piperidines and Ecchymosis

The development of Bruton's tyrosine kinase (BTK) inhibitors represents a major breakthrough in the treatment of chronic lymphocytic leukemia and other B cell malignancies. The first-generation inhibitor ibrutinib works by covalent irreversible binding to BTK, a non-receptor tyrosine kinase of the TEC (transient erythroblastopenia of childhood) family that plays a critical role in the B-cell receptor signaling pathway. It also induces an 'off-target' inhibition of a range of other kinases including (but not limited to) epidermal growth factor receptor (EGFR), SRC, and other kinases of the TEC family (interleukin-2-inducible T-cell kinase [ITK], Tec, BMX). Dermatological toxicities are among the most common toxicities of ibrutinib, but remain of mild to moderate intensity in most cases and are readily manageable. Their incidence is highest during the first year of treatment and declines over time. In addition, it has been postulated that ibrutinib-related dermatologic adverse events are mediated by the direct binding to both BTK and other 'off-target' kinases. Bruising, ecchymoses, and petechiae represent the most characteristic dermatologic adverse events. Nail and hair changes are also common, as skin infections (opportunistic infections including herpes simplex and herpes zoster virus reactivations, and Staphylococcus aureus superinfection), folliculitis, and other types of rashes. Panniculitis, aphthous-like ulcerations with stomatitis, neutrophilic dermatosis, peripheral edema, and skin cracking can also occur. Next-generation BTK inhibitors, acalabrutinib and zanubrutinib, have been designed to optimize BTK inhibition and minimize off-target inhibition of alternative kinases (Tec, ITK, EGFR, SRC-family kinases). These drugs have been recently FDA-approved for relapsed or refractory mantle cell lymphoma. Although the overall incidence of their toxicities is expected to be more limited, acalubrutinib and zanubrutinib are associated with a range of dermatologic toxic effects that appear to be similar to those previously described with ibrutinib, including bruising and ecchymoses, panniculitis, human herpesvirus infections, cellulitis, and skin rash. In particular, both drugs induce skin bleeding events in more than 30% of patients treated. However, the available dermatological data are still rather limited and will have to be consolidated prospectively. This review article analyses the wide spectrum of dermatological toxicities that can be encountered w

Topics: Adenine; Administration, Cutaneous; Agammaglobulinaemia Tyrosine Kinase; Benzamides; Biopsy; Drug Eruptions; Ecchymosis; Emollients; Humans; Incidence; Leukemia, Lymphocytic, Chronic, B-Cell; Necrosis; Patient Education as Topic; Piperidines; Protein Kinase Inhibitors; Pyrazines; Pyrazoles; Pyrimidines; Receptors, Antigen, B-Cell; Severity of Illness Index; Signal Transduction; Skin; Skin Care

This randomized, double-blind study was designed to assess the effect of perioperative remifentanil with controlled hypotension on intraoperative bleeding, postoperative edema, and ecchymosis.. Fifty-two patients undergoing rhinoplasty were divided into 2 groups. The remifentanil group received 1 µg · kg(-1) intravenously as a bolus before induction of anesthesia, 0.5 to 1 µg · kg(-1) · h(-1) by continuous intravenous infusion during the operation. After anesthesia induction with propofol (2-3 mg · kg(-1)) and fentanyl (1-15 µg · kg(-1)), muscle relaxation was achieved with rocuronium (0.45-0.90 mg · kg(-1)). Mean arterial pressure was maintained at 50 to 60 mm Hg in controlled hypotensive anesthesia achieved using remifentanil infusion. Perioperative hemodynamics and bleeding; early postoperative pain and agitation scale; postoperative first, third, and seventh day edema; and ecchymosis were evaluated. Edema and ecchymosis were evaluated using graded scale from 0 to 4.. Remifentanil reduced mean arterial pressure during the entire operative period and the first 30 minutes postoperatively (P < 0.05 for these comparisons). Intraoperative bleeding also decreased (P < 0.001). There was a significant decrease in edema in both upper and lower eyelid edema on the first and third days in the remifentanil group, although this difference was not detected on the seventh day (P(1upper) = 0.000, P(1lower) = 0.000, P(3upper) = 0.008, and P(3lower) = 0.002). Ecchymosis decreased significantly in both upper and lower eyelids on the first, third, and seventh days in the remifentanil group (P(1upper) = 0.000, P(3upper) = 0.000, P(3upper) = 0.002, P(3lower) = 0.002, P(7upper) = 0.049, and P(7lower) = 0.038). There were no differences in postoperative pain and agitation between 2 groups.. Remifentanil with controlled hypotension may reduce edema and ecchymosis of the upper and lower eyelids, by reducing mean arterial pressure and amount of bleeding in rhinoplasty.

