The Autonomic Nervous System Def: The ANS consists of all visceral motor neurons innervating smooth muscle, cardiac muscle and glands.

Divide Autonomic Pharmacology into Four Categories: 1 Divide Autonomic Pharmacology into Four Categories: 1. Drugs that increase the sympathetic nervous system response 2. Drugs that increase the parasympathetic response 3. Drugs that block the sympathetic nervous system response 4. Drugs that block the parasympathetic response

Sympathetic Nervous System Adrenaline Rush Autonomic nervous system response to fear, anger, stress

Parasympathetic Nervous System Rest and Digest Relax, Repair, Renew

Sympathetic Parasympathetic Agonist Antagonist

Sympathetic Parasympathetic Agonist Antagonist

Sympathetic Parasympathetic Agonist Antagonist

Autonomic Nervous System Autonomic means automatic You do not control your ANS, it works automatically Controls the functions of MANY organs automatically That’s why many drugs that affect the ANS affect many organs

Drugs that affect the ANS will affect many organs: Heart Lung airways Blood vessels Bowels Pancreas Ureters Bladder Eyes Pupils Lacrimal gland Salivary glands

Do not confuse the autonomic nervous system with: Peripheral Nervous System Outside of skull and spinal cord Neurons end on organs and muscle Central Nervous System Brain and spinal cord Neurons end on other neurons

Do not confuse the ANS with Voluntary Nervous System Voluntary means willing, like to volunteer You do control your voluntary nervous system You control your skeletal muscles to move your body

The autonomic nervous system is divided into two systems: Sympathetic Adrenaline rush Fear, flight, fight

B. Parasympathetic rest, repair, digest

Can you guess what is happening to this girl’s organ function?

Running is voluntary in this case (she has no choice)  But everything else is automatic Effects of epinephrine or adrenalin (heart is pounding)

Adrenergic Receptors Heart is innervated by sympathetic neurons Norepinephrine The heart senses Adrenaline from Adrenal Epinephrine is adrenalin Adrenergic Beta 1 receptors

Effects of Epinephrine – Adrenaline Lung Airways WIDE OPEN BP is high – systemic vessels constrict

Adrenergic Receptors Blood vessel smooth muscle is innervated by sympathetic neuron Norepinephrine Receptors also sense adrenaline from adrenal Epinephrine Adrenergic Alpha 1 receptors

Adrenergic Receptors Lung bronchiole smooth muscle is innervated by sympathetic neuron Norepinephrine Blood vessels sense adrenaline from adrenal Epinephrine Adrenergic Beta 2 Receptors

Effects of Epinephrine – Adrenalin Blood to muscles increased Blood to GI decreased Pupils dilated Norepinephrine – neurotransmitter that dilates lungs, constricts blood vessels, lung airways open, shutting down GI tract

Why are all these changes occuring? Sympathetic nervous system (Norepinephrine) Adrenal gland – on top of kidneys (that extra boost) Adrenalin (Epinephrine) Adrenergic Neurons or Adrenergic Agonist Adrenergic System

Adrenergic Agonists Adrenergic Agonist substances are also called sympathomimetics

Epinephrine or Adrenaline Adrenaline is an adrenergic agonist - increased heart rate - constricts blood vessels - dilates lung airways - dilates pupils

Albuterol Is an adrenergic beta agonist used in asthma, what are some of its other effects besides bronchodilation? Increased heart rate Increased blood pressure

Adrenergic Antagonists Beta blockers are common drugs used to treat high blood pressure Beta blockers are common drugs used to treat high eye pressures (glaucoma)

Asthma Do you understand why beta blockers can make asthma worse? That’s why one of the reasons we try to use cardioselective beta blockers in patients with asthma

Autonomic Nervous System Although we have discussed many organ functions We have only discussed HALF of the Autonomic Nervous System The other half does the opposite

Can you guess what is happening to his heart rate? His blood pressure?

