Short Duration Of Action Research Articles

750: EVALUATION OF IV FENTANYL INFUSION DOSE IN THE INTENSIVE CARE UNIT

Introduction: Fentanyl (F) has a rapid onset of action and short duration of action and is typically given as a continuous infusion for analgesia and sedation in the ICU. There has been concern that F dosing requirements have increased over the past few years. The goal of this study was to retrospectively evaluate the use of F in the ICU to assess whether doses increased over time. Methods: This IRB approved study included intubated ICU adult patients from 2017 - 2021. We identified all patients with F infusions over 24 hours and then randomly pulled 200 patients (40 in each calendar year) to abstract data on F dosing parameters included total length of therapy, time to max dose, and cumulative dose as primary outcomes. F side effects and concomitant diseases were also collected. Continuous variables were analyzed using ANOVA test and discrete variables were analyzed using Kruskal-Wallis test. Results are presented as mean ± SD or percentages. A significant difference in any variable was determined based on p < 0.05. Results: There were no significant differences among background demographics. The average age of the entire sample was 60.1 ± 16.5, and 52% male. Total length of therapy 102.9 ± 75.4, 111.0 ± 106.8, 139.1 ± 173.6, 101.6 ± 88.9, and 102.7 ± 71.6 hours, p>0.05 for each year. Time to max dose (41.2 ± 59.2, 29.6 ± 67.9, 40.2 ± 69.2, 52.9 ± 64.5, and 35.1 ± 37.6 hours), and cumulative dose (11025 ± 11758.7, 10887.5 ± 12450.7, 16587.5 ± 33974.5, 8912.5 ± 8961.4, and 11912.5 ± 10770.3 mcg) for each year was not different, p>0.05. Respiratory, renal, and psychiatric concomitant conditions were significantly different for all years. Regardless of the year, patients who received concomitant F and ketamine had a significant incidence of hypotension, p=0.006. Conclusions: The results of this retrospective review of intubated ICU patients found no difference in F dosing requirements over a five-year period. A significant higher incidence of hypotension was found when patients received F with ketamine. The data may be limited by the varying presence of comorbidities from year to year.

A Comprehensive Review: Transdermal Drug Delivery System: A Tool For Novel Drug Delivery System

In the recent decade, skin delivery (topical and transdermal) has gained an unprecedented popularity, especially due to increased incidences of chronic skin diseases, demand for targeted and patient compliant delivery and interest in life cycle management strategies among pharmaceutical companies. Transdermal drug delivery system was presented to overcome the difficulties of drug delivery especially oral route. Transdermal drug delivery refers to a means of delivering drugs through the surface of the skin for local or systemic treatment. The drug functions after absorption through the skin into the systemic circulation via capillary action at a certain rate. Transdermal patches are now widely used as cosmetic, topical and transdermal delivery systems. These patches represent a key outcome from the growth in skin science, technology and expertise developed through trial and error, clinical observation and evidence-based studies that date back to the first existing human records. A transdermal patch is a medicated adhesive patch that is placed on the skin to deliver a specific dose of medication through skin and into the bloodstream. An advantage of a transdermal drug delivery route over other types of delivery system such as oral, topical, intravenous (i.v.), intramuscular (i.m.), etc. is that the patch provides a controlled release of the medication into the patient, usually through either a porous membrane covering a reservoir of medication or through body heat melting thin layers of medication embedded in the adhesive. The main disadvantage to transdermal delivery systems stems from the fact that the skin composition offers very effective barrier that allow only small molecule based drugs to penetrate the skin and pass through the barrier. Sildenafil citrate (SLD) is a selective cyclic guanosine monophosphate-specific phosphodiesterase type 5 inhibitor used for the oral treatment of erectile dysfunction and more recently, it has been used for the treatment of pulmonary arterial hypertension and the enhancement of uteroplacental perfusion in case of fetal growth retardation. The challenges facing the oral administration of the drug include poor bioavailability and short duration of action that requires frequent administration. The main objective of transdermal drug delivery system is to deliver drugs into systemic circulation through skin at predetermined rate with minimal inter and intrapatient variations. Keyword: Skin delivery, Transdermal drug delivery, Oral rout, Sildenafil citrate, Pulmonary arterial hypertension

