Autonomic Nervous System Drugs

UNIT 5–AUTONOMIC NERVOUS SYSTEM DRUGS Ivory List Drugs Covered in this Unit Generic/Trade Name 31 epinephrine/Adrenalin 33 pseudoephedrine/Sudafed* 104 oxymetazoline/Afrin* 27 albuterol/Proventil 72 clonidine/Catapres 79 terazosin/Hytrin 77 propranolol/Inderal 70 atenolol/Tenormin 106 timolol/Timoptic 30 donepezil/Aricept 105 pilocarpine/Ocusert 28 atropine/Generic 102 atropine/Generic 32 ipratropium/Atrovent 34 scopolamine/Transderm-V 29 benztropine/Cogentin

AHFS Subclass Class Class/subclass identify drug type Anom

Adrenergic bronchodilator

Descriptor Drug uses and other pertinent information TX ACUTE ASTHMA; anaphylactic shock; non-specific beta1 & 2 agonist; vasoconstrictor with local anesthetic; INJECTED TX NASAL CONGESTION; alpha1 adrenergic agonist TX NASAL CONGESTION; SPRAY TX ACUTE ASTHMA, INHALED; little cardiac stimulation

Anom Adrenergic vasoconstrictor EENT Adrenergic vasoconstrictor Anom Beta2 adrenergic bronchodilator Alpha2 stimulator; central CV vasodilator (antiadrenergic*) TX HTN; causes initial sedation, has mild orthostatic effects Alpha1 blocker; peripheral CV vasodilator TX HTN, 1 x day dose, also, tx BPH TX HTN; SLOWS HEART; ↓ sympathetic input, ↓ mortality after MI, tx CV Beta blocker angina, arrhythmias, thyrotoxicosis, & migraine CV Cardiospecific beta blocker TX HTN & angina, ↓ mortality after MI EENT Beta blocker TX GLAUCOMA; ↓ AQUEOUS HUMOR FORMATION, antiadrenergic Anom Cholinergic TX ALZHEIMER'S DEMENTIA, palliative, ↑ CNS acetylcholine TX GLAUCOMA; constricts pupil, ↑ aqueous humor outflow; EENT Cholinergic miotic put reservoir system in conjunctival sac, each eye each week PREVENTS BRADYCARDIA; USED PRE-OP; ↓ peristalsis Anom Anticholinergic & secretions EENT Anticholinergic mydriatic DIAGNOSTIC, DILATES PUPILS FOR EXAMINATION Anom Anticholinergic bronchodilator TX ACUTE ASTHMA; INHALED Anom Anticholinergic antiemetic PREVENTS MOTION SICKNESS, tx vertigo Anom Anticholinergic TX PARKINSON'S early in DISEASE & PSEUDOPARKINSONISM

*Over-the-counter drugs (#21) **Common doses to memorize (#7) <<<Using the CD review the drug pronunciations listed above>>> *Remember: clonidine/Catapres is an alpha 2 stimulator. Alpha2 stimulation blocks actions, inhibiting further release of norepinephrine at the nerve terminal. Thus, although it is an agonist, it is considered an antiadrenergic. Compare this action to activating the brakes of your car, which makes the car stop. Your action blocks the motion of the car.

Abrams Chapters & Study Notes for This Unit Chapter 16 Physiology of the Autonomic Nervous system 1. Design a tree showing the relationships of the nervous system; include the central with the brain and spinal cord, the peripheral nervous system, with the somatic and autonomic nervous system, and the major branches of the autonomic nervous system including the parasympathetic and sympathetic nervous systems (see Abrams, page 266). 2. On the Nervous System Transmitters diagram, (at the end of these LOs), see the long and short fibers, the synapses, and the neurotransmitters for the sympathetic nerves, the parasympathetic nerves, and the somatic nerves (also see Abrams, page 267). 3. On the Catecholamine Table, at the end of these LOs, identify the neurotransmitter sequence, the alpha 1 and 2 actions and drugs and the beta 1 and 2 actions and drugs. 4. Make a synthesis card for each element of the Catecholamine Table. (You will need to know this information throughout the course.) 5. Identify the physiologic effects of the sympathetic (adrenergic) nervous system (see the ANS Teacher's Note). 6. Identify the physiologic effects of the parasympathetic (cholinergic) nervous system (see the ANS Teacher's Note).

