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Anesthesia and Analgesia Dec 2020Cardioprotection encompasses a variety of strategies protecting the heart against myocardial injury that occurs during and after inadequate blood supply to the heart... (Review)
Review
Cardioprotection encompasses a variety of strategies protecting the heart against myocardial injury that occurs during and after inadequate blood supply to the heart during myocardial infarction. While restoring reperfusion is crucial for salvaging myocardium from further damage, paradoxically, it itself accounts for additional cell death-a phenomenon named ischemia/reperfusion injury. Therefore, therapeutic strategies are necessary to render the heart protected against myocardial infarction. Ischemic pre- and postconditioning, by short periods of sublethal cardiac ischemia and reperfusion, are still the strongest mechanisms to achieve cardioprotection. However, it is highly impractical and far too invasive for clinical use. Fortunately, it can be mimicked pharmacologically, for example, by volatile anesthetics, noble gases, opioids, propofol, dexmedetomidine, and phosphodiesterase inhibitors. These substances are all routinely used in the clinical setting and seem promising candidates for successful translation of cardioprotection from experimental protocols to clinical trials. This review presents the fundamental mechanisms of conditioning strategies and provides an overview of the most recent and relevant findings on different concepts achieving cardioprotection in the experimental setting, specifically emphasizing pharmacological approaches in the perioperative context.
Topics: Analgesics, Opioid; Cardiotonic Agents; Humans; Ischemic Preconditioning, Myocardial; Myocardial Reperfusion Injury; Perioperative Care; Phosphodiesterase 3 Inhibitors; Postoperative Complications
PubMed: 33186163
DOI: 10.1213/ANE.0000000000005243 -
Journal of Advanced Research Dec 2023Tea (Camellia sinensis) has a rich history and is widely consumed across many countries, and is categorized into green tea, white tea, oolong tea, yellow tea, black tea,... (Review)
Review
BACKGROUND
Tea (Camellia sinensis) has a rich history and is widely consumed across many countries, and is categorized into green tea, white tea, oolong tea, yellow tea, black tea, and dark tea based on the level of fermentation. Based on a review of previous literature, the commonly recognized bioactive substances in tea include tea polyphenols, amino acids, polysaccharides, alkaloids, terpenoids, macro minerals, trace elements, and vitamins, which have been known to have various potential health benefits, such as anticancer, antioxidant, anti-inflammatory, anti-diabetes, and anti-obesity properties, cardiovascular protection, immune regulation, and control of the intestinal microbiota. Most studies have only pointed out the characteristics of tea's bioactivities, so a comprehensive summary of the pharmacological characteristics and mechanisms of tea's bioactivities and their use risks are vital.
AIM OF REVIEW
This paper aims to summarize tea's bioactive substances of tea and their pharmacological characteristics and mechanisms, providing a scientific basis for the application of bioactive substances in tea and outlining future research directions for the study of bioactive substances in tea.
KEY SCIENTIFIC CONCEPTS OF REVIEW
This review summarizes the main biologically active substances, pharmacological effects, and mechanisms and discusses the potential risks. It may help researchers grasp more comprehensive progress in the study of tea bioactive substances to further promote the application of tea as a natural bioactive substance in the medical field.
PubMed: 38056775
DOI: 10.1016/j.jare.2023.12.004 -
CMAJ : Canadian Medical Association... Nov 2023Pharmacogenomic testing to identify variations in genes that influence metabolism of antidepressant medications can enhance efficacy and reduce adverse effects of...
BACKGROUND
Pharmacogenomic testing to identify variations in genes that influence metabolism of antidepressant medications can enhance efficacy and reduce adverse effects of pharmacotherapy for major depressive disorder. We sought to establish the cost-effectiveness of implementing pharmacogenomic testing to guide prescription of antidepressants.
METHODS
We developed a discrete-time microsimulation model of care pathways for major depressive disorder in British Columbia, Canada, to evaluate the effectiveness and cost-effectiveness of pharmacogenomic testing from the public payer's perspective over 20 years. The model included unique patient characteristics (e.g., metabolizer phenotypes) and used estimates derived from systematic reviews, analyses of administrative data (2015-2020) and expert judgment. We estimated incremental costs, life-years and quality-adjusted life-years (QALYs) for a representative cohort of patients with major depressive disorder in BC.
