Nephrotoxicity of cisplatin (CP) involves renal oxidative stress and inflammation, and sesamin (a major liganin in many plants) has strong antioxidant and antiinflammatory actions. Therefore, we ...investigated here the possible mitigative action of sesamin on CP nephrotoxicity in rats. Sesamin was given orally (5 mg/kg/day, 10 days), and on the 7th day, some of the treated rats were injected intraperitoneally with either saline or CP (5 mg/kg). On the 11th day, rats were sacrificed, and blood and urine samples and kidneys were collected for biochemical estimation of several traditional and novel indices of renal damage in plasma and urine, several oxidative and nitrosative indices in kidneys, and assessment of histopathological renal damage. CP significantly and adversely altered all the physiological, biochemical and histopathological indices of renal function measured. Kidneys of CP-treated rats had a moderate degree of necrosis. This was markedly lessened when CP was given simultaneously with sesamin. Sesamin treatment did not significantly alter the renal CP concentration. The results suggested that sesamin had ameliorated CP nephrotoxicity in rats by reversing the CP-induced oxidative stress and inflammation. Pending further pharmacological and toxicological studies sesamin may be considered a potentially useful nephroprotective agent.
Cisplatin (
cis-diamminedichloroplatinum (II)) is an effective agent against various solid tumours. Despite its effectiveness, the dose of cisplatin that can be administered is limited by its ...nephrotoxicity. Hundreds of platinum compounds (e.g. carboplatin, oxaliplatin, nedaplatin and the liposomal form lipoplatin) have been tested over the last two decades in order to improve the effectiveness and to lessen the toxicity of cisplatin. Several agents have been tested to see whether they could ameliorate or augment the nephrotoxicity of platinum drugs. This review summarizes these studies and the possible mechanisms of actions of these agents. The agents that have been shown to ameliorate experimental cisplatin nephrotoxicity include antioxidants (e.g. melatonin, vitamin E, selenium, and many others), modulators of nitric oxide (e.g. zinc histidine complex), agents interfering with metabolic pathways of cisplatin (e.g. procaine HCL), diuretics (e.g. furosemide and mannitol), and cytoprotective and antiapoptotic agents (e.g. amifostine and erythropoietin). Only few of these agents have been tested in humans. Those agents that have been shown to augment cisplatin nephrotoxicity include nitric oxide synthase inhibitors, spironolactone, gemcitabine and others. Combining these agents with cisplatin should be avoided.
: The aminoglycoside antibiotic gentamicin (GM) is still widely used against infections by Gram‐positive and Gram‐negative aerobic bacteria. Its therapeutic efficacy, however, is limited by renal ...impairment that occurs in up to 30% of treated patients. The drug may accumulate in epithelial tubular cells causing a range of effects starting with loss of the brush border in epithelial cells and ending in overt tubular necrosis, activation of apoptosis and massive proteolysis. GM also causes cell death by generation of free radicals, phospholipidosis, extracellular calcium‐sensing receptor stimulation and energetic catastrophe, reduced renal blood flow and inflammation. Many drugs have been shown to either ameliorate or potentiate GM nephrotoxicity. This article aims at updating the literature that has been published in the past decade on the effects of agents that either ameliorate or augment the nephrotoxicity of this aminoglycoside. Notable among the new ameliorating procedures are gene therapy, such as intravenous cell therapy with serum amyloid A protein‐programmed cells, and the use of some novel antioxidant agents and oils of natural origin. These include, for example, green tea, garlic saffron, grape seed extracts as well as sesame and oleanolic oils. Agents that may augment GM nephrotoxicity include indomethacin, cyclosporin, uric acid and the Ca++‐channel blocker verapamil. Most of the nephroprotective agents mentioned here have not been tested in large controlled clinical trials. Because of their relative safety and effectiveness, antioxidant agents seem to be good candidates for testing in humans.
Opioid prescribing patterns among postpartum women Badreldin, Nevert; Grobman, William A.; Chang, Katherine T. ...
American journal of obstetrics and gynecology,
07/2018, Letnik:
219, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Women commonly receive opioid prescriptions following hospitalization. The rise of the opioid epidemic in the United States underscores the importance of a better understanding of prescribing ...patterns. Although delivery is the most frequent reason for hospitalization in the United States, there is inadequate knowledge regarding opioid prescribing at postpartum hospital discharge.
We sought to describe opioid prescribing patterns at the time of discharge following delivery in a large, diverse cohort, and to describe the relationship of these patterns with objective and subjective measures of pain prior to discharge.
