Toxicity In Overdose Research Articles

Trends in tricyclic antidepressant prescribing and poisoning in England and Wales 2016-2020.

Tricyclic antidepressants (TCAs) are commonly prescribed despite no longer being a NICE-recommended first-line treatment for depression and their recognized toxicity in overdose. This study examined prescribing, mortality, hospital admissions and clinical TCA data to quantify the use and impact of TCAs in England and Wales. Primary care prescription data for the eight TCAs currently licensed in England and Wales were analysed alongside hospital admission and mortality data relating to TCAs over the study period (January 2016-December 2020 inclusive). Monthly Toxbase™ accesses regarding TCAs during the study period for each TCA were quantified. National Poisons Information Service (NPIS) enquiry data involving TCA exposure were obtained and patient demographics, circumstance, dose ingested and poisoning severity were analysed. English and Welsh mean monthly TCA prescriptions per 100 000 people significantly increased during the study period, both driven by amitriptyline 10mg tablets (95% confidence interval [CI] 3.49-4.59 and 6.36-7.92, respectively). Deaths from poisoning where a TCA was mentioned on the death certificate fell. Toxbase™ accesses increased for amitriptyline and nortriptyline but decreased for all other TCAs. NPIS telephone enquiries relating to TCAs decreased. Hospital admission data did not demonstrate an increase in admissions related to TCAs. Reduced TCA poisoning mortality in England and Wales was seen despite increased dispensing of TCAs in both nations. The prescribing of low-dose amitriptyline formulations was associated with increased consultation with Toxbase™ but not increased hospital admissions or NPIS enquiries, suggesting a fall in TCA poisoning severity resulting from their changing pattern of usage.

A prospective study of acute propranolol overdose defining dose thresholds of severe toxicity (ATOM – 9)

Introduction Propranolol is a beta-adrenoceptor blocking drug with sodium channel-blocking properties that can cause life-threatening toxicity in overdose. Limited research defines dose thresholds of toxicity. We aimed to investigate propranolol overdose and dose thresholds for severe toxicity. Material and methods This is a prospective series of patients with acute propranolol overdose ≥360 mg from August 2014 to December 2023 enrolled through the Australian TOxicology Monitoring (ATOM) collaboration. Severe toxicity was defined as seizure, coma, inotrope therapy, electrocardiographic evidence of sodium channel blockade, or cardiac arrest. Results There were 209 presentations in 165 patients (median age 30 years [range 15–80 years]; 117 females, 71%). The median reported dose ingested was 1,000 mg (IQR: 600–2,000 mg; range 360–16,000 mg). Co-ingestion occurred in 155 (74%) patients, most commonly involving benzodiazepines (n = 52). Bradycardia (heart rate <50 beats/min) occurred in 41 (20%), and hypotension (systolic blood pressure <90 mmHg) in 88 (42%). Severe toxicity occurred in 51 patients (24%), with 17 (8%) having a seizure and 29 (14%) developing coma. Forty-one (20%) received inotropes, including 31(15%) who were given epinephrine and 20 (10%) high-dose insulin. Electrocardiographic evidence of sodium channel blockade occurred in 16 (8%). Seven (3%) had a cardiac arrest (reported dose range 2,400–16,000 mg), with two deaths following the ingestion of propranolol 4,000 mg and 16,000 mg. The median length of stay was 17 h (IQR: 11–32 h). In 79 patients who ingested only propranolol, the lowest reported propranolol dose for hypotension was 400 mg and for bradycardia, 800 mg. The lowest reported dose for severe toxicity was propranolol 2,000 mg. In those ingesting propranolol only, 17 of 32 (53%) patients who ingested ≥2,000 mg had severe toxicity. Discussion Severe toxicity was common, occurring in a quarter of all propranolol overdoses and half of the isolated propranolol ingestions (≥2,000 mg). The outcome was usually favourable with good supportive care, even in severe toxicity. Conclusion The dose threshold for severe toxicity in isolated propranolol overdose appeared to be 2,000 mg.

Propranolol in anxiety: poor evidence for efficacy and toxicity in overdose.

Propranolol in anxiety: poor evidence for efficacy and toxicity in overdose.

Review of the fluoropyrimidine antidote uridine triacetate.

