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Cholinomimetic Drugs

Cholinomimetic drugs, also known as parasympathomimetics or cholinergic agonists Cholinergic Agonists Drugs that bind to and activate cholinergic receptors. Glaucoma, increase acetylcholine Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS ( ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS), which acts on cholinergic muscarinic and nicotinic receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors. Other cholinomimetic drugs result in a net cholinergic effect by inhibiting the cholinesterase Cholinesterase Liver Function Tests enzyme. Muscarinic receptors Muscarinic Receptors Asthma Drugs are found in the CNS and are part of the parasympathetic nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification, which responds to cholinomimetics. Nicotinic receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors are found in the CNS at the neuromuscular junction Neuromuscular junction The synapse between a neuron and a muscle. Skeletal Muscle Contraction. Physiologic effects on muscarinic receptors Muscarinic Receptors Asthma Drugs include bronchoconstriction, lacrimation, and bradycardia Bradycardia Bradyarrhythmia is a rhythm in which the heart rate is less than 60/min. Bradyarrhythmia can be physiologic, without symptoms or hemodynamic change. Pathologic bradyarrhythmia results in reduced cardiac output and hemodynamic instability causing syncope, dizziness, or dyspnea. Bradyarrhythmias. Physiologic effects on nicotinic receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors include vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure, tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children, and elevated blood pressure. Cholinergic activation of muscarinic receptors Muscarinic Receptors Asthma Drugs on vascular endothelial cells cause an increase in nitric oxide Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from arginine by nitric oxide synthase. Nitric oxide is one of the endothelium-dependent relaxing factors released by the vascular endothelium and mediates vasodilation. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic gmp. Pulmonary Hypertension Drugs, which diffuses to the adjacent vascular smooth muscle cells, resulting in smooth muscle relaxation/ vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs and a paradoxical effect of the cholinomimetics on bronchial smooth muscle (constriction) and vascular smooth muscle (relaxation). Clinical uses of cholinomimetic agents include treatment of dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person's memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders, glaucoma Glaucoma Glaucoma is an optic neuropathy characterized by typical visual field defects and optic nerve atrophy seen as optic disc cupping on examination. The acute form of glaucoma is a medical emergency. Glaucoma is often, but not always, caused by increased intraocular pressure (IOP). Glaucoma, and as an aid for smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases cessation. The primary adverse effect of cholinergic drugs is overstimulation of the parasympathetic nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification. Symptoms result from excessive levels of ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS in synapses, glands, smooth muscles Smooth muscles Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. Muscle Tissue: Histology, and motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology endplates.

Last updated: Sep 6, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Chemistry and Pharmacodynamics

Acetylcholine Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS ( ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS) is a prototype direct-acting cholinergic drug. Cholinomimetics are direct activators of both the muscarinic and nicotinic cholinergic receptors Cholinergic receptors Cell surface proteins that bind acetylcholine with high affinity and trigger intracellular changes influencing the behavior of cells. Cholinergic receptors are divided into two major classes, muscarinic and nicotinic, based originally on their affinity for nicotine and muscarine. Each group is further subdivided based on pharmacology, location, mode of action, and/or molecular biology. Autonomic Nervous System: Anatomy.

Overview

  • A neurotransmitter at various synapses, nerves, and motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology endplates in muscles:
    • Nerve impulse → ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS stored in the vesicles Vesicles Female Genitourinary Examination is released into the synaptic cleft Synaptic cleft Synapses and Neurotransmission → binds to a postsynaptic receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors depolarization Depolarization Membrane Potential
    • ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS is degraded by the acetylcholinesterase (AChE) enzyme (present at tissue receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors sites and on RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology)
  • ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS is released from sympathetic and parasympathetic neuronal terminals on:
    • Lacrimal glands Lacrimal Glands Dacryocystitis 
    • Salivary glands Salivary glands The salivary glands are exocrine glands positioned in and around the oral cavity. These glands are responsible for secreting saliva into the mouth, which aids in digestion. There are 3 major paired salivary glands: the sublingual, submandibular, and parotid glands. Salivary Glands: Anatomy
    • Sweat glands Sweat glands Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. Soft Tissue Abscess
  • Overall effects are “wet”: tearing, sweating, and salivation
Acetylcholine secretion and reabsorption

Secretion Secretion Coagulation Studies and absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption of acetylcholine Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS ( ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS):
1: Acetylcholine Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS formed from choline and acetyl CoA
2: The enzyme acetylcholinesterase rapidly breaks down ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS in the synapse Synapse The junction between 2 neurons is called a synapse. The synapse allows a neuron to pass an electrical or chemical signal to another neuron or target effector cell. Synapses and Neurotransmission
3. Choline transported to the axon terminal to make more ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS

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Mechanism of action and physiologic effects

