1. 2021;24;E37-E44Morphine Versus Loperamide with Intrasite Gel in the Treatment of Painful Dermal Ulcers: A Randomized, Crossover Study
   Randomized Crossover Study
   Vishwajeet V. Korikanthimath, MBBS, Mahesh D. Kurugodiyavar, MD, Safiya I. Shaikh, MD, B. Jyothi, MD, and Milon V. Mitragotri, MD.

BACKGROUND: Topical morphine along with intrasite gel has been proven to be a simple and effective method to relieve pain. However, morphine is still not freely available in developing countries due to drug restrictions and stringent laws governing it. Loperamide has been reported to relieve pain caused by stomatitis effectively when given topically. Loperamide, being an mu receptor agonist with no systemic absorption, can serve a dual purpose here. Also loperamide being freely available as an over-the-counter drug can be a surrogate drug for topical application.

OBJECTIVES: The primary aim was to compare the efficacy of loperamide and morphine in treating pain when applied topically along with intrasite gel.

STUDY DESIGN: Adult patients with healthy wounds with pain on Numeric Rating Scale (NRS-11) greater than 5 with no systemic comorbid illness were divided randomly into 2 groups – group morphine or group loperamide – for 24 hours followed by a 1-day washout and crossover in the other group for 24 hours. Pain was assessed once every day.

SETTING: Medical college and hospital.

METHODS: The parameters assessed included: (1) characteristics of the ulcer; (2) pain was assessed by NRS-11 at 12-hour intervals for a period of 72 hours; and (3) patient satisfaction. Statistical analysis used repeated measures analysis of variance to measure change in mean NRS-11 within each group. Analysis of covariance was used to compare the mean change in NRS-11 in the 2 groups.

RESULTS: Morphine and loperamide were equivocal in pain relief after 12 and 24 hours (P = 0.400 and P = 0.753); however, the patient satisfaction scores were better in the morphine group.

LIMITATIONS: The earlier studies performed used injectable forms of morphine, for the sake of comparison, we used powdered morphine and powdered Loperamide diluted with saline. Confounding variables include ulcer size and aetiology, which can be a source of bias. The ulcer size was not standardized due to the paucity of sample to study. Equianalgesic doses of loperamide and morphine could not be found even after an extensive literature search. The loperamide dose used in our case was equal to the dose used orally since the same dose appears effective across a range of oral opioid analgesics. The morphine dose was standardized as 10 mg based on a mixture previously used to treat pain due to epidermolysis bullosa.

CONCLUSIONS: Topical loperamide can be an efficacious and novel intervention to treat painful ulcers while avoiding systemic effects.

KEY WORDS: Loperamide, morphine, painful ulcer