Chapter 17, Adrenergic Drugs 1. Describe the actions, indications for use, and contraindications, for epinephrine/Adrenalin, pseudoephedrine/Sudafed, albuterol/Proventil (see Chapter 44), and oxymetazoline/Afrin (see Chapter 46).

Chapter 18, Antiadrenergic Drugs 1. Describe the actions, indications for use, and contraindications, for clonidine/Catapres, terazosin/Hytrin, propranolol/Inderal, atenolol/Tenormin, and timolol/timoptic. 2. State the precaution for the use of propranolol/Inderal with severe congestive heart failure or asthma. 3. Explain why propranolol/Inderal can be illustrated as a Hawaiian Vacation for the Heart" (see illustration at the end of these LOs.

Chapter 19, Cholinergic Drugs 1. Describe the actions, indications for use, and contraindications for donepezil/Aricept. 2. Briefly evaluate the efficacy of donepezil/Aricept in the treatment of Alzheimer's disease.

Chapter 20, Anticholinergic Drugs 1. Describe the actions, indications for use, and contraindications, for atropine/Generic, ipratropium/Atrovent, 16254037.doc

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scopolamine/Transderm V, benztropine/Cogentin, and oxybutynin/Ditropan.

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Autonomic Nervous System and Drugs Chapter 16, Anatomy and Physiology 1. Design a tree showing the relationships of the nervous system; include the central with the brain and spinal cord, the peripheral nervous system, with the somatic and autonomic nervous system, and the major branches of the autonomic nervous system including the parasympathetic and sympathetic nervous systems. See the diagram at the end of these LOs and Abrams, Page 266, “Divisions of the Human Nervous System” 2. On the Nervous System Transmitters diagram at the end of these LOs, see the long and short fibers, the synapses, and the neurotransmitters for the sympathetic nerves, the parasympathetic nerves, and the somatic nerves. Also see “Organization of the Autonomic and Somatic Nervous Systems in Abrams, page 267. 3. Identify the neurotransmitter sequence, the alpha 1 and 2 actions and drugs and the beta 1 and 2 actions and drugs. See the table "Catecholamine (Monoamines), at the end of these LOs. 4. Make a synthesis card for each element of the Catecholamine Table. (You will need to know this information throughout the course.) Review “Synthesis Cards” under the burgundy "Course Guide" button. 5. Identify the physiologic effects of the sympathetic (adrenergic) nervous system. See “Autonomic Nervous System Responses:” Flight & fight (FF) response at the end of these Learning Objectives. 6. Identify the physiologic effects of the parasympathetic (cholinergic) nervous system. See “Autonomic Nervous System Responses:” Feed & breed (FB) response at the end of these Learning Objectives.

Chapter 17, Adrenergic Drugs 1. Describe the actions, indications for use, and contraindications, for epinephrine/Adrenalin Epinephrine/Adrenalin is an adrenergic bronchodilator. It is used to treat acute asthma; anaphylactic shock; nonspecific beta1 & 2 agonist; vasoconstrictor with local anesthetic. It is injected. It is a stimulant and can cause increased heart rate, increased blood pressure, nervousness and sleeplessness, dry mouth, and urinary retention in men with enlarged prostates. Describe the actions, indications for use, and contraindications, for pseudoephedrine/Sudafed Pseudoephedrine/Sudafed is an over-the-counter drug. It is an adrenergic vasoconstrictor. It is used to treat nasal congestion; it is an alpha1 adrenergic agonist. It is a stimulant and can cause increased heart rate, increased blood pressure, nervousness and sleeplessness, dry mouth, and urinary retention in men with enlarged prostates. Describe the actions, indications for use, and contraindications, for oxymetazoline/Afrin Oxymetazoline/Afrin is an over-the-counter drug. It is an adrenergic vasoconstrictor and is used to treat nasal congestion. It comes as a spray. Because it is topical it does not cause the systemic stimulation of other adrenergic drugs. If used over six doses it can cause rebound nasal congestion. . Describe the actions, indications for use, and contraindications, for albuterol/Proventil. Albuterol/Proventil is a Beta2 adrenergic bronchodilator. It is used to treat acute asthma. It causes little cardiac stimulation because it is designed to affect primarily the lungs and to spare the heart. Phenylpropanolamine, another adrenergic vasoconstrictor, has been off the market for a few years. Phenylpropanolamine is similar to pseudoephedrine and was used as a nasal decongestant and as a weight loss pill. It was taken off the market after several young women suffered strokes after using it for a few days as a diet drug.

