Anticholinergic
Anticholinergic is a group of substances that blocks the action of the neurotransmitter acetylcholine at synapses in the central and the peripheral nervous system, and, in broad terms, neuromuscular junction.
These agents 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; cholinergic process otherwise by enhancing ACh function.
In broad terms, anticholinergics are divided into two categories in accordance with their specific targets in the central, peripheral nervous system and neuromuscular junction: antimuscarinic agents, and antinicotinic agents.
In strict terms, anticholinergic only comprises antimuscarinic which competitively inhibits binding of the neurotransmitter acetylcholine to muscarinic acetylcholine receptors though.; anticholinergic agents do not antagonize the binding at nicotinic acetylcholine receptors at the neuromuscular junction, for example.
Medical uses
Anticholinergic drugs are used to treat a variety of conditions:- Dizziness
- Extrapyramidal symptoms, a potential side-effect of antipsychotic medications.
- Gastrointestinal disorders
- Genitourinary disorders
- Insomnia, although usually only on a short-term basis
- Respiratory disorders
- Sinus bradycardia due to a hypersensitive vagus nerve
- Organophosphate based nerve agent poisoning, such as VX, sarin, tabun, and soman
Until the beginning of the 20th century anticholinergic drugs were used widely in psychiatric disorders.
Physiological effects
- delirium
- ocular symptoms--mydriasis, pupil dilation, and acute angle-closure glaucoma in those with shallow anterior chamber.
- anhidrosis/dry mouth/dry skin
- fever
- constipation
- tachycardia
- urinary retention
- cutaneous vasodilation
Side effects
Long-term use may increase the risk of both cognitive and physical decline. It is unclear whether they affect the risk of death generally. However, in older adults they do appear to increase the risk of death.Possible effects of anticholinergics include:
- Poor coordination
- Dementia
- Decreased mucus production in the nose and throat; consequent dry, sore throat
- Dry-mouth with possible acceleration of dental caries
- Cessation of sweating; consequent decreased epidermal thermal dissipation leading to warm, blotchy, or red skin
- Increased body temperature
- Pupil dilation; consequent sensitivity to bright light
- Loss of accommodation
- Double-vision
- Increased heart rate
- Tendency to be easily startled
- Urinary retention
- Urinary incontinence while sleeping
- Diminished bowel movement, sometimes ileus
- Increased intraocular pressure; dangerous for people with narrow-angle glaucoma.
- Confusion
- Disorientation
- Agitation
- Euphoria or dysphoria
- Respiratory depression
- Memory problems
- Inability to concentrate
- Wandering thoughts; inability to sustain a train of thought
- Incoherent speech
- Irritability
- Mental confusion
- 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 and significantly increased risk of falls in the elderly population.
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 or suggestion of tricyclic antidepressant ingestion is generally considered a contraindication to physostigmine administration.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.
Examples
- Antimuscarinic agents
- * Antipsychotics
- * Atropine
- * Benztropine
- * Biperiden
- * Chlorpheniramine
- * Certain SSRIs
- * Dicyclomine
- * Dimenhydrinate
- * Diphenhydramine
- * Doxepin
- * Doxylamine
- * Glycopyrrolate
- * Glycopyrronium
- * Hyoscyamine
- * Ipratropium
- * Orphenadrine
- * Oxitropium
- * Oxybutynin
- * Promethazine
- * Propantheline bromide
- * Scopolamine
- * Solifenacin
- * Tolterodine
- * Tiotropium
- * Tricyclic antidepressants
- * Trihexyphenidyl
- * Tropicamide
- * Umeclidinium
- Antinicotinic agents
- * Bupropion – Ganglion blocker
- * Dextromethorphan - Cough suppressant and ganglion blocker
- * Doxacurium – Nondepolarizing skeletal muscular relaxant
- * Hexamethonium – Ganglion blocker
- * Mecamylamine – Ganglion blocker and occasional smoking cessation aid
- * Tubocurarine - Nondepolarizing skeletal muscular relaxant
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 can counteract the anticholinergic symptoms by reducing sedation and increasing acetylcholine activity, thereby causing alertness and arousal.
Recreational uses
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. In the context of recreational use, anticholinergics are often called deliriants.Plant sources
The most common plants containing anticholinergic alkaloids are:- Atropa belladonna
- Brugmansia species
- Datura species
- Garrya species
- Hyoscyamus niger
- Mandragora officinarum
Use as a deterrent