In 2015, the United States Food and Drug Administration (FDA) approved uridine triacetate to treat overdose and severe toxicity of the fluoropyrimidine chemotherapy agents 5-fluorouracil (5-FU) and its oral prodrug capecitabine. Uridine triacetate is as an oral prodrug of uridine that competes with cytotoxic fluoropyrimidine metabolites for incorporation into nucleotides. Two million people worldwide start fluoropyrimidine chemotherapy each year, with 20-30% developing severe or life-threatening adverse effects, often attributable to a genetic predisposition such as dihydropyrimidine dehydrogenase deficiency. Whilst genetic prescreening is recommended prior to starting fluoropyrimidine agents, this only prevents 20-30% of early-onset life-threatening toxicity and so does not obviate the need for an antidote. Initial in-human studies established that uridine triacetate more than doubles the maximum tolerated weekly 5-FU bolus dose. A lack of clinical equipoise meant a placebo-controlled phase III trial was not ethical and so the phase III trials used historical controls. These found that uridine triacetate improved survival in those with fluoropyrimidine overdose and severe toxicity from 16% to 94%, with 34% able to resume chemotherapy within 30 days. Five case reports of delayed fluoropyrimidine toxicity demonstrate improvement following uridine triacetate treatment 120-504 h after last fluoropyrimidine administration, suggesting efficacy beyond the FDA licencing indications. Mechanistically uridine triacetate would be expected to be effective for overdose and severe toxicity of tegafur (a 5-FU prodrug), but there are no published case reports describing this. Uridine triacetate is available internationally through an expanded access scheme and has been available in the UK since 2019 on a named patient basis.

Rationalising the dose threshold for severe carbamazepine toxicity: a retrospective series

Introduction Carbamazepine causes dose-dependent toxicity in overdose. Resources commonly state that severe toxicity occurs with ingestions >50 mg/kg without supporting evidence. We aimed to compare ingested dose with clinical toxicity. Methods This was a retrospective series of patients reportedly ingesting carbamazepine >2,000 mg referred to a clinical toxicology unit and state poisons information centre. Medical records were reviewed to extract patient demographics, ingestion details, clinical effects and management. Severe toxicity was defined as the presence of coma (Glasgow Coma Scale <9), seizure, or hypotension (systolic blood pressure <90 mmHg). Results There were 69 presentations in 42 patients with a median ingested carbamazepine dose of 113 mg/kg (IQR: 71–151 mg/kg). Coma occurred in 10 cases, eight having ingested >200 mg/kg and the remaining two ingesting 113 mg/kg and 151 mg/kg, respectively. Seizures occurred in four cases (lowest ingested dose 143 mg/kg). Hypotension occurred in five cases (lowest ingested dose 113 mg/kg). Discussion Severe carbamazepine toxicity did not occur with reported ingestions <100 mg/kg and was uncommon in ingestions <200 mg/kg. Conclusion Severe toxicity was common in ingestions >200 mg/kg. Using the suggested threshold of severe toxicity of >50 mg/kg appeared overly conservative in this series.

Usefulness of lipid emulsion for the management of cardiac toxicity in acute flecainide overdose

Usefulness of lipid emulsion for the management of cardiac toxicity in acute flecainide overdose

Multiscale architecture design of 3D printed biodegradable Zn-based porous scaffolds for immunomodulatory osteogenesis

Reconciling the dilemma between rapid degradation and overdose toxicity is challenging in biodegradable materials when shifting from bulk to porous materials. Here, we achieve significant bone ingrowth into Zn-based porous scaffolds with 90% porosity via osteoinmunomodulation. At microscale, an alloy incorporating 0.8 wt% Li is employed to create a eutectoid lamellar structure featuring the LiZn4 and Zn phases. This microstructure optimally balances high strength with immunomodulation effects. At mesoscale, surface pattern with nanoscale roughness facilitates filopodia formation and macrophage spreading. At macroscale, the isotropic minimal surface G unit exhibits a proper degradation rate with more uniform feature compared to the anisotropic BCC unit. In vivo, the G scaffold demonstrates a heightened efficiency in promoting macrophage polarization toward an anti-inflammatory phenotype, subsequently leading to significantly elevated osteogenic markers, increased collagen deposition, and enhanced new bone formation. In vitro, transcriptomic analysis reveals the activation of JAK/STAT pathways in macrophages via up regulating the expression of Il-4, Il-10, subsequently promoting osteogenesis.