Chapter 18, Antiadrenergic Drugs 1. Describe the actions, indications for use, and contraindications, for clonidine/Catapres. Clonidine/Catapres is an alpha2 stimulator. It is a central vasodilator. Alpha2 stimulation blocks actions, inhibiting further release of norepinephrine at the nerve terminal. Thus, although it is an agonist, it is considered an antiadrenergic. Clonidine/Catapres is a treatment for hypertension that causes initial sedation and has mild orthostatic effects. Describe the actions, indications for use, and contraindications, for terazosin/Hytrin. Terazosin/Hytrin is an alpha1 blocker that causes peripheral vasodilation. It is treatment for hypertension. It is given once a day and is also a treatment for benign prostatic hypertrophy. 16254037.doc

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Describe the actions, indications for use, and contraindications, for propranolol/Inderal. Propranolol/Inderal is a nonselective beta blocker that blocks both alpha and beta receptors in both the heart and lungs. It is a treatment for hypertension. It slows the heart by decreasing sympathetic input and dilates blood vessels. It decreases mortality after a heart attack (myocardial infarction-MI). It is a treatment for angina because it slows the rate and decreases cardiac workload. It is a Hawaiian vacation for the heart see illustration at the end of these LOs. It treats arrhythmias by slowing the heart rate. One dose before a performance reduces performance anxiety. Thyrotoxicosis causes a very fast heart rate so propranolol/Inderal protects the heart by slowing the rate. Propranolol/Inderal treats migraine headaches by unknown mechanisms. Because it can have a deleterious effect on the lungs—it constricts bronchioles— it is contraindicated for people with severe asthma. It used to be contraindicated for people with congestive heart failure (CHF) because of its negative inotropic (strength) and chronotropic (speed) effects but is now considered an appropriate treatment (except for severe [uncompensated] CHF) because of its cardioprotective blockade of sympathetic stimulation. Propranolol/Inderal should not be discontinued suddenly. The nurse should watch for a severely decreased blood pressure, bradycardia, dyspnea, and severe fatigue or dizziness. Propranolol/Inderal will be studied further in the Cardiovascular Unit Describe the actions, indications for use, and contraindications, for atenolol/Tenormin. Atenolol/Tenormin blocks only beta 1 receptors so is cardio specific. It is treatment for hypertension and angina. It decreases mortality after MI. Because of its specificity for the heart, there is less chance of bronchospasm but it still should be used cautiously for persons with even mild asthma. Atenolol/Tenormin has the same precautions as propranolol/Inderal. Atenolol/Tenormin will be studied further in the Cardiovascular Unit Describe the actions, indications for use, and contraindications, for timolol/timoptic. Timolol/Timoptic is a beta blocker. It is used to treat glaucoma and sometimes hypertension. It decreases aqueous humor formation in the eye and is antiadrenergic. It will be covered in Eye and Skin Unit.

Chapter 19, Cholinergic Drugs 1. Describe the actions, indications for use, and contraindications for pilocarpine/Ocusert. Pilocarpine/Ocusert is a cholinergic miotic (decreases pupil size by constricting the iris) and thus decreasing aqueous humor outflow. It is a treatment for glaucoma. The patient puts the reservoir system in the conjunctival sac in each eye each week. It will be covered in Eye and Skin Unit. Describe the actions, indications for use, and contraindications for donepezil/Aricept. Donepezil/Aricept is an autonomic-cholinergic drug. It is the treatment for Alzheimer’s dementia. It increases CNS acetylcholine. It may cause nausea and vomiting, diarrhea and bradycardia. It should be used cautiously in patients with cardiac disease, peptic ulcer disease, seizures, asthma, or obstructive pulmonary disease. 2. Evaluate the efficacy of donepezil/Aricept in the treatment of Alzheimer's disease. It is only palliative.

