PHARMACOLOGY OF ANS part 1 General Pharmacology M212 Dr. Laila M. Matalqah Ph.D. Pharmacology

PNS Afferent neuron Efferent neurons the neurons of which bring information from the periphery to the CNS. Afferent neurons provide sensory input to modulate the function of the efferent division through reflex arcs. Efferent neurons carries nerve impulses from the CNS to the effector organs by way of two types of efferent neurons (the preganglionic neuron and the postganglionic neuron

Efferent neurons divisions: Somatic Nervous System: Carries nerve impulse to skeletal muscle (voluntary control) No ganglia A single myelinated motor neuron Faster response Autonomic Nervous System Parasympathetic Nervous System Sympathetic Nervous System Enteric Nervous system: GIT, pancreas, and gallbladder, Glands, Smooth Muscle & Cardiac Muscle (Involuntary control)

ANS: 1. Sympathetic NS Its function: adjusting in response to stressful situations, such as trauma, fear, hypoglycemia, cold, and exercise Effects of stimulation of the sympathetic division: Increase heart rate and blood pressure, To mobilize energy stores of the body, Increase blood flow to skeletal muscles and the heart while diverting flow from the skin and internal organs. Dilation of the pupils and the bronchioles Decrease GI motility Fight or flight response The changes experienced by the body during emergencies have been referred to as the “fight or flight”

ANS: 2. Parasympathetic NS is involved with maintaining homeostasis within the body. it maintains essential bodily functions, such as digestive processes and elimination of wastes “rest and digest” situations. Note: Dual innervation: Most organs in the body are innervated by both divisions of the ANS. PSNS acts opposite to SNS

ANS: 3. Enteric NS collection of nerve fibers that innervate the gastrointestinal (GI) tract, pancreas, and gallbladder, This system functions independently of the CNS and controls the motility, exocrine and endocrine secretions, and microcirculation of the GI tract. It is modulated by both the sympathetic and parasympathetic nervous systems.

Dual innervation: Most organs in the body are innervated by both divisions of the ANS.

Reflex arcs

CHEMICAL SIGNALING BETWEEN CELLS Hormones - chemicals released into the bloodstream  physiological effects on tissues - specific hormone receptors. Local mediators - Most cells in the body secrete chemicals that act locally, and they don’t enter blood. E.g, histamine and prostaglandins – Neurotransmitters: A specific chemical signals, released from the nerve terminals.

Neurotransmitters Norepinephrine and epinephrine - ANS Acetylcholine - ANS Dopamine - CNS Serotonin - CNS Histamine - CNS γ-aminobutyric acid (GABA)- CNS Co-transmitters, such as adenosine, often accompany neurotransmitter on nerve stimulation and modulate the transmission process.

Neurotransmitters of ANS Acetylcholine (ACh) (cholinergic ) mediates the transmission of nerve impulses across: autonomic ganglia in both sympathetic and parasympathetic NS. at adrenal medulla. Transmission from the postganglionic nerves to the effector organs in parasympathetic system, transmission at the neuromuscular junction A few sympathetic fibers, such as those involved in sweating, are cholinergic Norepinephrine (NE) and epinephrine (E) (adrenergic) Transmission from the postganglionic nerves to the effector organs in sympathetic system

Neurotransmission in cholinergic neurons involves six steps:

Cholinergic receptors (CHOLINOCEPTORS) Muscarinic receptors G protein–coupled receptors. Recognize muscarine, ACh, and weak affinity to nicotine NT. five subclasses of muscarinic receptors: M1, M2, M3, M4, and M5. Found on the effector organs of parasympathetic such as the gastric (M1) , heart and smooth muscle (M2), bladder and exocrine glands and smooth muscle (M3) When M receptor activated – G-protein – IP3 and DAG - intracelluar Ca2+ - cause hyperpolarization, secretion, or contraction

Cholinergic receptors (CHOLINOCEPTORS)

Cholinergic receptors (CHOLINOCEPTORS) Nicotinic receptors ligand-gated ion channel Recognize nicotine, ACh, and weak affinity to muscarine NT. Two types : Nm and Nn Located in the CNS, adrenal medulla, autonomic ganglia (called Nn), and the neuromuscular junction (NMJ) called Nm

A. Cholinergic agonists (parasympathomimetics) ACh has both muscarinic and nicotinic activity. Its actions include: Decrease in heart rate and cardiac output Decrease in blood pressure (VASODILATION)? HOW? Increases salivary secretion and intestinal secretions and motility. increases the tone of the detrusor urinae muscle, causing expulsion of urine. constriction of the pupillae sphincter muscle, causing miosis (marked constriction of the pupil).

1- Direct-acting Agonist Drugs Bethanechol: used for urinary retention Carbachol: as a miotic agent to treat glaucoma (decrease the IOP) Pilocarpine: to treat glaucoma and lower IOP of both narrow- angle (or closed-angle) and wide-angle (also called open- angle) glaucoma. directly stimulates muscarinic receptors

Physostigmine: used to stimulate the bladder and GI tract. 2. Indirect-acting Cholinergic Agonists: Acetylcholinesterase Inhibitors (Reversible) Drugs inhibit AChE the enzyme that cleaves ACh to acetate and choline and terminate ACh action this results in the accumulation of ACh in the synaptic space–so prolong ACh action Examples: Physostigmine: used to stimulate the bladder and GI tract. Neostigmine, ambenonium and Pyridostigmine: used to treat myasthenia gravis Rivastigmine: to delay the progression of Alzheimer disease Edrophonium It is used in the diagnosis of myasthenia gravis, which is an autoimmune disease caused by antibodies to the nicotinic receptor at NMJs.

Echothiophate: for the chronic treatment of open-angle glaucoma. 3. Indirect-acting cholinergic agonists: anticholinesterases (IRREVERSIBLE) Echothiophate: for the chronic treatment of open-angle glaucoma. Long duration of action (1 week) Reactivation of acetylcholinesterase (Antidote) Pralidoxime (PAM) can reactivate inhibited AChE. Look at page 57 , fig 4.11

Action of anticholinergic mydriasis (dilation of the pupil) antispasmodic (reduce motility of the GI tract) Reduce Hypermotility states of the urinary bladder. blocks the salivary glands secretion (xerostomia).

I. Antimuscarinic Agents 1. Atropine: used as an antispasmodic to reduce activity of the GI tract used to reduce hypermotility states of the urinary bladder. Used as antidote for cholinergic agonist Antisecretory before surgary. Contraindicated on narrow angle glucoma

I. Antimuscarinic Agents 2. Scopalamine used for motion sickness 3. Ipratropium as bronchodilators for maintenance treatment of chronic obstructive pulmonary disease (COPD) 4. Benztropine treatment of Parkinson disease

II. Neuromuscular-blocking drugs nicotinic receptors antagonist A. Nondepolarizing blockers Tubocurarine is the prototype agent in this class interact with the nicotinic receptors to prevent the binding of Ach --- inhibit muscular contraction Therapeutic uses: as adjuvant drugs in anesthesia during surgery to relax skeletal muscle and to facilitate intubation Depolarizing agents Succinylcholine rapid onset and short duration of action, useful when rapid endotracheal intubation is required