  • Muscarinic cholinergic receptors Cholinergic receptors Cell surface proteins that bind acetylcholine with high affinity and trigger intracellular changes influencing the behavior of cells. Cholinergic receptors are divided into two major classes, muscarinic and nicotinic, based originally on their affinity for nicotine and muscarine. Each group is further subdivided based on pharmacology, location, mode of action, and/or molecular biology. Autonomic Nervous System: Anatomy
    • All 5 types (M1, M2, M3, M4, and M5) are G protein-coupled receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors → increased intracellular levels of calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes, which lead to:
  • Muscarinic receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors locations → effects:
    • Autonomic ganglia and exocrine glands Exocrine glands Glands of external secretion that release its secretions to the body’s cavities, organs, or surface, through a duct. Glandular Epithelium: Histology: ↑ salivary/ gastric acid Gastric acid Hydrochloric acid present in gastric juice. Gastroesophageal Reflux Disease (GERD) secretion Secretion Coagulation Studies and diaphoresis
    • Blood vessel endothelium Endothelium A layer of epithelium that lines the heart, blood vessels (vascular endothelium), lymph vessels (lymphatic endothelium), and the serous cavities of the body. Arteries: Histology: M3 receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors → smooth muscle relaxation vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs
    • Respiratory: M3 receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors → smooth muscle contraction → bronchoconstriction
    • Stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy: M1 receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors → increase gastric acid Gastric acid Hydrochloric acid present in gastric juice. Gastroesophageal Reflux Disease (GERD) secretion Secretion Coagulation Studies 
    • Intestine: M3 receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors → increase peristalsis Peristalsis A movement, caused by sequential muscle contraction, that pushes the contents of the intestines or other tubular organs in one direction. Gastrointestinal Motility, contract the gastroesophageal sphincter, and relax the pyloric sphincter
    • Eye: M3 receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors → pupillary constriction ( miosis Miosis Pupil: Physiology and Abnormalities)
    • Heart: M2 receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors lead to:
      • Heart rate Heart rate The number of times the heart ventricles contract per unit of time, usually per minute. Cardiac Physiology due to sinoatrial (SA) node suppression Suppression Defense Mechanisms
      • ↓ Conduction velocity and increased refractory period in the atrioventricular (AV) node
      • ↓ Contractility (negative inotropy)
    • Genitourinary:
  • Nicotinic cholinergic receptors Cholinergic receptors Cell surface proteins that bind acetylcholine with high affinity and trigger intracellular changes influencing the behavior of cells. Cholinergic receptors are divided into two major classes, muscarinic and nicotinic, based originally on their affinity for nicotine and muscarine. Each group is further subdivided based on pharmacology, location, mode of action, and/or molecular biology. Autonomic Nervous System: Anatomy:
    • Ionotropic: act on ion channel receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors (e.g., calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channels Channels The Cell: Cell Membrane) (do not confuse with inotropic):
    • Located at the neuromuscular junction Neuromuscular junction The synapse between a neuron and a muscle. Skeletal Muscle Contraction skeletal muscle contraction Skeletal muscle contraction Skeletal muscle is striated muscle containing organized contractile structures known as sarcomeres that are made up of overlapping myofilaments: actin and myosin. When a nerve impulse arrives from a motor neuron, the signal triggers an action potential (AP) in the sarcolemma (muscle cell membrane), resulting in the release of Ca ions from the sarcoplasmic reticulum (SR) within the muscle cell. Skeletal Muscle Contraction
Cholinergic terminal neurotransmission and effects of cholinomimetic drugs

