Antiemetic Effect Research Articles

Diabetic Gastroparesis and Glycaemic Control.

Gastroparesis is an important complication of diabetes that may have a major impact on the quality of life as a result of upper gastrointestinal symptoms and impaired glycaemic control. Current management strategies include optimising blood glucose control, dietary modifications and supportive nutrition. Pharmacologic approaches with drugs that have prokinetic and/or antiemetic effects are also used widely; however, current available treatments have major limitations. There is increasing recognition that the rate of gastric emptying (GE) is a key determinant of the glycaemic response to a meal. There is ongoing uncertainty regarding the impact of longstanding hyperglycaemia on GE, which requires clarification. New diagnostic techniques have been developed to better characterise the mechanisms underlying gastroparesis in individual patients, and these have the potential to lead to more personalised therapy. Management of gastroparesis is complex and suboptimal; novel approaches are desirable. This review summarises recent advances in the understanding of diabetic gastroparesis, with an emphasis on the current therapies that influence GE, and the bidirectional relationship between glycaemic control and GE.

Honokiol Is a Potential Therapeutic Agent and Has a Synergistic Effect With 5-FU in Human Urothelial Cell Carcinoma Cells.

Honokiol is a biphenolic component of the bark of Magnolia, and has been shown to exert several activities, including anti-depressant, anti-emetic, anti-oxidative, anti-thrombotic, anti-angiogenesis, anti-anxiolytic, anti-inflammatory and anti-tumor effects. The anti-tumor activities of honokiol and its synergistic effect with 5-fluorouracil (5-FU) in human urothelial cell carcinoma (UCC) cells were investigated. Honokiol significantly suppressed the proliferation of UCC cells in a dose- and time-dependent manner. Moreover, honokiol inhibited the tumorigenesis of UCC cells in vitro. In addition, honokiol induced cell cycle arrest at G0/G1 phase and caused apoptosis of UCC cells through the intrinsic pathway. Importantly, we demonstrated that honokiol potentiated the cytotoxic effect of 5-FU, and displayed a synergistic effect with 5-FU in UCC cells. Honokiol causes growth inhibition, tumorigenesis suppression, cell cycle arrest, apoptosis, and importantly has a synergistic effect with 5-FU in human UCC cells. Therefore, this agent displays a therapeutic potential for treating human UCC.

Full-length transcriptome analysis of shade-induced promotion of tuber production in Pinellia ternata

BackgroundPinellia ternata is native to China and has been used as a traditional herb due to its antiemetic, antitussive, analgesic, and anxiolytic effects. When exposed to strong light intensity and high temperature during the reproductive growth process, P. ternata withers in a phenomenon known as “sprout tumble”, which largely limits tuber production. Shade was previously found to delay sprout tumble formation (STF); however, no information exists regarding this process at the molecular level. Hence, we determined the genes involved in tuber development and STF in P. ternata.ResultsCompared to that with natural sun-light (control), shade significantly induced chlorophyll accumulation, increased chlorophyll fluorescence parameters including initial fluorescence, maximal fluorescence, and qP, and dramatically repressed chlorophyll a:b and NPQ. Catalase (CAT) activity was largely induced by shade, and tuber products were largely increased in this environment. Transcriptome profiles of P. ternata grown in natural sun-light and shaded environments were analyzed by a combination of next generation sequencing (NGS) and third generation single-molecule real-time (SMRT) sequencing. Corrections of SMRT long reads based on NGS short reads yielded 136,163 non-redundant transcripts, with an average N50 length of 2578 bp. In total, 6738 deferentially-expressed genes (DEGs) were obtained from the comparisons, specifically D5S vs D5CK, D20S vs D20CK, D20S vs D5S, and D20CK vs D5CK, of which, 6384 DEGs (94.8%) were generated from the D20S vs D20CK comparison. Gene annotation and functional analyses revealed that these genes were related to auxin signal transduction, polysaccharide and sugar metabolism, phenylpropanoid biosynthesis, and photosynthesis. Moreover, the expression of genes enriched in photosynthesis appeared to be significantly altered by shade. The expression patterns of 16 candidate genes were consistent with changes in their transcript abundance as identified by RNA-Seq, and these might contribute to STF and tuber production.ConclusionThe full-length transcripts identified in this study have provided a more accurate depiction of P. ternata gene transcription. Further, we identified potential genes involved in STF and tuber growth. Such data could serve as a genetic resource and a foundation for further research on this important traditional herb.

