Cholinergic blockers

Drugs Affecting the Drugs Affecting the Autonomic Nervous SystemAutonomic Nervous System

Cholinergic Agents andCholinergic Agents andCholinergic Blocking AgentsCholinergic Blocking Agents

Cholinergic AgentsCholinergic Agents

• Drugs that stimulate theDrugs that stimulate theparasympathetic nervous system (PSNS)parasympathetic nervous system (PSNS)

• The PSNS is the opposing system to The PSNS is the opposing system to the SNSthe SNS


Also known asAlso known as

• cholinergic agonistscholinergic agonists

oror

• parasympathomimeticsparasympathomimetics


• Mimic the effects of the PSNS Mimic the effects of the PSNS neurotransmitterneurotransmitter

• Acetylcholine (ACh)Acetylcholine (ACh)

Cholinergic ReceptorsCholinergic Receptors

Two types, determined by:Two types, determined by:

• LocationLocation

• Action once stimulatedAction once stimulated

Nicotinic receptors and Muscarinic receptorsNicotinic receptors and Muscarinic receptors

Nicotinic ReceptorsNicotinic Receptors

• Located in the ganglia of both the Located in the ganglia of both the PSNS and SNSPSNS and SNS

• Named “nicotinic” because can be stimulated Named “nicotinic” because can be stimulated by the alkaloid nicotineby the alkaloid nicotine

Muscarinic ReceptorsMuscarinic Receptors

• Located postsynaptically:Located postsynaptically:

– Smooth muscleSmooth muscle

– Cardiac muscleCardiac muscle

– Glands of parasympathetic fibersGlands of parasympathetic fibers

– Effector organs of cholinergic sympathetic fibersEffector organs of cholinergic sympathetic fibers

• Named “muscarinic” because can be Named “muscarinic” because can be stimulated by the alkaloid muscarinestimulated by the alkaloid muscarine

Adrenergic Agents: Adrenergic Agents: Mechanism of ActionMechanism of Action

• Direct-acting (agonist)Direct-acting (agonist)

– Bind to cholinergic receptors, causing stimulationBind to cholinergic receptors, causing stimulation

Adrenergic Agents: Adrenergic Agents: Mechanism of ActionMechanism of Action

• Indirect-actingIndirect-acting

– Inhibit the enzyme “cholinesterase”Inhibit the enzyme “cholinesterase”

Result: more ACh is available at the receptorsResult: more ACh is available at the receptors

Indirect-Acting Cholinergic Agents Indirect-Acting Cholinergic Agents (Cholinesterase Inhibitors)(Cholinesterase Inhibitors)

• ReversibleReversible

– Bind to cholinesterase for a period of Bind to cholinesterase for a period of minutes to hoursminutes to hours

• IrreversibleIrreversible

– Bind to cholinesterase and form a permanent Bind to cholinesterase and form a permanent covalent bondcovalent bond

– The body must make new cholinesteraseThe body must make new cholinesterase

Drug Effects of Cholinergic AgentsDrug Effects of Cholinergic Agents

• Effects seen when the PSNS is stimulated.Effects seen when the PSNS is stimulated.

• The PSNS is the “rest and digest” system.The PSNS is the “rest and digest” system.


““SLUDGE”SLUDGE”

• SSalivationalivation

• LLacrimationacrimation

• UUrinary incontinencerinary incontinence

• DDiarrheaiarrhea

• GGastrointestinal crampsastrointestinal cramps

• EEmesismesis


• Stimulate intestine and bladderStimulate intestine and bladder– Increased gastric secretionsIncreased gastric secretions– Increased gastrointestinal motilityIncreased gastrointestinal motility– Increased urinary frequencyIncreased urinary frequency

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

• Increased salivation and sweatingIncreased salivation and sweating


• Cardiovascular effectsCardiovascular effects

– Decreased heart rateDecreased heart rate

– VasodilationVasodilation

• Respiratory effectsRespiratory effects

– Bronchial constriction, narrowed airwaysBronchial constriction, narrowed airways


• At recommended doses, the cholinergics At recommended doses, the cholinergics primarily affect the MUSCARINIC receptors.primarily affect the MUSCARINIC receptors.

• At high doses, cholinergics stimulate the At high doses, cholinergics stimulate the NICOTINIC receptors. NICOTINIC receptors.


