Characteristics of the Analgesic Effects and Drug Interactions of Intrathecal Carbachol in Rats

1995 ◽  
Vol 83 (4) ◽  
pp. 844-849. ◽  
Author(s):  
Stephen E. Abram ◽  
Therese C. O'Connor
Keyword(s):  
Adverse Effects ◽  
Drug Interactions ◽  
Stimulus Intensity ◽  
Hind Limb ◽  
Intrathecal Morphine ◽  
Radiant Heat ◽  
Limb Weakness ◽  
Analgesic Effects ◽  
Low Intensity ◽  
Significant Difference

Background Intrathecal carbachol produces consistent analgesia in animals without appreciable adverse effects. Little is known about the ability of this drug to provide analgesia as stimulus intensity is increased. Likewise, there are few data regarding interactions between carbachol and other intrathecal analgesics. Methods Using two different noxious radiant heat intensities, one applied to each hind limb, analgesic effects of 1, 3, 10, and 30 micrograms intrathecal carbachol on paw withdrawal latencies were measured. Similar testing was done for intrathecal morphine and clonidine. ED50 fractions (1/2, 1/4, 1/8, 1/16) of drug combinations of carbachol-morphine and carbachol-clonidine were administered, responses to the low intensity stimulus were recorded, and the ED50 of each combination was established and isobolographic analysis of the drug interactions was carried out. Results The 30-micrograms dose of carbachol was associated with transient agitation, salivation, and hind limb weakness. No other adverse effects were noted. The ED50 (95% confidence interval) of intrathecal carbachol was 2.34 micrograms (1.34-4.04) for low intensity stimulation and 12.64 micrograms (4.18-38.25) for high intensity. There was no significant difference between high- and low-intensity ED50 values for intrathecal morphine and clonidine. The analgesic effect of the carbachol-morphine and carbachol-clonidine combinations were significantly greater than the calculated additive effects. The ED50 for the carbachol-morphine combination was 12% of the expected additive value and the ED50 for the carbachol-clonidine combination was 30% of the expected additive value. Conclusions Intrathecal carbachol provides analgesia to noxious thermal stimulation of the hind paw in rats. It is relatively less effective at providing analgesia than intrathecal morphine or clonidine when stimulus intensity is raised. Intrathecal carbachol is synergistic when combined with intrathecal morphine or clonidine.

scholarly journals A comparative study of hemodynamic changes and adverse effects of intrathecal bupivacaine with fentanyl and intrathecal bupivacaine with clonidine in infra-umbilical abdominal and lower limb surgery

2019 ◽  
Vol 6 (11) ◽  
pp. 4048
Author(s):  
Krishna Prasad G. V. ◽  
Vipin Jaishree Sharma
Keyword(s):  
Adverse Effects ◽  
Lower Limb ◽  
Analgesic Effects ◽  
Anesthetic Agents ◽  
Group I ◽  
Significant Difference ◽  
Lower Limb Surgery ◽  
Hemodynamic Profile ◽  
Group Ii ◽  
Intrathecal Clonidine

Background: Adjuvants prolong the action of intrathecal local anesthetic agents. They have shown to have significant analgesic effects in the postoperative period much after the regression of the sensory and motor blockade. Our objective of the current study was to compared the hemodynamic profile and adverse effects (nausea, pruritus, sedation and respiratory depression) in two groups of adult patients undergoing infra-umbilical and lower limb surgery under spinal anaesthesia using either intrathecal clonidine or intrathecal fentanyl as an adjuvant to intrathecal bupivacaine (0.5% heavy).Methods: This randomized, prospective and observational study was undertaken in the Department of Anaesthesiology and Critical Care, 5 Airforce Hospital, Kanpur from the period of January 2014 to February 2016 on 120 patients fulfilling the inclusion criteria. Study patients were randomly allocated to the two groups Group I: Cases who received intrathecal 0.5% heavy bupivacaine (2.5 ml) + fentanyl (50 mcg/ml) (0.5 ml) (n=60 patients) and Group II: cases who received intrathecal 0.5% heavy bupivacaine (2.5 ml) + clonidine (60 mcg/ml) (0.5 ml) (n=60 patients).Results: Mean age of patients in Group I and Group II was 42.60±5.93 and 42.03±7.16 years, respectively. Mean BMI of patients in Group I and Group II was 22.0±1.92 and 21.54±2.14 kg/m2, respectively. Comparison of baseline hemodynamic parameters (heart rate (bpm), mean arterial pressure (mmhg), respiratory rate (/min) and oxygen saturation (%) did not show a significant difference between two groups.Conclusions: With respect to the side effects like nausea and pruritus, these are significantly more in fentanyl group as compared to clonidine group.

