Opioids as MedicationsPage 10 of 17

8. Opioid Antagonists to Counter Dependency

Nalorphine is similar to morphine in structure, yet it is an antagonist of morphine action and was among the first drugs to imply that there was a specific receptor for morphine. It is a competitive inhibitor of morphine at low doses on MOR but probably has some weak agonist effects for analgesia on DOR and KOR at higher doses, though dysphoria can become a serious drawback. Once used for heroin overdoses, it also can cause respiratory depression, so it has been replaced in practice by naloxone.

Naloxone is a pure opioid antagonist at all three receptors and also blocks the endogenous neuropeptides such as endorphins and enkephalins. It can rapidly reverse the effects of morphine and other related opiates, and causes hyperalgesia (increased pain) in stressful situations where natural endorphins would have normally reduced pain. It is used to counteract opiate overdose, restoring respiration, and to reverse opiate analgesia in childbirth, to benefit breathing in the newborn child. Given by IV, its action is almost immediate, but the short 1 to 2 hour time of action, due to rapid liver metabolism, may require repeat dosing. Though it has no effects alone, it is effective in diagnosing addiction to opiates by rapidly inducing withdrawal symptoms.

Naltrexone is similar to nalaxone except that it is active for a much longer time (10-hr half life) and may be used in opiate addicts to prevent relapse, as no euphoria (or analgesia) would arise from a new injection. A single 100-mg dose can block heroin effects for 48 hours.

Buprenorphine is a highly lipophilic, partial MOR agonist that exhibits only limited activity, yet it can block other opiates at MOR. It can induce some withdrawal symptoms in those who have taken other opiates for weeks. It can relieve respiratory repression induced by fentanyl without reversing all of the analgesic effects, as would occur with naloxone.

Buprenorphine is given by IV for use in pain relief, whereas oral formulations are used in treatment for opioid dependence. In 2002 the FDA approved Subutex (buprenorphine) and Suboxone tablets (buprenorphine and naloxone) for the treatment of opiate dependence. Subutex and Suboxone treat opiate addiction by preventing symptoms of withdrawal from heroin and other opiates. Naloxone has been added to Suboxone to guard against IV abuse of buprenorphine by opiate addicts (FDA, 2002).