Marijuana Use in Patients with Symptoms of Gastroparesis: Prevalence, Patient Characteristics, and Perceived Benefit.

Marijuana may be used by some patients with gastroparesis (Gp) for its potential antiemetic, orexigenic, and pain-relieving effects. The aim of this study was to describe the use of marijuana by patients for symptoms of Gp, assessing prevalence of use, patient characteristics, and patients' perceived benefit on their symptoms of Gp. Patients with symptoms of Gp underwent history and physical examination, gastric emptying scintigraphy, and questionnaires assessing symptoms. Patients were asked about the current use of medications and alternative medications including marijuana. Fifty-nine of 506 (11.7%) patients with symptoms of Gp reported current marijuana use, being similar among patients with delayed and normal gastric emptying and similar in idiopathic and diabetic patients. Patients using marijuana were younger, more often current tobacco smokers, less likely to be a college graduate, married or have income > $50,000. Patients using marijuana had higher nausea/vomiting subscore (2.7 vs 2.1; p = 0.002), higher upper abdominal pain subscore (3.5 vs 2.9; p = 0.003), more likely to be using promethazine (37 vs 25%; p = 0.05) and dronabinol (17 vs 3%; p < 0.0001). Of patients using marijuana, 51% had been using it for more than 2years, 47% were using this once or more per day, and 81% of marijuana users rated their benefit from marijuana as better or much better. A subset of patients (12%) with symptoms of Gp use marijuana. Patients with severe nausea and abdominal pain were more likely to use marijuana and perceive it to be beneficial for their symptoms. ClinicalTrials.gov Identifier: NCT01696747.

Granisetron plus aprepitant versus granisetron in preventing nausea and vomiting during CHOP or R-CHOP regimen in malignant lymphoma: a retrospective study

BackgroundCyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) regimen includes a high dose of prednisolone (100 mg/body), which exhibits an anticancer and antiemetic effect. However, its optimal use for antiemetic therapy has not been established yet. We assessed the efficacy of granisetron plus aprepitant versus granisetron for CHOP or rituximab-CHOP (R-CHOP) regimen-induced nausea and vomiting in malignant lymphoma.MethodsThis retrospective and observational clinical study included patients who received CHOP or R-CHOP regimen as initiating chemotherapy between July 2010 and March 2016 (N = 39). Patients were assigned to an aprepitant [aprepitant (125 mg on day 1, 80 mg on days 2–3) plus granisetron (3 mg); n = 15] or control regimen group [granisetron (3 mg); n = 24]. Complete response (CR), defined as no vomiting and no use of rescue therapy during overall phase (0–120 h), was the primary endpoint. Secondary endpoints included the time to first vomiting and using rescue medication and complete protection (CP) defined as no vomiting and no retching and/or no nausea and no rescue therapy. The patient records were investigated, and data were retrospectively analyzed.ResultsCR rate CP rates did not significantly differ between the groups during the observation period (80.0% versus 83.3%, p = 1.000; and 80.0% versus 79.2%, p = 1.000, respectively). Additionally, the time to first vomiting and using rescue medication in did not significantly differ between the groups (p = 0.909).ConclusionsThis study suggests that granisetron alone could be one treatment option in the management of CINV in patients with non-Hodgkin lymphoma receiving CHOP or R-CHOP regimen.

Δ9-THC and related cannabinoids suppress substance P- induced neurokinin NK1-receptor-mediated vomiting via activation of cannabinoid CB1 receptor

