Drugs Affecting the Autonomic Nervous System

Cholinergic Agents and Cholinergic Blocking Agents

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Cholinergic Agents
• Drugs that stimulate the parasympathetic nervous system (PSNS)
• The PSNS is the opposing system to the SNS

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Cholinergic Agents
Also known as
• cholinergic agonists or • parasympathomimetics

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Instructors may wish to use EIC Image #56: The Parasympathetic and Sympathetic Nervous Systems and Their Relationships to One Another

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Cholinergic Agents
• Mimic the effects of the PSNS neurotransmitter
• Acetylcholine (ACh)

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Cholinergic Receptors
Two types, determined by:
• Location • Action once stimulated

Nicotinic receptors and Muscarinic receptors

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Nicotinic Receptors
• Located in the ganglia of both the PSNS and SNS
• Named ―nicotinic‖ because can be stimulated by the alkaloid nicotine

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Muscarinic Receptors
• Located postsynaptically:
– Smooth muscle – Cardiac muscle – Glands of parasympathetic fibers – Effector organs of cholinergic sympathetic fibers

• Named ―muscarinic‖ because can be stimulated by the alkaloid muscarine
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Instructors may wish to insert EIC Image #57: The Sympathetic, Parasympathetic, and Somatic Nervous Systems
This slide illustrates location of the nicotinic and muscarinic receptors within the PSNS.

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Lisa L. HHS: Hernandez: HHS: Is there copy missing at the end? Inhibiting what?

Adrenergic Agents: Mechanism of Action
• Direct-acting (agonist)
– Bind to cholinergic receptors, causing stimulation

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Adrenergic Agents: Mechanism of Action
• Indirect-acting
– Inhibit the enzyme ―cholinesterase‖

Result: more ACh is available at the receptors

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Indirect-Acting Cholinergic Agents (Cholinesterase Inhibitors)
• Reversible
– Bind to cholinesterase for a period of minutes to hours

• Irreversible
– Bind to cholinesterase and form a permanent covalent bond

– The body must make new cholinesterase

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Drug Effects of Cholinergic Agents
• Effects seen when the PSNS is stimulated.
• The PSNS is the ―rest and digest‖ system.

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Drug Effects of Cholinergic Agents
―SLUDGE‖
• Salivation • Lacrimation • Urinary incontinence • Diarrhea • Gastrointestinal cramps • Emesis
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Drug Effects of Cholinergic Agents
• Stimulate intestine and bladder
– Increased gastric secretions – Increased gastrointestinal motility – Increased urinary frequency

• Stimulate pupil
– Constriction (miosis) – Reduced intraocular pressure

• Increased salivation and sweating
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Drug Effects of Cholinergic Agents
• Cardiovascular effects
– Decreased heart rate – Vasodilation

• Respiratory effects
– Bronchial constriction, narrowed airways

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Drug Effects of Cholinergic Agents
• At recommended doses, the cholinergics primarily affect the MUSCARINIC receptors.
• At high doses, cholinergics stimulate the NICOTINIC receptors.

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Drug Effects of Cholinergic Agents
• DESIRED EFFECTS: from muscarinic receptor stimulation
• Many undesirable effects are due to stimulation of the nicotinic receptors

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Cholinergic Agents: Therapeutic Uses
Direct-Acting Agents
• Reduce intraocular pressure • Useful for glaucoma and intraocular surgery Examples: acetylcholine, carbachol, pilocarpine

Topical application due to poor oral absorption

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Cholinergic Agents: Therapeutic Uses
Direct-Acting Agent—bethanechol
• Increases tone and motility of bladder and GI tract • Relaxes sphincters in bladder and GI tract, allowing them to empty • Helpful for postsurgical atony of the bladder and GI tract Oral dose or SC injection

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Cholinergic Agents: Therapeutic Uses
Indirect-Acting Agents
• Cause skeletal muscle contractions • Used for diagnosis and treatment of myasthenia gravis • Used to reverse neuromuscular blocking agents • Used to reverse anticholinergic poisoning (antidote) Examples: physostigmine, pyridostigmine

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Cholinergic Agents: Therapeutic Uses
Indirect-Acting Agent—donepezil (Aricept)
• Used in the treatment of mild to moderate Alzheimer’s disease.

• Helps to increase or maintain memory and learning capabilities.