scholarly journals Effectiveness of Intrathecal Morphine for Analgesia following Elective Caesarean Section

2015 ◽  
Vol 10 (1) ◽  
pp. 57-61
Author(s):  
RB Koju ◽  
BS Gurung ◽  
Y Dongol
Keyword(s):  
Adverse Effects ◽  
Cesarean Section ◽  
Intrathecal Morphine ◽  
Elective Caesarean Section ◽  
Elective Cesarean Section ◽  
Controlled Study ◽  
Active Movement ◽  
Study Results ◽  
Significant Difference ◽  
Post Operative Nausea

Aims: This study evaluates the effectiveness of usage of 0.2 mg intrathecal morphine as post-operative analgesia and its effect on activity of mother after elective cesarean section. Methods: This hospital based prospective, randomized, double-blinded and placebo controlled study was carried out at Nagarik Community Teaching Hospital, Bhaktapur between 2012 January to 2014 November after the approval was taken from the hospital authority and the written informed consent from the participating patients. Fifty women of ASA I or II physical status undergoing cesarean section under sub-arachnoid block was randomized into two groups – P group (placebo group, n = 25) and M group (Treatment group, n = 25). P Group received hyperbaric bupivacaine 2.3ml, 0.5% bupivacaine (11.5 mg) and M Group received morphine 0.2 ml (0.2 mg) plus bupivacaine 2.3ml, 0.5% (11.5 mg) intrathecally. All subjects received 8 mg ondansetron intravenously 30 minutes before surgery to prevent possible drug-induced pruritus and post-operative nausea and vomiting. 1000 mg rectal acetaminophen suppository was given at the end of the surgery. Pain, nausea and pruritus during the first 24 hours using visual analog scale were recorded by a trained nurse or attending doctor who was not involved in the study. Results: Duration of complete analgesia and the time to request for additional analgesics was longer in M Group than in P Group. Similarly, the active movement is earlier in M Group than in P Group. There were no significant differences in adverse effects between the groups. Conclusions: Addition of morphine 0.2 mg to heavy bupivacaine intrathecally reduced post-operative pain and analgesic requirements without any significant difference in adverse effects. 

scholarly journals Intrathecal Morphine Versus Transversus Abdominis Plane Block for Caesarean Delivery: a Systematic Review and Meta-analysis

2021 ◽  
Author(s):  
Tao-ran Yang ◽  
Xue-han Li ◽  
Xue-mei He ◽  
Ru-rong Wang
Keyword(s):  
Pain Score ◽  
Cesarean Delivery ◽  
Subgroup Analysis ◽  
Intrathecal Morphine ◽  
Transversus Abdominis ◽  
Morphine Consumption ◽  
Tap Block ◽  
Analgesic Effects ◽  
Cesarean Deliveries ◽  
Significant Difference

Abstract Background: In recent years, the number of cesarean deliveries is on the rise. Although intrathecal morphine (ITM) can relieve pain and is widely applied in cesarean deliveries, it is also associated with many side effects. As a new analgesic technology, transversus abdominis plane (TAP) block has also begun to play a certain role after cesarean delivery, with fewer adverse effects. This article mainly compares the analgesic and adverse effect of ITM and TAP block in cesarean delivery.Methods: We systematically searched PubMed, Cochrane library, Embase and Web of Science, for randomized controlled trials before October 5, 2020 to compare ITM and TAP block. Our main result is the pain score at rest 24 hours after cesarean delivery, and the secondary result is the pain score at movement 24 hours after operation, postoperative nausea and vomiting (PONV), itching, and morphine consumption. We conducted a subgroup analysis based on economic development.Result: Six articles with 563 sample sizes were included. The results showed there was no significant difference between ITM and TAP block in the pain score at rest 24 hours after surgery (95% CI: -1.33 to 0.40; P=0.29). After subgroup analysis based on economic development, Parturients in the ITM group have lower rest pain score than those in the TAP group (95% CI: -1.27 to -0.28; P=0.002) in the developed area. There was no significant difference in the 24h moving pain score (95% CI:-1.47 to 0.29;P=0.19）and incidence of pruritus (95% CI:0.87 to 8.85;P=0.08). The ITM group showed less morphine consumption when compared with the TAP group (95% CI:-13.12 to -2.95;P=0.002）. The incidence of PONV was lower in the TAP group as compared to the ITM group (95% CI:1.92 to 4.87; P<0.00001).Conclusion: We found that Parturients in the ITM and TAP block groups had similar analgesic effects. However, after subgroup analysis, in developed countries, Parturients in the ITM group has better analgesic effects than those in the TAP block group with less morphine consumption. Differently, TAP block had low side effects such as nausea, vomiting. Therefore, if patients cannot use ITM for analgesia after cesarean delivery, or patients have high risk of PONV, then TAP is still a valuable analgesia option.Registration number: Registered on Prospero with the registration number of CRD42020210135

