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Indian Journal of Medical Ethics 2023I have been practising medicine in an under-served rural setting since 1976, and have published around 109 papers in PubMed-indexed journals - including The Lancet, BMJ,...
I have been practising medicine in an under-served rural setting since 1976, and have published around 109 papers in PubMed-indexed journals - including The Lancet, BMJ, NEJM and several tropical medicine journals - on scorpion and snakebite cases causing acute life-threatening conditions. I have researched in detail, with restricted resources, the acute clinical effects of envenomation and management of scorpion and snakebite cases [1, 2]. In Mahad, the fatality rate due to refractory heart failure arising from autonomic storm evoked by scorpion venom was previously 30% [3]. Since the advent of prazosin and scorpion antivenom, it has dropped to less than 1% [4]. Similarly, fatalities due to snakebite poisoning have been reduced from 18% to 5.
Topics: Animals; Humans; Snake Bites; Scorpion Stings; Prazosin; Antivenins; Scorpion Venoms; Scorpions
PubMed: 36420604
DOI: 10.20529/IJME.2022.068 -
Systematic Reviews Apr 2017Scorpion stings cause an estimated 3000 deaths per annum worldwide. We conducted a systematic review of all controlled clinical trials related to scorpion sting... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Scorpion stings cause an estimated 3000 deaths per annum worldwide. We conducted a systematic review of all controlled clinical trials related to scorpion sting management.
METHODS
We searched PubMed, EMBASE, Scopus, Web of Science and CINAHL and included controlled prospective clinical trials (randomized or non-randomized). The following interventions were assessed: adults and children with scorpion stings treated with (a) steroids vs. placebo, (b) different methods of pain relief, (c) antivenom vs. supportive treatment, (d) prazosin vs. supportive treatment, (e) antivenom vs. prazosin and (f) antivenom plus prazosin vs. prazosin alone. When trials had comparative outcomes, they were combined in a meta-analysis. Data was analysed with Review Manager 5. Dichotomous data were compared with relative risk (RR), and continuous data were compared with mean differences using a fixed effect model. There is no PROSPERO registration number for this study.
RESULTS
Antivenom against Centruroides sp. are effective in reversing the clinical syndrome faster than no antivenom treatment in children (RR, 0.02; 95% CI, 0.01 to 0.06; 322 participants; three trials). Antivenom (against Mesobuthus tamulus) and prazosin combination is better than prazosin alone for faster resolution of symptoms (mean difference, -12.59 h; 95% CI, -14.01 to -11.17; 173 participants; three trials).
CONCLUSIONS
The polyvalent antivenom against Centruroides sp. in USA/Mexico and the monovalent antivenom against M. tamulus in India are effective for rapid resolution of symptoms. Prazosin is useful as an add-on therapy for M. tamulus stings.
Topics: Adrenergic alpha-1 Receptor Antagonists; Animals; Antivenins; Controlled Clinical Trials as Topic; Drug Therapy, Combination; Humans; Pain; Prazosin; Scorpion Stings; Scorpion Venoms; Scorpions; Steroids
PubMed: 28390429
DOI: 10.1186/s13643-017-0469-8 -
Frontiers in Behavioral Neuroscience 2021Major depressive disorder (MDD) remains a significant public health problem worldwide, and revised treatment strategies are therefore urgently needed, including the...
Major depressive disorder (MDD) remains a significant public health problem worldwide, and revised treatment strategies are therefore urgently needed, including the creation of novel antidepressant compounds or using existing molecular entities in new ways. Etiologic theories of MDD from decades ago have suggested that synaptic deficiencies of monoaminergic neurotransmitters play a causative role in this neuropsychiatric disorder, and that boosting monoamines with drugs such as SSRIs, SNRIs, TCAs, and MAOIs has antidepressant effects and in some individuals can even induce hypomania or mania. While other factors, such as various intracellular molecular pathways and hippocampal neurogenesis, undoubtedly also play a role in MDD, monoaminergic boosting drugs nonetheless have clearly demonstrated antidepressant properties. There is also, however, a body of studies in the preclinical literature suggesting that monoaminergic transmission drugs, including noradrenergic ones, also have antidepressant-like behavioral properties in rodents. Given that there is increasing evidence that the monoamines have u-shaped or Janus-faced dose-response properties, in which a mid-range value is "optimal" in a variety of behavioral and physiological processes, it is plausible that either too much or too little synaptic norepinephrine in key circuits may exacerbate MDD in some individuals. Here we briefly review rodent depression-related behavioral data, focusing on the forced swim test, from three major classes of noradrenergic transmission reducing drugs (alpha2 agonists, beta blockers, alpha1 antagonists), and find much support for the hypothesis that they have antidepressant-like properties. Whether these drugs are antidepressants in human subjects remains to be determined.