Δ9-THC suppresses cisplatin-induced vomiting through activation of cannabinoid CB1 receptors. Cisplatin-evoked emesis is predominantly due to release of serotonin and substance P (SP) in the gut and the brainstem which subsequently stimulate their corresponding 5-HT3-and neurokinin NK1-receptors to induce vomiting. Δ9-THC can inhibit vomiting caused either by the serotonin precursor 5-HTP, or the 5-HT3 receptor selective agonist, 2-methyserotonin. In the current study, we explored whether Δ9-THC and related CB1/CB2 receptor agonists (WIN55,212–2 and CP55,940) inhibit vomiting evoked by SP (50 mg/kg, i.p.) or the NK1 receptor selective agonist GR73632 (5 mg/kg, i.p.). Behavioral methods were employed to determine the antiemetic efficacy of cannabinoids in least shrews. Our results showed that administration of varying doses of Δ9-THC (i.p. or s.c.), WIN55,212–2 (i.p.), or CP55,940 (i.p.) caused significant suppression of SP-evoked vomiting in a dose-dependent manner. When tested against GR73632, Δ9-THC also dose-dependently reduced the evoked emesis. The antiemetic effect of Δ9-THC against SP-induced vomiting was prevented by low non-emetic doses of the CB1 receptor inverse-agonist/antagonist SR141716A (<10 mg/kg). We also found that the NK1 receptor antagonist netupitant can significantly suppress vomiting caused by a large emetic dose of SR141716A (20 mg/kg). In sum, Δ9-THC and related cannabinoids suppress vomiting evoked by the nonselective (SP) and selective (GR73632) neurokinin NK1 receptor agonists via stimulation of cannabinoid CB1 receptors.

Sub-hypnotic dose of propofol as antiemetic prophylaxis attenuates intrathecal morphine-induced postoperative nausea and vomiting, and pruritus in parturient undergoing cesarean section \u2014 a randomized control trial

BackgroundPostoperative Nausea and Vomiting (PONV) is a dreadful and uncomfortable experience that significantly detracts patients’ quality of life after surgery. This study aimed to examine the antiemetic effect of a single sub-hypnotic dose of propofol as prophylaxis for PONV.MethodIn this prospective, double-blind, randomized control trial, 345 parturients presented for elective cesarean section at the Obstetric unit of Tamale Teaching Hospital were recruited. Each recruited parturient was randomly assigned to one of three groups; Propofol group (n = 115) represented those who received propofol 0.5 mg/kg, Metoclopramide group (n = 115) represented those who received metoclopramide 10 mg and, Control group (n = 115) represented those who received 0.9% saline. Spinal anesthesia with 0.5% hyperbaric bupivacaine 7.5–10 mg, and intrathecal morphine 0.2 mg was employed for the anesthesia.ResultsThe data indicate that 108 (93.9%) parturients from the control group, 10 (8.7%) from the propofol group and 8 (7.0%) from the metoclopramide group experienced some incidence of PONV. There was no significant difference in the incidence of PONV (nausea, vomiting, and none) between the propofol and the metoclopramide groups (P = 0.99; 0.31; and 0.35 respectively). Parturients who received antiemetic agents were 105 (97.2%), 1 (10.0%) and 3 (37.5%) from the control, propofol and metoclopramide groups respectively. The data indicated that 98 (85.2%) parturients from the control, 3 (2.6%) from propofol group, and 100 (87.0%) from the metoclopramide group experienced some levels of pruritus. There was a significant difference in the incidence of pruritus (mild, moderate, and no pruritus) between the metoclopramide and propofol groups (P < 0.01; P < 0.01; and P < 0.01 respectively).ConclusionA sub-hypnotic dose of propofol is effective as metoclopramide in the prevention of PONV in parturient undergoing cesarean section under spinal anesthesia with intrathecal morphine. Sub-hypnotic dose of propofol significantly reduces the incidence of postoperative pruritus following intrathecal morphine use.Trial registrationCurrent control trial, registered at ISRCTN trial registry: ISRCTN15475205. Date registered: 03/04/2019. Retrospectively registered.

