Cholinergic Transmission and Pharmacology Quiz

Drugs Acting on Cholinergic Receptors

• Cholinergic receptors are found throughout the body.
• Learning objectives include identifying the locations and types of acetylcholine receptors in various organ systems.
• The mechanism of action and major clinical indications and contraindications of organophosphate pesticide poisoning and antidotes should be explained.
• Antimuscarinic agents and their uses, including mydriasis, cycloplegia, Parkinson's disease, asthma, bladder spasm, and muscarinic toxicity of insecticides, need to be related.

Learning Objectives

• Identify the locations and types of acetylcholine receptors in major organ systems (CNS, autonomic ganglia, eye, heart, vessels, bronchi, gut, genitourinary tract, skeletal muscle, and exocrine glands).
• Explain the mechanism of action, clinical indications, and contraindications of organophosphate insecticide poisoning.
• Relate antimuscarinic agents to their uses in treating conditions like mydriasis, cycloplegia, Parkinson's disease, asthma, bladder spasm, and muscarinic insecticide toxicity.
• Relate antimuscarinic agents to their uses in treating various conditions, including mydriasis, cycloplegia, Parkinson's, asthma, bladder spasms, and muscarinic toxicity.

Overview of Nervous System

• The nervous system is responsible for controlling bodily functions.
• It has both voluntary (somatic) and involuntary (autonomic) components.
• The autonomic nervous system further divides into sympathetic and parasympathetic divisions.

Craniocaudal vs. Thoracolumbar

• Visual diagrams demonstrate the different pathways of the cholinergic and adrenergic systems throughout the body.
• It shows how both systems innervate various organs.
• The diagram illustrates the "feed and breed" or "fight or flight" function based on innervation.

Overview of Autonomic Transmission

• Diagram depicts the synthesis and degradation of acetylcholine (ACh).
• This process illustrates the breakdown and subsequent synthesis of ACh at cholinergic nerve synapses.

Cholinergic Receptors

• Muscarinic receptors (M₁-M₅) have varying locations and mechanisms.
• Nicotinic receptors are categorized into subtypes based on their locations and functions.
• Both types are critical for cholinergic neurotransmission.

Cholinergic Transmission

• Synthesis, uptake into storage vesicles, release, and degradation of ACh are described.
• The steps in cholinergic neurotransmission from synthesis to receptor binding are visualized.

Botulinum Toxin (Botox)

• FDA approved botulinum toxin (BoNT) for short-term wrinkle treatment around the eyes and mouth.
• It's also used to treat generalized spastic disorders, like cerebral palsy.

Cholinergic Agonists

• Cholinergic stimulants are a group of drugs mimicking the effects of parasympathetic stimulation.
• Cholinergic agonists are categorized into direct and indirect acting.

Classification of Cholinergic Agonists

• Direct-acting agonists bind directly to muscarinic or nicotinic receptors.
• Indirect-acting (anticholinesterases) prevent the degradation of acetylcholine, causing elevated ACh levels.
• The mechanism of action of common indirect-acting agonists (organophosphates) involves irreversible binding to the acetylcholinesterase (AChE).

Direct-acting Cholinergic Agonists: Acetylcholine (ACh)

• Acetylcholine (ACh) is a critical neurotransmitter.
• It plays many roles in the body, including actions on the heart, blood vessels, gastrointestinal tract, bronchi, genitourinary tract, and eye.

Direct-acting Cholinergic Agonists: Bethanechol

• Bethanechol is a cholinergic agonist chemically related and similar to acetylcholine.
• It has a longer duration of action due to its resistance to acetylcholinesterase.
• Its primary action targets smooth muscles of the bladder and gastrointestinal tract.
• It has specific therapeutic uses and adverse effects.

Direct-actin Cholinergic Agonists: Pilocarpine

• Pilocarpine is a less potent agonist than acetylcholine.
• It can penetrate the central nervous system and is more resistant to hydrolysis by acetylcholinesterase.
• Its therapeutic uses include glaucoma and xerostomia.

