scholarly journals Oliceridine as a Novel Selective mu-receptor G-protein Pathway Modulator: A Narrative review

2022 ◽  
Vol 9 (3) ◽  
pp. 3-7
Author(s):  
Uma Advani ◽  
Ravi Prakash ◽  
Parmanand Swami ◽  
Neha Sharma ◽  
Charu Jain ◽  
...  
Keyword(s):  
Postoperative Pain ◽  
G Protein ◽  
English Language ◽  
Opioid Analgesic ◽  
Rapid Onset ◽  
Repeat Dose ◽  
Opioid Agonist ◽  
Onset Of Action ◽  
Previous Response ◽  
Mu Receptor

Abstract Objective: To review the literature on equianalgesic efficacy and better safety(less respiratory depression and gastrointestinal dysfunction) of oliceridine versus opioid analgesic in moderate to severe postoperative pain. Methodology: A comprehensive literature search was conducted in PubMed (January 2021 to March 2021) using keywords as ‘oliceridine’, ‘ligand biased mu receptor agonist’, ‘acute postoperative pain’, ‘conventional opioids’ and ‘morphine’. All English language full text pre-clinical and clinical research articles were searched. In addition, other data source was from ClinicalTrial. Gov. Data Synthesis: Oliceridine is a novel selective µ (mu)-receptor G-protein pathway modulator. G protein biased mu receptor agonists are a new class of opioids exhibiting analgesic properties at par to morphine with less respiratory depressant properties. Oliceridine a first-in-class intravenous (IV) analgesic has received the US FDA approval in August 2020, for management of moderate to severe acute pain in adults. The drug can be administered in cases where the pain is severe enough to require an intravenous opioid and when alternative treatments become inadequate. Oliceridine is an opioid agonist with a rapid onset of action within two to five minutes, was administered via clinician-administered bolus dosing, patient-controlled analgesia (PCA), or a combination of the two. Bolus dosing was initiated at 1 to 2 mg, with supplemental doses of 1 to 3 mg every one to three hours, as needed, based on individual patient need and previous response to oliceridine in management of acute post-operative pain. If oliceridine was administered via PCA, the loading dose was 1.5 mg, the demand dose was 0.5 mg, and the lockout interval (repeat dose)was six minutes. The clinically relevant concentration range of 0 to 35 ng/ml. It is indicated for short-term use only & limited to hospitals or other controlled clinical settings. Oliceridine requires no dosage adjustments in patients with renal impairment as well as in patient with significant medical complications. Therefore, opioids that bias towards G-protein and away from β arrestin signaling should produce analgesia with reduced side effects.

Oliceridine for the Management of Acute Postoperative Pain

2021 ◽  
pp. 106002802098767
Author(s):  
Yang Liu ◽  
Qiang Hu ◽  
Junyi Yang
Keyword(s):  
Postoperative Pain ◽  
G Protein ◽  
Severe Pain ◽  
English Language ◽  
Data Extraction ◽  
Data Sources ◽  
Tolerability Profile ◽  
Acute Postoperative Pain ◽  
Onset Of Action ◽  
Favorable Safety

Objective To review the pharmacological characteristics, clinical evidence, and place in the management of acute postoperative pain severe enough to require an intravenous opioid. Data Sources A comprehensive literature search was conducted in PubMed (January 2000 to December 1, 2020). Key search terms included oliceridine or acute postoperative pain. Other sources were derived from product labeling and ClinicalTrials.gov. Study Selection and Data Extraction All English-language articles identified from the data sources were reviewed and evaluated. Phase I, II, and III clinical trials were included. Data Synthesis Oliceridine is a novel selective µ-receptor G-protein pathway modulator. It has the property of activating G-protein signaling while causing low β-arrestin recruitment to the µ-receptor. Intravenous oliceridine showed statistically superior analgesia than placebo in patients with moderate or severe pain after surgery, with a favorable safety and tolerability profile regarding respiratory and gastrointestinal adverse effects, compared with morphine. Relevance to Patient Care and Clinical Practice The analgesic capacity of oliceridine is at least comparable to that of morphine at clinically relevant dosages, with a rapid onset of action. Also, it may be associated with a lower incidence of adverse events at dosing regimens associated with comparable analgesia. These data suggest that oliceridine may provide an important new treatment option for the management of moderate to severe postoperative pain where an intravenous opioid is warranted. Conclusion Oliceridine has obvious analgesic effects in patients with moderate or severe pain after surgery; additionally, it has a favorable safety and tolerability profile.

scholarly journals Full Opioid Agonists and Tramadol: Pharmacological and Clinical Considerations

