Anticholinergic

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Main article: Cholinergic blocking drugs

An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. An example of an anticholinergic is dicyclomine, and the classic example is atropine. Anticholinergics are administered to reduce the effects mediated by acetylcholine on acetylcholine receptors in neurons through competitive inhibition. Therefore, their effects are reversible.

Anticholinergics are a class of medications that 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 movements of smooth muscles present in the gastrointestinal tract, urinary tract, lungs, etc. 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.

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, along with a few of the depolarising agents and drugs of other categories structurally related to curare.

Examples of anticholinergics • ipratropium bromide (Atrovent) • oxitropium bromide (Oxivent) • tiotropium (Spiriva)

Physostigmine is one of a few drugs that are used as antidotes for anticholinergic poisoning. Nicotine also counteracts anticholinergics.

Effects

Anticholinergic drugs are used in treating a variety of conditions:

• Gastrointestinal disorders (e.g., gastritis, pylorospasm, diverticulitis, ulcerative colitis)

• Genitourinary disorders (e.g., cystitis, urethritis, prostatitis)

• Respiratory disorders (e.g., asthma, chronic bronchitis)

• Parkinson’s disease and Parkinson-like adverse medication effects

• Sinus bradycardia - Hypersensitive vagus nerve

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 experienced recreational drug users,^{[citation needed]} possibly due to the lack of euphoria caused by them. (For some of the recreational effects, see the article on deliriants.) Because most users do not enjoy the experience, they do not use it again, or do so very rarely. The risk of addiction is low in the anticholinergic class. The effects are usually more pronounced in the elderly, due to natural reduction of acetylcholine production associated with age.

Exceptions to the above include scopolamine, orphenadrine, dicycloverine/dicyclomine and first-generation antihistamines with central nervous system penetration.

Possible effects of anticholinergics include:

• Ataxia; loss of coordination
• Decreased mucus production in the nose and throat; consequent dry, sore throat
• Xerostomia or dry-mouth with possible acceleration of caries
• Cessation of perspiration; consequent decreased epidermal thermal dissipation leading to warm, blotchy, or red skin
• Increased body temperature
• Pupil dilation (mydriasis); consequent sensitivity to bright light (photophobia)
• Loss of accommodation (loss of focusing ability, blurred vision — cycloplegia)
• Double-vision (diplopia)
• Increased heart rate (tachycardia)
• Tendency to be easily startled
• Urinary retention
• Diminished bowel movement, sometimes ileus - (decreases motility via the vagus nerve)
• Increased intraocular pressure; dangerous for people with narrow-angle glaucoma
• Shaking

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
• Inability to concentrate
• Wandering thoughts; inability to sustain a train of thought
• Incoherent speech
• 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
  • Hallucinated presence of people not actually there
• Rarely: seizures, coma, and death

Acute anticholinergic syndrome is completely reversible and subsides once all of the toxin has been excreted. Previously, reversible cholinergic agents such as physostigmine was used but this was found to increase the risk of cardiac toxicity. The current recommended treatment is symptomatic and supportive management.

Plant sources

The most common plants containing anticholinergic alkaloids are:

• Atropa belladonna (Deadly Nightshade)
• Brugmansia species (Brugmansia)
• Datura species (Datura)
• Hyoscamus niger (Henbane)
• Mandragora officinarum (Mandrake).

Use as a deterrent

Certain preparations of some drugs, such as hydrocodone, are mixed with an anticholinergic agent to deter intentional overdose, although at normal dosages it can help the opiate itch.

In chemical warfare

Certain of these drugs have been trialed for their role as chemical weapons fin chemical warfare because of their possible role as Incapacitating agents:

• EA-3167

References

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