the parasympathetic system promotes 'rest and digest,' focusing on bodily functions when not under threat. These systems operate oppositely; activation of one inhibits the other to conserve resources effectively in different situations. Understanding these dynamics is crucial as today's focus will primarily be on pharmacology related to the parasympathetic side.

The parasympathetic nervous system regulates involuntary visceral organs and has craniosacral outflow, originating from cranial nerves down to sacral nerves. Four key cranial nerves exhibit parasympathetic activity: Cranial Nerve III (Edinger-Westphal nucleus for meiosis and accommodation), Cranial Nerve VII (Superior salivary nucleus for lacrimal gland secretion), Cranial Nerve IX (Inferior salivary nucleus for parotid gland secretion), and Cranial Nerve X (Dorsal vagal nucleus controlling GI tract secretions). Acetylcholine is the primary neurotransmitter in this system, crucial for understanding related pharmacology. The focus on muscarinic receptors—where acetylcholine binds—is essential as they are more relevant than nicotinic receptors in exams.

Understanding Muscarinic Receptors: Cognition and Heart Rate Effects Muscarinic receptors M1, M4, and M5 in the central nervous system enhance cognitive functions such as learning and attention when activated by agonists. Conversely, antagonists at these receptors impair cognition. The m2 receptor affects heart rate; agonism leads to bradycardia while antagonism results in tachycardia. Agonist action on the m3 receptor causes bladder contraction for urination but antagonist action leads to urinary retention.

M3 Receptor Functions Across Body Systems M3 receptors are also found in various body systems including the gastrointestinal tract where agonists promote peristalsis (bowel movements) while antagonists cause constipation. In exocrine glands, muscarinic activation increases secretions whereas blockade reduces them leading to dry mouth symptoms. Eye effects include meiosis with agonistic stimulation versus mydriasis from antagonism; this is relevant for glaucoma treatments. Lastly, airway responses show that bronchoconstriction occurs with m3 receptor activation while bronchodilation happens with its inhibition.

Muscarinic antagonists, or anticholinergics, block parasympathetic effects in the body. This leads to increased heart rate (tachycardia), bladder relaxation preventing urination, reduced bowel movement due to decreased peristalsis, diminished secretions, pupil dilation for better vision under stress, and bronchodilation for improved breathing. For instance, when faced with a threat like a bear attack—akin to administering an antagonist—the body prioritizes survival by shutting down non-essential functions such as digestion and urination while enhancing alertness and physical readiness.

Understanding Anticholinergic Medications Medications affecting the parasympathetic nervous system can either mimic its effects or block them. Cholinergic agents, like acetylcholine, activate muscarinic receptors while anticholinergic drugs inhibit these receptors. Key anticholinergics to memorize include atropine for cholinergic poisoning and bradycardia treatment; scopolamine for motion sickness; benztropine and trihexyphenidyl for extrapyramidal side effects in Parkinson's disease; oxybutynin for overactive bladder; dicyclomine for irritable bowel syndrome symptoms.

Clinical Applications of Anticholinergics Atropine is crucial in treating organophosphate poisoning by reversing cholinergic symptoms. Scopolamine alleviates seasickness, making it popular near coastal areas. Oxybutynin effectively manages overactive bladder issues while dicyclomine addresses cyclical diarrhea associated with irritable bowel syndrome by slowing GI peristalsis. Glycopyrrolate controls salivation during surgery and regulates heart rate, whereas ipratropium and tiotropium are beneficial in COPD management through bronchodilation.

The parasympathetic nervous system utilizes muscarinic receptors, and drugs that block acetylcholine are classified as anti-muscarinic or anticholinergic. These blockers mimic the effects of activating the sympathetic nervous system by inhibiting parasympathetic functions. Conversely, cholinergic agents stimulate these muscarinic receptors directly or indirectly to produce similar physiological responses as natural acetylcholine activation. Direct agonists bind to specific muscarinic receptors while indirect agonists enhance endogenous acetylcholine activity through more complex mechanisms.

The neuromuscular junction involves acetylcholine, a neurotransmitter that binds to postsynaptic muscarinic receptors. To prevent excessive binding and its associated effects, the body uses an enzyme called acetylcholinesterase to break down acetylcholine in the synapse. Indirect muscarinic agonists work by inhibiting this enzyme, leading to increased levels of acetylcholine available for receptor binding and enhancing parasympathetic effects. There are two categories of these drugs: direct muscarinic agonists like bethanechol, carbachol, methacholine, and pilocarpine; with most having 'col' in their names indicating they are cholinergic agents.

Key Uses of Direct Cholinergic Agonists Direct cholinergic agonists include medications like bethanechol, carbachol, methacholine, and pilocarpine. Bethanechol treats urinary retention by stimulating bladder contraction through M3 receptors. Carbachol reduces intraocular pressure in glaucoma via meiosis; methacholine is used for bronchial challenge tests to diagnose asthma; while pilocarpine aids in treating Sjogren's syndrome and diagnosing cystic fibrosis due to its ability to increase secretions such as sweat.

Understanding Indirect Muscarinic Agonists Indirect muscarinic agonists are acetylcholinesterase inhibitors that enhance the availability of acetylcholine for increased parasympathetic effects. Key drugs include physostigmine (for atropine overdose), pyridostigmine (for myasthenia gravis), edrophonium (diagnostic tool for myasthenia gravis), and donepezil (treatment for Alzheimer's disease). Mnemonics help remember their uses: "fisa stigma" relates physostigmine with physical symptoms from atropine overdose, while "done" signifies memory loss treated by donepezil.

Understanding the pharmacology of the parasympathetic nervous system is crucial for grasping its role in cognitive decline, particularly in Alzheimer's. Instead of memorizing individual agents, focus on comprehending the physiology and functions of m1 to m5 receptors. Recognize how stimulating or inhibiting these receptors affects bodily responses and appreciate the balance between parasympathetic and sympathetic systems. This foundational knowledge will enhance your understanding significantly more than rote memorization would.