Boromycin has Rapid-Onset Antibiotic Activity Against Asexual and Sexual Blood Stages of Plasmodium falciparum

Boromycin is a boron-containing macrolide antibiotic produced by Streptomyces antibioticus with potent activity against certain viruses, Gram-positive bacteria and protozoan parasites. Most antimalarial antibiotics affect plasmodial organelles of prokaryotic origin and have a relatively slow onset of action. They are used for malaria prophylaxis and for the treatment of malaria when combined to a fast-acting drug. Despite the success of artemisinin combination therapies, the current gold standard treatment, new alternatives are constantly needed due to the ability of malaria parasites to become resistant to almost all drugs that are in heavy clinical use. In vitro antiplasmodial activity screens of tetracyclines (omadacycline, sarecycline, methacycline, demeclocycline, lymecycline, meclocycline), macrolides (oleandomycin, boromycin, josamycin, troleandomycin), and control drugs (chloroquine, clindamycin, doxycycline, minocycline, eravacycline) revealed boromycin as highly potent against Plasmodium falciparum and the zoonotic Plasmodium knowlesi. In contrast to tetracyclines, boromycin rapidly killed asexual stages of both Plasmodium species already at low concentrations (~ 1 nM) including multidrug resistant P. falciparum strains (Dd2, K1, 7G8). In addition, boromycin was active against P. falciparum stage V gametocytes at a low nanomolar range (IC50: 8.5 ± 3.6 nM). Assessment of the mode of action excluded the apicoplast as the main target. Although there was an ionophoric activity on potassium channels, the effect was too low to explain the drug´s antiplasmodial activity. Boromycin is a promising antimalarial candidate with activity against multiple life cycle stages of the parasite.

Intranasal dexmedetomidine and intranasal ketamine association allows shorter induction time for pediatric sedation compared to intranasal dexmedetomidine and oral midazolam

Background Non-painful diagnostic procedures require an inactive state for a prolonged time, so that sedation is often needed in younger children to perform the procedures. Our standard of care in this setting consists of the association between oral midazolam (0.5 mg/kg) and intranasal dexmedetomidine (4 mcg/kg). One of the limits of this approach is that the onset of action is quite delayed (up to 55 min) and poorly predictable. We chose to compare this association with intranasal-ketamine and intranasal-dexmedetomidine. Methods This is a “pre-post” study. The study population included the first forty children receiving sedation with the “new” combination intranasal ketamine (3 mg/kg) and intranasal dexmedetomidine (4 mcg/kg) compared to a historical cohort including the last forty children receiving sedation with our standard of care combination of intranasal dexmedetomidine (4mcg/kg) and oral midazolam (0,5 mg/kg). Results The association intranasal dexmedetomidine and intranasal ketamine allowed for a significantly shorter sedation induction time than the combination intranasal dexmedetomidine and oral midazolam (13,5 min versus 35 min). Both group’s cumulative data showed a correlation between age and sedation effectiveness, with younger children presenting a higher success rate and shorter induction time (p 0,001). Conclusions: This study suggests that the ketamine and dexmedetomidine intranasal association may have a shorter onset of action when compared to intranasal dexmedetomidine and oral midazolam.

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

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.

Enhancement of Aqueous Solubility and Dissolution Profile of Atorvastatin Calcium: In vitro Evaluation of Solid Dispersion

Purpose: The objective of the present study was to formulate solid dispersions (SD) of Atorvastatin calcium to improve the aqueous solubility and dissolution rate to facilitate faster onset of action. Atorvastatin calcium is a lipid lowering agent belonging to BCS-II having low solubility and high permeability.

Formulation and Quality Control of Orally Disintegrating Tablets (ODTs): Recent Advances and Perspectives

Orally disintegrating tablets (ODTs) rapidly disintegrate or dissolve in the oral cavity without using water. Demand for ODTs has increased, and the field has overgrown in the pharmaceutical industry and academia. It is reported that ODTs have several advantages over other conventional tablets. Since some of them are absorbed from the mouth, pharynx, and esophagus as the saliva passes down into the stomach, in such cases, the bioavailability of the drug improves meaningfully. Furthermore, the immediate release property of ODTs makes them a popular oral dosage form in patients with swallowing challenges, children, and for cases with a need for rapid onset of action. The current review article explains the features of active ingredients and excipients used in the formulation of ODTs, discusses multiple ODT formulation and preparation techniques with their merits and demerits, and also, offers remedies for problems associated with ODTs. Moreover, quality control steps and required considerations are presented.