Design, Development and Evaluation of Gastroretentive Drug Delivery System of Antacids

Magaldrate is an antacid have been widely used in the treatment of various gastric and duodenal disorders such as heartburn, reflux esophagitis, acid indigestion, gastritis, sour stomach, upset stomach, irritable stomach, gastric and duodenal ulcers. The conventional antacids dosage forms have a short duration of action which is about 2-3 hours due to gastric emptying process. A gastroretentive dosage form of antacid is needed since the healing of gastric ulcers occurs when gastric pH is kept above 3-4 during 24 hours. The present study was aimed at developing Gastro retentive bilayer drug delivery systems containing Magaldrate to minimize the side effect, improve the prolongation of action, to reduce the frequency of drug administration. A wet granulation technique was used to formulate 9 batches. Superdisintegrants like Polyplasdone XL-10, Ac-Di-Sol, and sodium starch glycolate was used for immediate release layer and HPMC K4 M, Ac-Di-Sol and lactose like polymers were used in floating layer. Preformulation studies were carried out to optimize the ratios required for various grades of polymers. The prepared floating tablets were evaluated for hardness, weight variation, thickness, friability, drug content uniformity, buoyancy lag time, total floating time, water uptake (swelling index), and in vitro dissolution studies. Successful formulation was developed having floating lag time as low as 30 sec and drug release was sustained up to 12 hrs. A biphasic drug release can be obtained by using bilayer tableting technology which involved compression of immediate and sustained release layer together. Bilayered floating tablets with release characteristics offer critical advantages such as, site specificity with improved absorption and efficacy. This technology can be inculcated to various medicaments which have stomach as the major site of absorption.&#x0D; Keywords: Magaldrate, Antacid, Gastroretentive dosage form, Bilayer floating tab, Superdisintegrant

300 LITERATURE CASE SERIES REVIEW ON LANDIOLOL IN ACUTE DECOMPENSATED HEART FAILURE SECONDARY TO TACHYARRHYTHMIAS

Abstract Introduction Landiolol is a recently innovated ultra-short-acting beta-blocker. Landiolol is the only beta-blocker with a specific dose recommendation for patients with cardiac dysfunction and acute atrial fibrillation (Class I recommendation according to the ESC guidelines). Landiolol has a shorter elimination half-life than any other beta-blocker, and it can be administered safely to patients with various tachyarrhythmias. The short duration of action and titratability of landiolol makes it ideal for use in critically ill patients. Purpose of the Study Review the case reports in the literature on the administration of landiolol in critically ill patients with acute decompensated heart failure (ADHF) secondary to tachyarrhythmias. Methods 11 case reports of ADHF secondary to tachyarrhythmias were identified. Personal, clinical and humoral data were collected. The heart rate and systolic pressure values in the time before and after the administration of Landiolol were plotted in a summary graph. Results The mean age of the 11 patients was 55 years old with high proBNP values at admission. The etiological diagnosis of heart failure was heterogeneous but tachyarrhythmia was the trigger event in all patients. Patients were critically ill with a mean EF of 26 ± 16% and an initial shock index of 1.4 ±0.5. Landiolol administered together with other antiarrhythmic drugs (amiodarone in 4/11 patients), epinephrine/norepinephrine (9/11) and levosimendan (4/11) favoured heart rate lowering and an increase in systolic blood pressure.At discharge, 4/11 had improved EF, in 10/11 sinus rhythm was restored, and all patients recovered hemodynamic stability without adverse events related to Landiolol (Figure 1). Conclusion In this case series review, Landiolol was a useful strategy in patients with ADHF refractory to conventional therapy by facilitating rate/rhythm control, limiting the toxicity of inotropic drugs and improving the hemodynamic profile. Figure 1

Solid lipid nanoparticle as an effective drug delivery system of a novel curcumin derivative: formulation, release in vitro and pharmacokinetics in vivo

