Anticholinergic Drugs

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 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. General Structure of the Nervous System, resulting in effects on the smooth muscle in the respiratory tract, vascular system, urinary tract Urinary tract The urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra. Urinary Tract, GI tract, and pupils of the eyes. These medications are used in the management of a wide range of diseases, most notably in the treatment of overactive bladder, irritable bowel syndrome Irritable bowel syndrome Irritable bowel syndrome (IBS) is a functional bowel disease characterized by chronic abdominal pain and altered bowel habits without an identifiable organic cause. The etiology and pathophysiology of this disease are not well understood, and there are many factors that may contribute. Irritable Bowel Syndrome, 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)), and allergic rhinitis Rhinitis Rhinitis refers to inflammation of the nasal mucosa. The condition is classified into allergic, nonallergic, and infectious rhinitis. Allergic rhinitis is due to a type I hypersensitivity reaction. Non-allergic rhinitis is due to increased blood flow to the nasal mucosa. Infectious rhinitis is caused by an upper respiratory tract infection. Rhinitis. Atropine specifically is used in emergency medicine in the advanced cardiac life support (ACLS) protocol for severe bradycardia and as an antidote Antidote An antidote is a substance that counteracts poisoning or toxicity. Substances that can cause poisoning include heavy metals (from occupation, treatments, or diet), alcohols, environmental toxins, and medications. Overview of Antidotes to organophosphate poisoning with insecticides or chemical warfare agents. Atropine is also used in anesthesiology Anesthesiology Anesthesiology is the field of medicine that focuses on interventions that bring a state of anesthesia upon an individual. General anesthesia is characterized by a reversible loss of consciousness along with analgesia, amnesia, and muscle relaxation. Anesthesiology: History and Basic Concepts as an antisialagogue or to reverse neuromuscular blocking agents. The term “anticholinergic” is often used to describe the adverse effects of drugs with anticholinergic properties (e.g., tricyclic antidepressants Tricyclic antidepressants Tricyclic antidepressants (TCAs) are a class of medications used in the management of mood disorders, primarily depression. These agents, named after their 3-ring chemical structure, act via reuptake inhibition of neurotransmitters (particularly norepinephrine and serotonin) in the brain. Tricyclic Antidepressants); these include dry mouth, constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation, blurred vision, and orthostatic hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension.

Last update:

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Table of Contents

Share this concept:

Share on facebook
Share on twitter
Share on linkedin
Share on reddit
Share on email
Share on whatsapp

Chemistry and Pharmacodynamics

Atropine is the prototypical anticholinergic drug owing to its antagonism of acetylcholine (ACh) receptors.

Overview

  • Also called:
    • Antimuscarinics/muscarinic receptor antagonists
    • Cholinergic blockers
    • Parasympatholytics
  • Chemistry of anticholinergics:
    • Have a primary point of attachment to cholinergic receptors through their cationic (positively charged) nitrogen atom
    • Are either tertiary amines or quaternary ammonium compounds
    • A hydroxyl group enhances antimuscarinic activity over that of similar compounds without a hydroxyl group.
  • Anticholinergic actions of chemicals:
    • Block the activity of ACh receptors → prevent transmission of signals through certain parts of the 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. General Structure of the Nervous System
    • Atropine (prototypical drug) antagonizes ACh receptors (anticholinergic).