Cholinergic terminal neurotransmission Neurotransmission The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across electrical synapses. Synapses and Neurotransmission and the effects of cholinomimetic drugs:
Acetylcholine Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS ( ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS) is released into the synaptic cleft Synaptic cleft Synapses and Neurotransmission, the choline transporter (CHT) uptakes choline into the presynaptic neuron Presynaptic neuron Synapses and Neurotransmission, and the vesicular ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS transporter (VAChT) uptakes ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS into the storage vesicle Vesicle Primary Skin Lesions.
Nondepolarizing neuromuscular blockers Neuromuscular blockers Neuromuscular blockers are skeletal muscle relaxant medications that block muscle contraction through a couple of mechanisms. Depolarizing neuromuscular blockers bind to nicotinic cholinergic receptors (nAChRs), locking the ion channel open. This results in muscle relaxation and paralysis. Neuromuscular Blockers (NMBs) antagonize nicotinic receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors at neuromuscular junctions. Rocuronium Rocuronium An androstanol non-depolarizing neuromuscular blocking agent. It has a mono-quaternary structure and is a weaker nicotinic antagonist than pancuronium. Neuromuscular Blockers is used in anesthesia Anesthesia A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. Anesthesiology: History and Basic Concepts. Lambert-Eaton myasthenic syndrome Lambert-Eaton Myasthenic Syndrome Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder affecting the neuromuscular junction and has a strong association with small cell lung carcinoma. Lambert-Eaton myasthenic syndrome affects the voltage-gated calcium channels at the presynaptic membrane. Lambert-Eaton Myasthenic Syndrome ( LEMS LEMS Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder affecting the neuromuscular junction and has a strong association with small cell lung carcinoma. Lambert-Eaton myasthenic syndrome affects the voltage-gated calcium channels at the presynaptic membrane. Lambert-Eaton Myasthenic Syndrome) produces autoantibodies Autoantibodies Antibodies that react with self-antigens (autoantigens) of the organism that produced them. Blotting Techniques blocking presynaptic calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes ( Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)+) channels Channels The Cell: Cell Membrane, causing decreased ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology into the synaptic cleft Synaptic cleft Synapses and Neurotransmission and muscle weakness. Pyridostigmine is an AChE inhibitor used to treat myasthenia gravis Myasthenia Gravis Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles caused by dysfunction/destruction of acetylcholine receptors at the neuromuscular junction. MG presents with fatigue, ptosis, diplopia, dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement. Myasthenia Gravis. Nicotine Nicotine Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. Stimulants (in cigarettes) agonizes and varenicline (used for smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases cessation support) partially agonizes nicotinic ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors. Succinylcholine Succinylcholine A quaternary skeletal muscle relaxant usually used in the form of its bromide, chloride, or iodide. It is a depolarizing relaxant, acting in about 30 seconds and with a duration of effect averaging three to five minutes. Succinylcholine is used in surgical, anesthetic, and other procedures in which a brief period of muscle relaxation is called for. Neuromuscular Blockers, a depolarizing NMB, agonizes ganglionic nicotinic receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors, leading to receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors desensitization and neuromuscular blockade Neuromuscular Blockade The intentional interruption of transmission at the neuromuscular junction by external agents, usually neuromuscular blocking agents. It is distinguished from nerve block in which nerve conduction (neural conduction) is interrupted rather than neuromuscular transmission. Neuromuscular blockade is commonly used to produce muscle relaxation as an adjunct to anesthesia during surgery and other medical procedures. It is also often used as an experimental manipulation in basic research. It is not strictly speaking anesthesia but is grouped here with anesthetic techniques. The failure of neuromuscular transmission as a result of pathological processes is not included here. Aminoglycosides. Donepezil (for dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders) inhibits the breakdown of ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS, leading to ↑ ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS in the synaptic cleft Synaptic cleft Synapses and Neurotransmission. Cholinomimetics (e.g., bethanechol for neurogenic bladder Neurogenic bladder Dysfunction of the urinary bladder due to disease of the central or peripheral nervous system pathways involved in the control of urination. This is often associated with spinal cord diseases, but may also be caused by brain diseases or peripheral nerve diseases. Urinary Incontinence) and pilocarpine agonize muscarinic receptors Muscarinic Receptors Asthma Drugs.
Na+/K+ channel: sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia/ potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia channel

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Classification and Pharmacokinetics

Cholinomimetic drugs either act directly on cholinergic receptors Cholinergic receptors Cell surface proteins that bind acetylcholine with high affinity and trigger intracellular changes influencing the behavior of cells. Cholinergic receptors are divided into two major classes, muscarinic and nicotinic, based originally on their affinity for nicotine and muscarine. Each group is further subdivided based on pharmacology, location, mode of action, and/or molecular biology. Autonomic Nervous System: Anatomy or inhibit AChE (the enzyme breaking down ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS). Important points about the pharmacokinetic properties of the medications include onset, duration, metabolism, and availability.

Classification

  • ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS:
    • Both muscarinic and nicotinic actions
    • Rapidly hydrolyzed by AChE
  • Some agents stimulate either the nicotinic or the muscarinic receptors Muscarinic Receptors Asthma Drugs.
  • Direct-acting cholinomimetics:
    • Choline esters
      • ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS
      • Bethanechol
      • Methacholine
    • Plant alkaloids:
      • Nicotine Nicotine Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. Stimulants
      • Muscarine
      • Pilocarpine
  • AChE inhibitors are indirect-acting cholinomimetics (AChE inhibiting, causing a net-positive cholinergic effect):
    • Reversible:
      • Donepezil and rivastigmine (used in the treatment of Alzheimer disease Alzheimer disease As the most common cause of dementia, Alzheimer disease affects not only many individuals but also their families. Alzheimer disease is a progressive neurodegenerative disease that causes brain atrophy and presents with a decline in memory, cognition, and social skills. Alzheimer Disease)
      • Neostigmine and physostigmine (used to reverse the effects of anesthesia Anesthesia A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. Anesthesiology: History and Basic Concepts/ neuromuscular blockade Neuromuscular Blockade The intentional interruption of transmission at the neuromuscular junction by external agents, usually neuromuscular blocking agents. It is distinguished from nerve block in which nerve conduction (neural conduction) is interrupted rather than neuromuscular transmission. Neuromuscular blockade is commonly used to produce muscle relaxation as an adjunct to anesthesia during surgery and other medical procedures. It is also often used as an experimental manipulation in basic research. It is not strictly speaking anesthesia but is grouped here with anesthetic techniques. The failure of neuromuscular transmission as a result of pathological processes is not included here. Aminoglycosides)
      • Pyridostigmine (used in the treatment of myasthenia gravis Myasthenia Gravis Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles caused by dysfunction/destruction of acetylcholine receptors at the neuromuscular junction. MG presents with fatigue, ptosis, diplopia, dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement. Myasthenia Gravis)
    • Irreversible:
      • Malathion (antiparasitic for lice)
      • Isoflurophate (in eyedrops for glaucoma Glaucoma Glaucoma is an optic neuropathy characterized by typical visual field defects and optic nerve atrophy seen as optic disc cupping on examination. The acute form of glaucoma is a medical emergency. Glaucoma is often, but not always, caused by increased intraocular pressure (IOP). Glaucoma)
      • Sarin (used in nerve gas Nerve Gas Insecticide Poisoning for bioterrorism Bioterrorism The use of biological agents in terrorism. This includes the malevolent use of bacteria; viruses; or other biological toxins against people, animals; or plants. Anthrax)

