Averting Opioid-induced Respiratory Depression without Affecting Analgesia

被引:89
作者
Dahan, Albert [1 ]
van der Schrier, Rutger [1 ]
Smith, Terry [1 ]
Aarts, Leon [1 ]
van Velzen, Monique [1 ]
Niesters, Marieke [1 ]
机构
[1] Leiden Univ, Dept Anesthesiol, Med Ctr, H5-22,Albinusdreef 2, NL-2333 ZA Leiden, Netherlands
关键词
THYROTROPIN-RELEASING-HORMONE; INDUCED VENTILATORY DEPRESSION; CAROTID-BODY RESECTION; CHANNEL BLOCKER GAL021; EXCITATORY AMINO-ACIDS; RECEPTOR AGONIST; HEALTHY-VOLUNTEERS; AMPA RECEPTORS; CARDIORESPIRATORY DEPRESSION; SELECTIVE; 5-HT1A-R-AGONIST;
D O I
10.1097/ALN.0000000000002184
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
The ventilatory control system is highly vulnerable to exogenous administered opioid analgesics. Particularly respiratory depression is a potentially lethal complication that may occur when opioids are overdosed or consumed in combination with other depressants such as sleep medication or alcohol. Fatalities occur in acute and chronic pain patients on opioid therapy and individuals that abuse prescription or illicit opioids for their hedonistic pleasure. One important strategy to mitigate opioid-induced respiratory depression is cotreatment with nonopioid respiratory stimulants. Effective stimulants prevent respiratory depression without affecting the analgesic opioid response. Several pharmaceutical classes of nonopioid respiratory stimulants are currently under investigation. The majority acts at sites within the brainstem respiratory network including drugs that act at alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (ampakines), 5-hydroxytryptamine receptor agonists, phospodiesterase-4 inhibitors, D-1-dopamine receptor agonists, the endogenous peptide glycyl-glutamine, and thyrotropin-releasing hormone. Others act peripherally at potassium channels expressed on oxygen-sensing cells of the carotid bodies, such as doxapram and GAL021 (Galleon Pharmaceuticals Corp., USA). In this review we critically appraise the efficacy of these agents. We conclude that none of the experimental drugs are adequate for therapeutic use in opioid-induced respiratory depression and all need further study of efficacy and toxicity. All discussed drugs, however, do highlight potential mechanisms of action and possible templates for further study and development.
引用
收藏
页码:1027 / 1037
页数:11
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