Autonomic Nervous System and Cholinergic Transmission

Autonomic Nervous System

• The autonomic nervous system includes the central nervous system (CNS) and peripheral nervous system (PNS).
• CNS consists of the spinal cord and brain.
• PNS includes sensory and motor neurons, connecting the CNS to stimulus receptors and effectors (muscles and glands).

Cholinergic Transmission

• Acetylcholine (ACh) is synthesized, released, and stored for neurotransmission.
• Cholinergic drugs can be classified based on their mechanisms: directly-acting and indirectly-acting.

Cholinergic Drugs

• Directly-acting drugs include choline esters (e.g., Acetylcholine, Bethanechol) and alkaloids (e.g., Pilocarpine).
• Indirectly-acting drugs (anticholinesterases) inhibit cholinesterase, increasing ACh levels. They are categorized into reversible (e.g., Physostigmine, Neostigmine) and irreversible (e.g., Echothiophate, Malathion).

Cholinergic Receptors

• Muscarinic receptors (M) are G-protein coupled, located in autonomic ganglia, the heart, and various glands.
• Nicotinic receptors (N) are ion-channel linked, present at neuromuscular junctions and autonomic ganglia.

Therapeutic Use of Acetylcholine

• ACh is not typically used therapeutically due to its rapid hydrolysis and nonselective action.

Pharmacological Actions of Cholinergic Drugs

• Muscarinic Actions:

  • Eye: causes miosis, improves near vision, reduces intraocular pressure.
  • Gastrointestinal (GI) tract: increases motility and secretion.
  • Respiratory: bronchoconstriction and increases mucus secretion.
  • Urinary: contracts bladder and facilitates urination.
  • Cardiovascular system: decreases heart rate, produces vasodilation.

• Nicotinic Actions:

  • Increased heart rate and blood pressure with sympathetic stimulation.
  • Increased GI motility and urinary frequency.

Adverse Effects of Cholinergic Drugs

• Side effects include sweating, salivation, flushing, decreased heart rate and blood pressure, nausea, diarrhea, and bronchospasm.

Pilocarpine

• Pilocarpine, an alkaloid, primarily stimulates muscarinic receptors.
• This drug can treat glaucoma, Sjögren's syndrome, and xerostomia.
• Common adverse effects include excessive salivation and sweating.

Acetylcholinesterase Inhibitors

• These drugs inhibit the breakdown of ACh, with reversibles like Physostigmine and Neostigmine being crucial in clinical settings.
• Irreversible inhibitors, primarily organophosphates, are more relevant as toxic agents rather than therapeutic drugs.

Organophosphate Poisoning

• Exposure results in excessive stimulation of muscarinic and nicotinic receptors leading to symptoms like diarrhea, urination, miosis, bradycardia, and muscle excitation.
• Management includes administering atropine to block muscarinic effects and reactivating acetylcholinesterase with Pralidoxime (PAM) to counteract poisoning.

Myasthenia Gravis

• Myasthenia gravis is a chronic autoimmune disorder leading to muscle weakness due to impaired communication between nerves and muscles.
• Symptoms include ptosis, diplopia, difficulty swallowing, and muscle fatigue.
• Treatment involves acetylcholinesterase inhibitors (e.g., pyridostigmine) and potentially immunosuppressants or thymectomy.

Key Uses of Cholinergic Drugs

• Pilocarpine and Physostigmine for glaucoma, Neostigmine and Pyridostigmine for myasthenia gravis, and bladder dysfunction treatment post-surgery.
• Antidote for drug poisoning: Atropine for cholinesterase inhibitor overdose.

Study Questions Overview

• Correct pair of cholinoreceptors with locations, uses of Pilocarpine, mechanism of anticholinesterase drugs, and defining characteristics of myasthenia gravis are emphasized in review questions.

Autonomic Nervous System

• The autonomic nervous system includes the central nervous system (CNS) and peripheral nervous system (PNS).
• CNS consists of the spinal cord and brain.
• PNS includes sensory and motor neurons, connecting the CNS to stimulus receptors and effectors (muscles and glands).

Cholinergic Transmission

• Acetylcholine (ACh) is synthesized, released, and stored for neurotransmission.
• Cholinergic drugs can be classified based on their mechanisms: directly-acting and indirectly-acting.

Cholinergic Drugs

• Directly-acting drugs include choline esters (e.g., Acetylcholine, Bethanechol) and alkaloids (e.g., Pilocarpine).
• Indirectly-acting drugs (anticholinesterases) inhibit cholinesterase, increasing ACh levels. They are categorized into reversible (e.g., Physostigmine, Neostigmine) and irreversible (e.g., Echothiophate, Malathion).

Cholinergic Receptors

• Muscarinic receptors (M) are G-protein coupled, located in autonomic ganglia, the heart, and various glands.
• Nicotinic receptors (N) are ion-channel linked, present at neuromuscular junctions and autonomic ganglia.

Therapeutic Use of Acetylcholine

• ACh is not typically used therapeutically due to its rapid hydrolysis and nonselective action.

Pharmacological Actions of Cholinergic Drugs

• Muscarinic Actions:

  • Eye: causes miosis, improves near vision, reduces intraocular pressure.
  • Gastrointestinal (GI) tract: increases motility and secretion.
  • Respiratory: bronchoconstriction and increases mucus secretion.
  • Urinary: contracts bladder and facilitates urination.
  • Cardiovascular system: decreases heart rate, produces vasodilation.

• Nicotinic Actions:

  • Increased heart rate and blood pressure with sympathetic stimulation.
  • Increased GI motility and urinary frequency.

Adverse Effects of Cholinergic Drugs

• Side effects include sweating, salivation, flushing, decreased heart rate and blood pressure, nausea, diarrhea, and bronchospasm.

Pilocarpine

• Pilocarpine, an alkaloid, primarily stimulates muscarinic receptors.
• This drug can treat glaucoma, Sjögren's syndrome, and xerostomia.
• Common adverse effects include excessive salivation and sweating.

Acetylcholinesterase Inhibitors

• These drugs inhibit the breakdown of ACh, with reversibles like Physostigmine and Neostigmine being crucial in clinical settings.
• Irreversible inhibitors, primarily organophosphates, are more relevant as toxic agents rather than therapeutic drugs.

Organophosphate Poisoning

• Exposure results in excessive stimulation of muscarinic and nicotinic receptors leading to symptoms like diarrhea, urination, miosis, bradycardia, and muscle excitation.
• Management includes administering atropine to block muscarinic effects and reactivating acetylcholinesterase with Pralidoxime (PAM) to counteract poisoning.

Myasthenia Gravis

• Myasthenia gravis is a chronic autoimmune disorder leading to muscle weakness due to impaired communication between nerves and muscles.
• Symptoms include ptosis, diplopia, difficulty swallowing, and muscle fatigue.
• Treatment involves acetylcholinesterase inhibitors (e.g., pyridostigmine) and potentially immunosuppressants or thymectomy.

Key Uses of Cholinergic Drugs

• Pilocarpine and Physostigmine for glaucoma, Neostigmine and Pyridostigmine for myasthenia gravis, and bladder dysfunction treatment post-surgery.
• Antidote for drug poisoning: Atropine for cholinesterase inhibitor overdose.

Study Questions Overview

• Correct pair of cholinoreceptors with locations, uses of Pilocarpine, mechanism of anticholinesterase drugs, and defining characteristics of myasthenia gravis are emphasized in review questions.

Explore the autonomic nervous system, including the CNS and PNS, and learn about cholinergic transmission, including the synthesis and release of acetylcholine.