Pharmacology of Cholinergic Agonists

A family of acetylcholine receptors coupled to G proteins and are activated by muscarine, a substance derived from the mushroom Amanita muscaria.

A major type of muscarinic receptor coupled to Gq protein, found in the CNS, gastric parietal cells, salivary glands, and smooth muscle.

A type of muscarinic receptor coupled to Gi protein, predominantly found in cardiac muscle, smooth muscles, and also plays a role in reducing heart rate.

A prominent muscarinic receptor coupled to Gq protein, mainly present in smooth muscle, exocrine glands, and the eye, responsible for various muscle contraction and secretion.

A type of ligand-gated ion channel receptor activated by acetylcholine, highly sensitive to nicotine, and involved in nerve impulse transmission.

A mechanism by which nerve impulses are transmitted at the neuromuscular junction, involving the release of acetylcholine and its binding to nicotinic receptors.

A type of drug that blocks muscarinic receptors, thereby reducing the effects of acetylcholine.

The effect of acetylcholine on various organs, impacting heart rate, muscle contraction, glandular secretions, and other physiological functions.

Cholinergic neurons use acetylcholine (ACh) as their neurotransmitter. This means they synthesize, store, release, and respond to ACh.

Cholinergic receptors are proteins that bind to acetylcholine. They are responsible for mediating the effects of ACh in the body.

Acetylcholine is synthesized in cholinergic nerve terminals by combining choline and acetyl coenzyme A. This process is catalyzed by the enzyme choline acetyltransferase (ChAT).

ACh is packaged into vesicles and stored until it is released into the synapse. This release is triggered by an action potential and involves exocytosis.

Once released, ACh binds to its receptors on post-synaptic neurons or target cells. This binding triggers a signal transduction cascade that leads to a specific physiological response.

The action of ACh is terminated by the enzyme acetylcholinesterase (AChE). AChE hydrolyzes ACh into choline and acetate, which are then recycled for reuse or degraded.

A class of drugs that mimic the actions of acetylcholine at cholinergic receptors.

Cholinomimetics in the eye constrict the iris sphincter, opening the ocular angle and facilitating aqueous humor drainage. This is useful for closed angle glaucoma.

A selective M3 agonist used for the treatment of dry mouth (xerostomia) and Sjogren's syndrome.

A class of drugs that inhibit the breakdown of acetylcholine, causing accumulation and enhanced cholinergic signaling.

A short-acting AChE inhibitor (alcohol type), used for diagnosing Myasthenia Gravis because it has a rapid onset and offset.

The enzyme that breaks down acetylcholine into choline and acetate.

The accumulation of acetylcholine in the synapse leads to activation of both muscarinic and nicotinic receptors, resulting in a variety of effects.

Organophosphates are irreversible AChE inhibitors, often used as pesticides.

An autoimmune disorder where antibodies attack acetylcholine receptors at the neuromuscular junction, leading to muscle weakness.

A class of drugs that prevent the breakdown of acetylcholine, increasing its levels at the synapse.

A naturally occurring anticholinesterase that can penetrate the blood-brain barrier.

A synthetic anticholinesterase that is more polar than physostigmine and cannot cross the blood-brain barrier.

A long-acting anticholinesterase used in the treatment of myasthenia gravis.

A group of potent chemicals that covalently bind to acetylcholinesterase, inhibiting its activity for an extended period.

An organophosphate that binds covalently to acetylcholinesterase, leading to prolonged inhibition of the enzyme.

A state of severe cholinergic toxicity caused by excessive acetylcholine in the synapse.

Acetylcholine receptor subtypes mediate different effects in the body. Nicotinic receptors are found at neuromuscular junctions and autonomic ganglia, while muscarinic receptors are found in the adrenal medulla, heart, blood vessels, gastrointestinal tract, bronchi, urinary tract, and eye.

Nicotinic receptors are ligand-gated ion channels that allow sodium ions to enter when two acetylcholine molecules bind to them, leading to depolarization.

Muscarinic receptors are also ligand-gated ion channels, but their mechanism of action differs from nicotinic receptors. They are involved in regulating smooth muscle contraction, glandular secretions, and heart rate.

Nicotine initially stimulates nicotinic receptors, but at higher doses it blocks them. This explains the dual effect of nicotine on the body, from mild stimulation to paralysis.

Direct-acting parasympathomimetics mimic the effects of acetylcholine, directly activating muscarinic receptors.

Indirect-acting parasympathomimetics work by inhibiting the breakdown of acetylcholine, leading to its accumulation and prolonged effects.

Acetylcholine (ACh) is a neurotransmitter that has both muscarinic and nicotinic activity. It is rapidly inactivated by cholinesterase, limiting its therapeutic usefulness.

Carbachol is a synthetic cholinergic agent that has both muscarinic and nicotinic effects. It is a poor substrate for cholinesterase, resulting in a longer duration of action.

Carbachol is a medication that mimics the effects of acetylcholine and acts on muscarinic receptors, leading to a decrease in intraocular pressure by contracting the ciliary muscle to open the trabecular meshwork.

Carbachol is rarely used therapeutically due to its long duration of action and lack of selectivity for specific receptors. It is primarily used in the eye as a miotic agent, which constricts the pupil and reduces intraocular pressure by enhancing aqueous humor drainage.

Bethanechol is a direct-acting cholinomimetic that mimics acetylcholine's effects by activating muscarinic receptors. It is used to treat urinary retention and gastrointestinal motility disorders due to its ability to stimulate bladder contraction and increase intestinal movement.

Bethanechol is a carbamic acid ester that is not hydrolyzed by acetylcholinesterase, making it more resistant to breakdown compared to acetylcholine. This property contributes to its longer duration of action.

Pilocarpine is a muscarinic agonist that directly activates muscarinic receptors. It is commonly used to treat glaucoma by constricting the pupil and promoting drainage of aqueous humor. Pilocarpine's ability to stimulate secretions like saliva and sweat makes it valuable for managing dry mouth conditions.

Pilocarpine's unique molecular structure allows it to penetrate the blood-brain barrier, potentially leading to central nervous system side effects such as sweating and salivation.

Pilocarpine's action in glaucoma is to facilitate drainage of aqueous humor from the eye by opening the trabecular meshwork, which reduces intraocular pressure.

Pilocarpine is a cholinergic drug that primarily acts on muscarinic receptors. Despite its structural differences from acetylcholine, it effectively mimics its actions, leading to various therapeutic applications that rely on its ability to stimulate specific functions within the body.