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Drugs of the Peripheral Nervous System The Nervous System Review Organization of the Nervous System • Central nervous system (CNS) – Brain and spinal cord • Peripheral nervous system (PNS) – Neurons outside the CNS – Sensory division • Afferent fibers transmit impulses from receptors to CNS – Motor division • Efferent fibers transmit impulses from CNS to effector organs Relationship between motor and sensory fibers of the PNS and the CNS Autonomic Nervous System • Sympathetic – Fight or flight, stress – Excitatory effects elicited by norepinephrine activating beta receptors – Inhibitory effects elicited by activation of alpha receptors • Parasympathetic – Rest and digest – Digestive system activated, heart rate inhibited, blood vessels dilated – Vagus nerve primarily responsible for activating parasympathetic responses Fig. 8.39 Autonomic Neurotransmission • Two neurons – Presynaptic and postsynaptic • Presynaptic from the brain to autonomic ganglia – Acetylcholine released from prenaptic neuron across synapse to activate postsynaptic neuron • Postsynaptic neurons release norepinephrine (sympathetic) or acetylcholine (parasympathic) at the effector organ The Synapse Fig. 8.13 Neurotransmitters --packaged in synaptic vesicles. Nerve endings of the ANS secrete: • Acetylcholine (ACh)--Cholinergic neuron – Parasympathetic effector • Norepinephrine (NE)--Adrenergic neuron – Sympathetic effector • Neurotransmitters diffuse across the synaptic cleft and bind to receptor on the post-synaptic membrane • This can cause membrane channels (Na+, K+, or Cl-) to open or close depending on the neurotransmitter • If stimulatory, Na+ channels will open • If inhibitory, K+ or Cl- channels will open – Cell becomes more negative, hyperpolarized Catecholamines • Norepinephrine and epinephrine – Norepinephrine primarily neurotransmitter – Epinephrine primarily hormone • Primarily concerned with sympathetic transmission • Released at synaptic cleft and bind to alpha or beta receptors Acetylcholine • Responsible for all parasympathetic neurotransmission – Binds to mucarinic receptors at the end organ Ganglionic transmission – Transmits both parasympathetic and sympathetic preganglionic signals to nicotinic receptors (Nn) – All ganglionic transmission is cholinergic (acetylcholine) • Drugs that block ganglionic transmission block either parasympathetic or sympathetic depending on which is active • This is a paradox many have a problem grasping Fig. 8.39 Neuromuscular transmission • Somatic motor neurons release acetylcholine at neuromuscular junction – Acetycholine diffuses across synapse and binds to muscular nicotinic receptors (Nm) causing sodium influx The Neuromuscular Junction Central Neurotransmission • Acetylcholine the primary neurotransmitter in the brain • Works by interaction with muscarinic receptors Neurotransmitter degradation • Neurotransmitters which fail to bind to a post-synaptic receptor are – degraded by enzymes (acetylcholinersterase) – Taken up into the presynapse and recycled – Diffuse out of the synapse Receptors 2 types of cholinergic receptors: • Nicotinic – Preganglionic sympathetic and parasympathetic (Nn) – Also neuromuscular somatic motor (Nm) • Muscarinic – parasympathetic 2 types of adrenergic receptors: • Alpha – Generally inhibitory • Beta – Generally excitatory Neurotransmission Enhancers • Receptor agonists – Compound which bind to the receptor and activate • Can be cholinergic or adrenergic • Agents which induce neurotransmitter release – Stimulate release of neurotransmitter in absence of signal (or reduced signal) • Inhibitors of neurotransmitter degradation – Inhibit acetylcholinersterase Neurotransmission Inhibitors • Presynaptic nerve blockerss • Receptor antagonists – Bind to receptor and prevent activation • Ganglion blockers