Ramosetron versus Palonosetron in preventing postoperative nausea and vomiting in laparoscopic surgeries

Introduction: The incidence of postoperative nausea and vomiting (PONV) following laparoscopic surgeries is very high without antiemetic prophylaxis. 5HT3 receptor antagonists are the most commonly used drug for prevention of PONV. Aims: To compare the effectiveness of intravenous (IV) palonosetron versus ramosetron in prevention of PONV during the 24 hour period in patients undergoing laparoscopic surgeries. Materials and Methods: Sixty patients enrolled for the study were randomly allotted into two groups of thirty each. Group I received 0.075 mg of IV palonosetron and Group II received 0.3 mg of IV ramosetron two minutes before induction of anaesthesia. Both the Groups were similar with respect to age, sex, duration and types of surgery and anaesthetic management. Patients were assessed for the incidence of nausea, retching, vomiting, need for rescue antiemetic and adverse effects at 0-2 hour and 2-24 hours interval following surgery. Students ‘t’ test and chi-square test were used for comparing the parameters. A p-value Results: There was no significant difference between the groups with respect to incidence of nausea, retching and vomiting. The incidence of nausea in group I at 0-2 hours was 3.3% and 6.7% in Group II without a statistically significant difference (p=0.5) and at 2-24 hour interval Group I had 3.3% while Group II had 10% incidence of vomiting with p=0.3 and statistically non-significant. There was no significant difference with respect to incidence of retching, vomiting, need for rescue antiemetic and adverse effects between the two groups. Conclusion: Both palonosetron and ramosetron are equally effective in prevention of PONV in laparoscopic surgeries. Keywords: Laparoscopic surgery, Nausea, Palonosetron, Ramosetron, Retching, Vomiting.

Perioperative combined administration of tranexamic acid and dexamethasone in total knee arthroplasty-benefit versus harm?

Background:The purpose of this study was to investigate the benefits and harm of combined administration of tranexamic acid (TXA) and dexamethasone (Dexa) in total knee arthroplasty (TKA).Methods:A total of 88 consecutive patients undergoing TKA for knee osteoarthritis were stratified in 2 groups. All surgeries were performed under general anesthesia. Brief, patients in the TXA + Dexa group (n = 45) received 10 mg Dexa just after the anesthesia, and repeated at 24 hours after the surgery; and patients in the TXA group (n = 43) received 2 ml of normal saline solution at the same time. The measured outcomes were the C-reactive protein (CRP) and interleukin-6 (IL-6) from preoperatively to postoperatively, and postoperative nausea and vomiting (PONV), fatigue, range of motion (ROM), length of stay (LOS), and the analgesic and antiemetic rescue consumptionResults:The level of CRP and IL-6 in the TXA + Dexa group were lower than that in the TXA group at 24 hours (P < .001, P < .001), 48 hours (P < .001, P < .001), and 72 hours (P < .001, P < .001) after the surgery. The pain scores in the TXA + Dexa group were lower during walking at 24 hours (P < .001), 48 hours (P < .001), and 72 hours (P < .001) and at rest at 24 hours (P = .022) after the surgery. Patients in the TXA + Dexa group had a lower nausea score, the incidence of PONV, fatigue, and the analgesic and antiemetic rescue consumption, and had a greater ROM than that in the TXA group. No significant differences were found in LOS and complications.Conclusion:The combined administration of TXA + Dexa significantly reduced the level of postoperative CRP and IL-6, relieve postoperative pain, ameliorate the incidence of POVN, provide additional analgesic and antiemetic effects, reduce postoperative fatigue, and improve ROM, without increasing the risk of complications in primary TKA.

Metoclopramide for the treatment of diabetic gastroparesis

ABSTRACTIntroduction: Gastroparesis is a chronic disorder of the stomach characterized by delayed gastric emptying without mechanical obstruction. Diabetes is the most commonly known cause of gastroparesis. Management of diabetic gastroparesis involves lifestyle modifications, glycemic control, pharmacological drugs, and for refractory cases surgical treatments. Metoclopramide remains the only drug approved by the Food and Drug Administration for diabetic gastroparesis. The aim of this article is to provide a concise review of the pharmacology, clinical efficacy and tolerability of metoclopramide.Areas covered: We searched PubMed using the key words ‘metoclopramide’, ‘diabetic gastroparesis’, and ‘gastric emptying’. The relevant articles and their bibliography were reviewed. Metoclopramide acts on several different receptors; primarily as a dopamine receptor antagonist, both peripherally improving gastric emptying, and centrally resulting in an anti-emetic effect. Metoclopramide side effects, mostly related to its ability to cross the blood-brain barrier, include drowsiness, restlessness, hyperprolactinemia, and tardive dyskinesia (TD), a movement disorder that may be irreversible.Expert opinion: Metoclopramide carries a black box warning for use >12 weeks due to the risk of TD. However, gastroparesis patients experience chronic symptoms often requiring prolonged treatments. Physicians and patients look forward to FDA approval of new agents for gastroparesis with better efficacy and safety profile.