The role of QRS complex prolongation in predicting severe toxicity in single-xenobiotic overdose

Objective The QRS complex duration is commonly used to prognosticate severity, predict outcomes, and indicate treatment in overdose. However, literature to support this practice is mixed in tricyclic antidepressant overdoses and absent in non-tricyclic antidepressant overdoses. Our objective was to assess the validity of QRS complex duration as a prognostic marker in overdose. Methods This was a secondary analysis of cases reported to the Toxicology Investigators Consortium between January 1, 2010, and December 31, 2022. Cases were assessed to determine the six xenobiotics most associated with QRS complex prolongation. All cases involving these six xenobiotics, regardless of QRS complex duration, constituted the study cohort. Inclusion criteria were cases of patients older than 12 years old with single-xenobiotic exposures. Clinical outcomes evaluated were seizure, ventricular dysrhythmia, metabolic acidosis, and death. Results Of 94,939 total cases, diphenhydramine, amitriptyline, bupropion, quetiapine, nortriptyline, and cocaine were most associated with QRS complex prolongation. Inclusion criteria were met by 4,655 cases of exposure to these xenobiotics. QRS complex prolongation was associated with increased odds ratio of seizure in all included xenobiotics, of ventricular dysrhythmia in all included xenobiotics except nortriptyline, and of metabolic acidosis or death in all included xenobiotics except nortriptyline and quetiapine. A normal QRS complex duration had a negative predictive value of greater than or equal to 93.0 percent of developing metabolic acidosis and 98.0 percent of developing a ventricular dysrhythmia or death from the xenobiotics studied. Discussion This study demonstrates that patients with QRS complex prolongation from all six xenobiotics studied had an increased prevalence and odds of developing severe outcomes. Furthermore, patients who did not develop QRS complex prolongation were unlikely to develop a ventricular dysrhythmia, metabolic acidosis, or death. These findings were noted in six xenobiotics that mechanistically can cause QRS complex prolongation through sodium channel or gap junction inhibition. Conclusion Identification of patients at risk for severe outcomes after overdose can be aided by measuring the QRS complex duration. If prospectively validated, these outcomes have implications on risk stratification, disposition level of care, and appropriateness of treatments.

The cardiovascular safety of tricyclic antidepressants in overdose and in clinical use.

Tricyclic antidepressants (TCAs) remain widely prescribed for depression and many other conditions. There may be important differences between individual TCA in regard to their overdose toxicity and their cardiac toxicity in clinical use. We conducted a systematic review to compare the toxicity of individual TCA in overdose and the risk of serious adverse cardiac events occurring with therapeutic doses. We used the fatal toxicity index (FTI) and case fatality ratio as markers of fatality in overdose, and hazard ratios or odds ratios for the risk of cardiovascular adverse events during normal clinical use. In all, 30 reports of mortality in overdose and 14 observational studies assessing the risk of cardiovascular adverse events in clinical use were included. FTI values were of the same order of magnitude (101-102) for all TCAs except lofepramine. Desipramine appears to be somewhat more likely than other TCAs to lead to death in overdose. Amitriptyline, clomipramine, dothiepin/dosulepin, doxepin, trimipramine and imipramine showed broadly similar toxicity and were usually reported to be less toxic than desipramine. Data on nortriptyline were contradictory. Lofepramine had the lowest risk of death in overdose. The rank order of overdose toxicity was broadly consistent between different FTI definitions and between markers used. With respect to the risk of cardiovascular events at clinically relevant exposure, amitriptyline, nortriptyline and lofepramine were associated with a greater risk of in-use cardiotoxicity. All measures of overdose toxicity were subject to external influences and confounding. The continued use of TCAs in depression and other conditions should be minimized when considering their undoubted toxicity in overdose and possible toxicity in normal clinical use.

Selenium alleviates modafinil-induced neurobehavioral toxicity in rat via PI3K/Akt/mTOR/GSK3B signaling pathway and suppression of oxidative stress and apoptosis: in vivo and in silico study.

