Anticholinesterase

Anticholinesterase

Anticholinesterases are a class of drugs that inhibit the enzyme acetylcholinesterase, which is responsible for breaking down the neurotransmitter acetylcholine in the synaptic cleft. By inhibiting this enzyme, anticholinesterases increase the concentration of acetylcholine at synapses, enhancing cholinergic transmission.

Mechanism of Action

Anticholinesterases work by binding to the active site of acetylcholinesterase, preventing it from hydrolyzing acetylcholine into acetate and choline. This results in an accumulation of acetylcholine in the synaptic cleft, leading to prolonged activation of acetylcholine receptors on the postsynaptic membrane.

Types of Anticholinesterases

Anticholinesterases can be classified into two main types based on their duration of action:

• Reversible Inhibitors: These drugs bind temporarily to acetylcholinesterase and are used therapeutically. Examples include:

 * Neostigmine
 * Pyridostigmine
 * Physostigmine

• Irreversible Inhibitors: These compounds form a stable covalent bond with the enzyme, leading to long-lasting inhibition. They are often used as pesticides or chemical warfare agents. Examples include:

 * Organophosphates
 * Sarin

Clinical Uses

Anticholinesterases have several clinical applications, including:

• Treatment of Myasthenia Gravis: Drugs like neostigmine and pyridostigmine are used to increase neuromuscular transmission in patients with myasthenia gravis, an autoimmune disorder characterized by muscle weakness.

• Reversal of Neuromuscular Blockade: Anticholinesterases are used to reverse the effects of non-depolarizing neuromuscular blocking agents after surgery.

• Alzheimer's Disease: Certain anticholinesterases, such as donepezil, are used to manage symptoms of Alzheimer's disease by enhancing cholinergic function in the brain.

Side Effects

The increased levels of acetylcholine can lead to a range of side effects, primarily due to excessive stimulation of muscarinic and nicotinic receptors. Common side effects include:

• Bradycardia
• Hypotension
• Increased salivation
• Diarrhea
• Muscle cramps

Toxicity

Overdose of anticholinesterases, particularly irreversible inhibitors, can lead to a cholinergic crisis, characterized by excessive muscarinic and nicotinic stimulation. Symptoms include:

• Miosis (constricted pupils)
• Bronchospasm
• Seizures
• Respiratory failure

Treatment involves the administration of atropine, a muscarinic antagonist, and pralidoxime, which can reactivate acetylcholinesterase if given early.

See Also

• Cholinergic crisis
• Acetylcholine receptor
• Neurotransmitter

References

• Katzung, B. G., Masters, S. B., & Trevor, A. J. (2012). Basic & Clinical Pharmacology. McGraw-Hill Medical.
• Rang, H. P., Dale, M. M., Ritter, J. M., & Flower, R. J. (2007). Rang & Dale's Pharmacology. Churchill Livingstone.