Diphenhydramine also acts as an intracellular sodium channel blocker, which is responsible for its actions as a local anesthetic. Diphenhydramine has also been shown to inhibit the reuptake of serotonin. It has been shown to be a potentiator of analgesia induced by morphine, but not by endogenous opioids, in rats. The drug has also been found to act as an inhibitor of histamine N-methyltransferase (HNMT). Pharmacokinetics
Oral bioavailability of diphenhydramine is in the range of 40% to 60%, and peak plasma concentration occurs about 2 to 3 hours after administration.The primary route of metabolism is two successive demethylations of the tertiary amine. The resulting primary amine is further oxidized to the carboxylic acid. Diphenhydramine is metabolized by the cytochrome P450 enzymes CYP2D6, CYP1A2, CYP2C9, and CYP2C19.The elimination half-life of diphenhydramine has not been fully elucidated, but appears to range between 2.4 and 9.3 hours in healthy adults. A 1985 review of antihistamine pharmacokinetics found that the elimination half-life of diphenhydramine ranged between 3.4 and 9.3 hours across five studies, with a median elimination half-life of 4.3 hours. A subsequent 1990 study found that the elimination half-life of diphenhydramine was 5.4 hours in children, 9.2 hours in young adults, and 13.5 hours in the elderly. A 1998 study found a half-life of 4.1 ± 0.3 hours in young men, 7.4 ± 3.0 hours in elderly men, 4.4 ± 0.3 hours in young women, and 4.9 ± 0.6 hours in elderly women. In a 2018 study in children and adolescents, the half-life of diphenhydramine was 8 to 9 hours.
Fracture blisters occur on skin overlying a fractured bone, and fractures complicated by the development of overlying blisters remain a clinical dilemma in orthopedics. : 43 Fracture blisters are tense vesicles or bullae that arise on markedly swollen skin directly overlying a fracture. Fracture blisters pop up in trauma patients occasionally. A fracture blister typically occurs near fractures where the skin has little subcutaneous tissue between it and bone. These include elbows, knees, ankles, and wrists. They tend to complicate fracture management because they interfere with splinting, casting, and incision planning for open reduction procedures. They can appear anytime within a few hours of injury to 2–3 weeks later. These blisters are thought to be caused by shearing forces applied at the time of injury. There are two types described, based on their color: clear fluid and hemorrhagic. The difference lies in the level of the shear. Clear fluid blisters have separated within the epidermis, and hemorrhagic blisters separate at the dermal-epidermal junction. The clinical difference is healing time; clear blisters take about 12 days and hemorrhagic blisters heal in about 16 days. The decision to pop the blisters in order to treat the fracture, or wait for them to heal first usually hinges on the preferences of the orthopaedic surgeon as there is a lack of data on what treatment is ideal. Waiting delays care an average of 7 days, and longer for tibial plateau and calcaneal fractures. Operating immediately anecdotally increases wound infection rates. Additional images


== References ==