Cholinergic Agonists:

Cholinergic Agonists: 

Cholinergic Drugs: 

  • Drugs that stimulate the parasympathetic nervous system (PSNS) 

    • Opposite of SNS 

  • Parasympathomimetic drugs (mimic PSNS) 

    • Specifically mimics acetylcholine ACh  

  • Cholinergic receptors: 

    • Two types that are determined by: 

      • Location 

      • Action once stimulated  

    • Nicotinic receptors  

      • Stimulated by acetylcholine and nicotine  

    • Muscarinic receptors  

      • Stimulated by acetylcholine  

      • Located in the effector organs of the PSNS 

        • Smooth muscle, cardiac muscle and glands  

  • Mechanisms of actions 

    • Direct acting cholinergic agonists 

      • Bind to cholinergic receptors and activate them  

    • Indirect acting cholinergic agonists  

      • Also known as cholinesterase inhibitors  

      • Inhibit the enzyme that breaks down Ach 

        • This means more Ach is available at the receptors  

      • Increases ACh without technically causing a specific receptor  

  • Indirect Acting Cholinesterase Inhibitors  

    • Reversible  

      • Bind to cholinesterase for a short period of time  

    • Irreversible  

      • Bind to cholinesterase for long periods of time  

        • Form a permanent covalent bond  

        • In order to break the bond, body must make new cholinesterase to break said bonds 

Drug Effects: 

  • Rest and digest system  

  • SLUDD 

    • Salivation, lacrimation, urination, digestion, defecation  

  • Pulmonary and cardiac effects as well  

    • Opposite of adrenergic stimulation 

      • Slow heartrate instead of speeding it up and cause bronchoconstriction rather than dilation  

  • Stimulation of intestines and bladder 

    • Increased gastric secretions 

    • Increased gastric motility  

    • Increased urinary frequency  

  • Stimulate pupils  

    • Constriction, miosis (small pupils) 

    • Reduced intraocular pressure  

      • Helpful when dealing with glaucoma  

  • Increased salivation and sweating  

Cholinergic Drug Effects: 

  • Cardiovascular  

    • Decreased heart rate  

    • Vasodilation  

  • Respiratory  

    • Bronchial constriction  

    • Narrowed airways  

  • At recommended doses, cholinergic primarily affect 

    • Muscarinic receptors  

      • Results in desired effects 

  • At high doses, cholinergic stimulate nicotinic receptors  

    • Causes undesired effects  

      • Such as extremes of SLUDD 

Indications: 

  • Direct acting drugs 

    • Reduce intraocular pressure 

      • Useful for glaucoma and intraocular surgery  

        • Echothiopate  

        • Carbachol  

        • Pilocarpine  

    • Topical application because of poor oral absorption 

    • Bethanechol  

      • Increases tone and motility of bladder and GI  

      • Relaxes sphincter in bladder and GI, allowing emptying  

      • Used for postsurgical atony of the bladder and GI  

      • Can be given orally or subcutaneous  

    • Cevimeline (direct acting drug) 

      • Used to treat excessively dry mouth (xerostomia) resulting from a disorder known as Sjogren's syndrome  

    • Succinylcholine (direct acting) 

      • Used as a neuromuscular blocker in general anesthesia  

      • Paralysis agent that is fast acting  

    • Nicotine (direct acting) 

      • Used as nicotine replacements for smoking cessation  

        • Patches, lozenge, gum, inhaled 

        • Often prescribed in hospitals to alleviate withdrawal symptoms for patients who are smokers  

          • Gums or lozenges can be used concurrently for breakthrough withdrawal  

  • Indirect Acting Drugs  

    • Inhibit acetylcholinesterase and increase Ach concentrations at receptor sites  

    • Causes skeletal muscle contraction  

    • Used for diagnosis and treatment of myasthenia gravis  

    • Used to reverse neuromuscular blocking drugs (paralytic agents) 

    • Used to reverse anticholinergic poisoning (antidote) 

      • Pyridostigmine  

    • Indirect acting anticholinesterase drugs  

      • Used for treatment of mild to moderate Alzeimer's disease  

        • Donepezil  

          • Not a cure, but does slow the disease down and helps with symptomology  

  • Contraindications:  

    • Allergy to drug  

    • GI or GU tract obstruction  

    • Bradycardia and defects in cardiac impulse conduction  

    • Hyperthyroidism  

    • Epilepsy  

    • Hypotension and chronic obstructive pulmonary disease 

    • Parkinson's disease  

  • Adverse Effects  

    • Result of overstimulation of the PSNS  

      • Too much of a good thing  

    • Cardiovascular  

      • Bradycardia and hypotension  

      • Syncope and conduction abnormalities such as AV block and cardiac arrest  

    • Central nervous system 

      • Headache and dizziness 

      • Convulsions and ataxia  

    • Gastrointestinal  

      • Abdominal cramps 

      • Increased secretions, nausea and vomiting  

    • Respiratory  

      • Increased bronchial secretions and bronchospasms  

    • Other  

      • Lacrimation, sweating, salivation and miosis (small eyes)  

