Cholinergic antagonists

• Cholinergic antagonists


  Muscarinic blocking agents
• Atropine


  Deadly Nightshade - Atropa belladonna
• Atropine

  • Dilates pupils
  • Decreases secretions
  • Increased heart rate (high doses)
  • Reduced detrusor contraction (decreased bladder contraction)
• Additional manifestations of anticholinergic effects include: Sinus tachycardia, Decreased bowel sounds, Functional ileus, Hypertension, Tremulousness, Myoclonic jerking
• Patients with central anticholinergic syndrome may present with: Ataxia, Disorientation, Short-term memory loss, Confusion, Hallucinations (visual, auditory), Psychosis, Agitated delirium, Seizures (rare), Coma, Respiratory failure, Cardiovascular collapse
• Anti-muscarinic effects

  • Cycloplegia (blurred vision), glaucoma, dry (sandy) eyes
  • Mydriasis
  • Reduced sweating, flushing
  • Xerostomia, Decreased bowel sounds, Functional ileus, Reduced motility and secretions (reduces GI cramping)
  • Increased heart rate (high doses)
  • Bronchial dilation and decreased secretion
  • Urinary retention, Reduces bladder overactivity, spasms
  • Drowsiness, hallucinations, excitement, agitation, coma

  
• "red as a beet, dry as a bone, blind as a bat, mad as a hatter, hot as a hare, and full as a flask." The mnemonic refers to the symptoms of flushing, dry skin and mucous membranes, mydriasis with loss of accommodation, altered mental status (AMS), fever, and urinary retention, respectively.
• Motion Sickness Drugs: Scopolamine, meclizine, dimenhydrinate

  Competitive antagonism at muscarinic receptors
• Motion Sickness Drugs: Scopolamine, meclizine, dimenhydrinate

  1. Onset: 4hrs

  2. Peak: 24hrs

  3. Duration: 72hrs
• Motion Sickness Drugs: Scopolamine, meclizine, dimenhydrinate

  • Steady and extensive absorption
  • Crosses blood-brain barrier
  • Hepatic metabolism to inactive metabolites
  • T1/2 8hrs
• Motion Sickness Drugs: Scopolamine, meclizine, dimenhydrinate

  Reduces vertigo, postoperative nausea
• Motion Sickness Drug Contraindications: Closed-angle glaucoma
• Motion Sickness Drug Adverse drug reactions: Tachycardia, blurred vision, xerostomia, delirium
• GI Drugs: Dicyclomine, L-Hyoscyamine, Glycopyrrolate

  • Competitive antagonism at M1 and M3 receptors
  • Reduces smooth muscle and secretory activity of gut
  • Tertiary amine (Minimal effect on salivary/sweat glands or on CV system)
• GI Drugs: Dicyclomine, L-Hyoscyamine, Glycopyrrolate

  1. Likely well absorbed

  2. Volume of distribution 3.65L/kg

  3. Short t1/2 (1.8hrs) but action lasts up to 6 hrs, 79.5% in urine, 8.4% in feces
• GI Drugs: Dicyclomine, L-Hyoscyamine, Glycopyrrolate

  Used for irritable bowel syndrome, minor diarrhea
• GI Drug Adverse drug reactions: Tachycardia, confusion, urinary retention, increased intraocular pressure

  
• GI Drug Interactions: With other antimuscarinics
• Ophthalmology Drug MOA

  • Competitive muscarinic receptor antagonist
  • Causes iris sphincter muscle relaxation (mydriasis); ciliary body relaxation (cycloplegia)
• Ophthalmology Drugs - Duration of Action:

  1. Atropine - 5–6 days, up to 2 weeks

  2. Homatropine - 12–24 h

  3. Cyclopentolate - 3–6 h

  4. Tropicamide - 15–60 min
• Ophthamology Drugs

  Causes refraction for assessment (secretions @ end-of-life)

  
• Ophthalmology Drug Contraindications: (narrow-angle) glaucoma
• Ophthalmology Drug - Adverse drug reactions: anti-SLUDGE
• Respiratory (Asthma, COPD) Drugs

  • Competitive muscarinic receptor antagonist
  • Therapeutic effect via M3 receptor (R - dissociates slower from M3 than M2)
  • Reduces or prevents bronchospasm
• Ipratropium, SAMA


  1. 33% reaches systemic circulation (inhalation solution), 20% (dry powder)

  2. Urinary excretion 13%, Renal clearance 3%
• Aclidinium, LAMA


  Rapidly and extensively hydrolyzed to inactive metabolites
• Revefenacin, LAMA


  Active metabolite
• Ipratropium, SAMA


  Additional bronchodilator in asthma, maintenance treatment of COPD symptoms
• Tiotropium, LAMA


  Maintenance treatment of COPD, airflow and symptoms improved, HRQoL improved, reduction in exacerbations, extensive safety and efficacy database up to 4 years
• Glycopyrrolate, LAMA


  Maintenance treatment of COPD, airflow and symptoms improved in one of two Phase III studies
• Aclidinium

  Maintenance treatment of COPD, full bronchodilator effect with 1st dose, airflow, symptoms, dyspnea and HRQoL improved, reduction in exacerbations, long-term safety study up to 3 years in cardio-/cerebro-vascular risk population

  
• Umeclidinium

  Maintenance treatment of COPD, airflow, symptoms, and HRQoL improved, reduction in exacerbations indirectly shown by superiority of umeclidinium/vilanterol/fluticasone vs. vilanterol/fluticasone
• Respiratory Drug Adverse reactions: Xerostomia, cough
• Respiratory Drugs - Other uses: Reduces rhinorrhea
• Glycopyrrolate


  Highly potent, kinetic receptor subtype selective M3 > M1 >> M2, modestly slow M3 receptor dissociation (t1/2=6.1h), low lipid solubility, predominantly cleared renally, available only in combination products
• Glycopyrrolate


  • Full bronchodilator effect with 1st dose, airflow, symptoms, dyspnea and HRQoL improved, reduction in exacerbations, long-term safety study up to 3 years in cardio-/cerebro-vascular risk population

  
• Aclidinium (bromide)


  Highly potent, kinetic receptor subtype selective M3 >∼ M1 >M2, modestly slow M3- receptor dissociation (t1/2=10.7 h), low lipid solubility, rapid hydrolytic inactivation
• Aclidinium (bromide)


  • Airflow, symptoms, and HRQoL improved, reduction in exacerbations indirectly shown by superiority of umeclidinium/vilanterol/fluticasone vs. vilanterol/fluticasone
• Umeclidinium (bromide)


  Highly potent, kinetic receptor subtype selective M3 >> M2, (M1 not published), slow M3 receptor dissociation (t1/2=1.37 h, tiotropium 4.55 h), low lipid solubility, hepatic metabolism and clearance
• Umeclidinium (bromide)


  • Airflow and symptoms improved, HRQoL improved in one of two Ph III studies. For patients preferring nebulizer