Topics: Adult; Anesthetics, Intravenous; Antihypertensive Agents; Blood Loss, Surgical; Blood Pressure; Double-Blind Method; Ecchymosis; Edema; Eyelid Diseases; Female; Humans; Hypotension, Controlled; Male; Piperidines; Postoperative Complications; Remifentanil; Rhinoplasty; Young Adult

The aim of this retrospective study was to evaluate the efficacy of dexamethasone with controlled hypotension on intraoperative bleeding and postoperative morbidity in rhinoplasty.. Sixty rhinoplasty patients required hump resection and lateral osteotomy were included in this study. The patients were randomized into four groups. In group I (n=15), a single dose of 10mg/kg dexamethasone was intravenously administered at the beginning of the operation. In group II (n=15), the patients were given 2 doses of 10mg/kg intravenously dexamethasone at the beginning of the operation, and 24 hours after the operation. In group III (n=15), 3 doses of 10mg/kg intravenously dexamethasone were given at the beginning of the operation, before osteotomy and 24 hours after the operation. Group IV (n=15) was assigned as control group and the patients were neither administered dexamethasone nor applied hypotension. All cases in groups I, II and III were operated under controlled hypotension. Systolic arterial pressure was aimed to keep between 65 and 75 mmHg for controlled hypotensive anaesthesia. Controlled hypotension was achieved by a remifentanil infusion of 0.1-0.5 microg/kg/min, following a bolus of 1 microg/kg. Degree of eyelid oedema and periorbital soft-tissue ecchymosis was evaluated separately using a scale of 0-4. Intraoperative blood loss was recorded for each patient. Patients were evaluated at 24 hours and postoperative days 2, 5, 7, and 10.. In groups I, II and III, intraoperative bleeding was more decreased and the operation time was significantly shorter compared with control group (P<0.001). Eyelid oedema and periorbital ecchymosis were significantly decreased in groups I, II and III at the following postoperative 7 and 10 days (P<0.001). There was statistically significant difference between group III and other groups at the postoperative 5 and 7 days in lower eyelid oedema (P<0.001), upper and lower eyelid ecchymosis (P<0.001 and 0.004, respectively). There were no postoperative complications with using steroid in any of the groups.. Three doses of dexamethasone with controlled hypotension considerably reduced postoperative morbidities of rhinoplasty with osteotomy as well as intraoperative bleeding. Thus, in group III receiving 3 doses of steroid, when compared to other groups, more uneventful postoperative period were provided for surgeon and the patients.

Topics: Adult; Anti-Inflammatory Agents; Blood Loss, Surgical; Blood Pressure; Dexamethasone; Ecchymosis; Edema; Eyelid Diseases; Female; Follow-Up Studies; Glucocorticoids; Humans; Hypnotics and Sedatives; Hypotension, Controlled; Male; Nasal Cartilages; Nasal Septum; Operative Time; Osteotomy; Patient Satisfaction; Piperidines; Postoperative Complications; Premedication; Remifentanil; Retrospective Studies; Rhinoplasty; Treatment Outcome; Young Adult