Context Curcumin (Cur) has a short duration of action which limits its therapeutic efficacy. Carbonic acid 17-(1,5-dimethyl-hexyl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl ester 4-[7-(4-hydroxy-3-methoxy-phenyl)-3,5-dioxo-hepta-1,6-dienyl]-2-methoxy-phenyl ester (CUD), as a small molecule derivative of Cur with superior stability, has been developed in our laboratory. Objective CUD-loaded solid lipid nanoparticles (CUD-SLN) were prepared to prolong the duration of the drug action of Cur. Materials and methods CUD-SLN were prepared with Poloxamer 188 (F68) and hydrogenated soybean phospholipids (HSPC) as carriers, and the prescription was optimized. The in vitro release of CUD and CUD-SLN was investigated. CUD-SLN (5 mg/kg) was injected into Sprague Dawley (SD) rats to investigate its pharmacokinetic behaviour. Results CUD-SLN features high entrapment efficiency (96.8 ± 0.4%), uniform particle size (113.0 ± 0.8 nm), polydispersity index (PDI) (0.177 ± 0.007) and an appropriate drug loading capacity (6.2 ± 0.1%). Optimized CUD-SLN exhibited sustained release of CUD for about 48 h. Moreover, the results of the pharmacokinetic studies showed that, compared to Cur, CUD-SLN had a considerably prolonged half-life of 14.7 h, slowed its metabolism in vivo by 35.6-fold, and had an improved area under the curve (AUC0– t ) of 37.0-fold. Conclusions CUD-SLN is a promising preparation for the development of a small molecule derivative of Cur.

Study to compare the effect of Dexmedetomidine vs MgSo4 (50%) intrathecally as an adjuvant with bupivacaine (0.5%) for lower limb orthopedic surgery under subarachnoid block

Lower limb surgeries may be performed under local, regional (spinal or epidural) or general anesthesia, but neuraxial blockade is the preferred mode of anesthesia. Sub-arachnoid block or Spinal anaesthesia is the most common central block used in a surgical setting, which is being the most versatile and commonly used regional block. With increasing use of hyperbaric bupivacaine for sub arachnoid block, their limitations like prolongation of onset of sensory and motor blockage effect, short duration of action and early postoperative requirement of an analgesic agent, require an intrathecal adjuvant to these local anaesthetic agents for a complete satisfactory period of anaesthesia and patient satisfaction. The aim of this study was to compare and evaluate the effect of Dexmedetomidine with MgSO4 (50%) intrathecally as an adjuvant for the characteristics of sensory and motor blockage for lower limb orthopedic surgery under subarachnoid block along with bupivacaine (0.5%). : Participants were randomly divided into two groups of 40 participants each. Group D (n=40) received Bupivacaine + dexmedetomidine, Group M (n=40) received Bupivacaine + MgSO4. Under strict aseptic and antiseptic precaution subarachnoid block was performed. Mixture of drugs according to group assign was injected. Assessment of sensory and motor characteristics was done. Inj. Dexmedetomidine as an adjuvant in spinal block, seems to be superior to intra-thecal MgSO4 as it has faster onset, longer duration of action, prolonged analgesia in comparison with Magnesium Sulphate without significant hemodynamic alterations. Dexmedetomidine, as an adjuvant to Inj. Bupivacaine intra-thecally in sub-arachnoid block, has faster onset, longer duration of action, prolonged analgesia in comparison with Magnesium Sulphate.

A novel glucagon analog with an extended half-life, HM15136, normalizes glucose levels in rodent models of congenital hyperinsulinism

Congenital hyperinsulinism (CHI) is a rare genetic condition characterized by uncontrolled insulin secretion, resulting in hypoglycemia. Although glucagon has lately been regarded as a therapeutic option for CHI, its use is severely hampered by its poor solubility and stability at physiological pH, as well as its short duration of action. To address these constraints, we developed HM15136, a novel long-acting glucagon analog composed of a glucagon analog conjugated to the Fc fragment of human immunoglobulin G4 via a polyethylene glycol linker. In this study, we established that HM15136 was more soluble than natural glucagon (≥ 150 mg/mL vs 0.03 mg/mL). Next, we confirmed that HM15136 activated glucagon receptor in vitro and induced glycogenolysis and gluconeogenesis in rat primary hepatocytes. Pharmacokinetics (PK)/Pharmacodynamics (PD) analysis of HM15136 shows that HM15136 has a markedly longer half-life (36 h vs. < 5 min) and increased bioavailability (90%) compared to native glucagon in mice. Further, HM15136 could effectively reverse acute hypoglycemia induced by insulin challenge, and multiple doses of HM15136 could sustain increased blood glucose levels in CHI rats. In conclusion, our findings indicate that HM15136 promotes sustained elevation of blood glucose, demonstrating the potential for development as a once-weekly therapy for CHI.