2021 ◽  
Vol 11 (4) ◽  
Author(s):  
Amber N. Edinoff ◽  
Leah A. Kaplan ◽  
Sami Khan ◽  
Murray Petersen ◽  
Emily Sauce ◽  
...  
Keyword(s):  
Pain Treatment ◽  
Opioid Analgesic ◽  
Sphincter Of Oddi ◽  
Opiate Withdrawal ◽  
Opioid Use ◽  
Opioid Agonist ◽  
Mu Receptor ◽  
Mu Receptors ◽  
Withdrawal Syndromes ◽  
Control Pain

: Opioids are mu receptor agonists and have been an important part of pain treatment for thousands of years. In order to use these drugs appropriately and successfully in patients, whether to control pain, to treat opiate-induced side effects, or opiate withdrawal syndromes, a solid understanding of the pharmacology of such drugs is crucial. The most recognized full agonist opioids are heroin, morphine, codeine, oxycodone, meperidine, and fentanyl. Phenanthrenes refer to a naturally occurring plant-based compound that includes three or more fused rings. The opioids derived from the opium plant are phenanthrene derivatives, whereas most synthetic opioids are simpler molecules that do not have multiple rings. Methadone acts as a synthetic opioid analgesic similar to morphine in both quality and quantity; however, methadone lasts longer and in oral form, has higher efficacy, and is considered a diphenylheptane. Fentanyl is a strong synthetic phenylpiperdine derivative that exhibits activity as a mu-selective opioid agonist approximately 50 to 100 times more potent than morphine. Meperidine is another medication which is a phenylpiperdine. Tramadol is considered a mixed-mechanism opioid drug, as it is a centrally acting analgesic that exerts its effects via binding mu receptors and blocking the reuptake of monoamines. Some of the most common adverse effects shared among all opioids are nausea, vomiting, pruritus, addiction, respiratory depression, constipation, sphincter of Oddi spasm, and miosis (except in the case of meperidine). Chronic opioid usage has also established a relationship to opioid-induced hypogonadism and adrenal suppression. Physicians must be stewards of opioid use and use opioids only when necessary.

scholarly journals Comparison among subarachnoid opioid mix for cesarean section – An observational study

2020 ◽  
Author(s):  
Cristina Isabel Osorio-Gutiérrez ◽  
Guillermo Alberto Ortiz-Gómez ◽  
Juan Felipe Valencia-Ríos ◽  
Fernando Arango-Gómez
Keyword(s):  
Postoperative Pain ◽  
Visual Analogue Scale ◽  
Adverse Effects ◽  
Cesarean Section ◽  
Analogue Scale ◽  
Safety Data ◽  
Analgesic Efficacy ◽  
Rapid Onset ◽  
Onset Of Action ◽  
Experienced Pain

Introduction: Classically, the local anesthetic (LA) has been combined with one lipophilic and another hydrophilic opioid for neuraxial anesthesia in cesarean section. In Colombia, the practice has been the use of morphine hydrochloride with fentanyl, but the occasional shortage of the former triggered an interest in new options. In response to the shortage of morphine in 2017-2018, a contingency plan was developed at the SES Hospital in Caldas, prefilling syringes at the hospital compounding central, with: bupivacaine, morphine y fentanyl (BMF); bupivacaine, fentanyl and hydromorphone (BHF); and bupivacaine and hydromorphone (BH). Hydromorphone has a rapid onset of action, long-lasting effect and is indicated for spinal administration in the safety data sheet; therefore, the advantages of adding fentanyl to this mix are questionable. Objective: To compare the clinical analgesic efficacy at the time of the incision and during the first 12 hours after surgery. Methods: An observational, analytical study was conducted, using the mixtures BMF, BHF and BH in patients receiving subarachnoid anesthesia for cesarean section. Pain was assessed at the time of the incision, as well as any adverse effects and the pain visual analogue scale over the following 12 hours. Results: Of the 71 patients participating in the study, 40.9 % received BMF; 22.5 %, BHF; and 36.6 %, BH. None of the patients experienced pain at the time of the incision. There was no difference in terms of adverse effects among the three groups. The mean difference in the visual analogue scale (VAS) for postoperative pain at 3, 6 and 12 hours was lower in the groups in which hydromorphone was used. Conclusions: BHF and BH combinations are comparable to the original preparation in terms of adverse effects, with the advantage of being more effective in controlling postoperative pain.

