Anticholinergic

Anticholinergics (anticholinergic agents) are substances that block the action of the acetylcholine (ACh) neurotransmitter at synapses in the central and peripheral nervous system.^[1][2]

These agents inhibit the

The term "anticholinergic" is typically used to refer to antimuscarinics which competitively inhibit the binding of ACh to muscarinic acetylcholine receptors; such agents do not antagonize the binding at nicotinic acetylcholine receptors at the neuromuscular junction, although the term is sometimes used to refer to agents which do so.^[3][5]

Medical uses

Anticholinergic drugs are used to treat a variety of conditions:

• Dizziness (including vertigo and motion sickness-related symptoms)
• Extrapyramidal symptoms, a potential side-effect of antipsychotic medications
• Gastrointestinal disorders (e.g.,
  peptic ulcers, diarrhea, pylorospasm, diverticulitis, ulcerative colitis, nausea, and vomiting
  )
• Genitourinary disorders (e.g.,
  cystitis, urethritis, and prostatitis
  )
• Insomnia, although usually only on a short-term basis
• Respiratory disorders (e.g., asthma, chronic bronchitis, and chronic obstructive pulmonary disease [COPD])
• Sinus bradycardia due to a hypersensitive vagus nerve
• Organophosphate based nerve agent poisoning, such as VX, sarin, tabun, and soman (atropine is favoured in conjunction with an oxime, usually pralidoxime)^[6][7]

Anticholinergics generally have antisialagogue effects (decreasing saliva production), and most produce some level of sedation, both being advantageous in surgical procedures.^[8][9]

Until the beginning of the 20th century, anticholinergic drugs were widely used to treat psychiatric disorders.^[10]

Physiological effects

Effects of anticholinergic drugs include:

• Delirium (often with hallucinations and delusions indistinguishable from reality)
• Ocular symptoms (from
  anterior chamber^[11][12][13]
• Anhidrosis
  , dry mouth, dry skin
• Fever
• Constipation
• Tachycardia
• Urinary retention
• Cutaneous vasodilation^[3]

Clinically the most significant feature is delirium, particularly in the elderly, who are most likely to be affected by the toxidrome.^[3]

Side effects

Long-term use may increase the risk of both cognitive and physical decline.^[14][15] It is unclear whether they affect the risk of death generally.^[14] However, in older adults they do appear to increase the risk of death.^[16]

Possible effects of anticholinergics include:

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

Older patients are at a higher risk of experiencing CNS side effects.^{[citation needed]} The link possible between anticholinergic medication use and cognitive decline/dementia has been noted in weaker observational studies.^[21] Although there is no strong evidence from randomized controlled trials to suggest that these medications should be avoided, clinical guidelines suggest that a consideration be made to decrease the use of these medications if safe to do so and the use of these medications be carefully considered to reduce any possible adverse effects including cognitive decline.^[21]

Toxicity

An acute anticholinergic syndrome is reversible and subsides once all of the causative agents have been excreted. Reversible acetylcholinesterase inhibitor agents such as physostigmine can be used as an antidote 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.^[22]

Pharmacology

Anticholinergics are classified according to the receptors that are affected:

• Antimuscarinic agents operate on the muscarinic acetylcholine receptors
  . The majority of anticholinergic drugs are antimuscarinics.
• Antinicotinic agents operate on the nicotinic acetylcholine receptors. The majority of these are non-depolarising skeletal muscle relaxants for surgical use that are structurally related to curare
  . Several are depolarizing agents.

Antidotes

• Atropa belladonna (deadly nightshade)
• Brugmansia species
• Datura species
• Garrya species
• Hyoscyamus niger (henbane)
• Mandragora officinarum (mandrake)

Use as a deterrent

Several narcotic and