RESULTS
Pharmacogenomic testing, if implemented in BC for adult patients with moderate-severe major depressive disorder, was predicted to save the health system $956 million ($4926 per patient) and bring health gains of 0.064 life-years and 0.381 QALYs per patient (12 436 life-years and 74 023 QALYs overall over 20 yr). These savings were mainly driven by slowing or avoiding the transition to refractory (treatment-resistant) depression. Pharmacogenomic-guided care was associated with 37% fewer patients with refractory depression over 20 years. Sensitivity analyses estimated that costs of pharmacogenomic testing would be offset within about 2 years of implementation.
INTERPRETATION
Pharmacogenomic testing to guide antidepressant use was estimated to yield population health gains while substantially reducing health system costs. These findings suggest that pharmacogenomic testing offers health systems an opportunity for a major value-promoting investment.
Topics: Adult; Humans; Depressive Disorder, Major; Pharmacogenetics; Depression; Cost-Benefit Analysis; Antidepressive Agents; Quality-Adjusted Life Years; British Columbia
PubMed: 37963621
DOI: 10.1503/cmaj.221785 -
Hospital Practice (1995) Mar 2020Substance use disorder prevalence in older adults is increasing as the baby boom generation ages. Of the different substances with concern for misuse and use disorder,...
Substance use disorder prevalence in older adults is increasing as the baby boom generation ages. Of the different substances with concern for misuse and use disorder, alcohol, prescription drugs, and illicit drugs are the leading causes. High-risk drinking and alcohol use disorder is the leading substance use disorder in older adults. Prescription drug misuse and use disorder in older adults are the second leading cause for substance use disorder and most commonly involves prescription opioids and benzodiazepines. Illicit drug use in older adults is also increasing. Substance use disorders are difficult to recognize in older adults due to medical comorbidity, neurocognitive impairment, and functional decline. Older adults are also more susceptible to drug effects due to decreased hepatic and renal clearance of the substances. Older adults should be screened and assessed for substance use disorders, and when diagnosed, non-pharmacologic as well as pharmacologic intervention should be performed.
Topics: Aged; Aged, 80 and over; Alcoholism; Analgesics, Opioid; Benzodiazepines; Cognitive Dysfunction; Comorbidity; Geriatric Assessment; Humans; Middle Aged; Physical Functional Performance; Substance-Related Disorders
PubMed: 32073917
DOI: 10.1080/21548331.2020.1733287 -
Expert Opinion on Pharmacotherapy 2023Comorbidity of substance use disorder (SUD) with schizophrenia, referred to as dual disorder (DD), significantly increases morbidity and mortality compared to... (Review)
Review
INTRODUCTION
Comorbidity of substance use disorder (SUD) with schizophrenia, referred to as dual disorder (DD), significantly increases morbidity and mortality compared to schizophrenia alone. A dopaminergic dysregulation seems to be a common pathophysiological basis of the comorbidity.
AREAS COVERED
This article reports the current evidence on the role of dopamine dysregulations in DD, the pharmacological profile of cariprazine, a partial agonist of D3 and D2 dopamine receptors, and first clinical observations that may support its usefulness in the therapy of DD. PubMed/MEDLINE was searched for the keywords 'cariprazine,' 'schizophrenia,' 'dual disorder,' 'dopamine,' and 'dopamine receptor.' Preclinical and clinical studies, and reviews published in English were retrieved.
EXPERT OPINION
Although the management of DD remains challenging, and the evidence for pharmacologic treatments is still unsatisfactory, cariprazine may be a candidate medication in DD due to its unique mechanism of action. Preliminary clinical experiences suggest that cariprazine has both antipsychotic and anticraving properties and should be considered early in patients with DD.