Neuromuscular blockade characteristics of cisatracurium in patients receiving chemotherapy: A preliminary study in breast cancer patients.

Cancer chemotherapeutic agents cause alteration in the response to neuromuscular blocking drugs, which can have serious perioperative implications. Magnesium, commonly found to be deficient in these patients, plays an indispensable role in neuromuscular transmission. This study aimed to understand the effect of neoadjuvant chemotherapy on the neuromuscular blocking properties of cisatracurium. One hundred female patients scheduled for breast cancer surgery were divided into two groups (n = 50 each). Group B received neoadjuvant chemotherapy with taxane, adriamycin, and cyclophosphamide, and Group A did not receive neoadjuvant chemotherapy. Neuromuscular block following cisatracurium 0.15 mg/kg was measured using peripheral nerve stimulator at the ulnar nerve. Onset time, duration of intense block, clinical duration of action, time to TOF4 after the last dose of cisatracurium, along with preoperative serum magnesium concentration were measured. Correlation and multiple regression were run to analyze the relationship between history of neoadjuvant chemotherapy, preoperative magnesium, and the abovementioned time points. Mediation analysis was done to ascertain if magnesium was mediating the observed effects. Onset time was prolonged by nearly 18% in Group B compared to Group A (P = 0.001). The duration of intense block was 35.27 ± 8.9 min in Group B and 42.07 ± 10.99 min in Group A (P < 0.001). The clinical duration of action of cisatracurium was significantly shorter in Group B (46.06 ± 8.68 min) compared to Group A (55.87 ± 11.04 min, P < 0.001). The time to TOF4 was 32.86 ± 5.66 min in Group B and 36.57 ± 8.49 min in Group A (P < 0.05). Preoperative serum magnesium levels were significantly lower in Group B (P < 0.001). Patients who had received neoadjuvant chemotherapy had a delayed onset, shorter duration of action, and faster recovery for cisatracurium. Although preoperative magnesium levels were lower in Group B, it was found to be an independent predictor rather than a mediator of these effects.

A novel long-acting local anesthetic – HTX-011 (ZYNRELEF™) for postoperative pain control

ABSTRACT Introduction Pain following most surgical procedures is expected. However, the treatment and management of postoperative surgical pain have remained challenging. The use of opioid therapy has become increasingly controversial given the limited therapeutic window of these drugs, the adverse side effects, and the potential for abuse. A multimodal approach to the treatment of postoperative pain has been shown to improve pain outcomes after surgery and improve patient satisfaction. Here, we examine a new formulation of bupivacaine and meloxicam extended-release solution HTX-011 (ZYNRELEF®) and its efficacy in postoperative pain control. Areas covered HTX-011 exists as an extended-release polymer that controls the release of the active ingredients over 72 hours. A systematic approach was taken to review PubMed (Medline) for prospective and retrospective studies related to the use of HTX-011 for the management of postoperative pain. Expert opinion HTX-011 represents a new tool to help modulate postoperative pain. Although multimodal analgesia has been effective in managing postoperative pain, direct surgical infiltration with local anesthetics has had limited efficacy due to their short duration of action. The HTX-011 formulation provides a long-acting local anesthetic at the surgical site, which provides a longer period of analgesia while maintaining a favorable safety profile.

An Update on Novel Ocular Nanosystems with Possible Benefits in the Treatment of Corneal Neovascularization.