This is a retrospective cohort study of all deliveries at a single, high-volume tertiary care center over a 1-year period. Women were excluded from analysis if they had evidence of recent opioid use, or their labor, delivery, or postpartum course was notable for rare, nonroutine events anticipated to increase pain. Medical records were queried for demographic and clinical data, including whether an opioid prescription was provided at discharge, and if so, details of that prescription. The primary outcome was amount of opioid morphine milligram equivalents prescribed at discharge, described separately for women after vaginal and cesarean deliveries. Among women who received a prescription, we additionally assessed associations between prescription quantity and subjective (patient-reported pain score) and objective (inpatient opioid requirement during the final 24 hours of hospitalization) assessments of pain. Descriptive and bivariable analyses were performed.
Of the total 12,611 women, 12,326 were eligible for inclusion. Of 9038 women postvaginal delivery and 3288 women postcesarean delivery, 30.4% and 86.7% received an opioid prescription at discharge, respectively. Of women receiving discharge opioid prescriptions, median morphine milligram equivalents received was 200 (interquartile range: 120–300) following vaginal and 300 (interquartile range: 200–300) following cesarean delivery. Nearly half (45.7%) of women postvaginal delivery and 18.5% of women postcesarean delivery who received an opioid prescription used 0 morphine milligram equivalent during the final hospital day. Similarly, 26.5% and 18.5% of women after vaginal and cesarean delivery, respectively, reported a pain score of 0 of 10 prior to discharge. Regardless of delivery mode, the amount of opioids prescribed did not differ between those who reported a pain score of 0 of 10 and those who reported a pain score of >0 of 10 immediately prior to discharge. Similarly, for women who underwent cesarean delivery, the morphine milligram equivalents prescribed did not differ between those who used 0 morphine milligram equivalents and those who used >0 in the 24 hours prior to hospital discharge.
Postpartum women are commonly prescribed opioids at the time of postpartum hospital discharge. There is a wide range of morphine milligram equivalents prescribed at hospital discharge following delivery, highlighting a lack of standardization. Furthermore, regardless of objective and subjective measures of pain prior to discharge, women received similar amounts of prescription morphine milligram equivalents following either vaginal or cesarean deliveries.
Nephrotoxicity of the anticancer drug cisplatin (CP) involves the generation of reactive oxygen species in renal cortex, and emodin (a rhubarb anthraquinone) has strong antioxidant and anticancer ...actions. Therefore, we tested here the possible ameliorative effect of emodin on CP nephrotoxicity in rats. Emodin was given orally (10 mg/kg/day for nine consecutive days), and on day 4, some of the treated rats were also injected intraperitoneally with either saline or CP (6 mg/kg). Five days after CP treatment, rats were killed, and blood and urine samples, and kidneys were collected for the assessment of histopathological renal damage and apoptosis, and for biochemical estimation of creatinine and urea concentrations in plasma and urine, several cytosolic antioxidant enzyme activities in kidneys, and urinalyses. CP significantly increased the concentrations of urea and creatinine, and decreased creatinine clearance. It also significantly reduced cortical glutathione concentration and the activity of superoxide dismutase. CP treatment significantly increased urine volume and N‐acetyl‐β‐D‐glucosaminidase activity and significantly decreased osmolarity and protein concentrations. Emodin treatment markedly and significantly mitigated all these effects. Sections from saline‐ and emodin‐treated rats showed apparently normal proximal tubules. However, kidneys of CP‐treated rats had a moderate degree of necrosis. This was markedly lessened when CP was given simultaneously with emodin. The concentration of CP in the cortical tissues was not significantly altered by emodin treatment. The results suggested that emodin had ameliorated CP nephrotoxicity in rats. Pending further pharmacological and toxicological studies emodin may be considered a potentially useful nephroprotective agent.
Inpatient opioid use after vaginal delivery Badreldin, Nevert; Grobman, William A.; Yee, Lynn M.
American journal of obstetrics and gynecology,
12/2018, Letnik:
219, Številka:
6
Journal Article
Recenzirano
Odprti dostop
More than half of patients hospitalized annually receive an opioid during their inpatient hospitalization, which may serve as a first opioid exposure. Although recent research addresses outpatient ...opioid prescribing following delivery, little is known regarding the extent to which opioids are used during the postpartum hospitalization following vaginal delivery.
Our objectives were as follows: (1) to describe the use of opioids during the last 24 hours of postpartum hospitalization in women following vaginal delivery and (2) to identify patient and provider characteristics associated with the use of opioids during this time period.
This is a retrospective case-control study of women who underwent vaginal delivery at a single tertiary care center from Dec. 1, 2015, to Nov. 30, 2016. Inpatient, pharmacy, and administrative records were queried for clinical and inpatient prescriber data. Opioid use during the last 24 hours of the postpartum hospitalization was determined. Significant factors on bivariable analysis were assessed in multivariable hierarchical logistic regression with random effects to identify patient and provider factors associated with any opioid use. A subgroup analysis of women who underwent an uncomplicated vaginal delivery, defined as lack of intrapartum, postpartum, or neonatal complications, was performed.