PubMed: 34658805
DOI: 10.3389/fnbeh.2021.673634 -
F1000Research 2020The management of resistant hypertension presents several challenges in everyday clinical practice. During the past few years, several studies have been performed to... (Review)
Review
The management of resistant hypertension presents several challenges in everyday clinical practice. During the past few years, several studies have been performed to identify efficient and safe pharmacological and non-pharmacological options for the management of such patients. The Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2) trial demonstrated significant benefits with the use of spinorolactone as a fourth-line drug for the treatment of resistant hypertension over doxazosin and bisoprolol. In addition, recent data support that spironolactone may demonstrate superiority over central acting drugs in such patients, as well. Based on the European guidelines, spironolactone is recommended as the fourth-line drug option, followed by amiloride, other diuretics, doxazosin, bisoprolol or clonidine. Among several device-based approaches, renal sympathetic denervation had fallen into hibernation after the disappointing results of the Renal Denervation in Patients With Uncontrolled Hypertension (SYMPLICITY HTN) 3 trial. However, the technique re-emerged at the epicenter of the clinical and research interest after the favorable results of three sham-controlled studies, which facilitated novel catheters and techniques to perform the denervation. Significant results of iliac anastomosis on blood pressure levels have also been demonstrated. Nevertheless, the technique-related adverse events resulted in withdrawal of this interventional approach. Last, the sympatholytic properties of the carotid baroreceptor activation therapy were associated with significant blood pressure reductions in patients with resistant hypertension, which need to be verified in larger controlled trials. Currently device-based approaches are recommended only in the setting of clinical trials until more safety and efficacy data become available.
Topics: Antihypertensive Agents; Bisoprolol; Catheters; Clinical Trials as Topic; Clonidine; Denervation; Doxazosin; Humans; Hypertension; Kidney; Spironolactone
PubMed: 32201574
DOI: 10.12688/f1000research.21669.1 -
Pharmacology Research & Perspectives Aug 2022The relationship between cardiovascular diseases and iron disorders has gained increasing attention; however, the effects of hypotensive drugs on iron metabolic...
The relationship between cardiovascular diseases and iron disorders has gained increasing attention; however, the effects of hypotensive drugs on iron metabolic alterations in hypertension are not well understood. The purpose of this study was to investigate iron metabolic changes after prazosin treatment of spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats. Our second objective was to examine the effects of hypertension and anti-hypertensive drugs on bone formation and resorption. SHRs and WKY rats were randomized into either prazosin-treated groups (WKY + PZ and SHR + PZ) or untreated groups (WKY and SHR). After 7 days of intragastric prazosin administration, the rats were sacrificed for analysis; blood samples and organs (the duodenum, liver, kidneys, spleen, and femur) were collected. Both WKY + PZ and SHR groups exhibited iron deficiency in the serum and liver. Prazosin increased the iron levels in the bone tissue of SHRs. Prazosin stimulated the expression of hepcidin mRNA in the liver of SHRs and inhibited the expression of this iron-regulatory hormone in WKY rats. FPN1 expression in the duodenum was increased significantly in SHRs, however markedly decreased after prazosin treatment. The expression of TLR4 and Ctsk was enhanced in the bone tissue of SHRs, whereas CLC-7 expression was inhibited. Both hypotension and hypertension can lead to iron deficiency. Treatment with prazosin restored iron homeostasis in SHRs. The inverse impacts of prazosin on hepatic hepcidin expression in SHRs versus WKY rats indicates differing iron regulatory mechanisms between hypertensive and normal animals. The osteoclast activity was found to be enhanced in SHRs. Further study is needed to address whether the changes in osteoblast and osteoclast activity in SHRs correlates with the effects on iron metabolism.
Topics: Animals; Hepcidins; Hypertension; Iron; Prazosin; Rats; Rats, Inbred SHR; Rats, Inbred WKY
PubMed: 35892277
DOI: 10.1002/prp2.991 -
Canadian Journal of Psychiatry. Revue... Mar 2017The present review aims to assess the clinical efficacy and safety of the α-1-adrenergic antagonist prazosin as primary pharmacologic treatment for post-traumatic... (Review)
Review
OBJECTIVE
The present review aims to assess the clinical efficacy and safety of the α-1-adrenergic antagonist prazosin as primary pharmacologic treatment for post-traumatic stress disorder (PTSD).
