Opioid reversal agents

Central Nervous System Drugs Opioid Reversal Agents... 

Analgesics, Cards 100-106 Opioid Reversal Agents, Card 107 Anesthetics and Sleep Inducers, Cards 1 08-115... 

Etorphine Hydrochloride Maximum care must be exercised when handling etorphine hydrochloride. Spillage on any part of the body must be washed immediately to avoid fatal reactions. When the drug is administered accidentally, a reversing agent should be given. Dependence and withdrawal symptoms are similar to those of opioid analgesics. 

Opioidergic agents. Naltrexone and nalmefene, opioid antagonists with no intrinsic agonist properties, have been studied for the treatment of alcohol dependence. Naltrexone has been studied much more extensively than nalmefene for this indication. In 1984 naltrexone was approved by the FDA for the treatment of opioid dependence, and in 1994 it was approved for the treatment of alcohol dependence. Nalmefene is approved in the United States as a parenteral formulation for the acute reversal of opioid effects (e.g., after opioid overdose or analgesia). 

Patients who are acutely intoxicated with an opioid usually present with miosis, euphoria, slow breathing and slow heart rate, low blood pressure, and constipation. Seizures may occur with certain agents such as meperidine (Demerol ). It is critically important to monitor patients carefully to avoid cardiac/ respiratory depression and death from an excessive dose of opioids. One strategy is to reverse the intoxication by utilizing naloxone (Narcan ) 0.4 to 2 mg IV every 2 to 3 minutes up to 10 mg. Alternatively, the IM/SC route may be used if IV access is not available. Because naloxone is shorter-acting than most abused opioids, it may need to be readministered at periodic intervals otherwise the patient could lapse into cardiopulmonary arrest after a symptom-free interval of reversed... 

There are two major classes of pain medications, nonopioids and opioids. The nonopioids used to treat mild pain include agents such as acetaminophen, both steroid and nonsteroidal antiinflammatory drugs (NSAIDs), and acetylsalicylic acid. Anticonvulsants suppress neuronal firing and are also helpful in neuropathic pain. Antiinflammatory agents (e.g., NSAIDs or corticosteroids) may be particularly helpful when bony involvement occurs and are often used for low-intensity pain. Steroids decrease inflammatory edema and are useful in cases of nerve and spinal cord compression, lymphedema, visceral pain caused by organ enlargement, and bone pain. Finally, short-term corticosteroid therapy may also produce euphoria (thus ameliorating less severe depressions) as well as reverse anorexia. 

The pure opioid antagonist drugs naloxone (Figure 31-1), naltrexone, and nalmefene are morphine derivatives with bulkier substituents at the Ni7 position. These agents have a relatively high affinity for opioid binding sites. They have lower affinity for the other receptors but can also reverse agonists at Jand a-sites. 

Interactions. Morphine (also pethidine and possibly other opioids) is potentiated by monoamine oxidase inhibitors. Any central nervous system depressant (including alcohol) will have additive effects. Patients recently exposed to neuromuscular blocking agents (unless this is adequately reversed, e.g. by neostigmine) are particularly at risk from the respiratory depressant effects of morphine. The effect of diuretic drugs may be reduced by release of antidiuretic hormone by morphine. Useful interactions include the potientating effect on pain relief of tricyclic antidepressants and of dexamfetamine. 

The anaesthetist ensures that the effects of neuromuscular blocking agents and opioid-induced respiratory depression have either worn off or have been adequately reversed by an antagonist the patient is not left alone until conscious, with protective reflexes restored, and a stable circulation. 

Basic and advanced life support measures should be initiated immediately. Activated charcoal may be utilized to adsorb illicit fentanyl derivatives following ingestion. Naloxone is the specific pharmacologic antagonist for fentanyl derivatives. Naloxone displaces these agents at the opioid receptor and reverses their clinical effects however, higher than customary doses may be needed to successfully overcome the opioid receptor. 

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