Cholinergic drugs are a class of medications that mimic or enhance the effects of acetylcholine. This neurotransmitter plays a vital role in the nervous system and the communication between nerve cells and muscles. Acetylcholine plays a role in various physiological processes, including muscle contraction, regulation of heart rate, gastrointestinal function, and memory.

Cholinergic drugs can be divided into two main categories:

1. Direct-Acting Cholinergic Agonists

These drugs directly bind to and activate cholinergic receptors, such as muscarinic or nicotinic. They mimic the effects of acetylcholine.

   a. Muscarinic Agonists

These drugs act on muscarinic receptors, which are present in various tissues, including smooth muscle, glands, and the heart. They can stimulate the parasympathetic nervous system. Examples include pilocarpine (used to treat glaucoma) and bethanechol (used to stimulate gastrointestinal and urinary tract muscles).

Pilocarpine: Primarily, pilocarpine treats glaucoma by increasing the drainage of aqueous humor from the eye, reducing intraocular pressure. It can also stimulate saliva production in dry mouth (xerostomia) cases due to Sjögren’s syndrome or radiation therapy.

Bethanechol: Bethanechol stimulates smooth muscle contractions in the gastrointestinal and urinary tracts. It is prescribed to treat conditions like urinary retention and atonic (non-functioning) bladder.

Carbachol: In ophthalmology, doctors use carbachol to reduce intraocular pressure and to constrict the pupil during eye surgery.

Methacholine: Doctors use methacholine as a bronchoconstrictor challenge test to diagnose airway hyperresponsiveness in conditions such as asthma.

Cevimeline: Cevimeline stimulates salivary gland secretion and is primarily prescribed to.

   b. Nicotinic Agonists

These drugs stimulate nicotinic receptors in skeletal muscles and autonomic ganglia. Nicotine, found in tobacco products, is a well-known nicotinic agonist.

Nicotine: Nicotine is a well-known nicotinic agonist found in tobacco products. While it is not a medication, it is a powerful stimulant of nicotinic receptors and is the primary psychoactive component in tobacco. It can lead to various effects, including increased heart rate and blood pressure, addiction, and dependence.

Varenicline: Varenicline is a medication used to help people quit smoking. It works by partially stimulating nicotinic receptors, which reduces withdrawal symptoms and cravings associated with nicotine addiction. At the same time, it also blocks nicotine from binding to these receptors, making smoking less rewarding.

Suxamethonium (succinylcholine): Suxamethonium is a depolarizing neuromuscular blocking agent used during certain medical procedures, such as intubation, to induce temporary muscle relaxation. It acts as a nicotinic receptor agonist at the neuromuscular junction, causing depolarization of muscle fibers and paralysis.

Rocuronium and Vecuronium: These are non-depolarizing neuromuscular blocking agents used in anesthesia to induce muscle relaxation during surgical procedures. They work by blocking the action of acetylcholine at the nicotinic receptors on skeletal muscle, leading to paralysis.

2. Indirect-acting Cholinergic Agonists (Cholinesterase Inhibitors)

These drugs increase the levels of acetylcholine by inhibiting the enzyme acetylcholinesterase, which normally breaks down acetylcholine. By preventing the breakdown of acetylcholine, these drugs prolong its action and enhance cholinergic transmission.

   a. Reversible Cholinesterase Inhibitors

Drugs like physostigmine and neostigmine temporarily inhibit acetylcholinesterase. In medical settings, healthcare professionals use them to treat conditions like myasthenia gravis and to reverse the effects of neuromuscular blocking agents used during surgery.

Pyridostigmine: Doctors commonly use pyridostigmine to treat myasthenia gravis, a neuromuscular disorder characterized by muscle weakness. It helps improve muscle strength by inhibiting acetylcholinesterase, allowing acetylcholine to remain in the neuromuscular junction for a longer period.

Neostigmine: Another medication used to treat myasthenia gravis and to reverse the effects of non-depolarizing neuromuscular blocking agents after surgery is neostigmine. It acts by inhibiting acetylcholinesterase, thereby increasing acetylcholine levels at the neuromuscular junction.

Physostigmine: Doctors use physostigmine to reverse the toxic effects of anticholinergic drugs, such as atropine or scopolamine, in cases of anticholinergic poisoning.It increases acetylcholine levels in the brain and peripheral nervous system.

Edrophonium: Edrophonium is a diagnostic agent to differentiate myasthenia gravis from other conditions causing muscle weakness. When injected, it induces a temporary improvement in muscle strength and undergoes rapid metabolism, rendering it a short-acting agent.

Ambenonium: Ambenonium is another medication used in the treatment of myasthenia gravis. It has a longer duration of action compared to some other cholinesterase inhibitors.

   b. Irreversible Cholinesterase Inhibitors

Compounds like organophosphates (found in pesticides and nerve agents) irreversibly inhibit acetylcholinesterase. Poisoning with these substances can lead to overstimulation of cholinergic receptors, resulting in symptoms and potential paralysis.

Organophosphates: Organophosphates are a class of chemicals commonly used in pesticides and nerve agents. They inhibit acetylcholinesterase irreversibly, leading to an accumulation of acetylcholine at cholinergic synapses. This excessive stimulation of cholinergic receptors can have a wide range of toxic effects on the nervous system and other body systems. Examples of organophosphates include:

Parathion: An organophosphate pesticide.

Malathion: Another organophosphate pesticide.

Sarin: A nerve agent that has been used as a chemical weapon.

VX: Another potent nerve agent.

Cholinergic drugs can affect the body, including increased muscle tone, salivation, improved cognitive function, and bradycardia (slowed heart rate). These drugs are used in medical practice to treat conditions characterized by a deficiency in cholinergic activity, such as myasthenia gravis, Alzheimer’s disease, and certain types of glaucoma.

Brimonidine: Brimonidine, primarily an alpha-2 adrenergic agonist, can also exhibit some muscarinic agonist effects and is used to reduce intraocular pressure in the treatment of glaucoma.

Contraindications

Hypersensitivity or Allergy

Asthma or Chronic Obstructive Pulmonary Disease (COPD)

Gastrointestinal Obstruction

Bradycardia

Urinary Retention

Corneal Ulcers

Pregnancy and Breastfeeding

Neurological Disorders

Peptic ulcers

Cardiovascular diseases

It’s important to use cholinergic drugs under medical supervision because they can have side effects and can be contraindicated in certain conditions. Overstimulation of cholinergic receptors can lead to symptoms like excessive salivation, diarrhea, bradycardia, and bronchoconstriction. Cholinergic drugs must be carefully monitored to ensure their safety and effectiveness.