Effect of Early Low-Intensity Exercise on Rat Hind-Limb Muscles Following Acute Ischemic Stroke

2006 ◽  
Vol 7 (3) ◽  
pp. 163-174 ◽  
Author(s):  
Myoung-Ae Choe ◽  
Gyeong Ju An ◽  
Yoon-Kyong Lee ◽  
Ji Hye Im ◽  
Smi Choi-Kwon ◽  
...  
Keyword(s):  
Hind Limb ◽  
Gastrocnemius Muscle ◽  
Exercise Group ◽  
Cross Sectional Area ◽  
Type I ◽  
Sectional Area ◽  
Muscle Type ◽  
Cross Sectional ◽  
Low Intensity ◽  
Low Intensity Exercise

This study examined the effects of daily low-intensity exercise following acute stroke on mass, Type I and II fiber cross-sectional area, and myofibrillar protein content of hind-limb muscles in a rat model. Adult male Sprague-Dawley rats were randomly assigned to 1 of 4 groups (n = 7-9 per group): stroke (occlusion of the right middle cerebral artery [RMCA]), control (sham RMCA procedure), exercise, and stroke-exercise. Beginning 48 hours post-stroke induction/sham operation, rats in the exercise group had 6 sessions of exercise in which they ran on a treadmill at grade 10 for 20 min/day at 10 m/min. At 8 days poststroke, all rats were anesthetized and soleus, plantaris, and gastrocnemius muscles were dissected from both the affected and unaffected sides. After 6 sessions of exercise following acute ischemic stroke, the stroke-exercise group showed the following significant (p < .05) increases compared to the stroke-only group: body weight and dietary intake, muscle weight of affected soleus and both affected and unaffected gastrocnemius muscle, Type I fiber cross-sectional area of affected soleus and both affected and unaffected gastrocnemius muscle, Type II fiber cross-sectional area of the unaffected soleus, both affected and unaffected plantaris and gastrocnemius muscle, Type II fiber distribution of affected gastrocnemius muscle, and myofibrillar protein content of both affected and unaffected soleus muscle. Daily low-intensity exercise following acute stroke attenuates hind-limb muscle atrophy in both affected and unaffected sides. The effects of exercise are more pronounced in the soleus and gastrocnemius as compared to the plantaris muscle.

scholarly journals Sex-dependent liver cancer xenograft models for predicting clinical data in the evaluation of anticancer drugs

2021 ◽  
Vol 37 (1) ◽  
Author(s):  
Sungryong Oh ◽  
Joohee Jung
Keyword(s):  
Liver Cancer ◽  
Adverse Effects ◽  
Anticancer Drugs ◽  
Clinical Data ◽  
Xenograft Model ◽  
In Vitro Test ◽  
Incidence And Mortality ◽  
Significant Difference ◽  
Xenograft Models

Abstract Background The incidence and mortality of liver cancer show a great difference between the sexes. We established sex-dependent liver cancer xenograft models and investigated whether such sex-dependent models could be used to simultaneously evaluate the therapeutic and adverse effects of anticancer drugs for drug screening. Results In the in-vitro test, the cytotoxicity of anticancer drugs (cisplatin, 5-fluorouracil, and doxorubicin) was compared between male- and female-derived liver cancer cell lines. Cisplatin and 5-fluorouracil exhibited cytotoxicity without sex-difference, but doxorubicin showed dose-dependently significant cytotoxicity only in male-derived cells. Our results showed a strong correlation between preclinical and clinical data with the use of sex-dependent liver cancer xenograft models. Moreover, the male-derived Hep3B-derived xenograft model was more sensitive than the female-derived SNU-387-derived xenograft model against doxorubicin treatment. Doxorubicin showed more severe cardiotoxicity in the male xenograft model than in the female model. We investigated the occurrence frequency of doxorubicin-related cardiotoxicity using data obtained from the Korea Institute of Drug Safety & Risk Management Database, but no significant difference was observed between the sexes. Conclusions Our results suggest that sex-dependent xenograft models are useful tools for evaluating the therapeutic and adverse effects of anticancer drugs, because sex is an important consideration in drug development.