Preparation and Evaluation of Diclofenac Sodium Effervescent Tablet

The oral dosage forms are the most popular way of taking medicine although having some disadvantages like deliberate absorption and thus onset of action is extend. This can be overcome by administrating the drug in a liquid form i.e. effervescent tablet. The research is a formulation of diclofenac sodium as a effervescent tablet by wet granulation method. The bitter taste of the drug are masked by added sweetening agent (lactose, glucose etc.) In the present work we are prepared effervescent tablet in that we are used active drug diclofenac sodium and other active ingredient acid like tartaric acid and base sodium bicarbonate in different concentrations. The formulation of tablet was done by using wet granulation, wet granulation is found to be acceptable method of effervescent tablet formulation. The various pre-formulation studies was performed hardness, weight variation, disintegration, dissolution etc.

A Recent Update on Oral Anticoagulants

Atrial Fibrillation is very common among Americana; it is the irregular rhythm of the heart usually present with or without symptoms. It causes the formation of clots, clots go to the brain and cause a stroke. Anticoagulants have been known for a few decades to cause abrupt decrease around 50%) in the rate of stroke and prevent clotting at the required location and can cause bleeding. Anticoagulants aims for the safeguard and therapy of thromboembolism to prevent stroke. Previously used Anticoagulants are Warfarin, low molecular weight heparin and heparin. There were shortcoming of the drugs like parenteral route of administration, requires frequent monitoring due to variability in response, the onset of action is slow and there is bleeding in response to the drugs .In addition to heparin and vitamin k antagonist, anticoagulants that act on enzymatic agility or vigor brought about by of thrombin and factor Xa was exquisitely formulated. Implementation of the foresaid oral Anticoagulants requires knowledge of necessitate the comprehension of discrete indication, contraindications, characteristics. Research and repeated clinical trials have led to acceptance of few newer drugs which are working classically styled but better than Warfarin. In the last few years, Pradaxa (dabigatran), Xarelto (rivaroxaban), and Eliquis (dabigatran) have all been authorised by the FDA (apixaban). All three are ‘blood thinners,’ like warfarin, that lessen the overall risk of stroke associated with atrial fibrillation while also causing bleeding.

Secukinumab efficacy in the treatment of various types of psoriasis: A case series

The aim of this article is to describe our experience in a tertiary care medical college hospital with secukinumab in the treatment of various types of psoriasis as a case series of 10 patients. All the patients showed significant improvement in psoriasis area severity index and dermatology life quality index scores with no major adverse event reported during the period of study for 6 months duration. Secukinumab may be effective and safe for the treatment of all types of psoriasis with rapid onset of action and improvement in the quality of life.

Systematic Review on Loxapine: A Typical Antipsychotic Drug Used to Treat Agitation in Schizophrenic Patients

Loxapine is an antipsychotic drug used in neuroleptic disorders since 1980 with an entrenched drug profile. Drug possesses dibenzoxazepine tricyclic 7-membered heterocyclic ring available commercially as oral, intramuscular and inhalation dosage forms. This review comprises the various study designs of loxapine irrespective of its dose formulations. A comprehensive and systematic search was conducted on “Scopus”, “Web of science” and “Pub-med” data base and findings were critically analyzed. The data suggests that there is no significant difference in efficacy between typical and atypical antipsychotics. Till now, oral and intramuscular route is widely in use. Oral dosage forms are available in the market for the treatment of agitation related to schizophrenia but it has limitation of delayed onset of action that results in increased risk. Intramuscular formulations reveal a significant difference compared to placebo with respect to agitation but time range could be in range of 15 to 60 minutes. Therefore, there is a need for a novel drug delivery system with rapid action, increased half life, better tolerance by the patient and sustained release to get enhanced patient compliance.

Conolidine: A Novel Plant Extract for Chronic Pain

: Pain, the most common symptom reported among patients in the primary care setting, is complex to manage. Opioids are among the most potent analgesics agents for managing pain. Since the mid-1990s, the number of opioid prescriptions for the management of chronic non-cancer pain (CNCP) has increased by more than 400%, and this increased availability has significantly contributed to opioid diversion, overdose, tolerance, dependence, and addiction. Despite the questionable effectiveness of opioids in managing CNCP and their high rates of side effects, the absence of available alternative medications and their clinical limitations and slower onset of action has led to an overreliance on opioids. Conolidine is an indole alkaloid derived from the bark of the tropical flowering shrub Tabernaemontana divaricate used in traditional Chinese, Ayurvedic, and Thai medicine. Conolidine could represent the beginning of a new era of chronic pain management. It is now being investigated for its effects on the atypical chemokine receptor (ACK3). In a rat model, it was found that a competitor molecule binding to ACKR3 resulted in inhibition of ACKR3’s inhibitory activity, causing an overall increase in opiate receptor activity. Although the identification of conolidine as a potential novel analgesic agent provides an additional avenue to address the opioid crisis and manage CNCP, further studies are necessary to understand its mechanism of action and utility and efficacy in managing CNCP.