METHOD
A systematic review was performed using keywords (i.e., prazosin, α-1-adrenergic antagonist, α-1-blocker, post-traumatic stress disorder) in the databases PubMed/Medline (1966-May 2016), Embase (1966-May 2016), ScienceDirect (1823-May 2016), OvidSP (1946-May 2016) and Nature (1845-May 2016). To be considered for inclusion, studies had to test the efficacy of prazosin either alone or added to ongoing treatment in adults with PTSD, use validated tools to assess and monitor the disorders, allow comparisons on the basis of univariate analyses (i.e., p-values of t-tests and effect sizes) and list the identified adverse reactions.
RESULTS
12 studies were included: 5 randomized controlled trials, 4 open-label prospective trials and 3 retrospective file reviews. The evaluation concerned 276 patients exposed to civilian trauma (19%) or war trauma (81%). Prazosin significantly decreases trauma nightmares, avoidance, hypervigilance and improves patient status in all studies. No significant difference of blood pressure was observed at the end of trials.
CONCLUSIONS
Beyond the methodological and clinical biases of these studies, the present review not only confirms the effectiveness and good tolerability of prazosin, but also suggests its possible use as primary pharmacologic treatment for PTSD. Uncertainties remain, however, regarding the prescription modalities and dosages.
Topics: Adrenergic alpha-1 Receptor Antagonists; Humans; Prazosin; Stress Disorders, Post-Traumatic
PubMed: 27432823
DOI: 10.1177/0706743716659275 -
Saudi Journal of Biological Sciences May 2022anethole (ANE) is a monoterpene present in many aromatic plants, especially (PA) In this regard, we previously reported the anti-depressant potential of PA. Here, we...
anethole (ANE) is a monoterpene present in many aromatic plants, especially (PA) In this regard, we previously reported the anti-depressant potential of PA. Here, we examined the anti-depressant activity of ANE and its possible mechanism in mice. In experiment 1 the animals received ANE (12.5-50 mg.kg ) 60 min prior to forced swimming and open-field tests. In experiment 2, the animals received several receptor antagonists to assess the possible mechanism of ANE. The administration of ANE (25 and 50 mg.kg ; p < 0.01 and p < 0.001, respectively) exhibited an anti-depressive-like effect in FST without any significant effect on animal locomotion(p > 0.05). Moreover, haloperidol(p < 0.001), SCH23390(p < 0.001), sulpiride(p < 0.001), ketanserin(p < 0.001), -chlorophenylalanine(p < 0.001), WAY100135(p < 0.001), reserpine, (p < 0.001) prazosin(p < 0.001), and yohimbine(p < 0.001) inhibited the anti-depressive-like effect of ANE. Furthermore, co-treatment of a subeffective dose of ANE with imipramine or fluoxetine induced synergistic anti-depressant-like effects(p < 0.001). Our data mainly showed that the anti-depressive-like effect of ANE, which can be attributed to the contribution of the monoaminergic system.
PubMed: 35844399
DOI: 10.1016/j.sjbs.2022.01.060 -
Biomedicine & Pharmacotherapy =... Apr 2020Prazosin, a non-selective α1-adrenoceptor and a selective α2B-adrenoceptor antagonist, is reported to possess anti-cancer activity in some types of cancer. The aim of...
BACKGROUND
Prazosin, a non-selective α1-adrenoceptor and a selective α2B-adrenoceptor antagonist, is reported to possess anti-cancer activity in some types of cancer. The aim of this study was to investigate the effect of prazosin on acute myeloid leukemia (AML) and the underlying relevant mechanisms.
METHODS
AML cell lines U937 and HL60 were treated with different concentration of prazosin (5, 10 and 15 μM), CCK8 and flow cytometry assays were performed to examine the effects of prazosin on cell viability, cell cycle distribution and apoptosis. Western blot assay was used to detect the expression of related proteins.
RESULTS
We observed that prazosin inhibited cell viability of U937 and HL60 cells and induced the rate of apoptosis in a dose-dependent manner, as well as induced cell cycle arrest at G1 phase. The activation of PI3K/Akt/mTOR signaling pathway was significantly suppressed by prazosin via reducing the phosphorylation of Akt and mTOR. Moreover, by RNA-seq analysis, we found that the expression of tensin 1 (TNS1) was down-regulated by prazosin, and down-regulation of TNS1 could inhibit cell viability of U937 and HL60 cells, as well as induced cell apoptosis. The PI3K/Akt/mTOR signaling pathway was also suppressed by depletion of TNS1. Furthermore, up-regulation of TNS1 could reverse the effects of prazosin on viability and apoptosis in U937 and HL-60 cells, as well as the PI3K/Akt/mTOR signaling pathway.
CONCLUSION
These results highlight an anti-cancer activity of prazosin on AML by inhibiting the PI3K/Akt/mTOR pathway and targeting TNS1.
