drugs affecting
the
parasympathetic nervous system
CHOLINERGIC AGENTS AND CHOLINERGIC BLOCKING AGENTS
Cholinergic Agents
•Drugs that stimulate the parasympathetic nervous system (PSNS)
•The PSNS is the opposing system to the SNS
Also known as
•cholinergic agonists or
•parasympathomimetic
Instructors may wish to use
EIC Image #56:
The Parasympathetic and Sympathetic Nervous Systems and Their Relationships to One Another
•Mimic the effects of the PSNS neurotransmitter
•Acetylcholine (ACh)
Cholinergic Receptors
Two types, determined by:
•Location
•Action once stimulated
Nicotinic receptors and Muscarinic receptors
Two types, determined by:
•Location
•Action once stimulated
Nicotinic receptors and Muscarinic receptors
Nicotinic Receptors
•Located in the ganglia of both the PSNS and SNS
•Named “nicotinic” because can be stimulated by the alkaloid nicotine
•Located in the ganglia of both the PSNS and SNS
•Named “nicotinic” because can be stimulated by the alkaloid nicotine
Adrenergic Agents:
Mechanism of Action
•Direct-acting (agonist) –Bind to cholinergic receptors, causing stimulation
•Indirect-acting –Inhibit the enzyme “cholinesterase”
Result: more ACh is available at the receptors
Mechanism of Action
•Direct-acting (agonist) –Bind to cholinergic receptors, causing stimulation
•Indirect-acting –Inhibit the enzyme “cholinesterase”
Result: more ACh is available at the receptors
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
•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
Drug Effects of Cholinergic Agents
•Effects seen when the PSNS is stimulated.
•The PSNS is the “rest and digest” system.
“SLUDGE”
•Salivation
•Lacrimation
•Urinary incontinence
•Diarrhea
•Gastrointestinal cramps
•Emesis
•Stimulate intestine and bladder
–Increased gastric secretions
–Increased gastrointestinal motility
–Increased urinary frequency
•Stimulate pupil
–Constriction (miosis)
–Reduced intraocular pressure
•Increased salivation and sweating
•Cardiovascular effects
–Decreased heart rate
–Vasodilation
•Respiratory effects
–Bronchial constriction, narrowed airways
•At recommended doses, the cholinergics primarily affect the MUSCARINIC receptors.
•At high doses, cholinergics stimulate the NICOTINIC receptors.
•DESIRED EFFECTS: from muscarinic receptor stimulation
•Many undesirable effects are due to stimulation of the nicotinic receptors
•Effects seen when the PSNS is stimulated.
•The PSNS is the “rest and digest” system.
“SLUDGE”
•Salivation
•Lacrimation
•Urinary incontinence
•Diarrhea
•Gastrointestinal cramps
•Emesis
•Stimulate intestine and bladder
–Increased gastric secretions
–Increased gastrointestinal motility
–Increased urinary frequency
•Stimulate pupil
–Constriction (miosis)
–Reduced intraocular pressure
•Increased salivation and sweating
•Cardiovascular effects
–Decreased heart rate
–Vasodilation
•Respiratory effects
–Bronchial constriction, narrowed airways
•At recommended doses, the cholinergics primarily affect the MUSCARINIC receptors.
•At high doses, cholinergics stimulate the NICOTINIC receptors.
•DESIRED EFFECTS: from muscarinic receptor stimulation
•Many undesirable effects are due to stimulation of the nicotinic receptors
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
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
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
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.
Direct-Acting Agents
•Reduce intraocular pressure
•Useful for glaucoma and intraocular surgery
Examples: acetylcholine, carbachol, pilocarpine
Topical application due to poor oral absorption
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
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
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.
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
•Respiratory:
–Increased bronchial secretions, bronchospasms
•Other:
–Lacrimation, sweating, salivation, loss of binocular accommodation, miosis
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
•Respiratory:
–Increased bronchial secretions, bronchospasms
•Other:
–Lacrimation, sweating, salivation, loss of binocular accommodation, miosis
Cholinergic Agents: Interactions
•Anticholinergics, antihistamines, sympathomimetics
•Antagonize cholinergic agents, resulting in decreased responses
•Anticholinergics, antihistamines, sympathomimetics
•Antagonize cholinergic agents, resulting in decreased responses
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.
•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.
•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.
•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.
Monitor for side effects, including:
♦ Increased respiratory ♦ Abdominal cramping secretions
♦ Bronchospasms ♦ Dysrhythmias
♦ Difficulty breathing ♦ Hypotension
♦ Nausea and vomiting ♦ Bradycardia
♦ Diarrhea ♦ Increased sweating
♦ Increase in frequency and urgency of voiding patterns
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
•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.
•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.
•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.
•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.
Monitor for side effects, including:
♦ Increased respiratory ♦ Abdominal cramping secretions
♦ Bronchospasms ♦ Dysrhythmias
♦ Difficulty breathing ♦ Hypotension
♦ Nausea and vomiting ♦ Bradycardia
♦ Diarrhea ♦ Increased sweating
♦ Increase in frequency and urgency of voiding patterns
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
Cholinergic Blocking Agents
•Drugs that block or inhibit the actions of acetylcholine (ACh) in the parasympathetic nervous system (PSNS)
•Drugs that block or inhibit the actions of acetylcholine (ACh) in the parasympathetic nervous system (PSNS)
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.
