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Pathway Description
Alvimopan Opioid Antagonist Action Pathway
Homo sapiens
Drug Action Pathway
Created: 2023-06-20
Last Updated: 2023-11-27
Alvimopan, also known as Entereg, is an opioid antagonist used to reduce the healing time of the upper and lower GI tract following surgical procedures. It is a μ-opioid antagonist action only on the peripheral receptors and not on the one in the central nervous system. Alvimopan competitively binds to the mu-opioid receptors in the GI tract, alvimopan owes its selectivity for peripheral receptors to its pharmacokinetics. The drug acts in the gastrointestinal tract by competing to bind the mu-opioid receptor. Alvimopan differs from other peripherally acting mu-receptor antagonists such as methylnaltrexone due to only acting on peripheral opioid receptors. It is used to permit a faster recovery of patients after surgical procedures that slow the GI tract transit (postoperative ileus). This drug is administered as an oral capsule.
Alvimopan inhibits the mu-opioid receptor located on neurons in the intestine. This inhibits the exchange of GTP for GDP which is required to activate the G-protein complex. This prevents the Gi subunit of the mu opioid receptor from inhibiting adenylate cyclase, which can therefore continue to catalyze ATP into cAMP. cAMP increases the excitability in spinal cord pain transmission neurons which allows the patient to feel pain rather than the analgesic effects of opioids. The inhibition of Mu-type opioid receptors also prevents the Gi subunit of the mu opioid receptor from activating the inwardly rectifying potassium channel increasing K+ conductance which would cause hyperpolarization. Alvimopan also prevents the gamma subunit of the mu opioid receptor from inhibiting the N-type calcium channels on the neuron. This allows calcium to enter the neuron and depolarize. The inhibition of mu-opioid receptors prevents hyperpolarization in the neuron, allowing it to fire at a normal rate. The neuron is able to depolarize and the high concentration of calcium releases acetylcholine and nitric acid into the neuromuscular junction. Acetylcholine binds to nicotinic acetylcholine receptors on the smooth muscles of the intestines, causing muscle contraction. The nitric oxide diffuses into the myocyte and causes muscle relaxation. The rythmic action of the neurotransmitters creates the peristalsis and the good GI transit.
References
Alvimopan Opioid Antagonist Pathway References
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