Chapter 20, Anticholinergic Drugs 1. Describe the actions, indications for use, and contraindications for atropine/Generic. Atropine/Generic is an anticholinergic autonomic drug. It prevents bradycardia. It is given by injection before surgery. It also decreases peristalsis and secretions. 2. Describe the actions, indications for use, and contraindications for ipratropium/Atrovent. Ipratropium/Atrovent is an autonomic drug, an anticholinergic bronchodilator. It is inhaled to treat acute asthma. 3. Describe the actions, indications for use, and contraindications for scopolamine/Transderm V. Scopolamine/Transderm V is an autonomic drug, an anticholinergic antiemetic. It prevents motion sickness and treats vertigo. 4. Describe the actions, indications for use, and contraindications for benztropine/Cogentin. Benztropine/Cogentin is an autonomic anticholinergic. It is used to treat early Parkinson’s disease and pseudoparkinsonism seen in the treatment of schizophrenia. 16254037.doc

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5. Describe the actions, indications for use, and contraindications for oxybutynin/Ditropan. Oxybutynin/Ditropan is an anticholinergic urinary tract antispasmodic treatment for overactive bladder. It inhibits the action of acetylcholine. <<<>>>

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Sympathetic Nervous System in Relation to the Entire Nervous System

Nervous System Central

Brain

Spinal Cord

Peripheral

Autonomic

Parasympathetic (Cholinergic) ACh

Somatic

Sympathetic (Adrenergic) Alpha

Beta

1

1

2

2

Parasympathetic system is the "Feed and Breed" system. Sympathetic system is the "Fright, Flight, Fight" system. Alpha 1 constricts blood vessels, dilates eyes. Alpha 2 (a blocker) dilates blood vessels. Beta 1 stimulates the heart. Beta 2 dilates bronchioles in the lungs.

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NERVOUS SYSTEM TRANSMITTERS AUTONOMIC NERVOUS SYSTEM 1. The sympathetic/adrenergic pre-ganglionic neurotransmitter is ACETYLCHOLINE (ACh). The post-ganglionic neurotransmitter at the junction with the organ is NOREPINEPHRINE (NE). ACh NE ________ ↓ _________________________________ ↓ OOO Short fiber

Long fiber

Organ

1. Sympathetic/Adrenergic Nerve(Fright, Flight, Fight) 2. The sympathetic/adrenergic hormone is EPINEPHRINE (EPI). It travels from the adrenals through the blood stream to the junction with the organ. _____________________________________ ///\\\EPI _____________________________________ OOO Adrenal Gland

Blood vessel

Organ

2. Sympathetic Transport Via Blood Vessels(Fright, Flight, Fight)

3. The parasympathetic pre-ganglionic neurotransmitter is ACETYLCHOLINE. The post-ganglionic neurotransmitter at the junction with the organ is also ACETYLCHOLINE. ACh

ACh

_________________________________ ↓ ________ ↓ OOO Long fiber

Short fiber

Organ

3. Parasympathetic/Cholinergic Nerve(Feed and Breed)

SOMATIC NERVOUS SYSTEM 4. The somatic nervous system (voluntary and reflex movement) does not have ganglia. The neurotransmitter at the junction with the muscle is ACETYLCHOLINE. AC h ____________________________________________ ↓ (((()))) Very long fiber

Muscle

4. Somatic Nerve(Innervates Muscles) <<<>>>

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CATECHOLAMINES (MONOAMINES) CENTRAL (brain) NEUROTRANSMITTERS:

PERIPHERAL (body) NEUROTRANSMITTERS:

Dopamine Norepinephrine Epinephrine

Norepinephrine at post-ganglionic sites Epinephrine from the adrenal medulla

NEUROTRANSMITTER SEQUENCE: Phenylalanine

becomes

Tyrosine

becomes

Dopamine

becomes

Norepinephrine

becomes

Epinephrine

(Tyramine is synthesized by the body from tyrosine and found in aged meats, ripe cheese; it has action like epinephrine, but weaker.)