scholarly journals Intrathecal morphine versus transversus abdominis plane block for caesarean delivery: a systematic review and meta-analysis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tao-ran Yang ◽  
Xue-mei He ◽  
Xue-han Li ◽  
Ru-rong Wang
Keyword(s):  
Sensitivity Analysis ◽  
Side Effects ◽  
Pain Score ◽  
Caesarean Delivery ◽  
Intrathecal Morphine ◽  
Transversus Abdominis Plane Block ◽  
Transversus Abdominis ◽  
Transversus Abdominis Plane ◽  
Analgesic Effects ◽  
Registration Number

Abstract Background The number of caesarean deliveries has been increasing. Although intrathecal morphine (ITM) can relieve pain and is widely applied in caesarean deliveries, it is associated with many side effects. Transversus abdominis plane block (TAPB), a new analgesic technology, has also began playing a certain role after caesarean delivery, with fewer adverse effects. This study mainly compares the analgesic and adverse effects of ITM and TAPB in caesarean delivery. Methods We systematically searched PubMed, Cochrane Library, EMBASE, and Web of Science, for randomised controlled trials (RCTs) published before 9 October, 2020 to compare the effects of ITM and TAPB. Primary outcome of the study was the pain score at rest 24 h after caesarean delivery, whereas the secondary outcomes were the pain score at movement 24 h after operation, postoperative nausea and vomiting (PONV), itching, and morphine consumption. For the outcome assessment, we conducted a sensitivity analysis. Result Six RCTs involving 563 patients and meeting the study inclusion criteria were included in this study. Results indicated no significant difference in the pain score between ITM and TAPB at 24 h of rest or movement. The sensitivity analysis results indicated that the resting pain score (95% CI = − 1.27 to − 0.28; P = 0.002) and 24-h moving pain score (95% CI = − 1.8 to − 0.07; P = 0.03) of the ITM group were lower than those of the TAPB group. The consumption of morphine in the ITM group was lower than in the TAPB group (95% CI = 1.92 to 4.87; P < 0.00001); however, in terms of adverse reactions, the incidence of pruritus (95% CI = 1.17 to 8.26; P = 0.02) and PONV (95% CI = 1.92 to 4.87, P < 0.00001) in the ITM group was higher than in the TAPB group. Conclusion Parturients in the ITM and TAPB groups exhibited similar analgesic effects. However, in the sensitivity analysis performed by eliminating the studies causing heterogeneity, the ITM group was found to have superior analgesic effects compared with the TAPB group, with less morphine consumption. Differently, the TAPB group displayed less side effects such as PONV. Therefore, TAPB is still a valuable analgesia option for patients who cannot use ITM for analgesia after caesarean delivery or those having a high risk of PONV. Trial registration Registration number: Registered on Prospero with the registration number of CRD42020210135.

scholarly journals Pharmacokinetic and safety study of co-administration of albendazole, diethylcarbamazine, Ivermectin and azithromycin for the integrated treatment of Neglected Tropical Diseases

2020 ◽  
Author(s):  
Lucy N John ◽  
Catherine Bjerum ◽  
Pere Millat Martinez ◽  
Rhoda Likia ◽  
Linda Silus ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Large Scale ◽  
Neglected Tropical Diseases ◽  
Pharmacokinetic Interaction ◽  
Integrated Treatment ◽  
Secondary Outcome ◽  
Pharmacokinetic Data ◽  
Tropical Diseases ◽  
Open Label ◽  
Significant Difference

Abstract Background Pharmacokinetic data are a pre-requisite to integrated implementation of large-scale mass drug administration (MDA) for neglected tropical diseases (NTDs). We investigated the safety and drug interactions of a combination of azithromycin (AZI) targeting yaws and trachoma, with the newly approved ivermectin, albendazole, diethylcarbamazine (IDA) regime for Lymphatic Filariasis. Methodology An open-label, randomized, 3-arm pharmacokinetic interaction study in adult volunteers was carried out in Lihir Island, Papua New Guinea. Healthy adult participants were recruited and randomized to (I) IDA alone, (II) IDA combined with AZI, (III) AZI alone. The primary outcome was lack of a clinically relevant drug interaction. The secondary outcome was the overall difference in the proportion of AEs between treatment arms. Results Thirty-seven participants, eighteen men and nineteen women, were randomized and completed the study. There were no significant drug-drug interactions between the study arms. The GMR of Cmax, AUC0–t, and AUC0–∞ for IVM, DEC, ALB-SOX, and AZI were within the range of 80–125% (GMR for AUC0–∞ for IVM, 87.9; DEC, 92.9; ALB-SOX, 100.0; and AZI, 100.1). There was no significant difference in the frequency of AEs across study arms (AZI and IDA alone arms 9/12 (75%), co-administration arm 12/13 (92%); p = 0.44). All AEs were grade 1 and self-limiting. Conclusions Co-administration of AZI with IDA did not show evidence of significant drug-interactions. There were no serious AEs in any of the study arms. Our data support further evaluation of the safety of integrated MDA for NTDs. Clinical Trials Registration. NCT03664063

