Acetylcholine Function In The Brain Short Notes

List the sites of the release of acetylcholine.

 

The sites of release of acetylcholine are:

1. Ganglia—all the preganglionic fibers of ANS, i.e. at both the sympathetic and parasympathetic ganglia.
2. The postganglionic parasympathetic nerve endings.
3. Sweat glands are the sympathetic postganglionic nerve endings supplying the sweat glands.
4. Skeletal muscles somatic nerve endings supplying skeletal muscles.
5. Adrenal medulla.
6. CNS brain and spinal cord.

Read And Learn More: Pharmacology Question And Answers

Cholinergic System Cholinesterases

Two types of cholinesterases are:

1. True cholinesterase (acetylcholinesterase).
2. Pseudocholinesterase (butyryl cholinesterase)

Types of cholinesterases:

Cholinergic Receptors

There are two classes of cholinergic receptors—muscarinic and nicotine:

1. Muscarinic receptors are present in the heart, smooth muscles, glands, eyes, and CNS. Muscarinic receptors are all G-protein coupled receptors. There are five subtypes of muscarinic receptors, M1–M5

2. Nicotinic receptors are present in the neuromuscular junction (NMJ), autonomic ganglia, and adrenal medulla.

• Nicotine receptors are ion channels—five subunits (2a, 1b, 1g, and 1d) enclose the channel
• Binding of acetylcholine to subunits opens the channel, allowing the entry of Na⁺ into the cell.
• Two subtypes of nicotinic receptors are N_M receptors present at the skeletal
  muscle end plate and N_N receptors at the autonomic ganglia and adrenal medulla.

Cholinergic Drugs

Cholinergic Drugs Classification:

1. Directly acting:

• Esters of choline: Acetylcholine, methacholine, carbachol, bethanechol
• Cholinomimetic alkaloids: Pilocarpine, mescaline, arecoline

2. Indirectly acting (anticholinesterases):

• Reversible (carbamates): Neostigmine, physostigmine, pyridostigmine, ammonium, euphonium, galantamine
• Irreversible

Organophosphates compounds:

• Echothiophate, malathion, parathion, submission
• Toxic nerve gases: Sarin, ta bun

Carbamate insecticides:

• Carbaryl proposers (Baygon), aldicarb

Actions Of Acetylcholine:

Uses of acetylcholine: Acetylcholine is not used therapeutically because:

• It is rapidly destroyed in the gut when given orally.
• On intravenous administration, it is rapidly metabolized by pseudocholinesterases in the plasma and by true cholinesterase at the site of action.
• Only used as 1% eye drops to rapidly produce mitosis during some eye surgeries.

Esters Of Choline

Esters of choline: Carbachol, bethanechol, and methacholine.

• Unlike acetylcholine, they are effective orally.
• Barbacoa and bethanechol are resistant to both cholinesterases and have a longer duration of action.
• Their muscarinic actions are prominent, with a sustained effect on GI smooth muscles and the urinary bladder.
• Barbacoa eye drops are used in glaucoma.
• Methacholine is resistant to pseudocode but is not in use.

Bethanechol uses:

• Hypotonia of the bladder.
• Hypotonia of the gastrointestinal smooth muscles and in congenital megacolon.
• Postoperative paralytic illus.
• Urinary retention and neurogenic bladder.
• Xerostomia (alternative to pilocarpine).

Choline Adverse effects:

Diarrhea, flushing, salivation, sweating, bradycardia, hypotension, syncope, and bronchospasm.

Cholinomimetic Alkaloids: Pilocarpine is a cholinomimetic alkaloid obtained from the Pilocarpus microfilms plant.

Cholinomimetic Alkaloids Actions:

• Muscarinic actions are prominent.
• It is a tertiary amine, crosses BBB, and can cause CNS effects.
• When applied to the eye it causes mitosis (contracts sphincter papillae), contraction of the ciliary muscle, spasm of accommodation, and a fall in intraocular tension.
• It increases sweat (diaphoretic) and salivary secretions (dialogue).

Cholinomimetic Alkaloids Adverse Effects:

• Topical: Eye drops cause a burning sensation, painful spasms of accommodation, brow ache, and corneal edema. Long-term use can cause retinal detachment.
• Systemic use: Salivation, sweating, bradycardia, diarrhea, and bronchospasm can occur.

Cholinomimetic Alkaloids Uses:

1. Glaucoma: Pilocarpine 0.5–4% eye drops cause mitosis and facilitates drainage of aqueous humor to reduce IOP. Pilocarpine-focused acts for 7 days.
2. To break the adhesions between the iris and lens: Pilocarpine used alternately with Mydriatic.
3. To counter the dryness of mouth seen following radiation of the head and neck.
4. Sjögren’s syndrome is characterized by dryness of mouth and lack of tears. Pilocarpine being a dialogue is useful.

Anticholinesterases/Cholinesterase Inhibitors