Mechanism of action and physiologic effects

  • Mechanism of action:
    • Competitively inhibit the neurotransmitter ACh at receptor sites within the cholinergic system 
    • This inhibition leads to blockade 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. General Structure of the Nervous System.
  • Physiologic effects:
    • Decreased production of secretions in the 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, bronchial tree Bronchial tree The collective term "bronchial tree" refers to the bronchi and all of their subsequent branches. The bronchi are the airways of the lower respiratory tract. At the level of the 3rd or 4th thoracic vertebra, the trachea bifurcates into the left and right main bronchi. Both of these bronchi continue to divide into secondary or lobar bronchi that bifurcate further and further. Bronchial Tree, and GI tract
    • Bronchodilation
    • Smooth muscle relaxation in the GI tract and bladder
  • Drug classes used for their anticholinergic activity:
    • Antispasmodics for GI conditions: antagonize ACh at muscarinic receptors, relax smooth muscle, inhibit histamine-induced spasms
    • Urinary antispasmodics: antagonize ACh at muscarinic receptors, relax bladder smooth muscle, inhibit involuntary detrusor muscle contractions
    • Inhaled long-acting muscarinic antagonists (LAMAs): bronchodilators; also decrease bronchial secretions (e.g., used for individuals with 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)))
    • Mydriatics in ophthalmology (eye drops): inhibit response of iris sphincter and ciliary body muscles
    • 1st-generation antihistamines Antihistamines Antihistamines are drugs that target histamine receptors, particularly H1 and H2 receptors. H1 antagonists are competitive and reversible inhibitors of H1 receptors. First-generation antihistamines cross the blood-brain barrier and can cause sedation. Antihistamines: act on histamine receptors but also inhibit muscarinic receptors and have anticholinergic effects (used therapeutically for motion sickness)
    • Antiparkinson drugs (largely replaced by newer medications)
    • Acetylcholinesterase (AChE) regenerators stimulate the breakdown of acetylcholine → anticholinergic effect on cholinergic excess:
      • Pralidoxime (2-pyridine aldoxime methyl chloride (2-PAM)): antidote Antidote An antidote is a substance that counteracts poisoning or toxicity. Substances that can cause poisoning include heavy metals (from occupation, treatments, or diet), alcohols, environmental toxins, and medications. Overview of Antidotes for organophosphate toxicity seen with insecticide poisoning Insecticide Poisoning Insecticides are chemical substances used to kill or control insects, to improve crop yields, and to prevent diseases. Human exposures to insecticides can be by direct contact, inhalation, or ingestion. Important insecticides that can affect humans include organochlorines (dichlorodiphenyltrichloroethane (DDT)), organophosphates (malathion and parathion), and carbamates (carbaryl, propoxur, aldicarb, and methomyl). Insecticide Poisoning and nerve agents in bioterrorism (AChE inhibitors)
      • Because AChE breaks down ACh, the AChE inhibitors cause cholinergic poisoning and AChE regenerators ( antidote Antidote An antidote is a substance that counteracts poisoning or toxicity. Substances that can cause poisoning include heavy metals (from occupation, treatments, or diet), alcohols, environmental toxins, and medications. Overview of Antidotes) → net decrease in ACh
Cholinergic terminal neurotransmission and mechanism of action of anticholinergics

Cholinergic terminal neurotransmission Neurotransmission 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. The plasma membranes of the 2 neurons are placed very close together, and the space between the 2 neurons is called the synaptic cleft. The molecules that mediate the interaction are called neurotransmitters. Synapses and Neurotransmission and mechanism of action of anticholinergics:
Acetylcholine (ACh) is terminated in the synaptic cleft by AChE (acetylcholinesterase).
Anticholinergic drugs antagonize different muscarinic receptors throughout the body depending on their selectivity.
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 ( 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) produces antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins that block presynaptic calcium channels → decreased ACh release and muscle weakness.
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 antagonize nicotinic receptors at neuromuscular junctions.
Galantamine: AChE inhibitor used in Alzheimer dementia; inhibits the breakdown of ACh for a net increase in ACh in the synaptic cleft
Pralidoxime (2-PAM): AChE regenerator, allows ↑ breakdown of ACh → net decrease in ACh in the synaptic cleft.
CHT: choline transporter
VAChT: vesicular acetylcholine transporter

Image by Lecturio.

Pharmacokinetics

The pharmacokinetic properties of anticholinergic drugs are diverse, as they are available in many forms for different medical uses, such as IV atropine for severe bradycardia, oral tablets for GI and bladder antispasmodic Antispasmodic Antispasmodics are a group of medications used to reduce excessive GI smooth muscle contractility and spasm. These medications may be helpful in those with abdominal pain due to conditions such as irritable bowel syndrome, although their efficacy is controversial. Antispasmodic Agents use, inhaled forms of LAMAs for bronchodilation, and eye drops for cycloplegia. 