At ALPHA(α) receptors neurotransmitters are: Norepinephrine & Epinephrine

At BETA(β) receptors the neurotransmitter is: Epinephrine

ALPHA1 stimulation causes ALPHA2 stimulation

BETA1 stimulation affects

BETA2 stimulation affects the

actions blocks actions 1. Constricts peripheral 1. Inhibits further release of vessels in the skin, kidney, norepinephrine at the and viscera, to raise BP in nerve terminal, dilating the heart and brain. peripheral blood vessels to lower blood pressure 2. Constricts vessels in nasal mucous mem branes, to relieve a stuffy nose

the heart 1. Stimulates the heart; increases rate and strength

lungs 1. Dilates the bronchioles

3. Contracts the radial muscle of the eyes, dilating the eyes (mydriasis). Agonist drugs: epinephrine/Adrenalin, oxymetazoline/Afrin, & pseudoephedrine/Sudafed

Agonist drug: clonidine/Catapres, an "alpha2 stimulator" hypotensive.*

Antagonist drug: terazosin/Hytrin

No antagonist drugs are commonly used.

2. Shunts blood from peritoneal cavity to mucosa, skeletal muscle, brain, and heart

Agonist drug: epinephrine/Adrenalin

Agonist drugs: epinephrine/Adrenalin and albuterol/Proventil Albuterol/Proventil is more lung-specific than epinephrine. They both dilate the bronchi. Antagonist drugs are "beta No antagonist drugs are blockers." commonly used. There is no Propranolol/Inderal and reason to constrict the atenolol/Tenormin bronchi. Propranolol does (cardiospecific) are both have antagonist activity as an hypotensives. undesirable side effect. It is Timolol/Timoptic decreases not used as a hypotensive for aqueous humor in glaucoma. asthmatics. O88/691/793/899

* Clonidine/Catapres acts in the medulla of the brain to stimulate alpha2-receptors that inhibit sympathetic vasomotor centers. (The action is comparable to "stimulating" a car's brakes to "inhibit" its motion.) Clonidine/Catapres causes sedation, a central (brain) action. It does not interfere with fine control of peripheral vessels, a peripheral action, so does not cause orthostatic hypotension. Serotonin (SE) is a naturally occurring derivative of tryptophan found in platelets, intestine, and brain. It is a potent vasoconstrictor, stimulates intestinal smooth muscle contraction, and is a brain neurotransmitter. It is also called 5hydroxytryptamine (5-HT). Fluoxetine/Prozac is a selective serotonin reuptake inhibitor to treat depression; amitriptyline/Elavil blocks reuptake of NE and SE to treat depression; lithium increases reuptake of NE and SE to treat mania, risperidone/Risperdal blocks receptors for dopamine and SE, to treat schizophrenia; sumatriptan/Imitrex is a selective serotonin agonist (vasoconstrictor) to treat migraines. Adapted from Baer & Williams, 1988 and Rang, Dale, Ritter, & Gardner, 1995

<<<>>>

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PROPRANOLOL A Hawaiian Vacation for the Heart

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AUTONOMIC NERVOUS SYSTEM RESPONSES Flight & fight (FF) response.

Feed & breed (FB) response.

Norepinephrine and epinephrine are associated

Acetylcholine is associated with the

with the FF/adrenergic/sympathetic response.

FB/cholinergic/parasympathetic response.

