Pharmacological research : the official journal of the Italian Pharmacological Society
-
Randomized Controlled Trial
Morphine at "sub-analgesic" background infusion rate plus low-dose PCA bolus control pain better and is as safe as twice a bolus-only PCA regimen: a randomized, double blind study.
Morphine for postoperative pain control is commonly titrated via intravenous patient-controlled analgesia (IV-PCA). An IV morphine background infusion is rarely used. We investigated whether analgesia is effectively attained and morphine consumption is reduced if PCA titration is coadjuvated by a continuous infusion protocol. ⋯ Four BI and three B0 patients required treatment for postoperative nausea and vomiting. One BI patient had transient pruritus and one B0 69-year individual became disoriented 24h into treatment; either event subsided soon after stopping their respective regimen without the need for treatment. The main conclusions of the results are that very-low-dose background morphine infusion combined with small-dose PCA boluses may provide better pain relief, lower morphine consumption, and minimal complication rate as a 1.5mg PCA bolus-only protocol.
-
Comparative Study
3,5-Di-t-butyl catechol is a potent human ryanodine receptor 1 activator, not suitable for the diagnosis of malignant hyperthermia susceptibility.
3,5-Di-t-butyl catechol (DTCAT) releases Ca(2+) from rat skeletal muscle sarcoplasmic reticulum (SR) vesicles. Hence, it is a candidate for use as a substitute for halothane or caffeine in the in vitro contracture test for the diagnosis of susceptibility to malignant hyperthermia (MH). To characterize the effect of DTCAT at cell level, Ca(2+) release experiments were performed on cultured, human skeletal muscle myotubes using the fluorescent Ca(2+) indicator fura2-AM. ⋯ In MHN skeletal muscle bundles, DTCAT induced contractures with an EC(50) value of 160 ± 91 μM. However, the sensitivity of MHS or MHEH muscles to DTCAT was similar to that of MHN muscles. In conclusion, DTCAT is not suitable for the diagnosis of MH susceptibility due to its failure to discriminate between MHN and MHS muscles.
-
Fatty-acid amide hydrolase (FAAH) catalyzes the intracellular hydrolysis of the endocannabinoid anandamide and other bioactive lipid amides. In the present study, we conducted a comparative characterization of the effects of the newly identified brain-impermeant FAAH inhibitor, URB937 ([3-(3-carbamoylphenyl)-4-hydroxy-phenyl] N-cyclohexylcarbamate), in various rodent models of acute and persistent pain. When administered by the oral route in mice, URB937 was highly active (median effective dose, ED(50), to inhibit liver FAAH activity: 0.3mgkg(-1)) and had a bioavailability of 5.3%. ⋯ Furthermore, URB937 reduced the number and severity of gastric lesions produced by indomethacin, while exerting no ulcerogenic effect when administered alone. The results indicate that the peripheral FAAH inhibitor URB937 is more effective than globally active FAAH inhibitors at inhibiting inflammatory pain. Our findings further suggest that FAAH and cyclooxygenase inhibitors interact functionally in peripheral tissues, to either enhance or hinder each other's actions.
-
Untreated acute postoperative pain can transform into chronic pain that may have major negative effects on the individual's quality of life. It can also prolong recovery, rehabilitation and length of hospital stay, thus affecting societal economic burden. ⋯ The most important adjuncts currently employed are ketamine and gabapentinoids. They have been shown to help in reaching the desired effect when administered at drug-specific modes and at proven effective dosing throughout the perioperative period.
-
Despite our insufficient understanding of the exact molecular mechanisms of general anesthetics and sedatives, every year millions of children are treated with these drugs in a seemingly safe manner. However, increasing evidence particularly from animal studies has suggested the possibility for deleterious effects in pediatric patients. ⋯ Moreover, anesthetic drugs may also confer neurological protection during hypoxic and ischemic insults. The mechanisms and human applicability of anesthetic neurotoxicity and neuroprotection remain under intense investigation and this Perspectives article summarizes the current state of research.