Corneal neovascularization (CNV) is an ocular pathological change that results from an imbalance between angiogenic factors and antiangiogenic factors as a result of various ocular insults, including infection, inflammation, hypoxia, trauma, corneal degeneration, and corneal transplantation. Current clinical strategies for the treatment of CNV include pharmacological treatment and surgical intervention. Despite some degree of success, the current treatment strategies are restricted by limited efficacy, adverse effects, and a short duration of action. Recently, gene-based antiangiogenic therapy has become an emerging strategy that has attracted considerable interest. However, potential complications with the use of viral vectors, such as potential genotoxicity resulting from long-term expression and nonspecific targeting, cannot be ignored. The use of ocular nanosystems (ONS) based on nanotechnology has emerged as a great advantage in ocular disease treatment during the last two decades. The potential functions of ONS range from nanocarriers, which deliver drugs and genes to target sites in the eye, to therapeutic agents themselves. Various preclinical studies conducted to date have demonstrated promising results of the use of ONS in the treatment of CNV. In this review, we provide an overview of CNV and its current therapeutic strategies and summarize the properties and applications of various ONS related to the treatment of CNV reported to date. Our goal is to provide a comprehensive review of these considerable advances in ONS in the field of CNV therapy over the past two decades to fill the gaps in previous related reports. Finally, we discuss existing challenges and future perspectives of the use of ONS in CNV therapy, with the goal of providing a theoretical contribution to facilitate future practical growth in the area.

Anti-inflammatory and antioxidant effects of rhein loaded nanomicelles in periodontitis

Drug therapy is an effective and essential treatment method for periodontitis. However, the systemic use of traditional antibiotic drugs has the disadvantages of low bioavailability, short duration of action and the possibility of causing a series of complications, which limits their use in the clinic. In this study, we prepared nanomicelles of distearoylphosphatidyl-ethanolamine-N-poly (ethyleneglycol) 2000 (DSPE-PEG) loaded with rhein (Rh-NMs) for local administration to treat periodontitis. In vitro, Rh-NMs slowly released approximately 55% of the active ingredient over 24 h, reduced the secretion of inflammatory cytokines and reactive oxygen species (ROS) by lipopolysaccharide (LPS)-stimulated cells. In vivo, Rh-NMs significantly inhibited gingivitis and alveolar bone resorption and played a therapeutic role in local tissue for more than 24 h. Therefore, Rh-NMs have the potential to be a novel and promising therapeutic agent for periodontitis management.

Enhanced Removal of Free Radicals by Aqueous Hydrogen Nanobubbles and Their Role in Oxidative Stress.

Elevated levels of reactive oxygen radicals caused by environmental stress are the key triggers of inflammation, aging, and disease; thus, it is critical to develop novel reactive oxygen radical scavenging methods with high efficiency and low toxicity. As a result of their selective reactive oxygen radical removal, hydrogen molecules are strong candidates, but their application is limited by the small hydrogen supply and short duration of action. In this study, we for the first time combined nanobubble (NB) technology and hydrogen water to remove reactive oxygen species (ROS) using copper ions as a representative environmental pollutant and Tetrahymena thermophila as a model organism. Hydrogen NBs displayed a remarkable capability of removing H2O2 and O2•- at molar ratios of 8:1 and 240:1, respectively, which were unable to be removed by dissolved hydrogen molecules only. During the oxidative defense phase, hydrogen NB water either directly removed ROS or increased the activity and relative expression of glutathione peroxidase (GSH-Px). During the oxidative inhibition phase, hydrogen NB water exerted antioxidant effects mainly by increasing the activities of superoxide dismutase and GSH-Px as well as the expression of the corresponding genes. Our results provide an important theoretical support for the wide application of hydrogen NBs in empowering the antioxidant defense system.

Cefovecin treatment of a dental abscess and associated Enterobacter cloacae infection in a red panda (Ailurus fulgens) utilising therapeutic drug monitoring

AbstractA red panda was presented with an abscess affecting the left maxillary premolar 2 caused by a foreign body and opportunistic infection with Enterobacter cloacae. As this panda was intolerant to the handling associated with frequent medication, cefovecin (Convenia Zoetis) was chosen to treat the infection. Cefovecin is a long‐acting antibiotic licensed for use in dogs and cats using a dose interval of 10–14 days. In many non‐domestic species, a much shorter duration of action (less than 24 hours) has been reported, so clinical justification for its use was necessary. A dose of 40 mg/kg body weight given at 7‐day intervals was chosen based on a clinical appraisal of the likely progression of this case. Therapeutic drug monitoring was used to validate this treatment; blood samples were collected at appropriate intervals and analysed by high‐pressure liquid chromatography. Plasma cefovecin was shown to have been maintained at values greater than 17 μg/ml for at least 7 days after each injection (minimum inhibitory concentration for the isolate 4 μg/ml–0.5 sssIr 8 Intermediate). Treatment was successful, and the tooth did not require removal.