Eye drops

  • Short-acting mydriatics dilate the pupils (e.g., cyclopentolate, tropicamide) and are preferred for ophthalmic diagnostic procedures.
  • Cycloplegics produce mydriasis, but they also paralyze the ciliary muscle in the treatment of uveitis Uveitis Uveitis is the inflammation of the uvea, the pigmented middle layer of the eye, which comprises the iris, ciliary body, and choroid. The condition is categorized based on the site of disease; anterior uveitis is the most common. Diseases of the Uvea and other painful ophthalmic conditions.
Table: Comparison of anticholinergic eye drops
Drug Maximum mydriasis Duration of cycloplegia
Atropine 30–40 minutes 7–12 days
Cyclopentolate ophthalmic 30 minutes 24 hours
Homatropine 40–60 minutes 24 hours
Tropicamide 30 minutes 6 hours

Oral anticholinergic agents

  • The lipophilicity of a drug correlates with its penetration into the CNS; ↑ lipophilicity causes dizziness, drowsiness, and cognitive impairment.
  • GI antispasmodics: dicyclomine and hyoscyamine
    • Used for irritable bowel syndrome Irritable bowel syndrome Irritable bowel syndrome (IBS) is a functional bowel disease characterized by chronic abdominal pain and altered bowel habits without an identifiable organic cause. The etiology and pathophysiology of this disease are not well understood, and there are many factors that may contribute. Irritable Bowel Syndrome, biliary colic
    • Excretion: primarily in urine 
    • Half-life: 2–3.5 hours; extended-release form, 7.5 hours
    • Both are lipophilic.
    • Metabolism: hepatic cytochrome P450 enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body's constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes
  • Urologic anticholinergic drugs/antispasmodics: 
    • Used for overactive bladder
    • Excretion: mostly in urine (except for trospium: 85% feces and 6% urine)
Table: Half-lives, lipophilicity, and metabolism of urinary anticholinergics
Drug Half-life Lipophilicity (CNS penetration) Metabolism
Darifenacin (Enablex) 13–19 hours Moderate
  • Hepatic CYP3A4
  • CYP2D6
Fesoterodine (Toviaz) 7 hours Low
  • Hepatic CYP3A4
  • CYP2D6
Oxybutynin (Ditropan, Ditropan XL, Oxytrol patch, Gelnique topical gel)
  • Short-acting: 2.5 hours
  • XL form: 13 hours
  • Patch: 7 hours
Lipophilic
  • Hepatic CYP3A4
  • High 1st-pass metabolism
  • Patch and gel avoid 1st-pass metabolism
Solifenacin (Vesicare) 45–68 hours Lipophilic Hepatic CYP3A4
Tolterodine (Detrol IR, LA, and ER forms)
  • Short-acting: 2–3 hours
  • Long-acting: 7 hours, plus active metabolites
Low
  • Hepatic CYP3A4
  • CYP2D6
Trospium (Sanctura, also XR form) 20–35 hours None Hepatic
ER, XR, and XL: extended-release
IR: immediate-release (short-acting)
LA: long-acting
CYP: cytochrome P450

Atropine (IV)

  • Nonselective muscarinic blocker
  • Tertiary amine; lipid-soluble, crosses the blood–brain barrier (BBB)
  • Used IV in advanced cardiac life support (ACLS) protocol for symptomatic bradycardia to increase HR
  • Onset of action: 30 seconds
  • Duration of action: approximately 4 hours
  • Maximum effect (IV): 2–6 minutes

Indications

Anticholinergic drugs are used in many forms. They are used via eye drops in ophthalmology as mydriatics/cycloplegics, included in inhalers as bronchodilators and to dry up secretions as LAMAs for individuals with 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), and used in oral pill form as antispasmodics. Atropine is also used IV for severe bradycardia and is part of the ACLS protocol.