Nonmedical use of modafinil (MOD) led to increased rates of overdose toxicity, road accidents, addiction, withdrawal, suicide, and mental illnesses. The current study aims to determine the probable MOD brain toxicity and elucidate the possible role of selenium (Se) in ameliorating the neurotoxicity in rat models. Fifty-four male Albino rats were randomly assigned into nine groups. The groups were G1 (control negative), G2 (Se0.1), G3 (Se0.2), G4 (MOD300), G5 (MOD600), G6 (Se0.1 + MOD300), G7 (Se0.2 + MOD300), G8 (Se0.1 + MOD600), and G9 (Se0.2 + MOD600). After finishing the experiment, blood and brain tissue were harvested for biochemical and histological investigation. Neurobehavior parameters were assessed. Tissue neurotransmitter levels and oxidative stress markers were assessed. Gene expression of PI3K/Akt/mTOR-GSK3B, orexin, and orexin receptor2 was measured by qRT-PCR. Histological and immunohistochemistry assessments, as well as molecular docking, were carried out. MOD-induced neurobehavioral toxicity exhibited by behavioral and cognitive function impairments, which are associated with decreased antioxidant activities, increased MDA levels, and decreases in neurotransmitter levels. Brain levels of mRNA expression of PI3K, Akt, and mTOR were decreased, while GS3K, orexin, and orexin receptors were significantly elevated. These disturbances were confirmed by histopathological brain changes with increased silver and Bax immunostaining and decreased crystal violet levels. MOD induced neurotoxic effects in a dose-dependent manner. Compared with the MOD groups, SE coadministration significantly attenuates MOD-induced toxic changes. Docking study shows the protective role of Se as an apoptosis inhibitor and inflammation inhibitor. In conclusion, Se could be used as a biologically effective antioxidant compound to protect from MOD neurobehavioral toxicity in Wistar rats by reversing behavioral alterations, inflammation, apoptosis, and oxidative injury.

A comparative overview of SSRI-sertraline and SNRI-desvenlafaxine

Depression is a mood disorder that causes a persistent feeling of sadness and loss of interest. The common features of all the depressive disorders are sadness, emptiness, or irritable mood, accompanied by somatic and cognitive changes that significantly affect the individual’s capacity to function. Depression is commonly treated in primary care, and SSRI drugs are frequently used as the first line of treatment. Selective Serotonin Reuptake Inhibitors (SSRIs) have the advantage of the ease of dosing and low toxicity in overdose. They are also the first-line medications for late-onset depression. Selective Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs), which include venlafaxine, desvenlafaxine, duloxetine, and levomilnacipran can be used as first-line agents, particularly in patients with significant fatigue or pain syndromes associated with the episode of depression. SNRIs also have an important role as second-line agents in patients who have not responded to SSRIs. The pharmacokinetics, pharmacodynamics, uses, side effects, and contraindications of desvenlafaxine, an SNRI, and sertraline, an SSRI are compared in this article.

Predicting serotonin toxicity in serotonin reuptake inhibitor overdose

Aims We aimed to investigate the frequency of serotonin toxicity following overdose of antidepressants that inhibit serotonin reuptake and the factors that influence the probability of serotonin toxicity occurring. Methods This was a retrospective cohort study of overdoses that included selective serotonin reuptake inhibitors (SSRIs) (70%) and serotonin norepinephrine reuptake inhibitors (SNRIs) (30%) admitted to a tertiary toxicology unit over 23 years. A multivariate mixed effects logistic regression model using NONMEM (7.2.0) was used to determine factors that influenced the probability of serotonin toxicity occurring. Results There were 1978 overdoses in 1520 patients; median age 33 y (range: 13–86 years) and 64% female. Median defined daily dose equivalent (DDD) was 15 (1–420). Co-ingestants were taken in 1678/1978 (85%) overdoses: 11 co-ingested the monoamine oxidase-A inhibitor (MAOI) moclobemide, 99 (5%) co-ingested olanzapine, 58 (3%) co-ingested risperidone and 417 co-ingested a benzodiazepine (21%). Serotonin toxicity occurred in 269 overdoses (13.6%). The probability of serotonin toxicity increased slightly per 10 DDD units dose [OR, 1.01; 95% confidence intervals (CIs): 0.93–1.10], increased for an SNRI vs. an SSRI [OR, 1.07; 95% CI: 0.99–1.15], and markedly increased with co-ingestion of moclobemide [OR, 33.12; 95% CI: 7.5–147]. The probability decreased per 10 y age [OR, 0.84; 95% CI: 0.74–0.95], and with co-ingestion of the serotonin 2 A receptor (5-HT2A) antagonists olanzapine [OR, 0.40; 95% CI: 0.17–0.94] or risperidone [OR, 0.13; 95% CI: 0.02–0.99]. The probability of serotonin toxicity was 12.5% at 1 DDD (therapeutic), 12.7% at 15 DDDs and 19% at 420 DDDs. In overdoses of the median dose of 15 DDDs, co-ingestion of moclobemide increased the probability to 83%, and co-ingestion of olanzapine or risperidone decreased it to 5.5% and 1.8%, respectively. Conclusions Serotonin toxicity is common following SSRI/SNRI overdose. Although dose increases probability, this was only a small effect. Co-ingestion with olanzapine or risperidone reduced the risk 2–6-fold, and moclobemide increased the risk 5-fold.