In this cohort of 9038 women after a vaginal delivery, almost a quarter (n = 2242, 24.8%) utilized opioids during the last 24 hours of the postpartum hospitalization. In a multivariable analysis, several patient characteristics were associated with increased odds of opioid use during the last 24 hours of admission, including higher body mass index, history of smoking and substance abuse, use of regional analgesia, vaginal birth after cesarean delivery, major laceration, postpartum hemorrhage, and infectious complication. Even after adjusting for these characteristics, greater use of acetaminophen (adjusted odds ratio, 0.81, 95% confidence interval, 0.77–0.85) and analgesia orders written by an advanced practitioner (adjusted odds ratio, 0.46, 95% confidence interval, 0.29–0.73) remained associated with decreased odds of using an opioid. The same 2 factors remained associated with less opioid use (acetaminophen doses adjusted odds ratio, 0.86, 95% confidence interval, 0.81–0.92 and analgesia orders written by an advanced practitioner adjusted odds ratio, 0.52, 95% confidence interval, 0.30–0.89) when only women who had an uncomplicated vaginal delivery were analyzed.
In a large cohort, nearly one-quarter of women use opioid analgesia during the last 24 hours of inpatient hospitalization following vaginal delivery. Although patient factors account for some of the variation in inpatient opioid use, both use of acetaminophen and having had postpartum orders written by an advanced practitioner were independently associated with lower odds of inpatient opioid use.
: Sildenafil, the first drug for erectile dysfunction, has cardiopulmonary protective actions. A recent study has reported that sildenafil given intraperitoneally (i.p.) attenuated cisplatin ...(CP)‐induced nephrotoxicity. Here, we evaluated whether sildenafil, given by two different routes and at two different doses, can attenuate CP‐induced nephrotoxicity and would also affect renal haemodynamics in CP‐treated rats. Six groups of rats were treated with saline (controls), CP 5 mg/kg, intraperitoneally (i.p.) once, sildenafil (0.4 mg/kg/day, i.p. for 5 days), sildenafil (0.4 mg/kg/day i.p. for 5 days) plus CP (5 mg/kg, i.p., once), sildenafil 10 mg/kg/day, subcutaneous (s.c.) for 5 days or sildenafil (10 mg/kg/day, s.c. for 5 days) plus CP (5 mg/kg, i.p. once). Five days after the end of the treatments, urine was collected from all rats, which were then anaesthetized for blood pressure and renal blood flow monitoring. This was followed by intravenous (i.v.) injection of norepinephrine for the measurement of renal vasoconstrictor responses. Thereafter, blood and kidneys were collected for measurement of several biochemical, functional and structural parameters. CP reduced body‐weight and renal blood flow but did not affect norepinephrine‐induced renal vasoconstriction. It increased the plasma concentrations of urea and creatinine, and reduced creatinine clearance. CP caused extensive renal tubular necrosis, increased urine volume and N‐acetyl‐β‐d‐glucosaminidase activity. When sildenafil (0.4 mg/kg/day, i.p. for 5 days) was combined with cisplatin, there was a dramatic improvement in renal histopathology, reduction in N‐acetyl‐β‐d‐glucosaminidase and increase in renal blood flow. However, sildenafil (10 mg/kg/day, s.c. for 5 days) did not affect CP nephrotoxicity, suggesting the importance of dose and route selection of sildenafil as a nephroprotectant.
The 3 phase 3 CHAMPION (Cangrelor vs Standard Therapy to Achieve Optimal Management of Platelet Inhibition) trials collectively demonstrated the safety of transitioning from cangrelor, a potent, ...parenteral rapidly-acting P2Y12 inhibitor, to clopidogrel in patients who underwent percutaneous coronary intervention (PCI). However, variation in timing of therapy, site-specific binding, and drug half-lives may theoretically complicate switching to other oral P2Y12 inhibitors. Since regulatory approval, limited data are available regarding the “real-world” safety and tolerability of transitioning to these more potent oral P2Y12 antagonists. From November 2015 to January 2017, we evaluated the clinical profiles and efficacy and safety outcomes in cangrelor-treated patients who underwent PCI transitioned to clopidogrel (n = 42) or ticagrelor (n = 82) at a large, tertiary care center. Most patients receiving cangrelor underwent PCI with a drug-eluting stent for acute coronary syndrome via a radial approach in the background of unfractionated heparin. Stent thrombosis within 48 hours was rare and occurred in 1 patient treated with ticagrelor. Global Use of Strategies to Open Occluded Coronary Arteries–defined bleeding occurred in 20% of patients switched to ticagrelor and 29% of patients switched to clopidogrel, but none were severe or life-threatening. In conclusion, rates of stent thrombosis and severe/life-threatening bleeding were low and comparable with those identified in the CHAMPION program, despite use of more potent oral P2Y12 inhibition.
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