Anticholinergic drugs

  • Antimuscarinic agents:
    • Atropine: used IV in ACLS protocol for symptomatic bradycardia
    • Glycopyrrolate: used as an anesthesia Anesthesia Anesthesiology is the field of medicine that focuses on interventions that bring a state of anesthesia upon an individual. General anesthesia is characterized by a reversible loss of consciousness along with analgesia, amnesia, and muscle relaxation. Anesthesiology: History and Basic Concepts adjunct, also as an antisialagogue
  • Medications for dystonia Dystonia Dystonia is a hyperkinetic movement disorder characterized by the involuntary contraction of muscles, resulting in abnormal postures or twisting and repetitive movements. Dystonia can present in various ways as may affect many different skeletal muscle groups. Dystonia/Parkinson disease (largely replaced by newer drugs):
    • Benztropine: antagonizes ACh and histamine receptors
    • Trihexyphenidyl: antagonizes ACh receptors
  • GI antispasmodics: used in the treatment of irritable bowel syndrome Irritable bowel syndrome Irritable bowel syndrome (IBS) is a functional bowel disease characterized by chronic abdominal pain and altered bowel habits without an identifiable organic cause. The etiology and pathophysiology of this disease are not well understood, and there are many factors that may contribute. Irritable Bowel Syndrome ( IBS IBS Irritable bowel syndrome (IBS) is a functional bowel disease characterized by chronic abdominal pain and altered bowel habits without an identifiable organic cause. The etiology and pathophysiology of this disease are not well understood, and there are many factors that may contribute. Irritable Bowel Syndrome)
  • Urinary antispasmodics: used in the treatment of overactive bladder (OAB)
  • Anticholinergics in eye drops:
    • Drugs that cause pupillary dilation: mydriatic
      • Affect only the iris, not the ciliary muscle
      • Used during ophthalmic exam Ophthalmic exam A comprehensive examination of the eyes and their functions is important for all individuals with ocular symptoms, and to screen for visual acuity, glaucoma, and retinal pathology. A routine examination includes testing for visual acuity, peripheral vision, and color vision, plus an examination of the external eye, conjunctiva, sclera, iris, pupil, and extraocular movements. Ophthalmic Exam of the posterior segment and fundus
    • Drugs that cause ciliary muscle paralysis and inhibit accommodation or focusing ability: cycloplegic 
      • Used in ophthalmic exams and the evaluation of hyperopia
      • Used for prevention and release of posterior synechiae in individuals with uveitis Uveitis Uveitis is the inflammation of the uvea, the pigmented middle layer of the eye, which comprises the iris, ciliary body, and choroid. The condition is categorized based on the site of disease; anterior uveitis is the most common. Diseases of the Uvea
      • Treat pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain associated with ciliary body spasm in the eye
    • Names of ophthalmic preparations:
      • Cyclopentolate
      • Homatropine
      • Tropicamide
    • Also used to treat amblyopia (lazy eye) in infants 
  • Bronchodilators: used in the treatment of 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)

Drugs with major anticholinergic side effects

  • Low-potency 1st-generation antipsychotic Antipsychotic Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics drugs (FGAs):
    • Work primarily on dopamine receptors
    • Also have an affinity for muscarinic receptors → anticholinergic side effects
    • Examples of low-potency FGAs:
      • Chlorpromazine 
      • Thioridazine
  • Tricyclic antidepressants: inhibit norepinephrine and serotonin reuptake 
  • Antihistamines (1st generation): 
    • Used for motion sickness (nausea), allergic rhinitis Rhinitis Rhinitis refers to inflammation of the nasal mucosa. The condition is classified into allergic, nonallergic, and infectious rhinitis. Allergic rhinitis is due to a type I hypersensitivity reaction. Non-allergic rhinitis is due to increased blood flow to the nasal mucosa. Infectious rhinitis is caused by an upper respiratory tract infection. Rhinitis, and dizziness/ vertigo Vertigo Vertigo is defined as the perceived sensation of rotational motion while remaining still. A very common complaint in primary care and the ER, vertigo is more frequently experienced by women and its prevalence increases with age. Vertigo is classified into peripheral or central based on its etiology. Vertigo
    • Examples of 1st-generation antihistamines Antihistamines Antihistamines are drugs that target histamine receptors, particularly H1 and H2 receptors. H1 antagonists are competitive and reversible inhibitors of H1 receptors. First-generation antihistamines cross the blood-brain barrier and can cause sedation. Antihistamines:
      • Chlorpheniramine
      • Dimenhydrinate (Dramamine)
      • Diphenhydramine 
      • Doxylamine
      • Hydroxyzine 
      • Ipratropium bromide (Atrovent nasal spray)
      • Meclizine (Antivert)
      • Promethazine
      • Scopolamine (patch)
  • Centrally acting skeletal muscle relaxants: 
    • Cyclobenzaprine
    • Metaxalone
    • Methocarbamol
    • Orphenadrine
    • Tizanidine

Adverse Effects, Contraindications, Drug–Drug Interactions, and Toxicity

Adverse effects are due to effects on the CNS and also to reduced activity 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. General Structure of the Nervous System. Anticholinergics must be used with caution or avoided in the elderly owing to the risks of side effects.