• DESIRED EFFECTS: from muscarinic DESIRED EFFECTS: from muscarinic receptor stimulationreceptor stimulation

• Many undesirable effects are due to Many undesirable effects are due to stimulation of the nicotinic receptorsstimulation of the nicotinic receptors

Cholinergic Agents: Cholinergic Agents: Therapeutic UsesTherapeutic Uses

Direct-Acting AgentsDirect-Acting Agents

• Reduce intraocular pressureReduce intraocular pressure

• Useful for glaucoma and intraocular surgeryUseful for glaucoma and intraocular surgery

Examples: acetylcholine, carbachol, pilocarpineExamples: acetylcholine, carbachol, pilocarpine

Topical application due to poor oral absorptionTopical application due to poor oral absorption


Direct-Acting Agent—bethanecholDirect-Acting Agent—bethanechol

• Increases tone and motility of bladder and GI tractIncreases tone and motility of bladder and GI tract

• Relaxes sphincters in bladder and GI tract, allowing Relaxes sphincters in bladder and GI tract, allowing them to emptythem to empty

• Helpful for postsurgical atony of the bladder Helpful for postsurgical atony of the bladder and GI tractand GI tract

Oral dose or SC injectionOral dose or SC injection


Indirect-Acting AgentsIndirect-Acting Agents

• Cause skeletal muscle contractionsCause skeletal muscle contractions

• Used for diagnosis and treatment of Used for diagnosis and treatment of myasthenia gravismyasthenia gravis

• Used to reverse neuromuscular blocking agentsUsed to reverse neuromuscular blocking agents

• Used to reverse anticholinergic poisoning (antidote)Used to reverse anticholinergic poisoning (antidote)

Examples: physostigmine, pyridostigmineExamples: physostigmine, pyridostigmine


Indirect-Acting Agent—donepezil (Aricept)Indirect-Acting Agent—donepezil (Aricept)

• Used in the treatment of mild to moderate Used in the treatment of mild to moderate Alzheimer’s disease.Alzheimer’s disease.

• Helps to increase or maintain memory and Helps to increase or maintain memory and learning capabilities.learning capabilities.

Cholinergic Agents: Side EffectsCholinergic Agents: Side Effects

Side effects are a result of overstimulation Side effects are a result of overstimulation of the PSNS.of the PSNS.

• Cardiovascular:Cardiovascular:

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

• CNS:CNS:

– Headache, dizziness, convulsionsHeadache, dizziness, convulsions

• Gastrointestinal:Gastrointestinal:

– Abdominal cramps, increased secretions, Abdominal cramps, increased secretions, nausea, vomitingnausea, vomiting

Cholinergic Agents: Side EffectsCholinergic Agents: Side Effects

Side effects are a result of Side effects are a result of overstimulation of the PSNS.overstimulation of the PSNS.

• Respiratory:Respiratory:

– Increased bronchial secretions, bronchospasmsIncreased bronchial secretions, bronchospasms

• Other:Other:

– Lacrimation, sweating, salivation, loss of Lacrimation, sweating, salivation, loss of binocular accommodation, miosisbinocular accommodation, miosis

Cholinergic Agents: InteractionsCholinergic Agents: Interactions

• Anticholinergics, antihistamines, Anticholinergics, antihistamines, sympathomimeticssympathomimetics

• Antagonize cholinergic agents, resulting Antagonize cholinergic agents, resulting in decreased responsesin decreased responses

Cholinergic Agents: Cholinergic Agents: Nursing Implications Nursing Implications

• Keep in mind that these agents will stimulate Keep in mind that these agents will stimulate the PSNS and mimic the action of ACh. the PSNS and mimic the action of ACh.

• Assess for allergies, presence of GI or GU Assess for allergies, presence of GI or GU obstructions, asthma, peptic ulcer disease, obstructions, asthma, peptic ulcer disease, or coronary artery disease.or coronary artery disease.

• Perform baseline assessment of VS and Perform baseline assessment of VS and systems overview.systems overview.

Cholinergic Agents: Cholinergic Agents: Nursing ImplicationsNursing Implications

• Medications should be taken as ordered Medications should be taken as ordered and not abruptly stopped. and not abruptly stopped.

• The doses should be spread evenly apart The doses should be spread evenly apart to optimize the effects of the medication.to optimize the effects of the medication.

• Overdosing can cause life-threatening Overdosing can cause life-threatening problems. Patients should not adjust the problems. Patients should not adjust the dosages unless directed by the physician.dosages unless directed by the physician.


• Encourage patients with myasthenia gravis Encourage patients with myasthenia gravis to take medication 30 minutes before eating to take medication 30 minutes before eating to help improve chewing and swallowing.to help improve chewing and swallowing.