Topics: Apoptosis; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cell Survival; Humans; Leukemia, Myeloid, Acute; Phosphatidylinositol 3-Kinases; Phosphorylation; Prazosin; Proto-Oncogene Proteins c-akt; Signal Transduction; TOR Serine-Threonine Kinases; Tensins
PubMed: 31954876
DOI: 10.1016/j.biopha.2019.109731 -
Il Giornale Di Chirurgia 2016Urology pertinent neuroendocrine neoplasias are more and more driving to research attractive contributions mainly as regards the urinary tract paragangliomas, besides...
Urology pertinent neuroendocrine neoplasias are more and more driving to research attractive contributions mainly as regards the urinary tract paragangliomas, besides the prostate cancer neuroendocrine differentiation. About such visceral sympathetic paragangliomas, a considerable attention is aroused by those concerning the renal pelvis, urinary bladder and, particularly, the prostate gland. Essential catecholamine/adrenergic signal-mediated pathophysiological implications and outlined diagnostic approaches are here taken into consideration. Particularly, to reach an accurate functional diagnostic assessment, both plasma and urine catecholamine level tests are required together with ¹²³I or ¹³¹I-meta-iodobenzylguanidine (MIBG) scan while ¹³¹I-, instead of ¹²³I-, labeled MIBG, proving to be also useful to targeted radionuclide therapy of sympathetic paragangliomas. Nevertheless, a thorough diagnostic confirmation should be obtained by a proper histologic/ immunohistochemical study, so that it respectively highlighting the typical "zellballen" cell setting and neuroendocrine tumor cell specific biomarkers such as chromogranin-A, synaptophysin, neuron-specific enolase. Open/laparoscopic/robot-assisted surgical procedures are performed under α1 (doxazosin, prazosin) - and β(propranolol)-adrenergic blockade to avoid the risk of an intraoperative adrenergic signal-triggered hypertensive crisis, what moreover may occur also during cystoscopy and biopsy in case of bladder or prostate paraganglioma. Given a conceivable likeness, about some adrenergic-mediated pathophysiological implications, between prostate paraganglioma and prostate cancer neuroendocrine transdifferentiation - although as regards two obviously different diseases - a reliable pathogenetic matter concerning prostate paraganglioma is requiring novel research approaches.
Topics: Biomarkers; Catecholamines; Chromogranin A; Diagnosis, Differential; Humans; Kidney Pelvis; Male; Neuroendocrine Tumors; Paraganglioma; Pelvic Neoplasms; Phosphopyruvate Hydratase; Predictive Value of Tests; Prostatic Neoplasms; Sensitivity and Specificity; Synaptophysin; Urinary Bladder Neoplasms; Urology
PubMed: 27381689
DOI: 10.11138/gchir/2016.37.2.055 -
International Journal of Molecular... Dec 2021Gastrointestinal disease is the most common health concern that occurs due to environmental, infectious, immunological, psychological, and genetic stress. Among them,...
Gastrointestinal disease is the most common health concern that occurs due to environmental, infectious, immunological, psychological, and genetic stress. Among them, the most frequent diseases are gastric ulcer (GU) and ulcerative colitis (UC). DSS-induced UC and ethanol-stimulated GU models resemble the pathophysiology of human gastrointestinal disease. The current study was designed to explore the anti-oxidation, anti-inflammation, anti-cell death properties of terazosin, an α-adrenergic receptor antagonist, in vivo and in vitro. Our results indicate that terazosin dramatically activates Pgk1, and upregulates glycose metabolism, evidenced by the enhanced ATP production and higher LDH enzymatic activity. Also, terazosin significantly enhances p-AKT expression and inhibits NF-κB p65 activation through abrogating the phosphorylation of IKBα, as well as lowers Caspase-1 and GSDMD expression. The findings in this study demonstrate that terazosin exhibits anti-inflammatory effects by downregulating NF-κB-GSDMD signal pathway, along with enhancing glycolysis for gastrointestinal disease treatment. Meanwhile, we also find terazosin ameliorates ethanol-induced gastric mucosal damage in mice. Collectively, as a clinical drug, terazosin should be translated into therapeutics for gastrointestinal disease soon.
Topics: Apoptosis; Caco-2 Cells; Cell Survival; Colitis; Cytokines; Deoxyglucose; Dextran Sulfate; Gastric Mucosa; Gastrointestinal Diseases; Glucose; Humans; Hydrogen Peroxide; Inflammation Mediators; Lactic Acid; Malondialdehyde; Models, Biological; Peroxidase; Phosphoglycerate Kinase; Prazosin; Pyroptosis; Stomach Ulcer; Superoxide Dismutase
PubMed: 35008842
DOI: 10.3390/ijms23010416