Anticholinergic drugs hinder or prevent (antagonists) the activity of some receptors, the acetylcholine receptors, located at the level of the synapses of the central and peripheral nervous system.
These drugs inhibit the nerve impulses of the parasympathetic system selectively blocking the binding of the neurotransmitter acetylcholine with its receptor, present in nerve cells. Acetylcholine is produced in neurons by the enzyme choline acetyl-transferase, using choline as a substrate, a substance produced in the liver from serine, and the acetyl group of acetyl-CoA, produced inside small organelles present in cells: the mitochondria.
Acetylcholine is one of the most important neurotransmitters, responsible for nerve transmission both in the central nervous system and peripherally in humans and many other organisms.
Depending on the district at which they act, and depending on the type of cholinergic receptor with which they interact, anticholinergic drugs are able to mediate various physiological processes.
They can, in fact, be divided into two groups, in relation to the receptors involved:
- muscarinic or antimuscarinic antagonists, since they act at the level of receptors for muscarinic acetylcholine, M1-M5
- nicotinic or antinicotin antagonists, since they interact with the receptors for nicotinic acetylcholine, ie neuronal nicotinic and muscular nicotinic
The muscarinic antagonists they are anticholinergic drugs that exert their activity by interacting with muscarinic-type acetylcholine receptors. There are five different types of muscarinic receptors:
- M1, located mainly in the central nervous system, and in gastric cells
- M2, present at the level of the musculature of the atria (two of the four chambers into which the heart is divided) and the conducting tissue of the heart
- M3, located at the level of all the glands that pour their secretions outside the body (exocrine, for example sweat, lacrimal, salivary glands, etc.) and in smooth muscles
- M4, present in the lungs, uterus and central nervous system
- M5, mainly present in the eyes and in the central nervous system
THE muscarinic type receptors they are receptors metabotropic, therefore associated with a protein G. Specifically, the M1, M3 and M5 receptors are coupled to a Gq / 11 protein (excitatory G protein) which promotes the activation of an enzyme, phospholipase C (PLC), with a consequent increase in the concentration of intracellular calcium. The M2 and M4 receptors, on the other hand, are coupled to a protein Gi (inhibitory G protein), whose activation promotes the inhibition of "adenylate cyclase (an enzyme of the class of lyase which favors the breakdown of various chemical bonds) and the formation of cAMP (cyclic AMP), thus blocking the passage of calcium inside the cell.
The progenitor of this type of anticholinergic drugs is atropine, a molecule capable of nonspecifically hindering all five types of muscarinic receptors present in the body.
There are anti-muscarinic drugs on the market, formulated in such a way as to perform their action selectively towards certain types of receptors.
Therefore, active ingredients such as:
- scopolamine, drug used to relieve nausea and dizziness and avoid vomiting in case of car sickness or when regaining consciousness after anesthesia. It can also be used in the treatment of muscle spasticity, irritable bowel syndrome and diverticulitis.
- ipratropium, a drug used as an inhaled bronchodilator, to treat difficulty in breathing (dyspnoea) in chronic bronchitis or asthma
- tiotropium, drug that reduces the frequency of acute episodes of COPD aggravation (chronic obstructive pulmonary disease)
- solifenacin, antispasmodic of the urinary tract
- oxybutynin, drug used to relieve bladder and urinary tract disorders
- trihexyphenidyl, a drug used to treat tremors caused by Parkinson's disease
- darifenacin, drug used in the treatment of disorders (symptoms) of urinary incontinence
THE muscarinic anticholinergic drugs, therefore, they are used in the treatment of various diseases, including:
- urinary incontinence
- overactive bladder (OAB)
- chronic obstructive pulmonary disease (COPD)
- gastrointestinal disorders
- dilation of the pupils (mydriasis)
- dizziness and motion sickness
- Parkinson's disease
The nicotinic antagonists they are anticholinergic drugs that act at the level of nicotinic acetylcholine receptors (neuronal and muscular). They are used, above all, as muscle relaxants. These drugs, therefore, are used to facilitate interventions in surgery or during "performing some types of endoscopic examinations.
In particular, antinicotin drugs that block the action of acetylcholine on the nicotinic receptors present on the neuromuscular plaque, can be divided into two categories:
- competitive blockers, like tubocurarine, cause paralysis of the muscles, starting from the facial ones up to the limbs
- depolarizing blockers, such as succinylcholine which, through an irreversible bond, desensitizes the nicotinic receptor, causing muscular and respiratory paralysis. These drugs are used, at appropriate dosages, in anesthesiology, in combination with anesthetics, to promote muscle relaxation before surgery.
