Muscarinic Receptor Antagonist

  • Muscarinic Receptor Antagonists are drugs that show specificity for the muscarinic receptor and thus largely antagonize the physiological effects of the parasympathetic nervous system at target organs. These drugs are competitive antagonists and have both central and peripheral effects. Below we discuss the general physiological and toxic effects of these drugs and then discuss the therapeutic uses of particular drugs, focusing on atropine, scopolamine, and ipratroprium.
Physiological and Toxic Effects
  • Eye
    • Antimuscarinics blocks parasympathetic contraction of the circular muscle of the iris and the ciliary muscle of the lens. Consequently, their administration results in dilation of the pupil (i.e. mydriasis) as well as inability to focus on near objects (i.e. cycloplegia). Predictably, this can yield dry eyes and blurry vision Particularly of concern in the elderly, is the possibility of precipitating an attack of acute angle closure glaucoma.
  • Cardiovascular
    • Antimuscarinics largely affect the heart rate by modulating parasympathetic output to the SA Node. Surprisingly, at low doses atropine may cause a mild decrease in heart rate, likely by blocking pre-synaptic muscarinic receptors at the SA Node that normally inhibit acetylcholine release. However, at moderate doses blockage of basal parasympathetic outflow to the SA Node will yield modest increases in heart rate and thus moderate tachycardia. The vasculature is largely impervious to atropine although at toxic doses dilation of the vasculature is common, likely as a reaction to atropine-mediated hyperthermia (see below).
  • Gastrointestinal
    • Antimuscarinics are effective in reducing parasympathetic tone on alimentary tract which normally promotes motility and secretions. These drugs are modestly effective in inhibiting GI motility and GI secretion and thus predictably result in constipation.
  • Genitourinary
    • Antimuscarinics will block parasympathetic tone on the GU system which normally promotes bladder contraction and uretral motility. Thus, these compounds result in urinary retention.
  • Respiratory
    • In healthy individuals parasympathetic tone on bronchial smooth muscle, yielding constriction, is minimal; however, parasympathetic-mediated bronchoconstriction plays an important role in bronchospastic disease states. In such contexts, muscarinic antagonism will yield bronchodilation. Furthermore, parasympathetic fibers promote respiratory secretions and thus muscarinic antagonism will tend to "dry out" the respiratory system.
  • Secretions
    • Salivary secretion is particularly dependent on parasympathetic outflow and thus antimuscarinics will result in reduced salivation. This can be used therapeutically in patients with excess salivation or may result in the adverse effect of xerostomia in others.
    • The sympathetic nervous system controls sweating via muscarinic receptors and thus their blockage results in reduced sweating, yielding hot, dry skin and thus anhydrosis. At toxic doses this can result in hyperthermia which is compensated for by dilation of the cutaneous vasculature in a physiological attempt to maximally radiate heat.
  • CNS
    • Muscarinic receptors play important roles in the brain and their progressive blockage and yield increasingly disruptive effects. At lower doses, antimuscarinics can display antiemetic properties, promote drowsiness, and yield amnesia. At toxic doses atropine can cause irritability, hallucinations, delirium and ultimately cardiorespiratory collapse. The elderly are the most prone to such effects as their central cholinergic pathways are already quite fragile.
Drug Members
  • Atropine
    • Although atropine is the prototype of the antimuscarinic drug class its clinical usage is quite limited today. The mydriatic and cycloplegic effects of atropine are frequently used with topical ocular application in order to facilitate examination of the retina during eye exams. Historically, the drug has been used an an antispasmodic and for peptic ulcer disease; however, it has largely been replaced with more effective drugs with more desirable side effect profiles. Although atropine is rarely used for treatment of overactive bladder, similar muscarinic receptor antagonists such as oxybutinin frequently are helpful in this context. Atropine is the drug of choice for reversing toxic doses of cholinergic agonists.
  • Scopolamine
    • Scopolamine has better penetration of the CNS than atropine. It is frequently used an an antiemetic, to induce sedation, and yield amnesia
  • Ipratropium
    • Ipratropium and it sister drug tiotropium have poor CNS penetration and are frequently used in inhaled form for treatment of bronchospastic diseases such as asthma and COPD.
The Toxic Patient
  • A patient with antimuscarinic toxicity will display mydriatic pupils and blurry vision. His skin will be dry, hot, and flushed while his mouth will display xerostomia. He may be constipated and display a full bladder due to urinary retention. He may be moderately tachycardic and be confused, delirious, hallucinating or in a coma.