Transcript 04_Cholinergic_Blockers_upd - Plattsburgh State Faculty and

Drugs Affecting the
Autonomic Nervous System
Cholinergic Agents and
Cholinergic Blocking Agents
Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
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
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Instructors may wish to use
EIC Image #56:
The Parasympathetic and
Sympathetic Nervous Systems
and
Their Relationships to One Another
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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:
Adrenergic Agents:
Mechanism of Action
Is there copy
missing at the
end? Inhibiting
what?
• 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
Dysrhythmias
Difficulty breathing
Hypotension
Nausea and vomiting
Bradycardia
Diarrhea
Increased sweating
Increase in frequency and
urgency of voiding patterns
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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
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Cholinergic Blocking Agents:
Chemical Class
Natural
Synthetic/Semisynthetic
atropine
anisotropine
clidinium
belladonna
dicyclomine
glycopyrrolate
hyoscyamine
hexocyclium
homatropine
scopolamine
ipratropium
isopropamide
oxybutynin
propantheline
tolterodine
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
Side/Adverse Effects
Cardiovascular
Increased heart rate,
dysrhythmias
CNS
CNS excitation, restlessness,
irritability, disorientation,
hallucinations, delirium
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Cholinergic Blocking Agents:
Side Effects
Body System
Side/Adverse Effects
Eye
Dilated pupils, decreased
visual accommodation,
increased intraocular pressure
Gastrointestinal
Decreased salivation,
decreased gastric secretions,
decreased motility
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Cholinergic Blocking Agents:
Side Effects
Body System
Side/Adverse Effects
Genitourinary
Urinary retention
Glandular
Decreased sweating
Respiratory
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
Tachycardia
Tremors
Confusion
Hallucinations
Sedation
Urinary retention
Hot, dry skin
Fever
CNS depression (occurs with large doses of atropine)
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