Effects of parasympathethic tone This is the rest and digest system - Acetylcholine – neurotransmitter - Muscurinic receptors

Parasympathetic Nervous System Cholinergic Agonism Cholinomimetic Rx: Bethanecol - cholinergic muscurinic agonist - used to stimulate bowel and bladder function

Indirect Cholinergic Agonism Acetylcholinesterase inhibitors Blocking the breakdown of acetylcholine increases acetylcholine levels Acetylcholineterase inhibitors are cholinomimetic Rx: Neostygmine Toxin: Organophosphate – acetylcholinesterase inhibitors

Cholinergic Antagonism Rx: Atropine – classic cholinergic antagonist Cholinergic muscuranic antagonist Anticholinergic Antimuscuranic

Rx: Atropine Speeds up heart rate Emergency treatment for bradycardia (slow heart rate) Atropine also causes mydriasis Atropine used for diarrhea Atropine used as antidote for organophosphate poisoning

Asthma Beta agonists are used in asthma But so are cholinergic muscuranic blockers

DuoNeb for Asthma contain two drugs Rx: Albuterol – beta2 agonist - sympathomimetic Rx: Ipratropium – anticholinergic - antimuscarinic - parasympatholytic

Heart rate up or down Blood pressure up or down Eye pressure up or down Lung airways open or closed Bladder relax or less relaxed GI stimulate or slow

Dilating the pupils is – Mydriasis

Dilating the pupils is – Mydriasis Both Sympathomimetic adrenergic drugs and Anticholinergic parasympatholytic drugs cause mydriasis

Constricting the pupils is Miosis

Both sympatholytic adrenergic antagonist drugs and - Cholinergic parasympathomimetic drugs cause miosis

Dry lacrimal glands Both sympathomimetic adrenergic drugs And Anticholinergic parasympatholytic drugs Cause dry eyes

Stimulate lacrimal glands to make tears Both sympatholytic adrenergic antagonist drugs and Cholinergic parasympathomimetic drugs Stimulate tear production

Dries salivary glands Both sympathomimetic adrenergic drugs And Anticholinergic parasympatholytic drugs Cause dry mouth

Stimulates salivary glands to make saliva Both sympatholytic adrenergic antagonist drugs and Cholinergic parasympathomimetic drugs Stimulate saliva production

Both sympathomimetic adrenergic drugs And Anticholinergic parasympatholytic drugs Dry respiratory airways

Both sympatholytic adrenergic antagonist drugs And cholinergic parasympathomimetic drugs Can stimulate airway secretion

Bronchodilation: relaxing bronchiole smooth muscle to open airways Both sympathomimetic adrenergic drugs and Anticholinergic parasympatholytic drugs Cause bronchodilation and are used in asthma

Bronchoconstriction/Bronchospasm: contracting bronchiole smooth muscle to close or constrict airways

Both sympatholytic adrenergic antagonist drugs And Cholinergic parasympathomimetic drugs Can cause bronchospasm

Drugs that cause tachycardia (fast heart rate) are called positive chronotropes Both sympathomimetic adrenergic drugs And Anticholinergic parasympatholytic drugs Cause tachycardia

Drugs that increase the force of contraction are positive inotropes

Sympathomimetic adrenergic drugs are positive inotropes

Drugs that cause bradycardia (slow heart rate) are called negative chronotropes

Both sympatholytic adrenergic antagonist drugs And Cholinergic parasympathomimetic drugs can cause bradycardia

Drugs that decrease the force of contraction are negative inotropes

Sympatholytic adrenergic antagonist drugs are negative inotropes

Vasoconstriction: contracting arteriole smooth muscle to raise blood pressure

Sympathomimetic adrenergic drugs raise blood pressure by vasoconstriction

Vasodilation: relaxing arteriole smooth muscle to drop blood pressure

Sympatholytic adrenergic antagonist drugs can drop blood pressure

Some drugs relax the GI tract and slow peristalsis

Both sympathomimetic adrenergic drugs And Anticholinergic parasympatholytic drugs Slow peristalsis, relax GI

Some drugs stimulate peristalsis in the GI tract

Cholinergic parasympathomimetic drugs are used to stimulate GI

Drugs that affect autonomic nervous system may affect the pancreas

Some drugs relax the bladder and urinary tract smooth muscle and slow peristalsis

Both sympathomimetic adrenergic drugs and anticholinergic parasympatholytic drugs slow ureter peristalsis and relax bladder

Some drugs stimulate the smooth muscle of the bladder and urinary tract, increasing peristalsis

Cholinergic parasympathomimetic drugs are used to stimulate the bladder

Sympathetic and Parasympathetic Divisions of the ANS How they are similar: Both divisions are part of the ANS Both have effects on smooth muscle, cardiac muscle and glands How they differ: Stimulation of effectors by each system vary from one body system to another. Effects may be stimulatory or inhibitory. Location Length of pre and postganglionic fiber Neurotransmitters used

Comparison of ANS and Somatic Motor Pathways Somatics Single neuron from spinal cord to effector One neuron innervates the effector cell NTS is acetylcholine (ACh) Autonomics Two neurons relay (ganglion) to effector Dual innervation of effectors NTS at ganglia (ACh); NTS at effector can be ACh or norepinephrine

