Safer Opioids can be Developed Without Respiratory Side Effects

By avoiding respiratory suppression side effect activating pathway, safer opioids can now be produced

Separating two common opioids pathways could help separate respiratory depression side effect associated with opioid drugs, found a new study published in Cell journal. Opioid pain relievers are extremely effective in relieving pain, but upon repeated use, can carry a high risk of addiction and ultimate overdose.

Opioid medications suppress pain by binding to specific receptors (proteins) in the brain; these same receptors also produce respiratory suppression. However, the way these receptors act to regulate pain and breathing may be fundamentally different.

Opioids Not Needed in Treating Post-delivery Pain in New Moms
Opioid prescription for women who have undergone vaginal delivery is not recommended after hospital discharge. Duration of pain reduces and functional recovery is faster.

‘The opioid drugs can be designed to turn on only the signaling pathways associated with pain relief and avoid those related to respiratory suppression, the common side effect with increased dose.’

Studies using mouse genetic models suggest that avoiding one particular signaling pathway led to more favorable responses to morphine (pain relief without respiration effects).

The investigators then explored if they could make drugs that would turn on the pathways associated with pain relief and avoid the pathways associated with respiratory suppression.

"We are pleased to have uncovered a potential new mechanism to create safer alternatives to opioid medications, ones that would be far less likely to cause the side effects that lead to overdose deaths associated with the misuse of opioids," said NIDA Director Nora D. Volkow, M.D.

Over-Prescription of Opioids After Rhinoplasty
Opioids are commonly prescribed after rhinoplasty. Characterizing opioid use after rhinoplasty could help identify ideal amounts to prescribe.

"We are excited that basic research on how opioid drugs work in the brain has led to this novel approach, and that we continue to make critical progress in this area."

How the pathways split following receptor activation is referred to as biased signaling. The study showed that as the degree of bias (divergence) increased, so too did the ability of an opioid to reduce pain in mice without affecting breathing.

Few Restrictions on Prescribing Opioids Through Medicare
An untapped opportunity for Medicare formularies to limit prescribing opioids. The risk of opioid overdoses rises when individuals are prescribed opiates at high dosages.

Similarly, compounds that favor the breathing pathway produced more respiratory side effects at lower doses. Ultimately, opioids with a larger divergence (bias factor) had a larger margin of safety, or therapeutic window, opening up an opportunity for medication intervention.

"In this study, we demonstrate that this divergence, which we call biased agonism, is not an 'all or none' phenomenon, but rather exists as a spectrum. As such, if a small degree of divergence between pathways in cell culture produces a minimal benefit in living organisms, there is potential to chemically improve the signaling bias and subsequently improve the therapeutic safety window," said Laura M. Bohn, Ph.D., principal investigator on the study from The Scripps Research Institute.

Patients Use Fewer Opioids Than Prescribed After Hernia Surgery
More than half the patients who took part in this study, relied completely on non-opioid medications to control postoperative pain, reveals a new study.

It is unclear how these divergent pathways affect other side effects of opioids, including addiction. However, this finding could represent a new direction in the pharmaceutical development of safer alternatives to current opioid pain relievers, which is part of the NIH initiative to address the opioid crisis.

Source-Eurekalert