Identifying the optimal timing of preoperative electroacupuncture for postoperative nausea and vomiting and pain in patients undergoing laparoscopic gynecologic surgery: Study protocol for a randomized controlled trial

IntroductionElectroacupuncture (EA) has been shown to have antiemetic and analgesic effects; however, optimal timing for the therapy is unclear. Our study aims firstly to investigate the effectiveness and safety of preoperative EA, delivered 24 h before surgery, on postoperative nausea and vomiting (PONV) and postoperative pain in patients undergoing gynecologic laparoscopic surgery; and secondly to identify the optimal timing and dose of stimulation of preoperative EA for preventing PONV and postoperative pain. MethodsThis is a single-center, randomized, controlled, four-arm clinical trial. Participants who meet the selection criteria will be randomly assigned to one of the following four groups: Group 1 (EA delivered 24 h before surgery, n = 103), Group 2 (EA delivered 30 min before surgery, n = 103), Group 3 (EA delivered both 24 h before, and 30 min before surgery, n = 103), Group 4 (usual care, n = 103). All groups will receive routine treatment for PONV and pain. EA will be delivered at bilateral Neiguan (PC6) and Zusanli (ST36). The primary outcomes are the incidence of postoperative nausea (PON) and postoperative vomiting (POV), and pain scores at 24 h after the operation. Secondary outcomes include the incidence of PON and POV, and pain scores at 6 h, 48 h and 72 h after the operation, also the severity of PON and POV, consumption of opioid medications, Quality of Recovery-15 (QoR-15), days in hospital and time to passage of first flatus. The assessor and the treating anesthetists will be blinded from group allocation. Participants in the three EA groups are unaware of the purpose of the study. DiscussionAn understanding of optimal timing and dosage of preoperative acupuncture will facilitate the implementation of this non-drug therapy and contribute to the overall improvement of post-surgical care.

Antiemetic effect of oral maropitant treatment before the administration of brimonidine ophthalmic solution in healthy cats.

The aim of this study was to investigate the antiemetic, behavioural and physiological effects of oral maropitant treatment before the administration of brimonidine ophthalmic solution in healthy cats. Five cats received oral maropitant 8 mg or no treatment (control) 18 h before the administration of one drop of brimonidine solution in both eyes. Each cat was administered each of the two treatments, with a washout period of 1 week. The incidence of emesis, retching, sialorrhoea and lip-licking after brimonidine administration was recorded, while behavioural and physiological parameters, including heart rate, mean blood pressure, respiratory frequency and rectal temperature, were recorded before and 0, 30, 60, 90, 120, 180 and 240 mins after brimonidine administration. Emesis and retching were not observed when maropitant was administered. However, 4/5 cats exhibited vomiting and retching in the absence of maropitant pretreatment. The incidence of emesis and retching after brimonidine administration was significantly lower in the treatment group than in the control group. Sialorrhoea occurred in one cat in the control group, while all cats showed lip-licking after brimonidine administration. There were no significant differences in the incidence of sialorrhoea and lip-licking between the two groups. Although behaviour scores were comparable between the two groups, those obtained during heart rate, mean blood pressure and respiratory frequency measurements were significantly lower than the baseline scores; this indicated a sedative effect after brimonidine administration. The heart rate and mean blood pressure significantly decreased after brimonidine administration in both groups, while there were no intergroup differences in the heart rate, mean blood pressure, respiratory frequency and rectal temperature. Oral maropitant treatment before the administration of brimonidine ophthalmic solution in cats can alleviate emesis and retching without affecting the sedative effects of brimonidine and important physiological parameters.