Pharmacokinetics Pharmacokinetics Pharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body. Pharmacokinetics and Pharmacodynamics

Table: Onset and duration of AChE inhibitors
Drug Onset Duration
Neostigmine (reversible) 10–15 minutes 1–2 hours
Physostigmine (reversible) 3–8 minutes 45–60 minutes
Pyridostigmine (reversible) Oral myasthenia gravis Myasthenia Gravis Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles caused by dysfunction/destruction of acetylcholine receptors at the neuromuscular junction. MG presents with fatigue, ptosis, diplopia, dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement. Myasthenia Gravis: 30–45 minutes Oral: 3–6 hours
IV myasthenia gravis Myasthenia Gravis Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles caused by dysfunction/destruction of acetylcholine receptors at the neuromuscular junction. MG presents with fatigue, ptosis, diplopia, dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement. Myasthenia Gravis: 2–5 minutes IV: 2–3 hours
IV = intravenous
Table: Bioavailability Bioavailability Pharmacokinetics and Pharmacodynamics and metabolism of AChE inhibitors
Drug Bioavailability Bioavailability Pharmacokinetics and Pharmacodynamics Metabolism
Central AChE inhibitors
Donepezil (reversible)
Rivastigmine (reversible) Inactivated by cholinesterases
Peripheral AChE inhibitors
Neostigmine (reversible) Poor oral absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption
  • Inactivated by cholinesterases
  • Hepatic metabolism
Physostigmine (reversible) Inactivated by cholinesterases
Pyridostigmine (reversible)
  • Inactivated by cholinesterases
  • Hepatic metabolism
Sialogogues
Pilocarpine Readily absorbed orally Inactivated by cholinesterases
Prokinetic/promotility agent
Bethanechol Poor oral absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption Not susceptible to degradation by cholinesterases

Clinical Indications

Cholinomimetic drugs are used to treat many conditions, including dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders, glaucoma Glaucoma Glaucoma is an optic neuropathy characterized by typical visual field defects and optic nerve atrophy seen as optic disc cupping on examination. The acute form of glaucoma is a medical emergency. Glaucoma is often, but not always, caused by increased intraocular pressure (IOP). Glaucoma, and as an aid in smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases cessation.