  • Toxicity and Overdose: Cholinergic Crisis  

    • LIFE threatening 

      • Causes circulatory collapse, hypotension, bloody diarrhea, shock and cardiac arrest  

    • Early signs  

      • Abdominal cramps, salivation (excessive), flushing of the skin  

      • Nausea and vomiting  

      • Transient syncope and transient complete heart block 

      • Dyspnea and orthostatic hypotension  

    • Muscarinic Overstimulation  

      • Covered in SLUDGE 

        • Salivation, lacrimation, urination, defecation, GI cramps, emesis  

    • Nicotinic Overstimulation  

      • MT WTF  

        • Mydriasia tachycardia MT 

        • Muscle weakness, twitching, fasciculation WTF  

        • High BP and paralysis  

  • Cholinergic Crisis Management  

    • Early phases of toxicity  

      • Use of Atropine  

        • Cholinergic antagonist  

    • Severe cardiovascular reaction or bronchoconstriction  

      • Use epinephrine  

        • Adrenergic agonist  

  • Usually in crash cart  

Drug-Drug Interactions: 

  • Anticholinergics, antihistamines, adrenergic agonists  

    • Antagonize cholinergic drugs  

      • Result in decreased responses as they cancel each other out  

  • Other cholinergic drugs 

    • Additive effect  

Prototype Drugs: 

  • Bethanechol  

    • DIRECT acting  

    • Uses 

      • Urinary retention (non obstructive) 

      • Post op, post partum, and neurogenic bladder  

    • Contraindications  

      • Drug allergy 

      • Hyperthyroidism, peptic ulcers and active bronchial asthma  

      • Cardiac disease or coronary artery disease  

      • Epilepsy and parkinsonism  

    • Adverse effects  

      • Syncope, hypotension with reflex tachycardia  

      • Headaches, seizure 

      • GI upset  

      • Asthma attacks  

    • Interactions  

      • Acetylcholinesterase inhibitors  

        • Indirect cholinergic  

          • Can cause a cholinergic crisis  

  • Donepezil  

    • Cholinesterase inhibitor  

      • Works centrally in the brain  

      • Increases levels of Ach by inhibiting acetylcholinesterase  

    • Uses: mild to moderate Alzheimer's 

    • Contraindications  

      • Known drug allergy  

    • Adverse effects 

      • GI upset and GI ulcers  

      • Drowsiness, dizziness, insomnia  

      • Muscle cramps 

      • Bradycardia, syncope, hypotension with reflex  

      • Tachycardia or hypertension  

    • Drug-Drug Interactions  

      • Anticholinergics and nonsteroidal anti-inflammatory drugs (NSAIDs) 

  • Pyridostigmine  

    • Indications: 

      • Myasthenia gravis  

      • Reversing the effects of neuromuscular blocking drugs  

      • Tricyclic antidepressant overdose 

      • Antidote in chemical warfare  

    • Contraindications and Precautions 

      • Hypersensitivity, prior severe cholinergic reactions  

      • Asthma 

      • Gangrene, hyperthyroidism, cardiovascular disease  

      • GI or GU obstruction  

    • Adverse Effects 

      • GI upset and excessive salivation  

      • Cholinergic crisis  

    • Interactions  

      • Anticholinergic drugs  

Nursing Process: 

  • Assessment  

    • Medication history and allergies  

    • Presence of GI and GU obstructions 

    • Asthma, peptic ulcer disease, coronary artery disease  

    • Neuro status  

    • Current symptoms 

    • Baseline assessment 

  • Diagnosis 

    • Oxygenation and perfusion  

    • Urination 

    • Cognition 

    • Specific to intended effects or adverse effects of drug  

  • Planning 

    • Specific to intended effects/adverse effects of the drug  

  • Implementation  

    • Administer as ordered  

    • Specific interventions related to intended effects  

      • No abrupt cessation 

      • Space doses evenly throughout day and night  

      • Monitor for S/S cholinergic crisis 

    • Always have atropine available as an antidote  

  • Evaluation  

    • Monitor for therapeutic effects  

      • Myasthenia gravis: symptoms should improve  

      • Postop decreased GI peristalsis: 

        • Increased bowel sounds 

        • Passage of flatus and BM 

      • Urinary retention or hypotonic bladder 

        • Should have urination within 60 minutes of bethanechol admin  

      • Alzeimer's disease:  

        • Symptom improvement  

        • ADLs and improved mood  

        • Decreased confusion  

    • Monitor for adverse effects  

      • SLUDGE  

      • Salivation and lacrimation  

      • Urination and defecation  

      • GI cramping and emesis  

Patient Education  

o       Take as directed and use a consistent dosing interval with no abrupt cessation  

o       Do not adjust dose without provider  

o       S/S of cholinergic crisis  

  • Notify provider immediately  

  • If severe: call EMS or send to ER 

o   For Alzheimer's disease have realistic expectations  

  • It is not a cure its management  

  • Results may take up to 6 weeks