Evaluation of in vivo analgesic, antiemetic and anxiolytic effect of methanolic extract of Litsea monopetala in animal model

Objective: The present study was conducted to investigate in vivo analgesic, antiemetic and anxiolytic effect of methanolic extract of Litsea monopetala in animal model.Materials and Methods:  Analgesic activity was performed by formalin induce method .The antiemetic activity was conducted by using chick animal model where mean decrease in number of retches were calculated and anxiolytic activity was done by using Elevated Plus Maze(EPM) and Hole board method.Results: The methanolic extract of Litsea monopetala at a dose of 400 mg/kg exhibited statistically significant(P&lt;0.05) and produced  66.67% of inhibition of paw licking in mice where standard drug showed 50 % inhibition. The extract further showed dose dependent and statistically(P&lt;0.05) significant antiemetic activity at a dose of 200 mg/kg and 400 mg/kg respectively. In addition the extract has showed excellent CNS depressant activity in both Elevated Plus Maze(EPM) and Hole board method in compare to standard drug diazepam.Conclusion: From our current study it is obvious that the extract has good analgesic, antiemetic and anxiolytic effect which may be due to the presence of different chemical constituents like terpenes , flavonoids, tannins, saponin and sterols.Â

Intravenous dexamethasone combined with intrathecal atropine to prevent morphine-related nausea and vomiting after cesarean delivery: A randomized double-blinded study

ABSTRACTBackground: Intrathecal morphine can be considered as a gold standard for analgesia following cesarean section (CS), which is not devoid of complications namely postoperative nausea and vomiting. We evaluated the antiemetic effect of intravenous dexamethasone combined with intrathecal atropine after CS.Methods: 120 parturient undergoing elective CS under spinal anesthesia were randomized into three groups. Dexamethasone group (D): Received intrathecal hyperbaric bupivacaine (0.5% in 2 ml) mixed with morphine (200 µg in 0.5 ml) and normal saline (0.5 ml as placebo) and intravenous (iv) dexamethasone (8 mg in 2 ml). Atropine group (A): Received hyperbaric bupivacaine (0.5% in 2 ml) mixed with morphine (200 µg in 0.5 ml) and atropine (100 µg in 0.5 ml), in addition to iv normal saline (2 ml as placebo). Dexamethasone and Atropine group (DA): Received intrathecally as group A, and iv dexamethasone (8 mg in 2 ml). Follow-up of both nausea and vomiting was done during the first 24 hours postoperatively.Results: Nausea was noticed in 7 patients (17.5%) in group D, 8 patients (20%) in group A, and one patient (2.5%) group DA, with significant differences between DA and D (p = 0.025) and DA and A (p = 0.013). Regarding vomiting, there were 5 patients (12.5%) in group D, 4 patients (10%) in group A only, with significant differences between DA and D (p = 0.021) and DA and A (p = 0.041).Conclusions: Combination of intravenous dexamethasone and intrathecal atropine has additive antiemetic effect after spinal anesthesia for cesarean delivery using bupivacaine and morphine.

Pharmacological effects of different ginger juices on the concurrent symptoms in animal models of functional dyspepsia: A comparative study.

ObjectivePatients with gastrointestinal disorders commonly suffer from poor treatment outcomes and adverse effects of traditional pharmacological therapy. Herbal medicine is a favorable alternative due to the low risk of side effects. This study was performed to explore the antiemetic effects and the improvement effect on gastrointestinal function of components of three ginger juice excipients.MethodsThe compositions were analyzed by liquid chromatograph mass spectrometer (LC‐MS), especially the gingerols of dried ginger juice (DGJ), fresh ginger juice (FGJ), and fresh ginger boiled juice (FGBJ). Furthermore, the respective gastrointestinal effects on rat models with functional dyspepsia (FD) were compared.ResultsThe 6‐keto‐PGF1α levels in the serum of the treated groups were significantly reduced (p < 0.05), as compared with the control group. Compared with the cisplatin group, there was an apparent reduction in kaolin intake for DGJ, FGJ, and FGBJ (p < 0.01; p < 0.01; p < 0.05). The intestinal propulsive rate of the rats in the treated group was significantly higher than that in the control group (p < 0.05). Ginger juices significantly improved gastrointestinal function in rats. Eight common components were found in DGJ, FGJ, and FGBJ, among which 6‐paradol, 10‐gingerol, and 12‐shogaol led to inhibited gastric mucosal damage function effect according to the Pearson correlation analysis. Only 6‐shogaol was found to have a positive correlation with gastrointestinal function effect through Pearson correlation analysis.ConclusionGinger juice should be recommended for the medicinal materials used in the treatment of concurrent symptoms of FD.

