scholarly journals Dependence, withdrawal and rebound of CNS drugs: an update and regulatory considerations for new drugs development

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Alicja Lerner ◽  
Michael Klein
Keyword(s):  
Drug Withdrawal ◽  
Multiple Scales ◽  
New Drugs ◽  
Systematic Evaluation ◽  
Dsm 5 ◽  
Drug Classes ◽  
Abrupt Discontinuation ◽  
Cns Drugs ◽  
Withdrawal Syndromes ◽  
Clinical Drug

Abstract The purpose of this article is to describe dependence and withdrawal phenomena related to CNS drugs discontinuation and to clarify issues related to the evaluation of clinical drug withdrawal and rebound as they relate to safety in new drug development. The article presents current understanding and definitions of drug dependence and withdrawal which are also relevant and important features of addiction, though not the same. Addiction, called substance use disorder in DSM-5, affects an individual’s brain and behaviour, represents uncontrollable drug abuse and inability to stop taking a drug regardless of the harm it causes. Characteristic withdrawal syndromes following abrupt discontinuation of CNS-active drugs from numerous drug classes are described. These include drugs both scheduled and non-scheduled in the Controlled Substances Act, which categorizes drugs in five schedules based on their relative abuse potentials and dependence liabilities and for regulatory purposes. Schedules 1 and 2 contain drugs identified as those with the highest abuse potential and strictest regulations. Less recognized aspects of drug withdrawal, such as rebound and protracted withdrawal syndromes for several drug classes are also addressed. Part I presents relevant definitions and describes clinical withdrawal and dependence phenomena. Part II reviews known withdrawal syndromes for the different drug classes, Part III describes rebound and Part IV describes protracted withdrawal syndromes. To our knowledge, this is the first compilation of withdrawal syndromes for CNS drugs. Part V provides details of evaluation of dependence and withdrawal in the clinical trials for CNS drugs, which includes general design recommendations, and several tools, such as withdrawal questionnaires and multiple scales that are helpful in the systematic evaluation of withdrawal. The limitations of different aspects of this method of dependence and withdrawal evaluation are also discussed.

scholarly journals Avoiding Adverse Drug Withdrawal Events When Stopping Unnecessary Medications According to the STOPPFrail Criteria

2021 ◽  
Vol 36 (3) ◽  
pp. 136-141 ◽  
Author(s):  
Joseph T. Hanlon ◽  
Jennifer Tjia
Keyword(s):  
Drug Withdrawal ◽  
Data Extraction ◽  
Drug Reactions ◽  
Data Synthesis ◽  
Symptom Monitoring ◽  
Randomized Controlled ◽  
Drug Classes ◽  
Study Selection ◽  
Cochrane Database ◽  
Abrupt Discontinuation

OBJECTIVE: To provide clinicians with information about avoiding adverse drug withdrawal events (ADWEs) when discontinuing unnecessary medications as per the STOPPFrail criteria. DATA SOURCES: Searches of MEDLINE (1970-June 2020), the Cochrane Database of Systematic Reviews (through June 2020), Google Scholar (through June 2020). STUDY SELECTiON: Reviews and original studies of ADWEs. DATA EXTRACTiON: Tapering protocols for specific drugs/ classes from randomized controlled deprescribing trials. DATA SYNTHESiS: Six drug classes were identified as being high risk for physiological ADWEs. CONCLUSiON: The occurrence of ADWEs is rare in comparison to adverse drug reactions in older adults. Few drugs/classes have been reported to have physiological ADWEs with abrupt discontinuation. For these we provide information about tapering protocols and symptom monitoring to avoid ADWEs.

Novel Drugs and Biologics of 2016: A Boom for Neurodrugs in the Pipelin

2017 ◽  
Vol 10 (5) ◽  
pp. 3809-3814
Author(s):  
D Samba Reddy
Keyword(s):  
Muscular Atrophy ◽  
Clinical Care ◽  
New Drugs ◽  
Essential Medicines ◽  
High Demand ◽  
The Past ◽  
Novel Drugs ◽  
Innovative Products ◽  
Cns Drugs ◽  
The U.S