Adverse effects

  • Neuropsychiatric: drowsiness, hallucinations, memory impairment 
  • Exocrine glandular secretion → dry mouth
  • Smooth muscle contraction Smooth muscle contraction Smooth muscle is primarily found in the walls of hollow structures and some visceral organs, including the walls of the vasculature, GI, respiratory, and genitourinary tracts. Smooth muscle contracts more slowly and is regulated differently than skeletal muscle. Smooth muscle can be stimulated by nerve impulses, hormones, metabolic factors (like pH, CO2 or O2 levels), its own intrinsic pacemaker ability, or even mechanical stretch. Smooth Muscle Contraction → urinary retention, constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation
  • Pupils → blurred vision, photophobia

Warnings/contraindications

  • Beers criteria: medications that should be used with caution/avoided in elderly individuals
    • Includes all anticholinergics
    • Elderly individuals are more vulnerable to anticholinergic adverse effects due to:
      • Increased permeability of the BBB 
      • Decreased ACh-induced transmission within the CNS
  • Strong anticholinergics have a cumulative dose–response relationship with the development of Alzheimer dementia.

Comparison of adverse effects, contraindications, and drug–drug interactions

Table: Adverse effects, warnings/contraindications, and drug-drug interactions for anticholinergic medications
Adverse effects Warnings/contraindications Drug–drug interactions
Atropine
  • Tachycardia
  • Palpitations
  • Anxiety
  • Drowsiness
  • Dizziness
  • Dry mouth
  • Constipation
  • Urinary retention
  • Blurred vision
  • Mydriasis
Caution with:
  • Elderly individuals
  • Recent myocardial infarction Myocardial infarction MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction
  • Chronic lung disease
  • Acute 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
  • Prostatic hypertrophy or obstructive uropathy (may cause urinary retention)
  • Pyloric stenosis
Avoid with:
  • Cholinomimetics
  • Concomitant use of cardiac stimulants Stimulants Stimulants are used by the general public to increase alertness and energy, decrease fatigue, and promote mental focus. Stimulants have medical uses for individuals with ADHD and sleep disorders, and are also used in combination with analgesics in pain management. Stimulants
  • Other anticholinergic agents
  • Concomitant use of opioids Opioids Opiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Opioid Analgesics can lead to ↑ constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation
GI antispasmodics: Dicyclomine and Hyoscyamine Antimuscarinic effects similar to atropine Warnings similar to atropine Similar to atropine drug interactions
Urinary antispasmodics:
  • Darifenacin
  • Fesoterodine
  • Oxybutynin
  • Solifenacin
  • Tolterodine
  • Trospium
  • Blurred vision
  • Cognitive impairment
  • Sedation
  • Dry mouth
  • Hallucinations
  • Dizziness
  • Warnings similar to atropine
  • Rare risk of angioedema Angioedema Angioedema is a localized, self-limited (but potentially life-threatening), nonpitting, asymmetrical edema occurring in the deep layers of the skin and mucosal tissue. The common underlying pathophysiology involves inflammatory mediators triggering significant vasodilation and increased capillary permeability. Angioedema
  • Constipation
  • Urinary retention
  • Narrow-angle 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
  • Anticholinergic agents
  • Strong CYP2D6 and CYP3A4 inhibitors

Toxicity/overdose

A cholinergic crisis may occur with an overdose or with using multiple drugs that have cholinergic effects.

  • Mnemonic: “Dry as a bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones, hot as a pistol, red as a beet, mad as a hatter”
    • Dry: excess of the antisialagogue effect
    • Hot: anhidrosis and inability to regulate body temperature → hyperthermia
    • Red: due to peripheral vasodilation
    • Mad: psychosis
  • Treatment: physostigmine ( antidote Antidote An antidote is a substance that counteracts poisoning or toxicity. Substances that can cause poisoning include heavy metals (from occupation, treatments, or diet), alcohols, environmental toxins, and medications. Overview of Antidotes)

