The Clinical Applications of Intranasal Opioids

Abstract

Opioids are widely used in all fields of pain management and may be delivered by a number of routes of administration. The intranasal administration of opioid is a convenient route of transmucosal drug delivery that has received limited attention. Potential advantages compared with parenteral or oral administration include avoidance of painful injection, avoidance of risks associated with intravenous access, rapid onset and titration to effect, good bioavailability, and high levels of acceptability and familiarity to patients. These features also lend themselves to the benefits of patient-controlled delivery systems and commercially available devices are described.In this paper we briefly consider the relevant pharmacology of intranasal drug delivery; opioid drugs and formulations; and delivery devices used clinically for intranasal administration. We review the clinical applications of intranasal opioid analgesia. These have included use for in-hospital pain management in adult and paediatric populations, in the emergency department, perioperatively and in burns units. Out-of-hospital use has included palliative care and paramedic use during retrieval and transfer to hospital. Many small trials suggest that intranasal opioids play a useful role in pain management, but large clinical trials are needed to better define advantages, safety and acceptability.

Pharmacokinetic Characterisation and Comparison of Bioavailability of Intranasal Fentanyl, Transmucosal, and Intravenous Administration through a Three-Way Crossover Study in 24 Healthy Volunteers

“…Intranasal administration delivers the drug first to the central blood compartment before it can cross the blood-brain barrier. This is supported by the nasal mucosa, which exhibits comparatively high blood circulation, even higher than the issue of the liver or muscles, and, as such, circumvents first-pass metabolism [ 39 ]. Also, the nasal administration route partly delivers the molecule directly to the site of action of the CNS [ 40 ].…”

Pharmacokinetics and Bioavailability of Hydromorphone Nasal Spray

“…Most nasal devices deliver a spray volume of approximately 0.1 mL, although many studies of nasal opioids have used larger spray volumes. 1,3,4,7,25 The majority of patients experienced a bitter taste after the nasal spray, which may be explained by mucociliary clearance of hydromorphone from the nasal mucosa into the nasopharynx, or by 'runoff' of an excessive spray volume of 0.2 mL. 1,26 We believe this is the first study to evaluate the clinical effects of intranasal hydromorphone, although the study design was such that interpretation of findings should be cautious.…”

“…Other postoperative studies have reported good efficacy with the intranasal route of opioid administration, especially when patient-controlled delivery is provided. 3,25 Intranasal pethidine causes a bitter or burning taste when overflow into the oral cavity occurs; pethidine is no longer recommended for postoperative pain relief. Fentanyl is suitable for postoperative intranasal use, showing bioavailability of approximately two-thirds compared with intravenous administration and acceptable clinical properties and patient acceptability.…”

“…An interest in non-invasive fast-acting modes of opioid administration has included investigation of the intranasal route, which for some drugs shows bioavailability approaching intravenous administration and which can produce similar analgesic efficacy to intravenous administration. [1][2][3][4][5][6][7][8] The rapid and reliable onset of action, avoidance of injection and ease and familiarity of administration make the intranasal route appealing for the adult and paediatric populations. 3,9 Hydromorphone, a semisynthetic drug derived from morphine, is similar in its effects to morphine and much cheaper than opioids like fentanyl.…”

“…[1][2][3][4][5][6][7][8] The rapid and reliable onset of action, avoidance of injection and ease and familiarity of administration make the intranasal route appealing for the adult and paediatric populations. 3,9 Hydromorphone, a semisynthetic drug derived from morphine, is similar in its effects to morphine and much cheaper than opioids like fentanyl. 10 Hydromorphone is eight times more potent than morphine on an equivalent milligram basis when given orally but has low systemic bioavailability (10-20%) after oral administration due to extensive hepatic first-pass metabolism.…”