Topics: Humans; Schizophrenia; Dopamine; Receptors, Dopamine D3; Receptors, Dopamine D2; Substance-Related Disorders
PubMed: 37817489
DOI: 10.1080/14656566.2023.2266359 -
Journal of Medicinal Chemistry Nov 2020This Perspective of the published essential medicinal chemistry of cannabidiol (CBD) provides evidence that the popularization of CBD-fortified or CBD-labeled health... (Review)
Review
This Perspective of the published essential medicinal chemistry of cannabidiol (CBD) provides evidence that the popularization of CBD-fortified or CBD-labeled health products and CBD-associated health claims lacks a rigorous scientific foundation. CBD's reputation as a cure-all puts it in the same class as other "natural" panaceas, where valid ethnobotanicals are reduced to single, purportedly active ingredients. Such reductionist approaches oversimplify useful, chemically complex mixtures in an attempt to rationalize the commercial utility of natural compounds and exploit the "natural" label. Literature evidence associates CBD with certain semiubiquitous, broadly screened, primarily plant-based substances of undocumented purity that interfere with bioassays and have a low likelihood of becoming therapeutic agents. Widespread health challenges and pandemic crises such as SARS-CoV-2 create circumstances under which scientists must be particularly vigilant about healing claims that lack solid foundational data. Herein, we offer a critical review of the published medicinal chemistry properties of CBD, as well as precise definitions of CBD-containing substances and products, distilled to reveal the essential factors that impact its development as a therapeutic agent.
Topics: Animals; Cannabidiol; Chemistry, Pharmaceutical; Clinical Trials as Topic; Humans; Placebo Effect
PubMed: 32804502
DOI: 10.1021/acs.jmedchem.0c00724 -
American Journal of Health-system... Nov 2019This article presents updated information on kratom (Mitragyna speciosa), a natural opioid with stimulant properties that is currently sold in the United States without... (Review)
Review
PURPOSE
This article presents updated information on kratom (Mitragyna speciosa), a natural opioid with stimulant properties that is currently sold in the United States without a prescription.
SUMMARY
Kratom exerts opioid and alpha-2 agonistic effects, as well as anti-inflammatory and mild stimulant effects. Respiratory depression has not been commonly reported, but kratom does cause a host of adverse effects. While kratom may have a role in patients who are in chronic pain or dependent on opioid painkillers or heroin, this needs to be established in clinical trials. Kratom may have drug interactions as both a cytochrome P-450 system substrate and inhibitor. Kratom does not appear in normal drug screens and, especially when ingested with other substances of abuse, may not be recognized as an agent of harm. There are numerous cases of death in kratom users, but many involved polypharmaceutical ingestions. There are assessments where people have been unable to stop using kratom therapy and withdrawal signs/symptoms occurred in patients or their newborn babies after kratom cessation. Both banning and failure to ban kratom places people at risk; a middle-ground alternative, placing it behind the pharmacy counter, might be useful.
CONCLUSION
Kratom has a unique pharmacologic profile that might offer advantages over other opioids, but its high abuse liability, potential for drug interactions and adverse events, and inadequate research into the balance of benefits to harm are concerning. There is mounting information on the adverse events associated with kratom use and potential treatments that can be useful to clinicians.
Topics: Analgesics, Opioid; Biological Products; Chronic Pain; Clinical Trials as Topic; Humans; Mitragyna; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Withdrawal Syndrome
PubMed: 31626272
DOI: 10.1093/ajhp/zxz221 -
Advanced Drug Delivery Reviews Jan 2021Deoxyribonucleic acid (DNA) is a promising synthesizer for precisely constructing almost arbitrary geometry in two and three dimensions. Among various DNA-based soft... (Review)
Review
Deoxyribonucleic acid (DNA) is a promising synthesizer for precisely constructing almost arbitrary geometry in two and three dimensions. Among various DNA-based soft materials, DNA hydrogels are comprised of hydrophilic polymeric networks of crosslinked DNA chains. For their properties of biocompatibility, porosity, sequence programmability and tunable multifunctionality, DNA hydrogels have been widely studied in bioanalysis and biomedicine. In this review, recent developments in DNA hydrogels and their applications in drug delivery systems are highlighted. First, physical and chemical crosslinking methods for constructing DNA hydrogels are introduced. Subsequently, responses of DNA hydrogels to nonbiological and biological stimuli are described. Finally, DNA hydrogel-based delivery platforms for different types of drugs are detailed. With the emergence of gene therapy, this review also gives future prospects for combining DNA hydrogels with the gene editing toolbox.