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Cholinergic Agents: Side Effects
Side effects are a result of overstimulation of the PSNS.
• Cardiovascular:

– Bradycardia, hypotension, conduction abnormalities (AV block and cardiac arrest)
• CNS:

– Headache, dizziness, convulsions
• Gastrointestinal: – Abdominal cramps, increased secretions, nausea, vomiting
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Cholinergic Agents: Side Effects
Side effects are a result of overstimulation of the PSNS.
• Respiratory:

– Increased bronchial secretions, bronchospasms
• Other: – Lacrimation, sweating, salivation, loss of binocular accommodation, miosis

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Cholinergic Agents: Interactions
• Anticholinergics, antihistamines, sympathomimetics
• Antagonize cholinergic agents, resulting in decreased responses

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Cholinergic Agents: Nursing Implications
• Keep in mind that these agents will stimulate the PSNS and mimic the action of ACh.
• Assess for allergies, presence of GI or GU obstructions, asthma, peptic ulcer disease, or coronary artery disease. • Perform baseline assessment of VS and systems overview.

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Cholinergic Agents: Nursing Implications
• Medications should be taken as ordered and not abruptly stopped.
• The doses should be spread evenly apart to optimize the effects of the medication. • Overdosing can cause life-threatening problems. Patients should not adjust the dosages unless directed by the physician.

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Cholinergic Agents: Nursing Implications
• Encourage patients with myasthenia gravis to take medication 30 minutes before eating to help improve chewing and swallowing.
• When donepezil is prescribed for Alzheimer’s disease, be honest with caregivers and patients that the drug is for management of symptoms, not for a cure. • Therapeutic effects of donepezil may not occur for up to 6 weeks.
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Cholinergic Agents: Nursing Implications
• Atropine is the antidote for cholinergics. It should be available in the patient’s room for immediate use if needed.
• Patients should notify their physician if they experience muscle weakness, abdominal cramps, diarrhea, or difficulty breathing.

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Cholinergic Agents: Nursing Implications
Monitor for side effects, including:
Increased respiratory secretions Abdominal cramping

Bronchospasms
Difficulty breathing Nausea and vomiting

Dysrhythmias
Hypotension Bradycardia

Diarrhea
Increase in frequency and urgency of voiding patterns

Increased sweating

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Cholinergic Agents: Nursing Implications
Monitor for therapeutic effects:
• Alleviated signs and symptoms of myasthenia gravis • In postoperative patients with decreased GI peristalsis, look for: – Increased bowel sounds – Passage of flatus

– Occurrence of bowel movements
• In patients with urinary retention/hypotonic bladder, urination should occur within 60 minutes of bethanecol administration
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Cholinergic Blocking Agents
• Drugs that block or inhibit the actions of acetylcholine (ACh) in the parasympathetic nervous system (PSNS)

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Cholinergic Blocking Agents: Mechanism of Action
• Competitive antagonists
• Compete with ACh • Block ACh at the muscarinic receptors in the PSNS
– As a result, ACh is unable to bind to the receptor site and cause a cholinergic effect.

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Cholinergic Blocking Agents: Mechanism of Action
• Once these drugs bind to receptors, they inhibit nerve transmission at these receptors.

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Instructors may wish to use EIC Image #58: Site of Action of Cholinergic Blockers Within the PSNS

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Cholinergic Blocking Agents: Chemical Class
Natural
atropine belladonna hyoscyamine scopolamine

Synthetic/Semisynthetic
anisotropine dicyclomine hexocyclium ipratropium oxybutynin tolterodine clidinium glycopyrrolate homatropine isopropamide propantheline tridihexethyl

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Drug Effects of Cholinergic Blocking Agents
• Cardiovascular
– Small doses: decrease heart rate – Large doses: increase heart rate

• CNS
– Small doses: decrease muscle rigidity and tremors – Large doses: drowsiness, disorientation, hallucinations
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Drug Effects of Cholinergic Blocking Agents
• Eye
– Dilated pupils (mydriasis) – Decreased accommodation due to paralysis of ciliary muscles (cycloplegia)

• Gastrointestinal
– Relax smooth muscle tone of GI tract – Decrease intestinal and gastric secretions – Decrease motility and peristalsis
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Drug Effects of Cholinergic Blocking Agents
• Genitourinary
– Relaxed detrusor muscle – Increased constriction of internal sphincter – Result: urinary retention

• Glandular
– Decreased bronchial secretions, salivation, sweating

• Respiratory
– Decreased bronchial secretions – Dilated bronchial airways
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Cholinergic Blocking Agents: Therapeutic Uses
CNS
Decreased muscle rigidity and muscle tremors • Parkinson’s disease • Drug-induced extrapyramidal reactions

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Cholinergic Blocking Agents: Therapeutic Uses
Cardiovascular
Affect the heart’s conduction system
• Low doses: slow the heart rate

• High doses: block inhibitory vagal effects on the SA and AV node pacemaker cells
– Result: increased heart rate

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Cholinergic Blocking Agents: Therapeutic Uses
Atropine
Used primarily for cardiovascular disorders
• Sinus node dysfunction

• Symptomatic second-degree heart block
• Sinus bradycardia with hemodynamic compromise (advanced life support)

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Cholinergic Blocking Agents: Therapeutic Uses
Respiratory
Blocking the cholinergic stimulation of the PSNS allows unopposed action of the SNS.