• When donepezil is prescribed for Alzheimer’s When donepezil is prescribed for Alzheimer’s disease, be honest with caregivers and disease, be honest with caregivers and patients that the drug is for management patients that the drug is for management of symptoms, not for a cure.of symptoms, not for a cure.

• Therapeutic effects of donepezil may not Therapeutic effects of donepezil may not occur for up to 6 weeks.occur for up to 6 weeks.


• Atropine is the antidote for cholinergics. Atropine is the antidote for cholinergics. It should be available in the patient’s room for It should be available in the patient’s room for immediate use if needed.immediate use if needed.

• Patients should notify their physician if they Patients should notify their physician if they experience muscle weakness, abdominal experience muscle weakness, abdominal cramps, diarrhea, or difficulty breathing.cramps, diarrhea, or difficulty breathing.


Monitor for side effects, including:Monitor for side effects, including:

Increased respiratory Increased respiratory Abdominal crampingAbdominal crampingsecretionssecretions

BronchospasmsBronchospasms DysrhythmiasDysrhythmias

Difficulty breathingDifficulty breathing HypotensionHypotension

Nausea and vomitingNausea and vomiting BradycardiaBradycardia

DiarrheaDiarrhea Increased sweatingIncreased sweating

Increase in frequency andIncrease in frequency andurgency of voiding patternsurgency of voiding patterns

Cholinergic Agents: Cholinergic Agents: Nursing ImplicationsNursing ImplicationsMonitor for therapeutic effects:Monitor for therapeutic effects:

• Alleviated signs and symptoms of myasthenia gravisAlleviated signs and symptoms of myasthenia gravis

• In postoperative patients with decreased GI peristalsis, In postoperative patients with decreased GI peristalsis, look for:look for:

– Increased bowel soundsIncreased bowel sounds

– Passage of flatusPassage of flatus

– Occurrence of bowel movementsOccurrence of bowel movements

• In patients with urinary retention/hypotonic bladder, In patients with urinary retention/hypotonic bladder, urination should occur within 60 minutes of bethanecol urination should occur within 60 minutes of bethanecol administrationadministration

Cholinergic Blocking AgentsCholinergic Blocking Agents

• Drugs that block or inhibit the actions of Drugs that block or inhibit the actions of acetylcholine (ACh) in the parasympathetic acetylcholine (ACh) in the parasympathetic nervous system (PSNS)nervous system (PSNS)

Cholinergic Blocking Agents: Cholinergic Blocking Agents: Mechanism of ActionMechanism of Action

• Competitive antagonistsCompetitive antagonists

• Compete with AChCompete with ACh

• Block ACh at the muscarinic receptors Block ACh at the muscarinic receptors in the PSNSin the PSNS

– As a result, ACh is unable to bind to theAs a result, ACh is unable to bind to thereceptor site and cause a cholinergic effect.receptor site and cause a cholinergic effect.

Cholinergic Blocking Agents: Cholinergic Blocking Agents: Mechanism of ActionMechanism of Action

• Once these drugs bind to receptors, they Once these drugs bind to receptors, they inhibit nerve transmission at these receptors.inhibit nerve transmission at these receptors.

Cholinergic Blocking Agents: Cholinergic Blocking Agents: Chemical ClassChemical Class

NaturalNatural Synthetic/SemisyntheticSynthetic/Semisynthetic

atropineatropine anisotropineanisotropine clidiniumclidinium

belladonnabelladonna dicyclominedicyclomine glycopyrrolateglycopyrrolate

hyoscyaminehyoscyamine hexocycliumhexocyclium homatropinehomatropine

scopolaminescopolamine ipratropiumipratropium isopropamideisopropamide

oxybutyninoxybutynin propanthelinepropantheline

tolterodinetolterodine tridihexethyltridihexethyl

Drug Effects of Drug Effects of Cholinergic Blocking AgentsCholinergic Blocking Agents

• CardiovascularCardiovascular

– Small doses: decrease heart rate Small doses: decrease heart rate

– Large doses: increase heart rateLarge doses: increase heart rate

• CNSCNS

– Small doses: decrease muscle rigidity Small doses: decrease muscle rigidity and tremorsand tremors

– Large doses: drowsiness, disorientation, Large doses: drowsiness, disorientation, hallucinationshallucinations

Drug Effects of Drug Effects of Cholinergic Blocking AgentsCholinergic Blocking Agents

• EyeEye

– Dilated pupils (mydriasis)Dilated pupils (mydriasis)

– Decreased accommodation due to paralysis Decreased accommodation due to paralysis of ciliary muscles (cycloplegia)of ciliary muscles (cycloplegia)

