Mucous membranes provide a non-invasive alternative route for medication delivery, allowing drugs to be absorbed directly and rapidly through tissues such as the nasal lining or oral cavity (Lam et al., 2020). Medication placed on a mucosal surface can diffuse through the thin, vascular tissue and enter the bloodstream quickly, bypassing the gastrointestinal tract and reducing first-pass metabolism in the liver (Gavhane & Yadav, 2012). For example, drugs absorbed under the tongue or cheek drain into the jugular vein and reach systemic circulation directly, largely avoiding liver metabolism (Lam et al., 2020). This means a well-formulated mucosal drug can take effect in minutes, which is particularly valuable in acute or perioperative settings where fast-acting medication is needed. Transmucosal delivery also spares patients the pain and anxiety of needles, an important benefit in surgery, anesthesia, and emergency care when treating children or needle-averse individuals (Lam et al., 2020).
Because of these advantages, mucous membranes have found important niche uses as a route for certain anesthesia and surgery-related medication. Transmucosal drug delivery is equally valuable for analgesia and pain management in surgical contexts. Opioid pain relievers, which are mainstays of perioperative analgesia, can be formulated for mucosal absorption to achieve fast and effective pain control (Naji & Ramsingh, 2023). Fentanyl, a potent opioid, can be given intranasally for acute pain, including postoperative pain, when quick relief is needed and starting an IV may be impractical (Naji & Ramsingh, 2023). Clinical trials and meta-analyses in emergency and perioperative care have found that intranasal fentanyl provides pain relief comparable to intravenous opioids, especially in pediatric patients (Borland et al., 2007). In children with acute injuries, intranasal fentanyl showed superior pain reduction within the first 15 to 20 minutes compared to standard analgesics, essentially matching IV morphine’s efficacy at early time points (Alsabri et al., 2024).
Despite these successes, delivering medication through the route of mucous membranes comes with challenges (Lou et al., 2023). The mucosal surface area is relatively small—for example, the area under the tongue or inside the nose is limited—and only a limited volume of medication can be applied at once (Kim & De Jesus, 2023). The presence of the mucus layer and variable conditions (such as nasal congestion, saliva flow, or rectal contents) can affect how much drug is absorbed and how quickly (Lam et al., 2020). Not all medications are suitable for this route; a drug must be potent in small doses and able to penetrate the mucosal barrier. Many large-molecule drugs or those requiring large volumes are poorly absorbed unless formulation strategies like mucoadhesive agents or permeation enhancers are used (Lam et al., 2020). Although absorption can be quick in rectal delivery due to the rectum’s rich blood supply, it can be inconsistent if dosing is not optimized, and patients may be uncomfortable with the route (Hua, 2019). Nonetheless, the rectal route is valuable in certain emergencies or pediatric scenarios. For example, rectal sedatives or analgesics have been used effectively when oral and nasal routes were not available, providing rapid systemic drug levels in crises (Hua, 2019). Overall, careful dosing and formulation are required to ensure safety and reliable absorption for transmucosal medications.
Mucous membranes represent an important route for delivering anesthetic and analgesic medication in a manner that is rapid, minimally invasive, and capable of reducing some systemic side effects (Harris & Robinson, 1992). They enable clinicians to achieve sedation or pain control without intravenous access, which is especially beneficial in children, needle-phobic patients, or situations where IV placement is delayed. Drugs administered via the nasal or oral mucosa can take effect very quickly and with a high bioavailability, approaching the effectiveness of injectable routes (Alsabri et al., 2024; Lam et al., 2020). As ongoing studies continue to refine formulations and address limitations, the role of mucous membrane drug delivery in anesthesia and surgery will continue to be leveraged to improve patient comfort and outcomes with scientifically grounded medication delivery methods.
References
Alsabri, M., Hafez, A. H., Singer, E., Elhady, M. M., Waqar, M., & Gill, P. (2024). Efficacy and safety of intranasal fentanyl in pediatric emergencies: A systematic review and meta-analysis. Pediatric Emergency Care, 40(10), 748–752. https://doi.org/10.1097/PEC.0000000000003187
Borland, M., Jacobs, I., King, B., & O’Brien, D. (2007). A randomized controlled trial comparing intranasal fentanyl to intravenous morphine for managing acute pain in children in the emergency department. Annals of Emergency Medicine, 49(3), 335–340. https://doi.org/10.1016/j.annemergmed.2006.06.016
Gavhane, Y. N., & Yadav, A. V. (2012). Loss of orally administered drugs in GI tract. Saudi Pharmaceutical Journal, 20(4), 331–344. https://doi.org/10.1016/j.jsps.2012.03.005
Harris, D., & Robinson, J. R. (1992). Drug delivery via the mucous membranes of the oral cavity. Journal of Pharmaceutical Sciences, 81(1), 1–10. https://doi.org/10.1002/jps.2600810102
Hua, S. (2019). Physiological and pharmaceutical considerations for rectal drug formulations. Frontiers in Pharmacology, 10, 1196. https://doi.org/10.3389/fphar.2019.01196
Kim, J., & De Jesus, O. (2023). Medication routes of administration. In StatPearls. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK568677/
Lam, J. K. W., Cheung, C. C. K., Chow, M. Y. T., Harrop, E., Lapwood, S., Barclay, S. I. G., & Wong, I. C. K. (2020). Transmucosal drug administration as an alternative route in palliative and end-of-life care during the COVID-19 pandemic. Advanced Drug Delivery Reviews, 160, 234–243. https://doi.org/10.1016/j.addr.2020.10.018
Lou, J., Duan, H., Qin, Q., Teng, Z., Gan, F., Zhou, X., & Zhou, X. (2023). Advances in oral drug delivery systems: Challenges and opportunities. Pharmaceutics, 15(2), 484. https://doi.org/10.3390/pharmaceutics15020484
Naji, A., & Ramsingh, D. (2023). Oral transmucosal fentanyl. In StatPearls. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK554511/