Table: Muscarinic agonists Muscarinic Agonists Drugs that bind to and activate muscarinic cholinergic receptors (receptors, muscarinic). Muscarinic agonists are most commonly used when it is desirable to increase smooth muscle tone, especially in the GI tract, urinary bladder and the eye. They may also be used to reduce heart rate. Asthma Drugs
Drug Mechanism Indications
Bethanechol
  • Stimulation of cholinergic muscarinic receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors on the detrusor muscle Detrusor muscle Urinary Incontinence → detrusor contraction
  • Stimulation of cholinergic muscarinic receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors in the GI tract → increases gastric motility Motility The motor activity of the gastrointestinal tract. Gastrointestinal Motility
  • ↑ Pressure in the lower esophageal sphincter Lower Esophageal Sphincter Esophagus: Anatomy
  • Neurogenic bladder Neurogenic bladder Dysfunction of the urinary bladder due to disease of the central or peripheral nervous system pathways involved in the control of urination. This is often associated with spinal cord diseases, but may also be caused by brain diseases or peripheral nerve diseases. Urinary Incontinence
  • Urinary retention Urinary retention Inability to empty the urinary bladder with voiding (urination). Delirium
Carbachol Direct stimulation of muscarinic receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors in the eye → constriction of ciliary muscle and contraction of iris → ↑ aqueous humor Aqueous humor The clear, watery fluid which fills the anterior and posterior chambers of the eye. It has a refractive index lower than the crystalline lens, which it surrounds, and is involved in the metabolism of the cornea and the crystalline lens. Eye: Anatomy outflow → ↓ intraocular pressure Intraocular Pressure The pressure of the fluids in the eye. Ophthalmic Exam (IOP) Miosis Miosis Pupil: Physiology and Abnormalities for surgery (intraocular injection)
Pilocarpine
  • Stimulates secretion Secretion Coagulation Studies of exocrine glands Exocrine glands Glands of external secretion that release its secretions to the body’s cavities, organs, or surface, through a duct. Glandular Epithelium: Histology
  • Direct stimulation of muscarinic receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors in the eye → ↓ IOP
  • Oral forms treat xerostomia Xerostomia Decreased salivary flow. Sjögren’s Syndrome.
  • Ophthalmic drops ↓ IOP and treat glaucoma Glaucoma Glaucoma is an optic neuropathy characterized by typical visual field defects and optic nerve atrophy seen as optic disc cupping on examination. The acute form of glaucoma is a medical emergency. Glaucoma is often, but not always, caused by increased intraocular pressure (IOP). Glaucoma and mitosis Mitosis A type of cell nucleus division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. Cell Cycle induction.
Methacholine Inhaled → stimulates muscarinic receptors Muscarinic Receptors Asthma Drugs on bronchial smooth muscle → airway Airway ABCDE Assessment contraction Diagnostic test for asthma Asthma Asthma is a chronic inflammatory respiratory condition characterized by bronchial hyperresponsiveness and airflow obstruction. The disease is believed to result from the complex interaction of host and environmental factors that increase disease predisposition, with inflammation causing symptoms and structural changes. Patients typically present with wheezing, cough, and dyspnea. Asthma
Table: Nicotinic agonists
Drug Mechanism Indications
Nicotine Nicotine Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. Stimulants
  • Activates mesolimbic dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS (reward) pathway
  • Stimulates nicotinic receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors at the autonomic ganglia → peripheral effects (e.g., tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children, diaphoresis, and nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics) decline with repeated doses
Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases cessation
Succinylcholine Succinylcholine A quaternary skeletal muscle relaxant usually used in the form of its bromide, chloride, or iodide. It is a depolarizing relaxant, acting in about 30 seconds and with a duration of effect averaging three to five minutes. Succinylcholine is used in surgical, anesthetic, and other procedures in which a brief period of muscle relaxation is called for. Neuromuscular Blockers Stimulates motor endplate Motor endplate The specialized postsynaptic region of a muscle cell. The motor endplate is immediately across the synaptic cleft from the presynaptic axon terminal. Among its anatomical specializations are junctional folds which harbor a high density of cholinergic receptors. Skeletal Muscle Contraction ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors Neuromuscular blockade Neuromuscular Blockade The intentional interruption of transmission at the neuromuscular junction by external agents, usually neuromuscular blocking agents. It is distinguished from nerve block in which nerve conduction (neural conduction) is interrupted rather than neuromuscular transmission. Neuromuscular blockade is commonly used to produce muscle relaxation as an adjunct to anesthesia during surgery and other medical procedures. It is also often used as an experimental manipulation in basic research. It is not strictly speaking anesthesia but is grouped here with anesthetic techniques. The failure of neuromuscular transmission as a result of pathological processes is not included here. Aminoglycosides induction and maintenance ( anesthesia Anesthesia A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. Anesthesiology: History and Basic Concepts)
Varenicline (Chantix)
  • Alleviates nicotine Nicotine Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. Stimulants withdrawal symptoms by partial agonism of nicotinic receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors
  • Antagonist in the presence of nicotine Nicotine Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. Stimulants
Most effective monotherapy for smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases cessation
Table: Acetylcholinesterase inhibitors
Drug Mechanism Indications
Donepezil (Aricept) AChE inhibitor Treatment of Alzheimer dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders (all stages)
Galantamine Galantamine A benzazepine derived from norbelladine. It is found in galanthus and other amaryllidaceae. It is a cholinesterase inhibitor that has been used to reverse the muscular effects of gallamine triethiodide and tubocurarine and has been studied as a treatment for alzheimer disease and other central nervous system disorders. Major Neurocognitive Disorders (generic) AChE inhibitor and nicotinic receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors modulator Treatment of mild-to-moderate Alzheimer dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders
Neostigmine AChE inhibitor
  • NMB reversal
  • Requires coadministration of anticholinergic Anticholinergic Anticholinergic drugs block the effect of the neurotransmitter acetylcholine at the muscarinic receptors in the central and peripheral nervous systems. Anticholinergic agents inhibit the parasympathetic nervous system, resulting in effects on the smooth muscle in the respiratory tract, vascular system, urinary tract, GI tract, and pupils of the eyes. Anticholinergic Drugs agent (e.g., glycopyrrolate Glycopyrrolate A muscarinic antagonist used as an antispasmodic, in some disorders of the gastrointestinal tract, and to reduce salivation with some anesthetics. Anticholinergic Drugs) to prevent bradycardia Bradycardia Bradyarrhythmia is a rhythm in which the heart rate is less than 60/min. Bradyarrhythmia can be physiologic, without symptoms or hemodynamic change. Pathologic bradyarrhythmia results in reduced cardiac output and hemodynamic instability causing syncope, dizziness, or dyspnea. Bradyarrhythmias
Physostigmine (unavailable until end of 2022) AChE inhibitor
  • Treatment of anticholinergic Anticholinergic Anticholinergic drugs block the effect of the neurotransmitter acetylcholine at the muscarinic receptors in the central and peripheral nervous systems. Anticholinergic agents inhibit the parasympathetic nervous system, resulting in effects on the smooth muscle in the respiratory tract, vascular system, urinary tract, GI tract, and pupils of the eyes. Anticholinergic Drugs syndrome
  • NMB reversal
Pyridostigmine AChE inhibitor
  • Treatment of myasthenia gravis Myasthenia Gravis Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles caused by dysfunction/destruction of acetylcholine receptors at the neuromuscular junction. MG presents with fatigue, ptosis, diplopia, dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement. Myasthenia Gravis
  • Military preexposure prophylaxis Prophylaxis Cephalosporins for organophosphate ( nerve gas Nerve Gas Insecticide Poisoning) exposure
  • Nondepolarizing NMB reversal
  • Requires coadministration of anticholinergic Anticholinergic Anticholinergic drugs block the effect of the neurotransmitter acetylcholine at the muscarinic receptors in the central and peripheral nervous systems. Anticholinergic agents inhibit the parasympathetic nervous system, resulting in effects on the smooth muscle in the respiratory tract, vascular system, urinary tract, GI tract, and pupils of the eyes. Anticholinergic Drugs agent (e.g., glycopyrrolate Glycopyrrolate A muscarinic antagonist used as an antispasmodic, in some disorders of the gastrointestinal tract, and to reduce salivation with some anesthetics. Anticholinergic Drugs) to prevent bradycardia Bradycardia Bradyarrhythmia is a rhythm in which the heart rate is less than 60/min. Bradyarrhythmia can be physiologic, without symptoms or hemodynamic change. Pathologic bradyarrhythmia results in reduced cardiac output and hemodynamic instability causing syncope, dizziness, or dyspnea. Bradyarrhythmias
Rivastigmine AChE inhibitor
  • Mild-to-moderate Alzheimer dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders
  • Dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders of Parkinson disease Parkinson disease Parkinson’s disease (PD) is a chronic, progressive neurodegenerative disorder. Although the cause is unknown, several genetic and environmental risk factors are currently being studied. Individuals present clinically with resting tremor, bradykinesia, rigidity, and postural instability. Parkinson’s Disease
AChE: acetylcholinesterase
NMB: neuromuscular blockade Neuromuscular Blockade The intentional interruption of transmission at the neuromuscular junction by external agents, usually neuromuscular blocking agents. It is distinguished from nerve block in which nerve conduction (neural conduction) is interrupted rather than neuromuscular transmission. Neuromuscular blockade is commonly used to produce muscle relaxation as an adjunct to anesthesia during surgery and other medical procedures. It is also often used as an experimental manipulation in basic research. It is not strictly speaking anesthesia but is grouped here with anesthetic techniques. The failure of neuromuscular transmission as a result of pathological processes is not included here. Aminoglycosides