• GastrointestinalGastrointestinal

– Relax smooth muscle tone of GI tractRelax smooth muscle tone of GI tract

– Decrease intestinal and gastric secretionsDecrease intestinal and gastric secretions

– Decrease motility and peristalsis Decrease motility and peristalsis

Drug Effects of Drug Effects of Cholinergic Blocking AgentsCholinergic Blocking Agents• GenitourinaryGenitourinary

– Relaxed detrusor muscleRelaxed detrusor muscle– Increased constriction of internal sphincterIncreased constriction of internal sphincter– Result: urinary retentionResult: urinary retention

• GlandularGlandular– Decreased bronchial secretions, salivation, Decreased bronchial secretions, salivation,

sweatingsweating

• RespiratoryRespiratory– Decreased bronchial secretionsDecreased bronchial secretions– Dilated bronchial airwaysDilated bronchial airways

Cholinergic Blocking Agents: Cholinergic Blocking Agents: Therapeutic UsesTherapeutic Uses

CNSCNS

Decreased muscle rigidity and muscle tremorsDecreased muscle rigidity and muscle tremors

• Parkinson’s diseaseParkinson’s disease

• Drug-induced extrapyramidal reactionsDrug-induced extrapyramidal reactions


CardiovascularCardiovascular

Affect the heart’s conduction systemAffect the heart’s conduction system

• Low doses: slow the heart rateLow doses: slow the heart rate

• High doses: block inhibitory vagal effects on High doses: block inhibitory vagal effects on the SA and AV node pacemaker cellsthe SA and AV node pacemaker cells

– Result: increased heart rateResult: increased heart rate


AtropineAtropine

Used primarily for cardiovascular disordersUsed primarily for cardiovascular disorders

• Sinus node dysfunctionSinus node dysfunction

• Symptomatic second-degree heart blockSymptomatic second-degree heart block

• Sinus bradycardia with hemodynamic compromise Sinus bradycardia with hemodynamic compromise (advanced life support)(advanced life support)

Cholinergic Blocking Agents: Cholinergic Blocking Agents: Therapeutic Uses Therapeutic Uses RespiratoryRespiratoryBlocking the cholinergic stimulation of the PSNS Blocking the cholinergic stimulation of the PSNS

allows unopposed action of the SNS.allows unopposed action of the SNS.

• Results:Results:

– Decreased secretions from nose, mouth, Decreased secretions from nose, mouth, pharynx, bronchipharynx, bronchi

– Relaxed smooth muscles in bronchi Relaxed smooth muscles in bronchi and bronchiolesand bronchioles

– Decreased airway resistanceDecreased airway resistance

– BronchodilationBronchodilation


Respiratory agents are used to treat:Respiratory agents are used to treat:

• Exercise-induced bronchospasmsExercise-induced bronchospasms

• Chronic bronchitisChronic bronchitis

• AsthmaAsthma

• Chronic obstructive pulmonary diseaseChronic obstructive pulmonary disease

Cholinergic Blocking Agents: Cholinergic Blocking Agents: Therapeutic Uses Therapeutic Uses

GastrointestinalGastrointestinal

PSNS controls gastric secretions and smooth PSNS controls gastric secretions and smooth muscles that produce gastric motility.muscles that produce gastric motility.

• Blockade of PSNS results in:Blockade of PSNS results in:

– Decreased secretionsDecreased secretions

– Relaxation of smooth muscleRelaxation of smooth muscle

– Decreased GI motility and peristalsisDecreased GI motility and peristalsis


Gastrointestinal agents are used to treat:Gastrointestinal agents are used to treat:

• Peptic ulcer diseasePeptic ulcer disease

• Irritable bowel diseaseIrritable bowel disease

• GI hypersecretory statesGI hypersecretory states

Cholinergic Blocking Agents: Cholinergic Blocking Agents: Therapeutic Uses Therapeutic Uses

GenitourinaryGenitourinary

• Relaxed detrusor muscles of the bladderRelaxed detrusor muscles of the bladder

• Increased constriction of the internal Increased constriction of the internal sphinctersphincter

• Reflex neurogenic bladderReflex neurogenic bladder

• Incontinence Incontinence

Cholinergic Blocking Agents: Cholinergic Blocking Agents: Side EffectsSide Effects

Body SystemBody System Side/Adverse EffectsSide/Adverse Effects

CardiovascularCardiovascular Increased heart rate, Increased heart rate, dysrhythmiasdysrhythmias