Direct-acting Cholinergic Agonists: Carbachol

• Carbachol potently stimulates both muscarinic and nicotinic receptors.
• It's a poor substrate for acetylcholinesterase, resulting in a prolonged action duration.
• Its clinical uses consist mainly of reducing intraocular pressure.

Clinical Pharmacology of Direct-acting Cholinergic Agonists

• Summarizes the actions and clinical use of specific direct-acting cholinergic agonists.
• Information about their receptor sensitivity, cholinesterase activity, and clinical use.

Indirect-acting Cholinergic Agonists

• Indirect-acting agents work by inhibiting acetylcholinesterase.
• Agents include but are not limited to Physostigmine, Edrophonium, Neostigmine, Pyridostigmine, Echothiophate.

Indirect-acting Cholinergic Agonists: Edrophonium

• Edrophonium is a highly selective inhibitor of acetylcholinesterase.
• Useful in the diagnosis and treatment of myasthenia gravis, an autoimmune neuromuscular disease.
• It's also an antidote for non-depolarizing neuromuscular blockers.

Indirect-acting Cholinergic Agonists: Physostigmine

• Physostigmine is a reversible intermediate-acting inhibitor of acetylcholinesterase involved in the central as well as the peripheral nervous system.

Indirect-acting Cholinergic Agonists: Neostigmine

• Neostigmine is an intermediate-acting inhibitor of acetylcholinesterase.
• Its actions primarily affect the autonomic nervous system with effects on the bladder and gastrointestinal tract and muscle contractility in the skeletal muscles.

Indirect-acting Cholinergic Agonists: Pyridostigmine

• Pyridostigmine is an intermediate-acting acetylcholinesterase inhibitor.
• It has a longer duration of action compared to neostigmine and is better absorbed.
• Pyridostigmine is commonly used for treating myasthenia gravis.

Indirect-acting Cholinergic Agonists: Echothiophate

• Echothiophate is an irreversible anticholinesterase.
• It covalently binds to the active site of acetylcholinesterase.
• Its actions are used in glaucoma treatment.

Organophosphate Poisoning

• Organophosphates are potent acetylcholinesterase inhibitors.
• Exposure can lead to severe cholinergic symptoms due to the prolonged action of acetylcholine.

Summary: Clinical Use of Direct-acting Cholinergic Agonists

• Provides a summary table of various direct-acting cholinergics and their uses.

Summary: Clinical Use of Indirect-acting Cholinergic Agonists

• Lists the various indirect-acting cholinergics and their uses in various conditions.

Cholinergic Antagonists

• Cholinergic antagonists, also known as parasympatholytics, block the action of acetylcholine at cholinergic receptors.

Antimuscarinic Agents

• Antimuscarinic agents competitively block muscarinic receptors.

Atropine

• Atropine is the prototypical antimuscarinic agent.
• It has varied effects throughout the body.
• Atropine acts as a competitive antagonist of muscarinic receptors.

Scopolamine

• Scopolamine has a longer-lasting effect on the central nervous system compared to atropine.
• Scopolamine is often used to treat motion sickness.

Ipratropium & Tiotropium

• Ipratropium and tiotropium are quaternary ammonium derivatives of atropine that act as bronchodilators.
• They are used in chronic obstructive pulmonary diseases (COPDs).

Summary of Antimuscarinic Agents and their Therapeutic Uses

• Provides a compilation of antimuscarinic agents and their therapeutic applications.

Antimuscarinic Side Effects

• Presents a list of adverse effects associated with antimuscarinic agent use.

Anticotinic Agents (Ganglionic Blockers)

• Ganglionic blockers act on nicotinic receptors.
• They have broad effects on the autonomic nervous system and their clinical use is limited.

Acknowledgement

• Expresses gratitude to a colleague for providing lecture slides.

My Growth Mindset Statements

• Offers different phrases for positive self-talk, encouraging a growth mindset approach to learning.