Adverse Effects and Contraindications

The primary adverse effects of cholinergic drugs are the consequence of overstimulation of the parasympathetic nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification. Symptoms result from excessive levels of ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS in the synapses, glands, smooth muscles Smooth muscles Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. Muscle Tissue: Histology, and motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology endplates.

Adverse effects

  • Cholinomimetic hyperactivity may result in cholinergic crisis = the same signs and symptoms seen with cholinesterase inhibitor poisoning (nerve gas):
    • Organophosphates inhibit AChE.
    • Reversed by atropine 
    • Symptoms are more severe than the usual side effects of medications:
      • Decreased blood pressure
      • GI: abdominal cramps, diarrhea, and vomiting
      • Blurred vision
      • Pallor
      • Twitching of the facial muscles
  • Mnemonics to remember cholinergic effects:
    • Cholinomimetic muscarinic agonists exert side effects remembered by the mnemonic “SLUDGE“:
      • Salivation                                     
      • Lacrimation
      • Urination                             
      • Defecation/diarrhea
      • Gastric Emptying
    • Also “BBB“:
      • Bradycardia
      • Bronchoconstriction
      • Bronchorrhea (excess mucus discharge)
  • Side effects of AChE inhibitors (e.g., donepezil):
    • Most common: diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
    • AV block AV block Atrioventricular (AV) block is a bradyarrhythmia caused by delay, or interruption, in the electrical conduction between the atria and the ventricles. Atrioventricular block occurs due to either anatomic or functional impairment, and is classified into 3 types. Atrioventricular block (AV block)
    • Bradycardia Bradycardia Bradyarrhythmia is a rhythm in which the heart rate is less than 60/min. Bradyarrhythmia can be physiologic, without symptoms or hemodynamic change. Pathologic bradyarrhythmia results in reduced cardiac output and hemodynamic instability causing syncope, dizziness, or dyspnea. Bradyarrhythmias
    • Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
    • GI bleed
    • Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess
    • Insomnia Insomnia Insomnia is a sleep disorder characterized by difficulty in the initiation, maintenance, and consolidation of sleep, leading to impairment of function. Patients may exhibit symptoms such as difficulty falling asleep, disrupted sleep, trouble going back to sleep, early awakenings, and feeling tired upon waking. Insomnia
    • Mood disturbance (e.g., depression and anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder)

Contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation

  • AChE inhibitors:  
    • Cardiac conduction defects (risk of QT prolongation causing ventricular tachycardia Ventricular tachycardia Ventricular tachycardia is any heart rhythm faster than 100 beats/min, with 3 or more irregular beats in a row, arising distal to the bundle of His. Ventricular tachycardia is the most common form of wide-complex tachycardia, and it is associated with a high mortality rate. Ventricular Tachycardia)
    • Asthma Asthma Asthma is a chronic inflammatory respiratory condition characterized by bronchial hyperresponsiveness and airflow obstruction. The disease is believed to result from the complex interaction of host and environmental factors that increase disease predisposition, with inflammation causing symptoms and structural changes. Patients typically present with wheezing, cough, and dyspnea. Asthma or chronic obstructive pulmonary disease Chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by progressive, largely irreversible airflow obstruction. The condition usually presents in middle-aged or elderly persons with a history of cigarette smoking. Signs and symptoms include prolonged expiration, wheezing, diminished breath sounds, progressive dyspnea, and chronic cough. Chronic Obstructive Pulmonary Disease (COPD) ( COPD COPD Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by progressive, largely irreversible airflow obstruction. The condition usually presents in middle-aged or elderly persons with a history of cigarette smoking. Signs and symptoms include prolonged expiration, wheezing, diminished breath sounds, progressive dyspnea, and chronic cough. Chronic Obstructive Pulmonary Disease (COPD))
    • Urinary tract obstruction Urinary tract obstruction Urinary tract obstruction (UTO) refers to the blockage of the urinary tract, which can occur anywhere in the urinary tract. Urinary tract obstruction can be acute or chronic, partial or complete, and unilateral or bilateral. Urinary tract obstruction can cause acute or chronic kidney disease. Urinary Tract Obstruction
    • Seizure history or risk
    • GI bleed history or risk
  • Pilocarpine: Use eye drops to treat glaucoma Glaucoma Glaucoma is an optic neuropathy characterized by typical visual field defects and optic nerve atrophy seen as optic disc cupping on examination. The acute form of glaucoma is a medical emergency. Glaucoma is often, but not always, caused by increased intraocular pressure (IOP). Glaucoma and oral tablets to treat xerostomia Xerostomia Decreased salivary flow. Sjögren’s Syndrome (e.g., Sjögren syndrome Sjögren Syndrome Rheumatoid Arthritis):
    • Contraindicated in angle-closure glaucoma Glaucoma Glaucoma is an optic neuropathy characterized by typical visual field defects and optic nerve atrophy seen as optic disc cupping on examination. The acute form of glaucoma is a medical emergency. Glaucoma is often, but not always, caused by increased intraocular pressure (IOP). Glaucoma
    • Acute iritis Iritis Inflammation of the iris characterized by circumcorneal injection, aqueous flare, keratotic precipitates, and constricted and sluggish pupil along with discoloration of the iris. Leprosy 
    • Acute asthma Asthma Asthma is a chronic inflammatory respiratory condition characterized by bronchial hyperresponsiveness and airflow obstruction. The disease is believed to result from the complex interaction of host and environmental factors that increase disease predisposition, with inflammation causing symptoms and structural changes. Patients typically present with wheezing, cough, and dyspnea. Asthma
    • Use caution with hepatic impairment.

