New therapeutic principles for adverse effects on upper and lower gastrointestinal tract in patients treated with opioid analgesics

Abstract

Recent large scale surveys document that patients on opioid analgesics suffer adverse effects from increased tone in sphincters of both the upper and lower part of the gastrointestinal tract, decreased secretions into and increased absorption of fluids out of the bowel. These adverse effects often cause patients to discontinue opioid analgesics. Also patients treated with opioids for acute pain after surgery and in the intensive care units suffer gastrointestinal adverse effects. Constipation is the most common adverse effect of opioids. Most patients self-medicate with over-the-counter laxatives but suffer unpredictable responses and bothersome adverse effects of laxatives. Potent prescription laxatives may further adversely impact quality of life of chronic pain patients. Opioid-induced dysfunctions of the upper gastrointestinal tract are often misinterpreted by health care providers, and they are not relieved by laxatives. Two therapeutic developments make specific and effective prophylaxis and treatment possible: (1) Peripherally acting opioid antagonists that do not cross the blood brain barrier (methylnaltrexone and alvimopan), and (2) the opioid antagonist naloxone added to an opioid agonist in prolonged-release oral formulations (tilidin or oxycodone). Orally administered prolonged-release naloxone is almost completely eliminated during the first-pass through the liver and will therefore not reach opioid receptors in the central nervous system. These drugs relieve both upper and lower gastrointestinal adverse effects of opioid agonists, although their effects on constipation have been the focus of most clinical studies. These new pharmacological principles promise improved management of pain with opioids both for acute and chronic pain conditions.