Comparison of Mechanism of Action and Indications in Different Anticholinergics

Table: Anticholinergics mechanism of action and indications
Group Drug Mechanism of action Indications
Antimuscarinic agents Atropine
  • Antagonizes muscarinic receptors of:
    • Exocrine glands
    • Eyes
    • GI tract
    • Heart
    • Respiratory tract
  • Stimulates the CNS
  • ↑ HR
  • Used IV in the ACLS protocol for symptomatic bradycardia
  • Preanesthetic medication to ↓ salivation and respiratory secretions (aspiration prophylaxis)
  • Antidote for nerve agent or organophosphate insecticide poisoning Insecticide Poisoning Insecticides are chemical substances used to kill or control insects, to improve crop yields, and to prevent diseases. Human exposures to insecticides can be by direct contact, inhalation, or ingestion. Important insecticides that can affect humans include organochlorines (dichlorodiphenyltrichloroethane (DDT)), organophosphates (malathion and parathion), and carbamates (carbaryl, propoxur, aldicarb, and methomyl). Insecticide Poisoning
  • Emergency treatment of mushroom poisoning with cholinergic excess
Glycopyrrolate Antagonizes ACh receptors (anticholinergic)
  • Anesthesia adjunct; for neuromuscular blockade (NMB) reversal
  • Hyperhidrosis and as an antisialagogue
  • Emergency treatment of mushroom poisoning with cholinergic excess
Antiparkinson drugs
  • Benztropine
  • Trihexyphenidyl
Antagonize muscarinic receptors in the striatum
  • Parkinsonism adjunct therapy: ↓ rigidity and tremor
  • Drug-induced extrapyramidal symptoms and dystonia Dystonia Dystonia is a hyperkinetic movement disorder characterized by the involuntary contraction of muscles, resulting in abnormal postures or twisting and repetitive movements. Dystonia can present in various ways as may affect many different skeletal muscle groups. Dystonia (except tardive dyskinesia)
Antiemetics Antiemetics Antiemetics are medications used to treat and/or prevent nausea and vomiting. These drugs act on different target receptors. The main classes include benzodiazepines, corticosteroids, atypical antipsychotics, cannabinoids, and antagonists of the following receptors: serotonin, dopamine, and muscarinic and neurokinin receptors. Antiemetics Scopolamine (patch) Nonselective muscarinic receptor antagonism
  • Motion sickness: scopolamine mediates the vestibular nuclei in the inner ear, which provides its antiemetic effect
  • Prevention of postoperative nausea and vomiting
GI antispasmodics Dicyclomine Antagonism of muscarinic receptors → relaxation of GI smooth muscle and ↓ GI motility IBS IBS Irritable bowel syndrome (IBS) is a functional bowel disease characterized by chronic abdominal pain and altered bowel habits without an identifiable organic cause. The etiology and pathophysiology of this disease are not well understood, and there are many factors that may contribute. Irritable Bowel Syndrome
Hyoscyamine Nonselective muscarinic receptor antagonist—blocks ACh at postganglionic muscarinic acetylcholine receptors (mAChRs) at:
  • GI smooth muscle
  • Bronchial smooth muscle
  • Exocrine glands
  • Symptom relief in functional GI disorders: IBS IBS Irritable bowel syndrome (IBS) is a functional bowel disease characterized by chronic abdominal pain and altered bowel habits without an identifiable organic cause. The etiology and pathophysiology of this disease are not well understood, and there are many factors that may contribute. Irritable Bowel Syndrome, neurogenic colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix
  • Also used as a urinary antispasmodic Antispasmodic Antispasmodics are a group of medications used to reduce excessive GI smooth muscle contractility and spasm. These medications may be helpful in those with abdominal pain due to conditions such as irritable bowel syndrome, although their efficacy is controversial. Antispasmodic Agents
Urinary antispasmodics
  • Darifenacin
  • Fesoterodine
  • Oxybutynin
  • Solifenacin
  • Tolterodine
  • Trospium
  • Antagonize ACh at muscarinic receptors
  • Relax bladder smooth muscle, inhibit involuntary detrusor muscle contractions
OAB
Cycloplegics/mydriatics (ophthalmic solutions)
  • Atropine
  • Cyclopentolate
  • Homatropine
  • Tropicamide
  • Relaxation of the sphincter muscle of the iris → pupil Pupil The pupil is the space within the eye that permits light to project onto the retina. Anatomically located in front of the lens, the pupil's size is controlled by the surrounding iris. The pupil provides insight into the function of the central and autonomic nervous systems. Physiology and Abnormalities of the Pupil dilation (mydriasis)
  • Weakens contraction of the lens ciliary muscle → loss of accommodation (cycloplegia)
  • Amblyopia—penalization of the healthy eye
  • Cycloplegia, mydriasis
  • Uveitis
Bronchodilators (oral inhalation)
  • Aclidinium
  • Ipratropium
  • Tiotropium
  • Umeclidinium
  • Muscarinic M3 receptor antagonism causes bronchodilation.
  • Also called long-acting muscarinic antagonists (LAMAs)
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)
AChE regenerator Pralidoxime
  • Reactivates the cholinesterase enzyme AChE to reverse excess acetylcholine levels
  • Net effect is reducing the amount of ACh in the synaptic cleft.
Antidote for nerve agent or organophosphate insecticide poisoning Insecticide Poisoning Insecticides are chemical substances used to kill or control insects, to improve crop yields, and to prevent diseases. Human exposures to insecticides can be by direct contact, inhalation, or ingestion. Important insecticides that can affect humans include organochlorines (dichlorodiphenyltrichloroethane (DDT)), organophosphates (malathion and parathion), and carbamates (carbaryl, propoxur, aldicarb, and methomyl). Insecticide Poisoning