• Results:
– Decreased secretions from nose, mouth, pharynx, bronchi – Relaxed smooth muscles in bronchi and bronchioles – Decreased airway resistance – Bronchodilation
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Cholinergic Blocking Agents: Therapeutic Uses
Respiratory agents are used to treat:
• Exercise-induced bronchospasms • Chronic bronchitis • Asthma • Chronic obstructive pulmonary disease

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Cholinergic Blocking Agents: Therapeutic Uses
Gastrointestinal
PSNS controls gastric secretions and smooth muscles that produce gastric motility.
• Blockade of PSNS results in:
– Decreased secretions – Relaxation of smooth muscle – Decreased GI motility and peristalsis
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Cholinergic Blocking Agents: Therapeutic Uses
Gastrointestinal agents are used to treat:
• Peptic ulcer disease • Irritable bowel disease • GI hypersecretory states

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Cholinergic Blocking Agents: Therapeutic Uses
Genitourinary
• Relaxed detrusor muscles of the bladder • Increased constriction of the internal sphincter • Reflex neurogenic bladder • Incontinence

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Cholinergic Blocking Agents: Side Effects
Body System
Cardiovascular

Side/Adverse Effects
Increased heart rate, dysrhythmias

CNS

CNS excitation, restlessness, irritability, disorientation, hallucinations, delirium

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Cholinergic Blocking Agents: Side Effects
Body System
Eye

Side/Adverse Effects
Dilated pupils, decreased visual accommodation, increased intraocular pressure Decreased salivation, decreased gastric secretions, decreased motility

Gastrointestinal

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Cholinergic Blocking Agents: Side Effects
Body System
Genitourinary Glandular Respiratory

Side/Adverse Effects
Urinary retention Decreased sweating Decreased bronchial secretions

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Cholinergic Blocking Agents: Interactions
• Antihistamines, phenothiazines, tricyclic antidepressants, MAOIs
• When given with cholinergic blocking agents, cause ADDITIVE cholinergic effects, resulting in increased effects

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Cholinergic Blocking Agents: Nursing Implications
• Keep in mind that these agents will block the action of ACh in the PSNS.
• Assess for allergies, presence of BPH, glaucoma, tachycardia, MI, CHF, hiatal hernia, and GI or GU obstruction. • Perform baseline assessment of VS and systems overview.

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Cholinergic Blocking Agents: Nursing Implications
• Medications should be taken exactly as prescribed to have the maximum therapeutic effect.
• Overdosing can cause life-threatening problems.

• Blurred vision may cause problems with driving or operating machinery.
• Patients may experience sensitivity to light and may want to wear dark glasses or sunglasses.

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Cholinergic Blocking Agents: Nursing Implications
• When giving ophthalmic solutions, apply pressure to the inner canthus to prevent systemic absorption.
• Dry mouth may occur; can be handled by chewing gum, frequent mouth care, and hard candy. • Check with physician before taking any other medication, including OTC medications. • ANTIDOTE for atropine is physostigmine salicylate (Antilirium).

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Cholinergic Blocking Agents: Nursing Implications
• Anticholinergics may lead to higher risk for heat stroke due to effects on heat-regulating mechanisms.
• Teach patients to limit physical exertion, and avoid high temperatures and strenuous exercise. • Emphasize the importance of adequate fluid and salt intake.
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Cholinergic Blocking Agents: Nursing Implications
• Patients should report the following to their physician: urinary hesitancy and/or retention, constipation, palpitations, tremors, confusion, sedation or amnesia, excessive dry mouth (especially if they have chronic lung infections or disease), or fever

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Cholinergic Agents: Nursing Implications
• Monitor for therapeutic effects:
• For patients with Parkinson’s disease: fewer tremors and decreased salivation and drooling • For patients with peptic ulcer disease: decreased abdominal pain

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Cholinergic Blocking Agents: Nursing Implications
Monitor for side effects, including:
Constipation Tremors Hallucinations Urinary retention Fever CNS depression (occurs with large doses of atropine)
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Tachycardia Confusion Sedation Hot, dry skin

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