A118G Single Nucleotide Polymorphism of Human μ-Opioid Receptor Gene Influences Pain Perception and Patient-controlled Intravenous Morphine Consumption after Intrathecal Morphine for Postcesarean Analgesia

2008 ◽  
Vol 109 (3) ◽  
pp. 520-526 ◽  
Author(s):  
Alex T. Sia ◽  
Yvonne Lim ◽  
Eileen C. P. Lim ◽  
Rachelle W. C. Goh ◽  
Hai Yang Law ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Pain Perception ◽  
Intrathecal Morphine ◽  
Receptor Gene ◽  
Mu Opioid Receptor ◽  
Morphine Consumption ◽  
Mu Opioid ◽  
Pain Scores ◽  
Significant Difference ◽  
Intravenous Morphine

Background Previous studies have shown that genetic variability at position 118 of the human mu-opioid receptor gene altered patients' response to intravenous morphine. The purpose of this study was to investigate whether this polymorphism contributes to the variability in response to morphine for postcesarean analgesia. Methods After investigators obtained informed consent, 588 healthy women received 0.1 mg intrathecal morphine for postcesarean analgesia. Their blood samples were genotyped for the A118G polymorphism-A118 homozygous (AA), heterozygous (AG), or homozygous for the G allele (GG). Pain scores, the severity of nausea and vomiting, the incidence of pruritus, and the total self-administered intravenous morphine were recorded for the first 24 postoperative hours. Results Two hundred seventy women (46%) were AA, 234 (40%) were AG, and 82 (14%) were GG. The 24-h self-administered intravenous morphine consumption was lowest in the AA group (P = 0.001; mean, 5.9; 95% confidence interval, 5.1-6.8) versus the AG (8.0; 6.9-9.1) and GG groups (9.4; 7.3-11.5). Pain scores were lowest in the AA group and highest in the GG group, with a statistically significant difference detected between AA, AG, and GG (P = 0.049). Total morphine consumption was also influenced by patients' age and paying status. AA group was associated with the highest incidence of nausea (26 of 272 [9.6%]; P = 0.02) versus the other two groups (13 of 234 [5.6%] and 1 of 82 [1.2%] for AG and GG, respectively). Conclusion Genetic variation at position 118 of the mu-opioid receptor is associated with interindividual differences in pain scores, self-administered intravenous morphine, and the incidence of nausea postoperatively.

UJI EFEK ANALGESIK EKSTRAK ETANOL DAUN KERSEN (Muntingia calabura L.) PADA MENCIT PUTIH JANTAN (Mus musculus) DENGAN INDUKSI NYERI ASAM ASETAT

2017 ◽  
Vol 2 (2) ◽  
pp. 147
Author(s):  
Triswanto Sentat ◽  
Susiyanto Pangestu
Keyword(s):  
Analgesic Effect ◽  
Ethanol Extract ◽  
Positive Control ◽  
Negative Control ◽  
Control Treatment ◽  
Treatment Groups ◽  
Analgesic Effects ◽  
Significant Difference ◽  
Analgesic Dose ◽  
Muntingia Calabura

Kersen leaf (Muntingia calabura L.) contains tannins, flavonoids and polyphenol compounds allegedly have analgesic effect. The objective was to determine the analgesic effect of ethanol extract of kersen leaves and to determine the most effective analgesic dose. This study was an experimental research. Leaves were extracted with ethanol 70% and the analgesic effect test was divided into 5 groups: negative control treatment (distilled water), positive control (mefenamic acid 2.6mg/kg), kersen leaf ethanol extract first dose (100mg/kg), second dose (200mg/kg) and tthird dose (400mg/kg). Giving treatments by oral, after 30 minutes, the mices were given a pain inductor with 0.5% acetic acid by intra peritonial administration. Analgesic power was calculated by counting the number of writhing in mice for 1 hour. The results showed that the ethanol extract of cherry leaf has analgesic effect. From the calculation of the first dose analgesic power (42.9%), second dose (59.4%) and the third dose 69.9%. Statistical test results kruskal wallis value of p=0.011 (p<0.05) showed a significant difference between all analgesic treatment groups. The conclusion of this study is all of the ethanol extract had analgesic effects on male white mice, whereas a dose of 400mg/kg is the most effective analgesic dose.

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