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Anticholinergic drugs


Anticholinergic Agents

  An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system.

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.

Anticholinergics are divided into three categories in accordance with their specific targets in the central and peripheral nervous system:
1)Antimuscarinic agents,
2)Ganglionic blockers, and
3)Neuromuscular blockers.

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

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.

 Side effects 

Long-term use may increase the risk of both mental 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 Stopping of sweating; consequent decreased epidermal thermal dissipation leading to warm, blotchy, or red skin Increased body temperature Pupil dilation; consequent sensitivity to bright light (photophobia) Loss of accommodation (loss of focusing ability, blurred vision – cycloplegia) Double-vision Increased heart rate Tendency to be easily startled Urinary retention Urinary incontinence while sleeping Diminished bowel movement, sometimes ileus (decreases motility via the vagus nerve) Increased intraocular pressure; dangerous for people with narrow-angle glaucoma. 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 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. 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: 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) The Bowel and bladder lose their tone (or "Bloated as a toad"; ileus, urinary retention) And the heart runs alone (tachycardia)

 Toxicity 


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 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. 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.

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

 Examples of common anticholinergics: Antimuscarinic agents Antipsychotics (clozapine, quetiapine) Atropine Benztropine Biperiden Chlorpheniramine Certain SSRIs (citalopram, sertraline) Dicyclomine (Dicycloverine) Dimenhydrinate Diphenhydramine Doxepin Doxylamine Glycopyrrolate Glycopyrronium Ipratropium Orphenadrine Oxitropium Oxybutynin Promethazine Propantheline bromide Tolterodine Tiotropium Tricyclic antidepressants (28 compounds with numerous trade names) Trihexyphenidyl Scopolamine Solifenacin Tropicamide 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 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.

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