Comparison Table

Table: Comparison of cholinomimetics
Drug Mechanism Indications Contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation
Bethanechol Direct-acting choline ester
  • Xerostomia Xerostomia Decreased salivary flow. Sjögren’s Syndrome
  • Urinary retention Urinary retention Inability to empty the urinary bladder with voiding (urination). Delirium
  • Diabetic neuropathy Diabetic neuropathy Peripheral, autonomic, and cranial nerve disorders that are associated with diabetes mellitus. These conditions usually result from diabetic microvascular injury involving small blood vessels that supply nerves (vasa nervorum). Relatively common conditions which may be associated with diabetic neuropathy include third nerve palsy; mononeuropathy; mononeuropathy multiplex; diabetic amyotrophy; a painful polyneuropathy; autonomic neuropathy; and thoracoabdominal neuropathy. Chronic Diabetic Complications
  • Asthma Asthma Asthma is a chronic inflammatory respiratory condition characterized by bronchial hyperresponsiveness and airflow obstruction. The disease is believed to result from the complex interaction of host and environmental factors that increase disease predisposition, with inflammation causing symptoms and structural changes. Patients typically present with wheezing, cough, and dyspnea. Asthma
  • Coronary insufficiency
  • Peptic ulcer Peptic ulcer Peptic ulcer disease (PUD) refers to the full-thickness ulcerations of duodenal or gastric mucosa. The ulcerations form when exposure to acid and digestive enzymes overcomes mucosal defense mechanisms. The most common etiologies include Helicobacter pylori (H. pylori) infection and prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs). Peptic Ulcer Disease
  • Hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism
Pilocarpine Direct-acting plant alkaloid Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
Donepezil Reversible cholinesterase Cholinesterase Liver Function Tests inhibitor
  • Alzheimer disease Alzheimer disease As the most common cause of dementia, Alzheimer disease affects not only many individuals but also their families. Alzheimer disease is a progressive neurodegenerative disease that causes brain atrophy and presents with a decline in memory, cognition, and social skills. Alzheimer Disease
  • Lewy body dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders
  • Traumatic brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification injury
  • Peptic ulcer Peptic ulcer Peptic ulcer disease (PUD) refers to the full-thickness ulcerations of duodenal or gastric mucosa. The ulcerations form when exposure to acid and digestive enzymes overcomes mucosal defense mechanisms. The most common etiologies include Helicobacter pylori (H. pylori) infection and prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs). Peptic Ulcer Disease
  • Asthma Asthma Asthma is a chronic inflammatory respiratory condition characterized by bronchial hyperresponsiveness and airflow obstruction. The disease is believed to result from the complex interaction of host and environmental factors that increase disease predisposition, with inflammation causing symptoms and structural changes. Patients typically present with wheezing, cough, and dyspnea. Asthma
  • Neuroleptic malignant syndrome Neuroleptic malignant syndrome Neuroleptic malignant syndrome (NMS) is a rare, idiosyncratic, and potentially life-threatening reaction to antipsychotic drugs. Neuroleptic malignant syndrome presents with ≥ 2 of the following cardinal symptoms: fever, altered mental status, muscle rigidity, and autonomic dysfunction. Neuroleptic Malignant Syndrome
  • AV block AV block Atrioventricular (AV) block is a bradyarrhythmia caused by delay, or interruption, in the electrical conduction between the atria and the ventricles. Atrioventricular block occurs due to either anatomic or functional impairment, and is classified into 3 types. Atrioventricular block (AV block)
Neostigmine Reversible cholinesterase Cholinesterase Liver Function Tests inhibitor
  • Myasthenia gravis Myasthenia Gravis Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles caused by dysfunction/destruction of acetylcholine receptors at the neuromuscular junction. MG presents with fatigue, ptosis, diplopia, dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement. Myasthenia Gravis
  • Reverse muscle relaxant
  • Mechanical GI obstruction
  • Urinary obstruction
Pyridostigmine Reversible cholinesterase Cholinesterase Liver Function Tests inhibitor
  • Myasthenia gravis Myasthenia Gravis Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles caused by dysfunction/destruction of acetylcholine receptors at the neuromuscular junction. MG presents with fatigue, ptosis, diplopia, dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement. Myasthenia Gravis
  • Orthostatic hypotension Orthostatic hypotension A significant drop in blood pressure after assuming a standing position. Orthostatic hypotension is a finding, and defined as a 20-mm hg decrease in systolic pressure or a 10-mm hg decrease in diastolic pressure 3 minutes after the person has risen from supine to standing. Symptoms generally include dizziness, blurred vision, and syncope. Hypotension
  • Mechanical GI obstruction
  • Urinary obstruction
Malathion Irreversible cholinesterase Cholinesterase Liver Function Tests inhibitor
  • Lice
  • Scabies Scabies Scabies is an infestation of the skin by the Sarcoptes scabiei mite, which presents most commonly with intense pruritus, characteristic linear burrows, and erythematous papules, particularly in the interdigital folds and the flexor aspects of the wrists. Scabies
  • Infants
  • Neonates
AV: atrioventricular

References

  1. Neurotransmitters and Neuromodulators. In: Nelson, L.S., Howland, M., Lewin, N.A., Smith, S.W., Goldfrank, L.R., Hoffman, R.S. Goldfrank’s Toxicologic Emergencies, 11e. New York, NY: McGraw-Hill, 2019.
  2. IBM Micromedex® DRUGDEX® (electronic version). IBM Watson Health, Greenwood Village, Colorado, USA. Retrieved October 7, 2021, from https://www.micromedexsolutions.com
  3. Arvanitakis, Z., Shah, R.C., & Bennett, D.A. (2019). Diagnosis and management of dementia: Review. JAMA. 322(16), pp. 1589–1599. https://doi.org/10.1001/jama.2019.4782 
  4. 2019 American Geriatrics Society Beers Criteria Update Expert Panel (2019). American Geriatrics Society 2019 updated AGS Beers criteria® for potentially inappropriate medication use in older adults. Journal of the American Geriatrics Society. https://doi.org/10.1111/jgs.15767 
  5. Rickey, L.M. (2019). Chronic urinary retention in women. UpToDate. Retrieved October 7, 2021, from https://www.uptodate.com/contents/chronic-urinary-retention-in-women
  6. Lexicomp, Inc. (2021). Donepezil and memantine: Drug information. UpToDate. Retrieved October 7, 2021, from https://www.uptodate.com/contents/donepezil-and-memantine-drug-information
  7. Lexicomp, Inc. (2021). Pilocarpine (systemic): Drug information. UpToDate. Retrieved October 7, 2021, from https://www.uptodate.com/contents/pilocarpine-systemic-drug-information

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