1. Pupils dilate, to see better (mydriasis) 2. Bronchi dilate and respiratory rate increases, to get more oxygen more quickly. 3. Blood sugar from the liver increases, to provide more energy to run, think, or fight. 4. Heart beats faster and stronger to get more blood to lungs, brain, and muscles. Increased blood flow/oxygen, to the brain increases thinking and to the muscles increases muscle strength and speed. 5. Blood clotting increases, to decrease bleeding from a wound. 6. Cell metabolism increases, to do more cellular work when the body is running, thinking, and fighting. 7. Sweat increases, so it is easier to slip out of the grasp of an enemy. 8. Stomach, bowel, and peripheral blood vessels to the skin constrict, to shunt blood to the brain and heart and conserve blood for brain and muscle use. Blood pressure increases. Stomach and bowel peristalsis decreases, digestion slows, and bowel function slows (constipation) to conserve blood for muscles. Skin becomes pale and cool. Skin wounds do not bleed as much. 9 Digestive enzymes decrease.

1. Pupils constrict; pupils become smaller (miosis). 2. Bronchi "constrict." Actually, bronchi return to a normal state with no dilation and a normal respiratory rate. 3. Blood sugar decreases and returns to normal.

10. Urinary bladder relaxes and urinary sphincter contracts. There is no time to urinate now. 11. Genital blood vessels constrict to conserve blood for vital organs.

4. Heart rate slows and returns to a normal strength. Brain and muscle metabolism return to normal. 5. Blood clotting decreases to normal. 6. Cell metabolism slows and returns to normal. 7. Sweating decreases to normal. 8. Stomach, bowel, and skin blood vessels dilate. Blood pressure decreases. Stomach and bowel peristalsis increases, digestion resumes, and bowel function returns to normal. Skin becomes warm and pink. 9. Digestive enzymes increase from minimal amounts to normal. 10. Urinary bladder contracts and urinary sphincter: relaxes so urination can occur. 11. Genital blood vessels dilate to return to normal, not constricted; then with sexual excitement they dilate.

A LITTLE STORY ABOUT OUR ANCESTORS .......A cave person was in the forest picking berries when she noticed it was beginning to get dark. Suddenly fear seized her and she remembered that she was far away from her home cave. She began to hear the noises of the night. Her eyes dilated, her muscles tensed, and she drew in a gasp of air. Her heart began pounding as she started to run toward home. Suddenly she felt a burst of strength as her liver pumped a vast amount of sugar into her blood stream. Her heart was pounding so fast it felt like it would jump out of her chest. Her blood pressure skyrocketed as all her peripheral blood vessels constricted. The blood vessels to her muscles dilated and filled with life-giving blood as she sped through the dark forest. Her breathing was fast and deep, pulling oxygen into her body so she could use its strength to power her muscles to run faster and faster. .......The oxygen had magically cleared her brain of every thought except the best route to get to the cave and that map was brilliantly illustrated in her mind. Every cell in her body was functioning to one end--survival. She was ghostly pale and covered with a cold sweat and knew that she would be able to slip out of the grasp of an enemy. .......Suddenly, a huge roar sounded just behind her. Grrrrr! Growl! It was a saber-toothed tiger looking for his supper. He snarled as his razor sharp claws raked down the back of her leg. Blood spurted out of the wound but stopped almost immediately because the peripheral blood vessels had constricted and her clotting had increased. With one final burst of speed she dashed through the cave entrance to safety. .......As she lay panting on the cave floor she could hear the tiger growling as he paced back and forth in front of the fire at the cave entrance and another cold shiver ran down her body. Her cave partner wrapped the wounds on her leg and after she had rested a little, asked her to come and eat some stew. "I'm sorry, I can't eat. My stomach is hurting and I know I'll be sick if I eat anything." 16254037.doc

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.......She rested for a while and then said, "I am feeling a little better since I've caught my breath. Maybe now I'll be able to 'pass my water.' I needed to go while I was in the forest, but with that tiger after me, all I could do was run." My bowels feel twisted in knots. I don't think I'll be back to normal until tomorrow." .......A little time passed and the cave partner said, "I've just arranged all the furs on our bed. Since you don't want to eat, we might just as well lie down and I'll hold you and keep you warm." Time passes. The cave partner can't sleep and suggests a little bedtime activity. The cave person pushes her partner away. I'm not in the mood for that! I almost lost my life today and all you want is fun and games. She turns her back to her partner, closes her eyes and falls into an exhausted sleep. <<<>>>

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