This book succeeds Review of Medical Pharmacology , by Meyers, Jawetz, and Goldfien. Edited by B. G. Katzung, some of the important areas covered include drug receptors and pharmacodynamics, pharmacokinetics of absorption and biotransformation of drugs, autonomic pharmacology of cholinergic and adrenergic receptor stimulants and antagonists, antihypertensive agents, cardiac glycosides and other agents used in the treatment of congestive heart failure, therapeutic drugs for cardiac arrhythmias, diuretics, pharmacology of the CNS drugs such as anticonvulsants and anesthetics, antidepressants, narcotic analgesics, nonsteroidal anti-inflammatory agents, endocrine pharmacology, antimicrobial and antimycobacterial drugs, antiprotozoal and antihelmintic drugs, cancer chemotherapy, and drugs and the immune system. Written by several prominent researchers and scientists, each chapter begins with a section on the basic pharmacology, chemistry, pharmacokinetics, and pharmacodynamics of the agents under discussion. This is followed by a section on clinical pharmacology, which deals with relevant information regarding the clinical use of drugs on the various

Basic and Clinical Pharmacology

Background Opioid use, abuse, and adverse consequences, including death, have escalated at an alarming rate since the 1990s. In an attempt to control opioid abuse, numerous regulations and guidelines for responsible opioid prescribing have been developed by various organizations. However, the US opioid epidemic is continuing and drug dose deaths tripled during 1999 to 2015. Recent data show a continuing increase in deaths due to natural and semisynthetic opioids, a decline in methadone deaths, and an explosive increase in the rates of deaths involving other opioids, specifically heroin and illicit synthetic fentanyl. Contrary to scientific evidence of efficacy and negative recommendations, a significant proportion of physicians and patients (92%) believe that opioids reduce pain and a smaller proportion (57%) report better quality of life. In preparation of the current guidelines, we have focused on the means to reduce the abuse and diversion of opioids without jeopardizing access for those patients suffering from non-cancer pain who have an appropriate medical indication for opioid use. Objectives To provide guidance for the prescription of opioids for the management of chronic non-cancer pain, to develop a consistent philosophy among the many diverse groups with an interest in opioid use as to how appropriately prescribe opioids, to improve the treatment of chronic non-cancer pain and to reduce the likelihood of drug abuse and diversion. These guidelines are intended to provide a systematic and standardized approach to this complex and difficult arena of practice, while recognizing that every clinical situation is unique. Methods The methodology utilized included the development of objectives and key questions. The methodology also utilized trustworthy standards, appropriate disclosures of conflicts of interest, as well as a panel of experts from various specialties and groups. The literature pertaining to opioid use, abuse, effectiveness, and adverse consequences was reviewed, with a best evidence synthesis of the available literature, and utilized grading for recommendation as described by the Agency for Healthcare Research and Quality (AHRQ).Summary of Recommendations:i. Initial Steps of Opioid Therapy 1. Comprehensive assessment and documentation. (Evidence: Level I; Strength of Recommendation: Strong) 2. Screening for opioid abuse to identify opioid abusers. (Evidence: Level II-III; Strength of Recommendation: Moderate) 3. Utilization of prescription drug monitoring programs (PDMPs). (Evidence: Level I-II; Strength of Recommendation: Moderate to strong) 4. Utilization of urine drug testing (UDT). (Evidence: Level II; Strength of Recommendation: Moderate) 5. Establish appropriate physical diagnosis and psychological diagnosis if available. (Evidence: Level I; Strength of Recommendation: Strong) 6. Consider appropriate imaging, physical diagnosis, and psychological status to collaborate with subjective complaints. (Evidence: Level III; Strength of Recommendation: Moderate) 7. Establish medical necessity based on average moderate to severe (≥ 4 on a scale of 0 - 10) pain and/or disability. (Evidence: Level II; Strength of Recommendation: Moderate) 8. Stratify patients based on risk. (Evidence: Level I-II; Strength of Recommendation: Moderate) 9. Establish treatment goals of opioid therapy with regard to pain relief and improvement in function. (Evidence: Level I-II; Strength of Recommendation: Moderate) 10. Obtain a robust opioid agreement, which is followed by all parties. (Evidence: Level III; Strength of Recommendation: Moderate)ii. Assessment of Effectiveness of Long-Term Opioid Therapy 11. Initiate opioid therapy with low dose, short-acting drugs, with appropriate monitoring. (Evidence: Level II; Strength of Recommendation: Moderate) 12. Consider up to 40 morphine milligram equivalent (MME) as low dose, 41 to 90 MME as a moderate dose, and greater than 91 MME as high dose. (Evidence: Level II; Strength of Recommendation: Moderate) 13. Avoid long-acting opioids for the initiation of opioid therapy. (Evidence: Level I; Strength of Recommendation: Strong) 14. Recommend methadone only for use after failure of other opioid therapy and only by clinicians with specific training in its risks and uses, within FDA recommended doses. (Evidence: Level I; Strength of Recommendation: Strong) 15. Understand and educate the patients of the effectiveness and adverse consequences. (Evidence: Level I; Strength of Recommendation: Strong) 16. Similar effectiveness for long-acting and short-acting opioids with increased adverse consequences of long-acting opioids. (Evidence: Level I-II; Strength of recommendation: Moderate to strong) 17. Periodically assess pain relief and/or functional status improvement of ≥ 30% without adverse consequences. (Evidence: Level II; Strength of recommendation: Moderate) 18. Recommend long-acting or high dose opioids only in specific circumstances with severe intractable pain. (Evidence: Level I; Strength of Recommendation: Strong)iii. Monitoring for Adherence and Side Effects 19. Monitor for adherence, abuse, and noncompliance by UDT and PDMPs. (Evidence: Level I-II; Strength of Recommendation: Moderate to strong) 20. Monitor patients on methadone with an electrocardiogram periodically. (Evidence: Level I; Strength of Recommendation: Strong). 21. Monitor for side effects including constipation and manage them appropriately, including discontinuation of opioids when indicated. (Evidence: Level I; Strength of Recommendation: Strong)iv. Final Phase 22. May continue with monitoring with continued medical necessity, with appropriate outcomes. (Evidence: Level I-II; Strength of Recommendation: Moderate) 23. Discontinue opioid therapy for lack of response, adverse consequences, and abuse with rehabilitation. (Evidence: Level III; Strength of Recommendation: Moderate) CONCLUSIONS: These guidelines were developed based on comprehensive review of the literature, consensus among the panelists, in consonance with patient preferences, shared decision-making, and practice patterns with limited evidence, based on randomized controlled trials (RCTs) to improve pain and function in chronic non-cancer pain on a long-term basis. Consequently, chronic opioid therapy should be provided only to patients with proven medical necessity and stability with improvement in pain and function, independently or in conjunction with other modalities of treatments in low doses with appropriate adherence monitoring and understanding of adverse events.Key words: Chronic pain, persistent pain, non-cancer pain, controlled substances, substance abuse, prescription drug abuse, dependency, opioids, prescription monitoring, drug testing, adherence monitoring, diversionDisclaimer: The guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a "standard of care."