How anticholinergic drugs work
Anticholinergic drugs prevent acetylcholine from binding to its receptor (nicotinic or muscarinic), present in nerve cells, inhibiting the impulses of the parasympathetic nervous system. These nerve impulses are responsible for involuntary muscle movements in the gastrointestinal tract, in the lung, in the urinary tract and other parts of the body, and they help control functions such as salivation, digestion, urine output (urination) and mucus secretion.
When should anticholinergics be taken
Depending on their type (muscarinic or nicotinic) the field of use of anticholinergic drugs is very vast and cannot be fully listed. Generally speaking, anticholinergic drugs should be taken in cases of incorrect functioning of muscles of any type, voluntary or involuntary.
The most common, also sold as over-the-counter drugs, include drugs for:
- relieve cough
- control the production of mucus
- help wheezing or chest tightness
- painful spasms in the gastrointestinal tract and colitis of various kinds
- treatment of cramps
Side effects and contraindications
The type of undesirable (side) effects and the intensity with which they occur can vary considerably from individual to individual, also depending on the type of active ingredient used, the route through which the drug is administered (by mouth, by injection, etc. .) and the sensitivity that each person has towards the same drug.
In particular, when administered systemically, anticholinergic drugs can cause various undesirable effects (side effects), such as:
- gastrointestinal disorders, nausea, vomiting, dry mouth
- dermatological disorders, redness of the skin
- musculoskeletal disorders, muscle aches, abdominal pain, breathing problem, rapid heartbeat
- central nervous system disorders, confusion, agitation, neurological impairment, coma
- constipation, urinary retention, blurred vision
These side effects are less severe when the drugs are administered by inhalation or applied topically.
Excessive use of an anticholinergic drug can cause unconsciousness or even death, particularly if it is taken in combination with alcohol. Anticholinergics also reduce the amount of sweat emitted and consequently raise the temperature body, cause the so-called heat stroke.
Anticholinergics should be used with caution especially in the elderly. The cumulative effect of several drugs with anticholinergic properties is defined anticholinergic load (from English anticholinergic burden) and is associated with the risk of falls, fractures, cognitive impairment, pneumonia and hospitalization. Older people, and especially those with dementia, are particularly vulnerable to the unwanted neuropsychiatric effects of anticholinergics. Among the side effects of loading with anticholinergic drugs, the delirium represents an important neuropsychiatric condition characterized by defects in attention and reasoning (cognition). Appears suddenly (acute onset) and develops over a short period of time (hours or days); it is usually reversible and manifests itself as direct consequence of an organic or metabolic disease, of the overdose or withdrawal effects of a drug, of exposure to toxic agents or of all these factors.
In addition to the elderly, people who should not use anticholinergics are those with diseases such as:
- myasthenia gravis
- respiratory diseases
- excessive functioning of the thyroid gland (hyperthyroidism)
- glaucoma (high blood pressure in the eye)
- enlarged prostate
- high blood pressure (hypertension)
- blockage of the urinary tract
- increased heart rate (tachycardia)
- severe dry mouth
- hiatal hernia
- severe constipation
- liver disease
- down syndrome
If you suffer from any of the aforementioned diseases or allergy to anticholinergic drugs, you should inform your doctor.
Anticholinergics can interact with other drugs, producing effects other than those expected. In fact, they can interfere with the gastrointestinal absorption of controlled-release formulations of digoxin (increases in blood concentrations of digoxin may occur) and hinder (antagonize) the effects of drugs that promote gastrointestinal motility, such as metoclopramide. In addition, drugs such as amantidine, drugs belonging to the class of antiarrhythmics, antipsychotics, antihistamines, benzodiazepines, narcotic analgesic drugs, nitrates and nitrites, sympathomimetic drugs and tricyclic antidepressants, may increase some actions or side effects of anticholinergic drugs.Therefore, it is always necessary to ask the attending physician for directions and consult the information in the package leaflet.
Healthline. Anticholinergics (English)
Purves D, Augustine GJ, Fitzpatrick D, et al., Editors. Acetylcholine. Neuroscience 2nd edition. Sunderland (MA): Sinauer Associates, 2001 (English)
Gosens R, Gross N. The mode of action of anticholinergics in asthma. European Respiratory Journal. 2018; 52