Drugs Affecting the Autonomic 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

Cholinergic Agents Also known as cholinergic agonists or parasympathomimetics

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

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

Cholinergic 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

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

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.

Adrenergic Agents: Mechanism of Action Lisa L. Hernandez: Is there copy missing at the end? Inhibiting what? HHS: HHS: Adrenergic Agents: Mechanism of Action Direct-acting (agonist) Bind to cholinergic receptors, causing stimulation

Adrenergic Agents: Mechanism of Action 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

Drug Effects of Cholinergic Agents Effects seen when the PSNS is stimulated. The PSNS is the “rest and digest” system.

Drug Effects of Cholinergic Agents “SLUDGE” Salivation Lacrimation Urinary incontinence Diarrhea Gastrointestinal cramps Emesis

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

Drug Effects of Cholinergic Agents Cardiovascular effects Decreased heart rate Vasodilation Respiratory effects Bronchial constriction, narrowed airways

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

Drug Effects of Cholinergic Agents 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

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

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

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.

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

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

Cholinergic Agents: Interactions 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.

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.

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.

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.

Cholinergic Agents: Nursing Implications 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

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

Cholinergic Blocking Agents 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.

Cholinergic Blocking Agents: Mechanism of Action 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

Cholinergic Blocking Agents: Chemical Class 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

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

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

Cholinergic Blocking Agents: Therapeutic Uses CNS Decreased muscle rigidity and muscle tremors Parkinson’s disease Drug-induced extrapyramidal reactions

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

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)

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

Cholinergic Blocking Agents: Therapeutic Uses Respiratory agents are used to treat: Exercise-induced bronchospasms Chronic bronchitis Asthma Chronic obstructive pulmonary disease

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

Cholinergic Blocking Agents: Therapeutic Uses Gastrointestinal agents are used to treat: Peptic ulcer disease Irritable bowel disease GI hypersecretory states

Cholinergic Blocking Agents: Therapeutic Uses 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

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

Cholinergic Blocking Agents: Side Effects Body System Side/Adverse Effects 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

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.

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.

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).

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.

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

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

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)