Sedative effect of remimazolam combined with alfentanil in colonoscopic polypectomy: a prospective, randomized, controlled clinical trial

BackgroundRemimazolam is a newer benzodiazepine with properties of rapid onset, short duration of action, and fast recovery. Our study was to evaluate the effects of different doses of remimazolam combined with alfentanil in colonoscopic polypectomy.MethodsOne hundred twenty patients were randomly divided into four groups: alfentanil and propofol (AP) group, alfentanil and remimazolam 0.1 mg/kg (AR1 group), 0.15 mg/kg (AR2 group), or 0.2 mg/kg (AR3 group). Patients in the four groups received alfentanil 10 μg/kg, followed by propofol 2 mg/kg and three dosages of remimazolam. Modified Observer's Assessment of Alertness and Sedation (MOAA/S) scale, heart rate (HR), oxygen saturation (SpO2), respiratory rate (RR), bispectral index (BIS) values and mean arterial pressure (MAP) were collected at intervals of 5 min and analyzed at different time points: before anesthesia (T0), 5 min (T1), 10 min (T2), 15 min after anesthesia (T3) and at the end of surgery (T4). The average MAP was calculated utilizing the average of all MAP values. The primary outcome was the success rate of sedation. Secondary outcomes included time to full alert and adverse events.ResultsThe success rate of sedation was 100% among the four groups. The incidence of hypotension was significantly decreased (all P < 0.05) and the average MAP was higher in AR1-AR3 groups than AP group (all P < 0.001). None of the patients developed bradycardia or hypertension during surgery in all study groups. BIS values were higher (all P < 0.001) and the time to full alert was statistically shorter in AR1-AR3 groups (all P < 0.05) compared with the AP group. The MOAA/S score in AR1 was higher than AR2 (P < 0.05) and the AR3 group (P < 0.05) at T1 and BIS values in the AR1 group were significantly higher than AR3 group (P < 0.05) at T4.ConclusionsRemimazolam combined with alfentanil have a non-inferior sedative effect than propofol during the colonoscopic polypectomy. Moreover, this combination of two short-acting drugs might be a safer alternative.Trial registrationThe clinical trial was registered on (16/05/2021, ChiCTR2100046492).

Nicardia® XL (Nifedipine Extended Release): Technologically Advanced GITS Formulation Ensures Robust Efficacy and Assured Safety

Nifedipine is a classical dihydropyridine calcium channel blocker (CCB) indicated for the management of hypertension, vasospastic angina and chronic stable angina. Prestigious regulatory bodies like USFDA, EMA, CDSCO and TGA have approved long-acting Nifedipine for the management of hypertension and angina. Nifedipine was 1st introduced in United States as Adalat® (Bayer) in 1981 and in India as Nicardia® (J. B. Chemicals &amp; Pharmaceuticals) in 1985.&#x0D; Conventional Nifedipine shows the rapid onset and short duration of action which results in prompt and marked hypotensive effect but exhibits reflex SNS activation leading to flushing, tachycardia, worsening myocardial ischemia, and cerebrovascular ischemia. Nifedipine gastrointestinal therapeutic system (GITS) formulation addresses many of the concerns surrounding the older formulations of Nifedipine. Nifedipine GITS is a gold standard once-daily formulation of Nifedipine which allows relatively constant plasma drug concentrations over 24 hours. Nifedipine GITS provides a controlled release and gradual onset of action of Nifedipine, avoiding the reflex SNS activation resulting in improved tolerability and compliance.&#x0D; Clinical studies suggest that long-acting formulations of Nifedipine have slightly greater antihypertensive actions than Amlodipine. Nifedipine was also found to be more efficient than other CCBs like Amlodipine, Nicardipine, and Isradipine in resistant hypertensive patients. The addition of Nifedipine GITS to the conventional treatment of angina pectoris is safe and reduces the need for coronary angiography and interventions.&#x0D; Several landmark trials have demonstrated that long-acting Nifedipine improves endothelial function and arterial stiffness and reduces albuminuria, LV hypertrophy, atherosclerotic plaques and cardiovascular and cerebrovascular complications.&#x0D; This comprehensive review focuses on the superiority of the Nifedipine GITS formulation over the conventional Nifedipine and elaborates on the role of long-acting Nifedipine as a CCB of choice for the management of hypertension, resistant hypertension, angina pectoris and coronary artery disease.&#x0D; Keywords – Calcium Channel Blockers, Nifedipine, Long-Acting Nifedipine, Nifedipine GITS, Nifedipine Extended Release, Nicardia XL.