Cetirizine: A New, Nonsedating Antihistamine

1993 ◽  
Vol 27 (4) ◽  
pp. 464-470 ◽  
Author(s):  
Connie Lee Barnes ◽  
Constance A. McKenzie ◽  
Kathy D. Webster ◽  
Kim Poinsett-Holmes
Keyword(s):  
Adverse Effects ◽  
English Language ◽  
First Generation ◽  
Rapid Onset ◽  
Onset Of Action ◽  
Data Synthesis ◽  
Once Daily ◽  
Investigational Agent ◽  
Study Selection ◽  
Comparative Trials

OBJECTIVE: To introduce cetirizine, a nonsedating antihistamine, and discuss its mechanism of action, chemistry, clinical and comparative trials, and adverse effects. DATA SOURCES: An English-language literature search of MEDLINE was conducted. STUDY SELECTION: Human clinical trials were selected for evaluation. DATA SYNTHESIS: Cetirizine, an investigational agent and a potent histamine1-antagonist is a piperazine derivative and carboxylated metabolite of hydroxyzine. As a second-generation, nonsedating antihistamine, cetirizine is associated with fewer adverse effects compared with first-generation antihistamines. It appears to be at least as effective as the other nonsedating antihistamines in the treatment of allergic rhinitis, chronic idiopathic urticaria, and pollen-induced asthma. The recommended adult dosage of this agent is 5 or 10 mg/d. CONCLUSIONS: Clinical studies indicate that cetirizine may be more beneficial in some ways than other available agents. Two of these advantages are a rapid onset of action and a once-daily dosing regimen. Future postmarketing surveillance is warranted to further document these findings.

Rasburicase for the Treatment and Prevention of Hyperuricemia

2003 ◽  
Vol 37 (7-8) ◽  
pp. 1047-1054 ◽  
Author(s):  
Barbara T Yim ◽  
Rosalyn P Sims-McCallum ◽  
Pang H Chong
Keyword(s):  
Uric Acid ◽  
English Language ◽  
Data Extraction ◽  
Hematologic Malignancies ◽  
Rapid Onset ◽  
Urate Oxidase ◽  
Onset Of Action ◽  
Treatment And Prevention ◽  
Study Selection ◽  
Pediatric Use

OBJECTIVE: To review the information currently available on rasburicase for treatment and prevention of hyperuricemia. DATA SOURCES: MEDLINE (1966–August 2002) was searched for primary and review articles. STUDY SELECTION/DATA EXTRACTION: Studies evaluating rasburicase, including abstracts and proceedings, were considered for inclusion. English-language literature was evaluated for the pharmacology, pharmacodynamics, pharmacokinetics, therapeutic use, and adverse effects of rasburicase. DATA SYNTHESIS: Rasburicase, a recombinant urate oxidase, has been shown to be effective in lowering uric acid and preventing uric acid accumulation in patients with hematologic malignancies who had hyperuricemia or who were at high risk for developing hyperuricemia. It has been approved for pediatric use in the US. CONCLUSIONS: In addition to allopurinol, hydration, and urinary alkalinization, rasburicase is a new alternative for the treatment and prevention of hyperuricemia in patients with hematologic malignancies. Its rapid onset of action and the ability to lower preexisting elevated uric acid levels are the advantages of rasburicase compared with allopurinol. It may allow the patient to receive chemotherapy treatment without delay.

Brexanolone (Zulresso): Finally, an FDA-Approved Treatment for Postpartum Depression

2019 ◽  
Vol 54 (2) ◽  
pp. 157-163 ◽  
Author(s):  
Jason G Powell ◽  
Scott Garland ◽  
Kayla Preston ◽  
Chris Piszczatoski
Keyword(s):  
Postpartum Depression ◽  
English Language ◽  
Data Extraction ◽  
Clinical Information ◽  
Rapid Onset ◽  
Depression Symptoms ◽  
Onset Of Action ◽  
Fda Approval ◽  
Study Selection

Objective: To review the safety and efficacy of brexanolone for the treatment of moderate to severe postpartum depression (PPD). Data Sources: A literature search through PubMed was conducted (January 2012 to July 2019) using the keyword brexanolone for clinical trials published in the English language. Study Selection and Data Extraction: Articles were selected if they were related to the Food and Drug Administration (FDA) approval of brexanolone or provided novel clinical information regarding this drug entity. Data Synthesis: The findings of the review show that brexanolone administered via IV infusion is both an effective and a fairly safe option for the treatment of PPD. Relevance to Patient Care and Clinical Practice: There are several antidepressants currently used to treat PPD; however, this is the first with FDA approval for this indication. The rapid onset of action of brexanolone may offer a quicker relief of these symptoms and may possibly lead to improved quality of life for both the mother and the child. Conclusion and Relevance: The recent FDA approval of brexanolone may offer an effective treatment of moderate to severe PPD and has been shown to rapidly decrease depression symptoms.