References

  1. Brown, J., Brandl, K., Wess, J. (2018). Muscarinic receptor agonists, and antagonists. In: Brunton, L.L., Hilal-Dandan, R., Knollmann, B.C. (Eds.), Goodman & Gilman’s: The Pharmacological Basis of Therapeutics, 13th ed. McGraw-Hill.
  2. Henderer, J.D., Rapuano, C.J. (2018). Ocular pharmacology. In: Brunton, L.L., Hilal-Dandan, R., Knollmann, B.C. (Eds.), Goodman & Gilman’s: The Pharmacological Basis of Therapeutics, 13th ed. McGraw-Hill.
  3. Chey, W.D., Kurlander, J., Eswaran, S. (2015). Irritable bowel syndrome: a clinical review. JAMA 313:949–958. https://doi.org/10.1001/jama.2015.0954 
  4. American Geriatrics Society. (2019). Updated AGS Beers criteria for potentially inappropriate medication use in older adults. Journal of the American Geriatrics Society 67:674–694. https://doi.org/10.1111/jgs.15767 
  5. Lexicomp, Inc. (2021). Trihexyphenidyl: drug information. UpToDate. Retrieved October 12, 2021, from https://www.uptodate.com/contents/trihexyphenidyl-drug-information
  6. Su, K., Goldman, M. (2021). Anticholinergic poisoning. UpToDate. Retrieved October 12, 2021, from https://www.uptodate.com/contents/anticholinergic-poisoning
  7. Lukacz, E. S. (2021). Urgency urinary incontinence/overactive bladder (OAB) in females: treatment. UpToDate. Retrieved October 12, 2021, from https://www.uptodate.com/contents/urgency-urinary-incontinence-overactive-bladder-oab-in-females-treatment
  8. Dweik, R. (2021). Role of muscarinic antagonist therapy in COPD. UpToDate. Retrieved October 12, 2021, from https://www.uptodate.com/contents/role-of-muscarinic-antagonist-therapy-in-copd
  9. Rochon, P.A. (2021). Drug prescribing for older adults. UpToDate. Retrieved October 12, 2021, from https://www.uptodate.com/contents/drug-prescribing-for-older-adults
  10. Wiegand, T. J. (2021). Management of mushroom poisoning. UpToDate. Retrieved October 13, 2021, from https://www.uptodate.com/contents/management-of-mushroom-poisoning
  11. Deik, A., Comella, C. (2021). Treatment of dystonia in children and adults. UpToDate. Retrieved October 13, 2021, from https://www.uptodate.com/contents/treatment-of-dystonia-in-children-and-adults

USMLE™ is a joint program of the Federation of State Medical Boards (FSMB®) and National Board of Medical Examiners (NBME®). MCAT is a registered trademark of the Association of American Medical Colleges (AAMC). NCLEX®, NCLEX-RN®, and NCLEX-PN® are registered trademarks of the National Council of State Boards of Nursing, Inc (NCSBN®). None of the trademark holders are endorsed by nor affiliated with Lecturio.

Study on the Go

Lecturio Medical complements your studies with evidence-based learning strategies, video lectures, quiz questions, and more – all combined in one easy-to-use resource.

Learn even more with Lecturio:

Complement your med school studies with Lecturio’s all-in-one study companion, delivered with evidence-based learning strategies.

User Reviews

0.0

()

¡Hola!

Esta página está disponible en Español.

🍪 Lecturio is using cookies to improve your user experience. By continuing use of our service you agree upon our Data Privacy Statement.

Details