Physostigmine is a cholinesterase inhibitor used to treat glaucoma and anticholinergic toxicity. It is rapidly absorbed through membranes. It can be applied topically to the conjunctiva. It also can cross the blood-brain barrier and is used when central nervous system effects are desired, as in the treatment of severe anticholinergic toxicity. In the neuron, acetylcholine is synthesized form acetyl-coa and choline, and stored into synaptic vesicles. When an action potential arrives at the nerve terminal, voltage gated calcium channels open leading to an influx of calcium ions into the neuron. This triggers the docking of the synaptic vesicle and release of acetylcholine into the synapse. Acetylcholine acts on M3 receptors on the post synaptic membrane. M3 receptors are coupled to Gq signaling cascade. The downstream signaling causes the ciliary muscle of the eye to contract. This increase results in increased aqueous humor flow and a decrease in intraocular pressure. The acetylcholine in the synapse is cleared rapidly by acetylcholinesterase which breaks acetylcholine down into choline and acetate. Choline is taken back up into the presynaptic neuron and recycled to produce more acetylcholine. Physostigmine inhibits the acetylcholinesterase enzyme, which normally breaks down acetylcholine. The main pharmacological actions of this drug are believed to occur as the result of this enzyme inhibition, enhancing cholinergic transmission. Common adverse effects include nausea/vomiting, diarrhea, abdominal cramps, lacrimation, dyspnea, miosis, sweating.

Physostigmine Pathway References