Clinical Pharmacology Research for Promoting Individualized Cancer Chemotherapy

Cancer chemotherapy has progressed remarkably with conventional and molecular-targeted anticancer drugs as well as immune checkpoint inhibitors. However, adverse drug reaction (ADR) management remains a challenge in cancer chemotherapy. Therefore, improving the quality of medical care through clinical pharmacology research is warranted. Intravenous injection of bendamustine in patients with follicular or mantle cell lymphoma frequently causes venous irritation. Because the underlying mechanisms are not clear, we investigated the factors responsible for bendamustine-induced venous irritation. Based on the results of our analysis, we altered the administration regimen and observed that the incidence of venous irritation, which manifested in a concentration-dependent manner following conventional approaches, significantly decreased when following the modified regimen. Guidelines on the management of chemotherapy-induced nausea and vomiting recommend aprepitant, a selective neurokinin-1 (NK-1) receptor antagonist, 5-hydroxytryptamine 3 (5-HT3) receptor antagonists, and dexamethasone as prophylactic antiemetics. Pretreatment with high-dose chemotherapy before hematopoietic stem cell transplantation has extremely high emetogenic potential. This can be countered by using aprepitant in combination with conventional antiemetics. However, the safety and efficacy of such combinations are unexplored. Upon evaluation, we observed improved antiemetic effects without an increase in ADRs. At this symposium, I highlight the significance of clinical pharmacology research for promoting individualized cancer chemotherapy.

BALANCED ANESTHESIA;

Introduction: Porpofol is currently available popular intravenous anaesthetic agent. It is widely used for induction and maintenance of anaesthesia. Its main advantages are rapid induction and recovery, antiemetic and anticonvulsant effects. It has been used successfully for tracheal intubation without muscle relaxant, day surgery and for insertion of laryngeal mask airway. Its main disadvantages are pain on injection, dose dependent hypotension and severe bradycardia after induction. Objectives: The objective of the study was to compare mean hemodynamic changes using propofol as total intravenous anaesthesia with balanced anaesthesia technique (thiopentone-isoflurane-nitrousoxide). Setting: Department of Anaesthesia, Allied Hospital, Faisalabad. Duration: 6 months after approval of synopsis, from 18-7-2014 to 17-1-2015. Study Design: Randomized control trial. Results: In our study, out of 60 cases(30 in each group), 70%(n=21) in Group-A and 63.33%(n=19) in Group-B were between 12-30 years of age while 30%(n=9) in Group-A and 36.67%(n=11) in Group-B were between 31-60 years of age, mean+sd was calculated as 27.90+8.91 and 29.8+8.49 years respectively. 60%(n=18) in Group-A and 53.33%(n=16) in Group-B were male while 40%(n=12) in Group-A and 46.67%(n=14) in Group-B were females. Comparison of mean hemodynamic changes using propofol as total intravenous anaesthesia with balanced anaesthesia technique (thiopentone-isoflurane-nitrous oxide) shows that heart rate after intubation in Group-A was 83.4+2.36 and 90.36+1.95 in Group-B, p value was 0.001 while mean arterial pressure in Group-A was recorded as 78.6+2.25 and in Group-B 89.43+1.73, p value was 0.000. Conclusion: Propofol as total intravenous anaesthesia shows significanly better stability in haemodynamics when comapred with balanced anaesthesia technique (thiopentone-isoflurane-nitrous oxide) in surgical procedures.

Investigation of antiemetic, antimicrobial and anti-radical properties of methanolic extract of Foeniculum vulgare: A medicinal herb