A comparative study between the use of dexmedetomidine vs. dexamethasone as adjuvants to bupivacaine in ultrasound-guided transversus abdominis plane block for postoperative pain relief in patients undergoing lower abdominal surgeries

Background &amp; objective: Transversus abdominis plane (TAP) block using local anesthetics is associated with relatively shorter duration of action, and thus additional analgesic drugs are required in the postoperative period. We compared the efficacy and duration of postoperative analgesia achieved with using dexmedetomidine or dexamethasone as adjuvants to bupivacaine in TAP block for lower abdominal surgeries.&#x0D; Methodology: We enrolled 45 adult patients aged from 20-60 y, and randomly divided them into three equal groups. Group A received ultrasound guided TAP block with 0.25% bupivacaine 20 ml plus 4 mg dexamethasone on each side. Group B received 0.25% bupivacaine 20 ml plus dexmedetomidine 0.5 µg/kg on each side, and Group C (control group) patients received only 0.25% bupivacaine 20 ml on each side. Postoperative pain was assessed with VAS on arrival in post-anesthesia care unit (PACU), at 2 h, 6 h, 12 h, 18 h, and at 24 h postoperatively. Duration of analgesia was the time from drug injection to the time of first rescue of analgesia was recorded.&#x0D; Results: Mean duration to first dose of rescue analgesia among patients of dexmedetomidine group (Group B) was significantly prolonged as compared to dexamethasone group and bupivacaine only group. Regarding postoperative pain scores there were no statistically significant difference between the three groups; except at 6 h between the A and B groups and the control group. Both dexamethasone group and dexmedetomidine group showed better pain control than bupivacaine only at 6 h interval.&#x0D; Conclusion: Dexmedetomidine added to bupivacaine in ultrasound-guided transversus abdominis plane block for postoperative pain relief in patients undergoing lower abdominal surgeries prolongs the time to initial postoperative pain presented by time to first rescue analgesic demand than dexamethasone added to bupivacaine; the shortest time to first rescue analgesic was observed in bupivacaine alone group.&#x0D; Abbreviations: TAP: Transversus abdominis plane block; LA: Local anesthetic; PACU: Post anesthesia care unit; VAS: Visual Analogue Scale; ASA: American Society of Anesthesiologists; SD: Standard deviation; IQR: Inter quartile range.&#x0D; Citation: Sobhy YS, Gadalla RR, Nofal WH, Saleh MAE, Abdou KM. A comparative study between the use of dexmedetomidine .vs dexamethasone as adjuvants to bupivacaine in ultrasound-guided transversus abdominis plane block for postoperative pain relief in patients undergoing lower abdominal surgeries. Anaesth. pain intensive care 2022;26(5):681–688; DOI: 10.35975/apic.v26i5.2031

Evaporation of fentanyl from ceramics for pulmonary drug delivery: a pilot study

Fast and non-invasive pain relief has been one of the primary goals in patient care. One suggested solution is to target the lungs, which allows the drug to be absorbed on a large surface area resulting in a very fast onset reaction. Ceramics possess great properties such as adjustable porosity and mild manufacturing conditions making them good candidates for drug delivery systems. Fentanyl is a very suitable component for treating acute and chronic pain due to its short duration of action. In this study, the possibility of using heat to evaporate fentanyl from ceramics for pulmonary drug delivery was evaluated. A slightly modified commercially available product (PAX 3) was used for the evaporation of fentanyl. Calcium sulfate was used as the drug carrier, i.e. by heating the fentanyl loaded calcium sulfate, fentanyl is released and can be inhaled. The ceramic loaded with fentanyl was heated to 230-250°C for 1-10 minutes and the vapor was collected in a syringe. The evaporated drug was collected and quantified with HPLC (High Pressure Liquid Chromatography). It was possible to evaporate up to 1.2 μg of the applied drug, while the remaining drug was left in the ceramic. Furthermore, unknown peaks were detected by the HPLC when the ceramics were exposed to higher temperatures and longer heating times. The results showed that it was possible to evaporate fentanyl from ceramics at temperatures below 250°C.

