Section 6 - (PT1) Drugs Affecting the Autonomic Nervous System

Click to edit Master title style Click to edit Master text styles Second level Third level Fourth level Fifth level Click to edit Master title style Click to edit Master text styles Second level Third level Fourth level Fifth level Principles of Pharmacology and Toxicology (BIOL3020) The Autonomic Nervous System  Review of Neurons Neurons consist of a cell body, axon and nerve terminal Nerve terminal releases neurotransmitters that can act at other neurons, muscle or glands. Ganglion is a collection of neuron cell bodies outside the CNS with innervating nerve terminals Final Target Cell body Axon Nerve terminal CNS Ganglion Basic Anatomy of the Autonomic Nervous System Basic Anatomy of the Autonomic Nervous System How is information relayed n q Preganglionic Postganglionic CNS Which chemicals are involved in the autonomic nervous system (adren) PreG PostG Na E  mAcR GPCR Adren GPCR (adren) The Nicotinic Acetylcholine Receptors  Na Action Potential Na Target Cell acetylcholine Preganglionic neuron Postganglionic neuron Muscarinic acetylcholine receptor Nicotinic acetylcholine receptor Depolarization and possible Action Potential Parasympathetic System Action Potential Na Target Cell acetylcholine Preganglionic neuron Postganglionic neuron Nicotinic acetylcholine receptor Depolarization and possible Action Potential noradrenaline Sympathetic System Agonists that affect ganglionic nicotinic receptors Drugs (agonists) that affect ganglionic nicotinic receptors  Antagonists (Blockers) of ganglionic nicotinic receptors Y Y Action Potential Na acetylcholine Preganglionic neuron Postganglionic neuron Target Cell Muscarinic acetylcholine receptor Nicotinic acetylcholine receptor Depolarization and possible Action Potential Parasympathetic System The Muscarinic ACh Receptors  mAcR GPCR Action Potential Na acetylcholine Preganglionic neuron Postganglionic neuron M2 receptor Nicotinic acetylcholine receptor Depolarization and possible Action Potential Parasympathetic System Heart Cell M2 mAChRs inhibit the heart in two ways The first way The G-protein can activate a K channel directly causing hyperpolarization This inhibits muscle contraction of the heart ACh GP Extracellular Intracellular K K K M2 mAChR hyperpolarization 3 3 GPs AC Stimulatory GPCR PK Ca2 Ca2 cAMP However, the M2 mAChR reduces Ca2 channel opening by inhibiting adenylate cyclase This decreases cAMP concentration Therefore, decreases Ca2 conductance ACh GPi Extracellular Intracellular AC M2 mAChR Ca2 Ca2 M3 mAChRs stimulates glands and smooth muscle M  M3 mAChRs cause smooth muscle contraction GP PLC M3 mAChR IP3 Ca2 Ca2 Ca2 ACh Contraction ER or SR M3 mAChRs activation cause gland secretion GP PLC M3 mAChR IP3 Ca2 Ca2 Ca2 ACh ER or SR This increases the concentration of Ca2 Ca2 is responsible for a variety of cellular processes including secretion from glands Secretion of saliva is via this mechanism Salivia mAChRs agonists ) B  mAChRs antagonists I  Drugs and toxins that affect acetylcholine concentration at the presynaptic nerve terminal Ecothiopate Drugs and toxins that affect acetylcholine concentration at the presynaptic nerve terminal Once ACh leaves the neuron it is broken down by an enzyme AChE (acetylcholine esterase) AChE regulates free ACh by converting it back into choline and acetate Ecothiopate antiAChE used to treat glaucoma as eye drops Ecothiopate