Topics: Chemistry, Pharmaceutical; DNA; Drug Delivery Systems; Gene Editing; Hydrogels; Macromolecular Substances; RNA
PubMed: 32712197
DOI: 10.1016/j.addr.2020.07.018 -
Molecular Pharmaceutics Jul 2022For oral drugs, the formulator and discovery chemist have a tool available to them that can be used to navigate the risks associated with the selection and development... (Review)
Review
For oral drugs, the formulator and discovery chemist have a tool available to them that can be used to navigate the risks associated with the selection and development of immediate release oral drugs and drug products. This tool is the biopharmaceutics classification system (giBCS). Unfortunately, no such classification system exists for inhaled drugs. The perspective outlined in this manuscript provides the foundational principles and framework for a classification system for inhaled drugs. The proposed classification system, an inhalation-based biopharmaceutics classification system (iBCS), is based on fundamental biopharmaceutics principles adapted to an inhalation route of administration framework. It is envisioned that a classification system for orally inhaled drugs will facilitate an understanding of the technical challenges associated with the development of new chemical entities and their associated new drug products (device and drug formulation combinations). Similar to the giBCS, the iBCS will be based on key attributes describing the drug substance (solubility and permeability) and the drug product (dose and dissolution). This manuscript provides the foundational aspects of an iBCS, including the proposed scientific principles and framework upon which such a system can be developed.
Topics: Administration, Inhalation; Administration, Oral; Biopharmaceutics; Permeability; Pharmaceutical Preparations; Solubility
PubMed: 35576168
DOI: 10.1021/acs.molpharmaceut.2c00113 -
BMC Pediatrics Oct 2023Binge drinking is a widespread health compromising behavior among adolescents and young adults, leading to significant health problems, injuries and mortality. However,...
BACKGROUND
Binge drinking is a widespread health compromising behavior among adolescents and young adults, leading to significant health problems, injuries and mortality. However, data on alcohol consumption is often unreliable, as it is mainly based on self-reporting surveys. In this five-year study (2014-2019) at the University Children's Hospital Zurich, we analyzed blood samples from adolescent binge drinking patients to investigate blood alcohol concentrations (BACs), co-ingestion of drugs, assess compliance between self-reported and measured substance use, and test for genetic components of innate alcohol tolerance. Furthermore, hair analysis was performed to retrospectively access drug exposure and to evaluate the potential of hair analysis to assess binge drinking.
METHODS
In a prospective, single-center study, patients with alcohol intoxications aged 16 years and younger were included. Blood and hair samples were analyzed by sensitive liquid chromatography - tandem mass spectrometry drug analysis. HTTLPR genotyping was performed with PCR and fragment analysis.
RESULTS
Among 72 cases, 72 blood and 13 hair samples were analyzed. BACs ranged from 0.08-3.20‰ (mean 1.63‰, median 1.60‰), while a mean concentration of 3.64 pg/mg hair (median 3.0 pg/mg) of the alcohol marker ethyl glucuronide (EtG) was detected in eleven hair samples, providing no evidence of chronic excessive drinking. In 47% of the cases, co-ingested drugs were qualitatively detected next to ethanol, but only 9% of the detected drugs had blood concentrations classified as pharmacologically active. Cannabis consumption (22%) and stimulant intake (16%) were the most frequently observed drugs. Compliance between patients' statements and measured substances matched well. Although we investigated the genetic contribution to innate alcohol tolerance via the 5-HTTLPR polymorphism, the diverse genetic background of the cohort and small sample size did not allow any conclusions to be drawn.
CONCLUSION
Almost half of our binge drinking patients tested positive for other substances, primarily cannabis. We anticipate that our study enhances understanding of consumption behavior of young people and encourage continued efforts to address the harmful effects of binge drinking and co-occurring substance use.
Topics: Child; Young Adult; Humans; Adolescent; Retrospective Studies; Prospective Studies; Binge Drinking; Alcohol Drinking; Ethanol; Blood Alcohol Content; Biomarkers
PubMed: 37845619
DOI: 10.1186/s12887-023-04325-2