Evaluation of the hepatoprotective effect of naringenin loaded nanoparticles against acetaminophen overdose toxicity

Acute liver injury is a common clinical disease, which easily leads to liver failure and endangers life, seriously threatening human health. Naringenin is a natural flavonoid that holds therapeutic potential against various liver injuries; however it has poor water solubility and bioavailability. In this study, we aimed to develop naringenin-loaded bovine serum albumin nanoparticles (NGNPs) and to evaluate their hepatoprotective effect and underlying mechanisms against acetaminophen overdose toxicity. In vitro data indicated that NGNPs significantly increased the drug solubility and also more effectively protected the hepatocyte cells from oxidative damage during hydrogen peroxide exposure or lipopolysaccharide (LPS) stimulation. In vivo results confirmed that NGNPs showed an enhanced accumulation in the liver tissue. In the murine model of acetaminophen-induced hepatotoxicity, NGNPs could effectively alleviate the progression of acute liver injury by reducing drug overdose-induced levels of oxidative stress, inflammation and apoptosis in hepatocytes. In conclusion, NGNPs has strong hepatoprotective effects against acetaminophen induced acute liver injury.

Diphenhydramine: Time to Move on?

Diphenhydramine is one of the most widely available, longest-used antihistamine medications but has many side effects including sedation and risk of toxicity in overdose including cardiac toxicity. It is frequently inappropriately used when newer, more favorable antihistamine medications are available. Second-generation antihistamines are also widely available and affordable, with many of the same desired effects as diphenhydramine and fewer, if any, of the undesirable side effects. Because of the negative side effects and wide availability of alternative antihistamine medications, it is definitively time to move on from diphenhydramine.

Exposures to psycholeptics, psychoanaleptics, and cardiovascular drugs reported to the PIC erfurt during heat waves from 2003 to 2018

Psycholeptics, psychoanaleptics, and cardiovascular drugs alter individual tolerance to extreme heat. To explore the influence of heat waves on their toxicity in acute overdose, we retrospectively analyzed all human exposures to psycholeptics and psychoanaleptics (PLAexp) as well as cardiovascular drugs (CVDexp) registered by the Poisons Information Center (PIC) Erfurt between June to September of the years 2003 to 2018 for frequency, age groups, sex, circumstances of exposure, and symptom severity. The results of the non-heat years (NHY) 2004–2005 and 2007–2014 (average air temperature June-September 16.2 °C) were compared to the results of the heat years (HY) 2003, 2006 and 2015–2018 (average air temperature June-September 17.5 °C). In total, 13,191 cases (HY 5,117; NHY 8,074) of PLAexp and 2,960 cases (HY 1,168; NHY 1,792) of CVDexp were registered. During HY, accidental PLAexp (11.2% versus 9.7%) and CVDexp (40.6% versus 36.8%) were more often seen. Severe symptoms were less frequent in PLAexp (4.4% versus 6.3%) and CVDexp (3.3% versus 4.9%). Although in HY, no higher rates of moderate or severe PLAexp and CVDexp were detected than in NHY, patients with these medications should be observed carefully during heat waves because of affected body’s usual cooling mechanisms.

Psychiatric management of Patients in intensive care units.

Psychiatric management of Patients in intensive care units.

Evaluation of the hepatoprotective effect of curcumin-loaded solid lipid nanoparticles against paracetamol overdose toxicity: Role of inducible nitric oxide synthase