Objectives: This study was conducted to investigate the antiemetic, antimicrobial and anti-radical activity of methanolic extracts of Foeniculum vulgare.  Materials and Methods: The antiemetic assay was carried out by using chick emetic model with minor modifications by calculating the mean decrease in the number of retching. The antimicrobial activity of the crude extract was performed by Disc Diffusion method. The anti-radical activity was determined by the 2, 2-diphenyl-2-picrylhydrazyl hydrate (DPPH) method.Results: The anti-emetic activity of Foeniculum vulgare leaves on young chicks revealed that these extracts have a less anti-emetic effect. The group of chicks treated with Chlorpromazine was found to have 60.6 retches as compared to the 66 retches of the control group, thus Chlorpromazine reduced the retches by 7.93%. The chickens treated with leaves extracts inhibited the retches up to 2.03%. The minimum antimicrobial effect was found in this methanol crude extract. The extract did not appear potent in terms of both zones of inhibition and spectrum of activity. In anti-radical activity test, the extract showed moderate free radical scavenging activity with IC50 value 240.39μg/ml. while compared to that of the reference standard ascorbic acid.Conclusion: Methanolic extract of Foeniculum vulgare leaves have minimum anti-emetic and anti-microbial activities and moderate anti-radical properties.

Comparison of acute and delayed antiemetic effect of adding Aprepitant to Odansitron ‎and Dexamethasone regimen ‎in patients with Hodgkin lymphoma receiving highly emetogenic chemotherapy

Cancer is a class of ‎disease in which group of cells show out of control growth, invasions ‎and ‎sometimes metastasis to different parts of the body. Few side effects of cancer treatment are ‎more feared by the patient than nausea and vomiting. Although nausea and emesis (vomiting ‎and retching) can result from surgery or radiation therapy, chemotherapy-induced nausea ‎and vomiting (CINV) are potentially the most severe and most distressing. A randomized, single-blind controlled clinical trial conducted in Hiwa ‎Center for Cancer in Sulaimani city for the period ‎from January to December 2015. A total of 70 Hodgkin lymphoma patients presented to ‎Hiwa ‎Center for Cancer and treated with ABVD chemotherapy regimen ‎were selected. The patient's ‎received either the treatment (Aprepitant, ‎Odansitron and Dexamethasone) or the standard ‎regimen (Odansitron, ‎Dexamethasone) in a 1:1 ratio, ‎computer-generated, random allocation ‎schedule. A total of sixty-three Hodgkin lymphoma patients were included in ‎the present study ‎with a mean age was 47.8±14.4 years; 34.9 % of them were ‎ageing 60 years and more. Nausea and vomiting score was significantly higher in the treatment group from 2nd day to 4th days; the number of rescue therapy was significantly higher in the standard therapy group. In conclusion, the use of Aprepitant, Odansitron and Dexamethasone regimen ‎showed superior and valuable results in the prevention of cancer ‎induced nausea and vomiting by patients on chemotherapy.

Effects of ginger constituent 6-shogaol on gastroesophageal vagal afferent C-fibers.

Ginger has been used as an herbal medicine worldwide to relieve nausea/vomiting and gastrointestinal discomfort, but the cellular and molecular mechanisms of its neuronal action remain unclear. The present study aimed to determine the effects of ginger constituent 6-shogaol on gastroesophageal vagal nodose C-fibers. Extracellular single-unit recording and two-photon nodose neuron imaging were performed, respectively, in ex vivo gastroesophageal-vagal preparations from wild type and Pirt-GCaMP6 transgenic mice. The action potential discharge or calcium influx evoked by mechanical distension and chemical perfusions applied to the gastroesophageal vagal afferent nerve endings were recorded, respectively, at their intact neuronal cell soma in vagal nodose ganglia. The effects of 6-shogaol on nodose C-fiber neurons were then compared and determined. Gastroesophageal application of 6-shogaol-elicited intensive calcium influxes in nodose neurons and evoked robust action potential discharges in most studied nodose C-fibers. Such activation effects were followed by a desensitized response to the second application of 6-shogaol. However, action potential discharges evoked by esophageal mechanical distension, after 6-shogaol perfusion, did not significantly change. Pretreatment with TRPA1 selective blocker HC-030031 inhibited 6-shogaol-induced action potential discharges in gastric and esophageal nodose C-fiber neurons, suggesting that TRPA1 played a role in mediating 6-shogaol-induced activation response. This study provides evidence that ginger constituent 6-shogaol directly activates vagal afferent C-fiber peripheral gastrointestinal endings. This activation leads to desensitization to subsequent application of 6-shogaol but not subsequent esophageal mechanical distension. Further investigation is required to establish a possible contribution in its anti-emetic effects.