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Anticholinergics

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Anticholinergics

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, 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.[1]

Pharmacology

Anticholinergics are classified according to the receptors that are affected:

Examples

Examples of common anticholinergics:

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

Reversible agents

Main article: Stimulant

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) would counteract the anticholinergic symptoms by reducing sedation and increase acetylcholine activity, thereby causing alertness and arousal.

Medical and recreational uses

Anticholinergic drugs are used in treating a variety of conditions:

Anticholinergics generally have antisialagogue effects (decreasing saliva production), and most have at least some sedative effect, both being advantageous in surgical procedures.[2]

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, possibly due to the lack of euphoria caused by them. In terms of recreational use, these drugs are commonly referred to as 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.

Acute Anticholinergic Syndrome

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[3]
  • 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
    • Hallucinated presence of people not actually there
  • Rarely: seizures, coma, and death
  • Orthostatic hypotension (sudden dropping of systolic blood pressure when standing up suddenly) and significantly increased risk of falls in the elderly population.[4]

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

  • Hot as a hare (hyperthermia)
  • Blind as a bat (dilated pupils)
  • Dry as a bone (dry skin)
  • Red as a beet (vasodilation)
  • Mad as a hatter (hallucinations/agitation)
  • The bowel and bladder lose their tone and the heart goes on alone (ileus, urinary retention, tachycardia)

Remedies

Acute anticholinergic syndrome is completely reversible and subsides once all of the causative agent has been excreted. Reversible cholinergic agents such as physostigmine can be used in life-threatening cases. Wider use is discouraged due to the significant side effects, such as rapid heart beat and decreased blood pressure.

Piracetam (and other racetams), Alpha-GPC and Choline are known to activate cholinergic system and alleviate cognitive symptoms caused by extended use of anticholinergic drugs.

Plant sources

The most common plants containing anticholinergic alkaloids are:

Use as a deterrent

Certain preparations of some drugs, such as hydrocodone, are mixed with an anticholinergic agent to deter intentional overdose.[5]

References

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