Location and neurotransmitters used by Sympathetic/Parasymp adrenergic receptors sympathetic preganglionic neuron postganglionic neuron parasympathetic nicotinic receptors muscarinic receptors

Characteristics of Sympathetic and Parasympathetic Function Post-ganglionic sympathetic nerves release norepinephrine at their nerve endings these nerves are called adrenergic nerves Pre and post-ganglionic parasympathetic nerves release acetylcholine at their nerve endings (Nitric oxide- corpora cavernosa)‏ these nerves are called cholinergic nerves EXCEPTION FOR SYMPATHETIC: Cholinergic: mACH; used in body wall. Vasodilation of vessels in brain and skeletal muscle Piloerector muscles Sweat glands Nitric oxide: vasodilation of vessels in brain, skeletal muscle

Sympathetic Nervous System “Thoracolumbar” When active? Length of pre and postganglionic nerve? Location of cell bodies of preganglionic nerve? Location of cell bodies of postganglionic nerve? Neurotransmitters released? Adrenal medulla Figure 60-1; Guyton & Hall

 3  2  1  2c  2b  2a  1B  1a Actions Where found? Receptor Lipolysis and thermogenesis Adipose tissue  3 Inhibitory, relaxation of resp. tract to get dilation Respiratory tract, GI, glands, hepatocytes  2 Increased heart rate and inotropy HEART, kidney, adipocytes  1 Presynaptic control/ release of NT Vascular endothelium  2c Increase vasoconstriction (increased MI mortality w/polymorphism)‏  2b Lipid metabolism Vascular endothelium and adipocytes  2a Increased BP, vasoconstriction Arteries, heart  1B Increased inotropy, closure of GI sphincters, vasoconstriction, pupil dilation Iris, intestine, heart and arteries  1a Actions Where found? Receptor

Parasympathetic Nervous System “cranio-sacral” Parasympathetic nerves originate from cranial nerves III, VII, IX, and X and the sacral spinal cord. occulomotor nerve - fibers to the pupillary sphincters and ciliary muscle facial nerve - fibers to lacrimal and submandibular gland glossopharyngeal nerve - fibers to parotid gland vagus nerve - motor inputs to visceral organs sacral segments - fibers to descending colon, rectum, bladder and genitalia Vagus nerve doesn't innervate involuntary muscle preganglionic fiber Figure 60-3; Guyton & Hall

Effects of the ANS on the Organs eye sympathetic --pupillary dilation (alpha 1 receptor)‏ parasympathetic--pupillary constriction and accommodation (focusing) of the lens (mACh receptor)‏ glands of the body parasympathetic stimulate the nasal, lacrimal, salivary, and G.I. glands (mACh receptor)‏ sympathetic stimulates the sweat glands (mACh receptor)‏ Sphincter muscle: muscle will constrict pupil (parasympathetic)‏ radial muscle: muscle will dilate pupil (sympathetic)‏

Effect of the Autonomic Nervous System on the Organs G.I. tract parasympathetic stimulates overall activity including G.I. smooth muscle sympathetic has very little effect heart sympathetic increases the rate and contractility parasympathetic decreases heart rate blood vessels sympathetic causes vasoconstriction. Reduced sympathetic response accounts for most vasodilation. parasympathetic causes some vasodilation (e.g., penis)‏

Sympathetic and Parasympathetic “Tone” the basal rate of activity of each system this background activity allows for an increase or decrease in activity by a single system sympathetic tone normally causes about a 50 % vasoconstriction increasing or decreasing “tone” can change vessel diameter parasympathetic tone provides background G.I. activity

adrenergic or sympathomimetic drugs act like norepinephrine these drugs have an effect which is much more prolonged than that of either norepinephrine phenylephrine stimulates alpha receptors isoproterenol stimulates both beta1 and beta2 receptors albuterol stimulates only beta2 receptors some drugs act indirectly by increasing the release of norepi from its storage terminals ephedrine, amphetamine, pseudoephedrine,

Pharmacology of the Sympathetic Nervous System drugs that block the effect of norepinephrine alpha blockers phentolamine Cheap Viagra! beta blockers beta1 and 2 - propranolol

Pharmacology of the Parasympathetic Nervous System parasympathomimetic drugs muscarine pilocarpine activates muscarinic receptors, cause profuse sweating (why if sweat glands are controlled by sympathetic system?)‏ cholinesterase inhibitors neostigmine, potentiates the effect of acetylcholine antimuscarinic drugs atropine blocks the effect of acetylcholine on effector cells