CNSCNS CNS excitation, restlessness, CNS excitation, restlessness, irritability, disorientation, irritability, disorientation,

hallucinations, hallucinations, deliriumdelirium



EyeEye Dilated pupils, decreased Dilated pupils, decreased visual accommodation, visual accommodation,

increased increased intraocular pressureintraocular pressure

GastrointestinalGastrointestinal Decreased salivation, Decreased salivation, decreased gastric decreased gastric

secretions, secretions, decreased motilitydecreased motility



GenitourinaryGenitourinary Urinary retentionUrinary retention

GlandularGlandular Decreased sweatingDecreased sweating

RespiratoryRespiratory Decreased bronchial Decreased bronchial secretionssecretions

Cholinergic Blocking Agents: Cholinergic Blocking Agents: InteractionsInteractions

• Antihistamines, phenothiazines, Antihistamines, phenothiazines, tricyclic antidepressants, MAOIstricyclic antidepressants, MAOIs

• When given with cholinergic blocking When given with cholinergic blocking agents, cause ADDITIVE cholinergic agents, cause ADDITIVE cholinergic effects, resulting in increased effectseffects, resulting in increased effects

Cholinergic Blocking Agents: Cholinergic Blocking Agents: Nursing ImplicationsNursing Implications

• Keep in mind that these agents will blockKeep in mind that these agents will blockthe action of ACh in the PSNS.the action of ACh in the PSNS.

• Assess for allergies, presence of BPH, Assess for allergies, presence of BPH, glaucoma, tachycardia, MI, CHF, hiatal glaucoma, tachycardia, MI, CHF, hiatal hernia, and GI or GU obstruction.hernia, and GI or GU obstruction.

• Perform baseline assessment of VS Perform baseline assessment of VS and systems overview.and systems overview.


• Medications should be taken exactly as prescribed Medications should be taken exactly as prescribed to have the maximum therapeutic effect.to have the maximum therapeutic effect.

• Overdosing can cause life-threatening problems. Overdosing can cause life-threatening problems.

• Blurred vision may cause problems with driving Blurred vision may cause problems with driving or operating machinery.or operating machinery.

• Patients may experience sensitivity to light and Patients may experience sensitivity to light and may want to wear dark glasses or sunglasses.may want to wear dark glasses or sunglasses.


• When giving ophthalmic solutions, apply pressure to When giving ophthalmic solutions, apply pressure to the inner canthus to prevent systemic absorption.the inner canthus to prevent systemic absorption.

• Dry mouth may occur; can be handled by chewing Dry mouth may occur; can be handled by chewing gum, frequent mouth care, and hard candy.gum, frequent mouth care, and hard candy.

• Check with physician before taking any other Check with physician before taking any other medication, including OTC medications.medication, including OTC medications.

• ANTIDOTE for atropine is physostigmine salicylate ANTIDOTE for atropine is physostigmine salicylate (Antilirium).(Antilirium).


• Anticholinergics may lead to higher risk for Anticholinergics may lead to higher risk for heat stroke due to effects on heat-regulating heat stroke due to effects on heat-regulating mechanisms. mechanisms.

• Teach patients to limit physical exertion, and Teach patients to limit physical exertion, and avoid high temperatures and strenuous avoid high temperatures and strenuous exercise.exercise.

• Emphasize the importance of adequate fluid Emphasize the importance of adequate fluid and salt intake.and salt intake.


• Patients should report the following to their Patients should report the following to their physician: urinary hesitancy and/or retention, physician: urinary hesitancy and/or retention, constipation, palpitations, tremors, confusion, constipation, palpitations, tremors, confusion, sedation or amnesia, excessive dry mouth sedation or amnesia, excessive dry mouth (especially if they have chronic lung (especially if they have chronic lung infections or disease), or feverinfections or disease), or fever


• Monitor for therapeutic effects:Monitor for therapeutic effects:

• For patients with Parkinson’s disease: For patients with Parkinson’s disease: fewer tremors and decreased salivation fewer tremors and decreased salivation and droolingand drooling

• For patients with peptic ulcer disease: For patients with peptic ulcer disease: decreased abdominal paindecreased abdominal pain


Monitor for side effects, including:Monitor for side effects, including:

ConstipationConstipation TachycardiaTachycardia

TremorsTremors ConfusionConfusion

HallucinationsHallucinations SedationSedation

Urinary retentionUrinary retention Hot, dry skinHot, dry skin

FeverFever

CNS depression (occurs with large doses of atropine)CNS depression (occurs with large doses of atropine)

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Cholinergic blockers