Intranasal Leptin to Treat Opioid-Induced Respiratory Depression (OIRD) in Obese Patients

George Washington University Background
Respiratory depression is the leading cause of morbidity and mortality associated with opioids. Patients with obesity experience pain and need opioids more frequently than normal-weight individuals. Chronic consumption of opioids is associated with addiction, physical dependence, and tolerance. Tolerance leads to the requirement of higher doses of opioids for hospital procedures. Opioids remain an indispensable treatment for severe pain despite increased risk for obese patients with tolerance. Of particular concern is opioid-induced respiratory depression (OIRD), especially during sleep, due to comorbid obstructive sleep apnea common in obese patients. Naloxone is the only drug available that can reverse the adverse effects of opioids and prevent death. However, naloxone has limited use because it reverses analgesia and induces withdrawal. A preventive treatment for sleep-related OIRD that does not affect analgesia or induce withdrawal is critical in patients with obesity. 
Technology Overview
GW and JHU researchers found that intranasal leptin can reverse morphine-induced apneas, hypoventilation, and upper-airway obstruction while enhancing analgesic effects in mice with obesity. Studies demonstrated that mice with diet-induced obesity treated with morphine at 10 mg/kg subcutaneously and with leptin intranasally had attenuated obstructive sleep apnea and hypoventilation during sleep. Intranasal leptin did not interfere with analgesic properties of morphine and no withdrawal symptoms were observed. 

Benefits

Ease of administration
No interference with analgesic properties
No withdrawal symptoms

Applications

Treat opioid-induced respiratory depression effects in obese patients
Safer use of high-dose opioids in obese opioid tolerant patients

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