Curcumin (Cur) is a natural compound that exhibited therapeutic effects against various liver injuries however Cur showed poor water solubility and bioavailability. This study aimed to design Cur-loaded solid lipid nanoparticles (SLNs) and to evaluate the hepatoprotective and antioxidant effects in a model of acute hepatotoxicity induced by paracetamol (PCM) overdose compared to the raw Cur and N-acetylcysteine (NAC). SLNs were prepared by emulsion/solvent evaporation method and 32 factorial design was employed. Wistar rats were divided into Control, PCM, PCM + NAC, PCM + raw Cur, and PCM + Cur-SLNs groups and treated orally for 14 days before receiving a single PCM dose. The Cur-loaded SLNs showed high entrapment efficiency % ranging between 69.1 and 92.1%, particle size (PS) between 217 and 506 nm, and zeta potential values between −17.9 and −25.5 mV. The in vivo results revealed that the PCM group exhibited deterioration of liver functions, pathological lesions on the liver tissues, severe oxidative stress, and increases in both the serum and hepatic iNOS levels. Remarkably, the PCM + Cur-SLNs group showed significantly better liver functions and tissue integrity compared to the PCM group. Furthermore, higher reduced glutathione and catalase but lower malondialdehyde and iNOS levels were observed. In conclusion, Cur-loaded SLNs effectively prevented the liver damage induced by PCM overdose through alleviating the oxidative stress and inhibiting the serum and hepatic iNOS expression in an effect comparable to NAC and better than raw Cur.

Pain relief after maxillofacial surgery: efficacy in patients undergoing ultrasound- guided trigeminal nerve block – a randomized controlled trial

Background: Pain management is a critical factor for successful surgical outcomes, as it enables patients to recover more quickly. Maxillofacial surgery is typically complex and requires appropriate pain relief methods. In this study, the use of ultrasound to guide the blocking of the trigeminal nerve was investigated. Methods: The study enrolled 60 patients in a randomized controlled trial. The patients were divided into two groups: group T received a trigeminal (V) nerve block using ropivacaine under ultrasound guidance; and group C, the control group, received paracetamol infusion. During follow up, the following outcomes were assessed: time required for the first dose of pain relief; 24-hour dose of ketorolac in both groups; visual analog scale (VAS) score at rest and when moving; changes in hemodynamics, including pulse, systolic blood pressure, diastolic and blood pressure and changes in respiration including respiratory rate, and SpO2. Systemic complications such as allergies, anaphylaxis, drug overdose, and anesthetic toxicity, as well as local complications such as vascular puncture, nerve damage, hematoma at the injection site, facial paralysis, jaw dropping, and paresthesia/numbness of the lips and tongue were evaluated. Results &amp; Conclusion: The results showed that blocking branches V2 and V3 of the trigeminal nerve under ultrasound guidance improved pain relief in patients compared to the intravenous paracetamol. The VAS score of the study group was lower than that of the control group in most cases. In addition, the investigated group could tolerate pain longer until the later first dose of analgesic with a lower dose of ketorolac, which suggests the potential of this intervention in managing pain from maxillofacial surgery.

In Vivo and In Silico Assessment of Diabetes Ameliorating Potentiality and Safety Profile of Gynura procumbens Leaves.

Background Diabetes mellitus is one of the most notable health dilemmas. Analyzing plants for new antidiabetic remedies has become an impressive territory for life science researchers. Gynura procumbens has long been used to treat diabetes. Thus, we strived to ascertain the hypoglycemic potentiality of extract of leaves of G. procumbens by in vivo and in silico approaches. Methods Fresh leaves of G. procumbens were collected and shade-dried to prepare ethanolic extracts to evaluate pharmacological parameters. Diabetes was induced in rats via injecting alloxan through the intraperitoneal route at a dose of 150 mg/kg body weight. Humalyzer 3000 was used to perform a biochemical assay of collected samples from rats. Anti-hyperglycemic activity study along with overdose toxicity test was performed. The pharmacological activity of this plant was also evaluated through a molecular docking study. This in silico study investigated the binding affinity of natural ligands from G. procumbens against glycoside hydrolase enzymes. Results We detected a peak plasma concentration of G. procumbens at 3 hours 45 minutes that is roughly similar to the peak plasma concentration of metformin. Again, in OGTT and anti-hyperglycemic tests, it has been ascertained that both plant extract and metformin can exert significant (P < 0.05) and highly significant (P < 0.01) hypoglycemic activity in a dose-dependent manner. Metformin exhibited better therapeutic efficacy than that of plant extract, but it possessed null statistical significance. Also, our safety profile expressed that, similar to metformin, the plant extract can restore the disturbed pathological state in a dose-oriented approach with a wide safety margin. In silico study also validated the potentialities of natural constituents of G. procumbens. Conclusion. This study suggested that G. procumbens can be considered as potential antidiabetic plant. Robust and meticulous investigation regarding plant chemistry and pharmacology in the future may bring about a new dimension that will aid in discovering antidiabetic drugs from this plant in the diabetes management system.

Pharmacists have the right to refuse to fill ivermectin prescriptions

Pharmacists have the right to refuse to fill ivermectin prescriptions