Responsible, Safe, and Effective Prescription of Opioids for Chronic Non-Cancer Pain: American Society of Interventional Pain Physicians (ASIPP) Guidelines.

Diabetes mellitus is one of the major health problems in the world, the incidence and associated mortality are increasing. Inadequate regulation of the blood sugar imposes serious consequences for health. Conventional antidiabetic drugs are effective, however, also with unavoidable side effects. On the other hand, medicinal plants may act as an alternative source of antidiabetic agents. Examples of medicinal plants with antidiabetic potential are described, with focuses on preclinical and clinical studies. The beneficial potential of each plant matrix is given by the combined and concerted action of their profile of biologically active compounds.

https://www.mdpi.com/2218-273X/9/10/551/pdf

Antidiabetic Potential of Medicinal Plants and Their Active Components.

Withania somnifera, also called 'Indian ginseng', is an important medicinal plant of the Indian subcontinent. It is widely used, singly or in combination, with other herbs against many ailments in Indian Systems of Medicine since time immemorial. Withania somnifera contains a spectrum of diverse phytochemicals enabling it to have a broad range of biological implications. In preclinical studies, it has shown anti-microbial, anti-inflammatory, anti-tumor, anti-stress, neuroprotective, cardioprotective, and anti-diabetic properties. Additionally, it has demonstrated the ability to reduce reactive oxygen species, modulate mitochondrial function, regulate apoptosis, and reduce inflammation and enhance endothelial function. In view of these pharmacologic properties, W. somnifera is a potential drug candidate to treat various clinical conditions, particularly related to the nervous system. In this review, we summarize the pharmacologic characteristics and discuss the mechanisms of action and potential therapeutic applications of the plant and its active constituents.

