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About Respiratory Depression
Opiate Painkillers and Respiratory Depression
Opioid analgesic drugs are commonly used to control pain on an acute, post-operative basis after major surgery or on a chronic basis in cases of cancer-related or other chronic pain. However, µ-opioid receptor agonists such as fentanyl, morphine and other opioid painkillers can cause significant depression of respiratory function, due to binding at µ-opioid receptors on the respiratory rhythm generating neurons in the brainstem. Respiratory depression (RD) can be fatal and is a constant concern in the post-operative or general care setting after surgery, or in other situations, e.g., chronic pain, where potent opioid analgesics are administered. Susceptibility to opioid-induced RD varies among individuals and predicting which patients are most sensitive is difficult, although older age, obesity, diseases affecting the respiratory or cardiovascular system and sleep apnea are some of the risk factors.
Patient controlled analgesia (PCA) is another major area in which opioid-induced RD may be problematic. Many post-surgical patients are allowed to control their pain level during the first 1-2 days after surgery by self administration of painkiller through PCA devices. While PCA is generally safe because doses are limited, it can be difficult to know whether the patient is more sensitive to opioid drugs than normal. In addition, mistakes in programming the PCA devices can be made by hospital staff. Very importantly, pain management goals may not be achieved due to the administration of lower doses than optimal due to concern about RD.
Reversal agents, such as naloxone, are available, but all known reversal agents for opioid-induced RD are opioid receptor antagonists and thus also reverse the analgesic activity, leaving the rescued patient in severe pain. More often, if a patient is found not breathing by hospital staff (‘code blue’), the patient may be placed on a respirator, which can lead to an increased hospital stay and risk of infection. In some cases, respiratory arrest can lead to cardiac arrest and death.
Anesthetics and Respiratory Depression
Other central nervous system depressants, such as anesthetics (e.g., propofol) and anxiolytics (anti-anxiety drugs), may remain in blood circulation after surgery and contribute to RD. Propofol and other anesthetic agents may also produce RD on their own if not properly controlled, and in those cases naloxone is ineffective as an RD reversal or prevention agent. Thus, there is a significant need for an agent that could prevent or reverse RD but which would not affect propofol anesthetic activity or anxiolytic activity of benzodiazapines or other anxiolytic agents.
RespireRx and its collaborators have determined that RespireRx’s Ampakines have these desired activities and may be used to prevent or rescue from opioid-induced RD without affecting opiate analgesia or prevent or rescue from propofol or anxiolytic induced RD.
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