The impact and mechanism of ampakine CX1739 on protection against respiratory depression in rats

2020 ◽  
Vol 12 (23) ◽  
pp. 2093-2104
Author(s):  
Dian Xiao ◽  
Fei Xie ◽  
Xin Xu ◽  
Xinbo Zhou
Keyword(s):  
Respiratory Depression ◽  
Ampa Receptors ◽  
Emergency Treatment ◽  
Rapid Onset ◽  
High Dose ◽  
Opioid Agonist ◽  
Onset Of Action ◽  
Sedative Drugs ◽  
The Impact

Background: Abuse of analgesic and sedative drugs often leads to severe respiratory depression and sometimes death. Approximately 69,000 people worldwide die annually from opioid overdoses. Purpose: This work aimed to investigate whether CX1739 can be used for emergency treatment of acute respiratory depression due to drug abuse. Results: First, the results clarify that CX1739 is a low-impact ampakine that can safely activate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors without causing excito-neurotoxicity. Second, CX1739 rapidly crossed the blood–brain barrier (Tmax = 2 min), which meets the requirement of rapid onset of action in vivo. Our work provides preliminarily confirmation that high-dose intravenous administration of CX1739 can immediately reverse respiratory depression in animal models of respiratory depression caused by opioid agonist 030418, pentobarbital sodium and ethanol.

Nasal Opioid Agonist Treatment in Patients with Severe Opioid Dependence: A Case Series

2021 ◽  
Vol 28 (1) ◽  
pp. 80-86
Author(s):  
Marc Vogel ◽  
Patrick Köck ◽  
Johannes Strasser ◽  
Christoph Kalbermatten ◽  
Hannes Binder ◽  
...  
Keyword(s):  
Opioid Dependence ◽  
Case Series ◽  
Rapid Onset ◽  
First Line ◽  
Opioid Agonist ◽  
Onset Of Action ◽  
Opioid Agonist Treatment ◽  
Routes Of Administration ◽  
Alternative Treatment Option ◽  
Insufficient Response

<b><i>Introduction:</i></b> Opioid agonist treatment (OAT) is the first-line treatment for opioid dependence. Currently available OAT options comprise oral (methadone and morphine) and sublingual (buprenorphine) routes of administration. In Switzerland and some other countries, severely opioid-dependent individuals with insufficient response to oral or sublingual OAT are offered heroin-assisted treatment (HAT), which involves the provision of injected or oral medical heroin (diacetylmorphine [DAM]). However, many patients on treatment with injectable DAM (i-HAT) suffer from injection-related problems such as deteriorated vein status, ulcerations, endocarditis, and abscesses. Other patients who do not respond to oral OAT do not inject but snort opioids, and are not eligible for i-HAT. For this population, there is no other short-acting OAT with rapid onset of action available unless they switch to injecting, which is associated with higher risks. Nasal DAM (n-HAT) could be an alternative treatment option suitable for both populations of patients. <b><i>Methods:</i></b> We present a case series of 3 patients on i-HAT who successfully switched to n-HAT. <b><i>Results/Conclusions:</i></b> This is the first description of the clinical use of the nasal route of administration for HAT. n-HAT may constitute an important risk-reduced rapid-onset alternative to i-HAT. In particular, it may be suited for patients with injection-related complications, or noninjecting opioid-dependent patients failing to respond to oral OAT.

Pharmacokinetic peculiarities of drugs used in the form of rapidly dispersible tablets (oral delivery system)

2020 ◽  
pp. 7-24
Author(s):  
Zhanna Kozlova ◽  
Ivan Krasnyuk ◽  
Yuliya Lebedeva ◽  
Ekaterina Odintsova
Keyword(s):  
Oral Mucosa ◽  
Oral Delivery ◽  
Chemical Properties ◽  
Rapid Onset ◽  
Systemic Circulation ◽  
Systemic Delivery ◽  
Onset Of Action ◽  
Mucosal Drug Delivery ◽  
Physical And Chemical ◽  
Pass Metabolism

Oral mucosal drug delivery is an alternative method of systemic delivery with several advantages over both injectable and enteral methods. Drugs that are absorbed through the oral mucosa directly enter the systemic circulation, passing through the gastrointestinal tract and first-pass metabolism in the liver due to oral mucosa being highly vascularised. This results in rapid onset of action for some drugs because of a more comfortable and convenient way of delivery than the intravenous one. But not all drugs can be administered through the oral mucosa due to characteristics of the oral mucosa and physical and chemical properties of the drug.

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