•Once these drugs bind to receptors, they inhibit nerve transmission at these receptors.
•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.
•Once these drugs bind to receptors, they inhibit nerve transmission at these receptors.
Instructors may wish to use
EIC Image #58:
Site of Action of Cholinergic Blockers Within the PSNS
EIC Image #58:
Site of Action of Cholinergic Blockers Within the PSNS
Cholinergic Blocking Agents: Chemical Class
Natural Synthetic/Semisynthetic
atropine anisotropine clidinium
belladonna dicyclomine glycopyrrolate
hyoscyamine hexocyclium homatropine
scopolamine ipratropium isopropamide
oxybutynin propantheline
tolterodine tridihexethyl
Natural Synthetic/Semisynthetic
atropine anisotropine clidinium
belladonna dicyclomine glycopyrrolate
hyoscyamine hexocyclium homatropine
scopolamine ipratropium isopropamide
oxybutynin propantheline
tolterodine tridihexethyl
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
•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
•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
•Cardiovascular
–Small doses: decrease heart rate
–Large doses: increase heart rate
•CNS
–Small doses: decrease muscle rigidity and tremors
–Large doses: drowsiness, disorientation, hallucinations
•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
•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
Cholinergic Blocking Agents: Therapeutic Uses
♥ CNS
Decreased muscle rigidity and muscle tremors
•Parkinson’s disease
•Drug-induced extrapyramidal reactions
♥ 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
♥ Atropine
Used primarily for cardiovascular disorders
•Sinus node dysfunction
•Symptomatic second-degree heart block
•Sinus bradycardia with hemodynamic compromise (advanced life support)
♥ 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
Respiratory agents are used to treat:
•Exercise-induced bronchospasms
•Chronic bronchitis
•Asthma
•Chronic obstructive pulmonary disease
♥ 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
Gastrointestinal agents are used to treat:
•Peptic ulcer disease
•Irritable bowel disease
•GI hypersecretory states
♥ Genitourinary
•Relaxed detrusor muscles of the bladder
•Increased constriction of the internal sphincter
•Reflex neurogenic bladder
•Incontinence
♥ CNS
Decreased muscle rigidity and muscle tremors
•Parkinson’s disease
•Drug-induced extrapyramidal reactions
♥ 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
♥ Atropine
Used primarily for cardiovascular disorders
•Sinus node dysfunction
•Symptomatic second-degree heart block
•Sinus bradycardia with hemodynamic compromise (advanced life support)
♥ 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
Respiratory agents are used to treat:
•Exercise-induced bronchospasms
•Chronic bronchitis
•Asthma
•Chronic obstructive pulmonary disease
♥ 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
Gastrointestinal agents are used to treat:
•Peptic ulcer disease
•Irritable bowel disease
•GI hypersecretory states
♥ Genitourinary
•Relaxed detrusor muscles of the bladder
•Increased constriction of the internal sphincter
•Reflex neurogenic bladder
•Incontinence
Cholinergic Blocking Agents: Side Effects
Body System Side/Adverse Effects
Cardiovascular Increased heart rate, dysrhythmias
CNS CNS excitation, restlessness, irritability, disorientation, hallucinations, delirium
Eye Dilated pupils, decreased visual accommodation, increased intraocular pressure
Gastrointestinal Decreased salivation, decreased gastric secretions, decreased motility
Genitourinary Urinary retention
Glandular Decreased sweating
Respiratory Decreased bronchial secretions
Body System Side/Adverse Effects
Cardiovascular Increased heart rate, dysrhythmias
CNS CNS excitation, restlessness, irritability, disorientation, hallucinations, delirium
Eye Dilated pupils, decreased visual accommodation, increased intraocular pressure
Gastrointestinal Decreased salivation, decreased gastric secretions, decreased motility
Genitourinary Urinary retention
Glandular Decreased sweating
Respiratory Decreased bronchial secretions
Cholinergic Blocking Agents: Interactions
•Antihistamines, phenothiazines, tricyclic antidepressants, MAOIs
•When given with cholinergic blocking agents, cause ADDITIVE cholinergic effects, resulting in increased effects
•Antihistamines, phenothiazines, tricyclic antidepressants, MAOIs
•When given with cholinergic blocking agents, cause ADDITIVE cholinergic effects, resulting in increased effects
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.
•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.
•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).
•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.
•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
•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
Monitor for side effects, including:
♥ Constipation ♥Tachycardia
♥Tremors ♥Confusion
♥Hallucinations ♥ Sedation
♥Urinary retention ♥Hot, dry skin
♥Fever
CNS depression (occurs with large doses of atropine)
•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.
•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.
•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).
•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.
•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
•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
Monitor for side effects, including:
♥ Constipation ♥Tachycardia
♥Tremors ♥Confusion
♥Hallucinations ♥ Sedation
♥Urinary retention ♥Hot, dry skin
♥Fever
CNS depression (occurs with large doses of atropine)
CHOLINERGIC AGENTS CHOLINERGIC BLOCKING AGENTS