Anticholinergic

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An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. Anticholinergics inhibit parasympathetic nerve impulses by selectively blocking the binding of the neurotransmitter acetylcholine to its receptor in nerve cells. The nerve fibers of the parasympathetic system are responsible for the involuntary movement of smooth muscles present in the gastrointestinal tract, urinary tract, lungs, and many other parts of the body. Anticholinergics are divided into three categories in accordance with their specific targets in the central and/or peripheral nervous system: antimuscarinic agents, ganglionic blockers, and neuromuscular blockers.[1]

Medical uses[edit]

Anticholinergic drugs are used to treat a variety of conditions:

Anticholinergics generally have antisialagogue effects (decreasing saliva production), and most produce some level of sedation, both being advantageous in surgical procedures.[2][3]

Recreational uses[edit]

When a significant amount of an anticholinergic is taken into the body, a toxic reaction known as acute anticholinergic syndrome may result. This may happen accidentally or intentionally as a consequence of recreational drug use. Anticholinergic drugs are usually considered the least enjoyable by many recreational drug users,[4] possibly because they do not induce euphoria. There have, however, been a few reported cases of users experiencing what they described as "euphoria" from the use of an anticholinergic drug.[citation needed] In terms of recreational use, these drugs are commonly referred to as deliriants.[5] The risk of addiction is low in the anticholinergic class, and recreational use is uncommon.

Side effects[edit]

Long term use increases the risk of both mental and physical decline.[6][7][8][9][10][11] It is unclear if they affect the risk of death generally.[6] However, in older adults they do appear to increase the risk of death.[12] Possible effects of anticholinergics include:

Possible effects in the central nervous system resemble those associated with delirium, and may include:

  • Confusion
  • Disorientation
  • Agitation
  • Euphoria or dysphoria
  • Respiratory depression
  • Memory problems[14]
  • Inability to concentrate
  • Wandering thoughts; inability to sustain a train of thought
  • Incoherent speech
  • Irritability
  • Mental confusion (brain fog)
  • Wakeful myoclonic jerking
  • Unusual sensitivity to sudden sounds
  • Illogical thinking
  • Photophobia
  • Visual disturbances
    • Periodic flashes of light
    • Periodic changes in visual field
    • Visual snow
    • Restricted or "tunnel vision"
  • Visual, auditory, or other sensory hallucinations
    • Warping or waving of surfaces and edges
    • Textured surfaces
    • "Dancing" lines; "spiders", insects; form constants
    • Lifelike objects indistinguishable from reality
    • Phantom smoking
    • Hallucinated presence of people not actually there
  • Rarely: seizures, coma, and death
  • Orthostatic hypotension (severe drop in systolic blood pressure when standing up suddenly) and significantly increased risk of falls in the elderly population.[15]

Older patients are at a higher risk of experiencing CNS sideffects due to lower acetylcholine production.

A common mnemonic for the main features of anticholinergic syndrome is the following:[16]

  • Blind as a bat (dilated pupils)
  • Red as a beet (vasodilation/flushing)
  • Hot as a hare (hyperthermia)
  • Dry as a bone (dry skin)
  • Mad as a hatter (hallucinations/agitation)
  • Bloated as a toad (ileus, urinary retention)
  • And the heart runs alone (tachycardia)

Toxicity[edit]

Acute anticholinergic syndrome is reversible and subsides once all of the causative agent has been excreted. Reversible Acetylcholinesterase inhibitor agents such as physostigmine can be used in life-threatening cases. Wider use is discouraged due to the significant side effects related to cholinergic excess including: seizures, muscle weakness, bradycardia, bronchoconstriction, lacrimation, salivation, bronchorrhea, vomiting, and diarrhea. Even in documented cases of anticholinergic toxicity, seizures have been reported after the rapid administration of physostigmine. Asystole has occurred after physostigmine administration for tricyclic antidepressant overdose, so a conduction delay (QRS > 0.10 second) or suggestion of tricyclic antidepressant ingestion is generally considered a contraindication to physostigmine administration.[17]

Piracetam (and other racetams), α-GPC and choline are known to activate the cholinergic system and alleviate cognitive symptoms caused by extended use of anticholinergic drugs.[citation needed]

Pharmacology[edit]

Anticholinergics are classified according to the receptors that are affected:

Examples[edit]

Examples of common anticholinergics:

Plants of the Solanaceae family contain various anticholinergic tropane alkaloids, such as scopolamine, atropine, and hyoscyamine.

Physostigmine is one of only a few drugs that can be used as an antidote for anticholinergic poisoning. Nicotine also counteracts anticholinergics by activating nicotinic acetylcholine receptors. Caffeine (although an adenosine receptor antagonist) is able to counteract the anticholinergic symptoms by reducing sedation and increasing acetylcholine activity, thereby causing alertness and arousal.

Plant sources[edit]

The most common plants containing anticholinergic alkaloids (including atropine, scopolamine, and hyoscyamine among others) are:

Use as a deterrent[edit]

Several narcotic and opiate-containing drug preparations, such as those containing hydrocodone and codeine are combined with an anticholinergic agent to deter intentional misuse.[25] Examples include Hydromet/Hycodan (hydrocodone/homatropine), Lomotil (diphenoxylate/atropine) and Tussionex (hydrocodone polistirex/chlorpheniramine). However, it is noted that opioid/antihistamine combinations are used clinically for their synergistic effect in the management of pain and maintenance of dissociative anesthesia (sedation) in such preparations as Meprozine (meperidine/promethazine) and Diconal (dipipanone/cyclizine), which act as strong anticholinergic agents.[26]

References[edit]

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