Study an effect of various orgainic solvents for preparation of glipizide mucoadhesive microspheres

Glipizide is a potent, rapid-acting with short duration of action and well tolerated second-generation sulfonylureas effective in reducing postprandial glucose level. However, if a dosage is missed before a meal, the risk of postprandial hypoglycemia and post-meal glucose excursions is always linked with the use of glipizide for the treatment of type 2 diabetes mellitus. Type 2 diabetes mellitus is a polygenic illness that includes both insulin secretion dysfunction and peripheral insulin resistance. (1)The study an effect of organic solvents preparation of glipizide controlled released mucoadhesive microspheres. (2)The microspheres were formulated conventional tremendous technique by emulsion solvent evaporation technique. (3) Mucoadhesive microspheres were evaluation parameters Examine by their impact on mucoadhesion, drug encapsulation efficacy (EE%), and in-vitro drug release. The produced microspheres were subjected to physical characterizations such as FTIR, DSC, particle analyzer, and SEM. Using cock stomach tissue, the ex-vivo mucoadhesive properties of the various orgainic solvents microspheres were studied. When compared to the other solvents microspheres employing, such as ethanol, methanol, acetone, glipizide loaded ethanol mucoadhesive microspheres had a higher EE percent (83.63±0.17%), a more sustained release profile over 10 hours, and superior adherence to cock stomach mucosa.

Design, Synthesis, and Evaluation of Lung-Retentive Prodrugs for Extending the Lung Tissue Retention of Inhaled Drugs.

A major limitation of pulmonary delivery is that drugs can exhibit suboptimal pharmacokinetic profiles resulting from rapid elimination from the pulmonary tissue. This can lead to systemic side effects and a short duration of action. A series of dibasic dipeptides attached to the poorly lung-retentive muscarinic M3 receptor antagonist piperidin-4-yl 2-hydroxy-2,2-diphenylacetate (1) through a pH-sensitive-linking group have been evaluated. Extensive optimization resulted in 1-(((R)-2-((S)-2,6-diaminohexanamido)-3,3-dimethylbutanoyl)oxy)ethyl 4-(2-hydroxy-2,2-diphenylacetoxy)piperidine-1-carboxylate (23), which combined very good in vitro stability and very high rat lung binding. Compound 23 progressed to pharmacokinetic studies in rats, where, at 24 h post dosing in the rat lung, the total lung concentration of 23 was 31.2 μM. In addition, high levels of liberated drug 1 were still detected locally, demonstrating the benefit of this novel prodrug approach for increasing the apparent pharmacokinetic half-life of drugs in the lungs following pulmonary dosing.

Comparative study of epidural fentanyl with bupivacaine and epidural tramadol with bupivacaine for postoperative pain management in orthopedic lower limb surgeries

Introduction: Pain is a complex subjective sensation that is difficult to quantify in a repeatable manner. Surgical pain is observed to be more intense post-surgery and then fades in the next 24 h. Epidural anesthesia/analgesia is the most widely used technique for lower limb surgeries because of its good sensory and motor block property, reduces stress response, and maintains sufficient spontaneous respiration and hemodynamic stability. Materials and Methods: The study looked at 100 individuals between the ages of 20 and 60 who underwent elective lower limb surgery and were classified as ASA I and II. The patients were split into two 50-person groups. The adverse effects of nausea, vomiting, respiratory depression, urine retention, and pruritus, as well as the quality and duration of postoperative analgesia, were investigated. The patient was monitored for 48 h after surgery. Results: A total of 100 patients were included in the study, where the least age of the patient was 19 years and the greatest age was 75 years. In group T, maximum patients belong to the age group of 26–35 years, whereas in group F maximum patients belong to the age group of 36–45years. In group T, 41 (82%) were males and 9 (18%) were females. In group F, 37 (74%) were males and 13 (26%) were females. Conclusion: Our findings show that epidural tramadol and epidural fentanyl are equally effective, except for fentanyl’s shorter duration of action. Fentanyl also has a moderate sedative effect, which is beneficial in the postoperative period.