Pharmacologic overview of Withania somnifera, the Indian Ginseng

The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2009)

Objectives

Withania somnifera has been in use for several thousand years in Ayurveda to treat various neurological disorders. There is, however, not much scientific data on its protective role in neuronal pathology specifically against brain oxidative stress. Hence, an attempt is made in this work for systematic review and meta-analysis of W. somnifera on neurobehavioural disorders induced by brain oxidative stress in rodents.



Methods

A systematic search of the effect of W. somnifera on brain oxidative stress-induced neuronal pathology was performed using electronic databases. The systematic review was performed on neurobehavioural parameters, whereas meta-analysis of W. somnifera effect was done on oxidative stress markers (superoxide dismutase, catalase, glutathione peroxidase, glutathione and lipid peroxidation), nitrite, protein carbonyl, AchE, ChAT and Ach of rodent brain. Data were analysed using Review Manager Software.



Key findings

Twenty-eight studies were selected based upon the inclusion and exclusion criteria. W. somnifera appreciably inhibited the neurological abnormalities due to oxidative stress in rodent brain produced by different physical and chemical stimuli. W. somnifera also significantly restored the altered oxidative and other stress markers in different parts of rodent brain.



Summary

The systematic review provides scientific evidence for the traditional claim of W. somnifera use in different neurological aliments. However, future clinical trials are mandated to establish the therapeutic efficacy and safety in human beings.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/jphp.12398

Withania somnifera (Ashwagandha) in neurobehavioural disorders induced by brain oxidative stress in rodents: a systematic review and meta-analysis.

Antidiabetic activity of Embelia ribes, embelin and its derivatives: A systematic review and meta-analysis.

Withania somnifera (Indian ginseng) in male infertility: An evidence-based systematic review and meta-analysis.

Embelin lipid nanospheres for enhanced treatment of ulcerative colitis – Preparation, characterization and in vivo evaluation

Sickness behaviour is a coordinated set of adaptive behavioural changes that develop in ill individuals during the course of an infection. It is relevant to understanding depression and some aspects of the suffering that in cancer. Embelin has been reported to possess antiinflammatory, neuroprotective and anxiolytic assets and has been shown to inhibit nuclear factor κB pathway and cytokine production. The present study was undertaken to investigate the effect of embelin isolated from Embelia ribes Burm in lipopolysaccharide (LPS)-induced sickness behaviour in mice. Adult male Swiss albino mice were pre-treated with embelin (10 and 20 mg/kg, p.o.) or dexamethasone (1 mg/kg, i.p.) for 3 days and then challenged with LPS (400 µg/kg, i.p.). At different time intervals of post-LPS challenge, sickness behaviour was evaluated in the animals by battery of behavioural tests (plus maze, open field, light-dark box, forced swim, social behaviour assessment, sucrose preference and food and water intake). Levels of oxidative stress makers (reduced glutathione and lipid peroxidation) in mice brain were also analysed. LPS induced behavioural alterations, anhedonia and anorexia, in mice. Pre-treatment with embelin attenuated behavioural changes induced by LPS. In addition, embelin prevented anhedonia, anorexia and ameliorated brain oxidative stress markers. The experimental outcomes of the present study demonstrated protective effect of embelin in LPS-induced sickness behaviour in mice. Copyright © 2016 John Wiley & Sons, Ltd.

Sharanbasappa Durg

Papers

Withania somnifera (Ashwagandha) in neurobehavioural disorders induced by brain oxidative stress in rodents: a systematic review and meta-analysis.

Antidiabetic activity of Embelia ribes, embelin and its derivatives: A systematic review and meta-analysis.

Withania somnifera (Indian ginseng) in male infertility: An evidence-based systematic review and meta-analysis.

Embelin lipid nanospheres for enhanced treatment of ulcerative colitis – Preparation, characterization and in vivo evaluation

Effect of Embelin Against Lipopolysaccharide-induced Sickness Behaviour in Mice.