This article provides a brief overview of novel drugs approved by the U.S. FDA in 2016.  It also focuses on the emerging boom in the development of neurodrugs for central nervous system (CNS) disorders. These new drugs are innovative products that often help advance clinical care worldwide, and in 2016, twenty-two such drugs were approved by the FDA. The list includes the first new drug for disorders such as spinal muscular atrophy, Duchenne muscular dystrophy or hallucinations and delusions of Parkinson’s disease, among several others. Notably, nine of twenty-two (40%) were novel CNS drugs, indicating the industry shifting to neurodrugs. Neurodrugs are the top selling pharmaceuticals worldwide, especially in America and Europe. Therapeutic neurodrugs have proven their significance many times in the past few decades, and the CNS drug portfolio represents some of the most valuable agents in the current pipeline. Many neuroproducts are vital or essential medicines in the current therapeutic armamentarium, including dozens of “blockbuster drugs” (drugs with $1 billion sales potential).  These drugs include antidepressants, antimigraine medications, and anti-epilepsy medications. The rise in neurodrugs’ sales is predominantly due to increased diagnoses of CNS conditions. The boom for neuromedicines is evident from the recent rise in investment, production, and introduction of new CNS drugs.  There are many promising neurodrugs still in the pipeline, which are developed based on the validated “mechanism-based” strategy. Overall, disease-modifying neurodrugs that can prevent or cure serious diseases, such as multiple sclerosis, epilepsy, and Alzheimer’s disease, are in high demand. 

The Chemistry of Drugs to Treat Candida albicans

2019 ◽  
Vol 19 (28) ◽  
pp. 2554-2566 ◽  
Author(s):  
Aurelio Ortiz ◽  
Estibaliz Sansinenea
Keyword(s):  
Candida Species ◽  
Antifungal Drugs ◽  
New Drugs ◽  
Drug Classes ◽  
Life Threatening ◽  
Antifungal Substances ◽  
High Level ◽  
Systemic Infections ◽  
New Compounds ◽  
Level Resistance

Background:: Candida species are in various parts of the human body as commensals. However, they can cause local mucosal infections and, sometimes, systemic infections in which Candida species can spread to all major organs and colonize them. Objective:: For the effective treatment of the mucosal infections and systemic life-threatening fungal diseases, a considerably large number of antifungal drugs have been developed and used for clinical purposes that comprise agents from four main drug classes: the polyenes, azoles, echinocandins, and antimetabolites. Method: : The synthesis of some of these drugs is available, allowing synthetic modification of the molecules to improve the biological activity against Candida species. The synthetic methodology for each compound is reviewed. Results: : The use of these compounds has caused a high-level resistance against these drugs, and therefore, new antifungal substances have been described in the last years. The organic synthesis of the known and new compounds is reported. Conclusion: : This article summarizes the chemistry of the existing agents, both the old drugs and new drugs, in the treatment of infections due to C. albicans, including the synthesis of the existing drugs.

scholarly journals What I have learnt from helping thousands of people taper off antidepressants and other psychotropic medications

2021 ◽  
Vol 11 ◽  
pp. 204512532199127
Author(s):  
Adele Framer
Keyword(s):  
Withdrawal Syndrome ◽  
Online Community ◽  
Medical Information ◽  
Scientific Literature ◽  
Drug Withdrawal ◽  
Psychotropic Medications ◽  
Lessons Learned ◽  
Medical Providers ◽  
Drug Reactions ◽  
Withdrawal Syndromes

Although psychiatric drug withdrawal syndromes have been recognized since the 1950s – recent studies confirm antidepressant withdrawal syndrome incidence upwards of 40% – medical information about how to safely go off the drugs has been lacking. To fill this gap, over the last 25 years, patients have developed a robust Internet-based subculture of peer support for tapering off psychiatric drugs and recovering from withdrawal syndrome. This account from the founder of such an online community covers lessons learned from thousands of patients regarding common experiences with medical providers, identification of adverse drug reactions, risk factors for withdrawal, tapering techniques, withdrawal symptoms, protracted withdrawal syndrome, and strategies to cope with symptoms, in the context of the existing scientific literature.

scholarly journals Clinical Drug Trials on Human Beings viz-a-viz Sanctions related to Animal Experimentation: Need to do Introspection?

2012 ◽  
Vol 46 (3) ◽  
pp. 113-116
Author(s):  
Roosy Aulakh ◽  
Chander Shekhar Gautam ◽  
Prabhjot Singh Cheema
Keyword(s):  
Animal Experimentation ◽  
New Drugs ◽  
Drug Trials ◽  
Human Beings ◽  
Animal Protection ◽  
Research Organizations ◽  
Legal Sanctions ◽  
Clinical Drug Trials ◽  
Health Care Law ◽  
Clinical Drug

ABSTRACT Health care law is totally localized in its nature, but research for the development of new drugs has crossed man-made geographical limits. Weaker legal sanctions, poverty, illiteracy and inaccessibility to legal system have all contributed to make India a favored hub for contact research organizations. Many recent clinical drug trials in India have sparked controversy. However, in India today, we are more bothered about animal protection, but show little concern for volunteers in human trials. It is gradually becoming difficult to conduct research on animals; however, research on human beings is far easier. Sanctions against violation of rights of human volunteers in clinical trials are often only a perceived phenomenon. They are not protected as they should be. Regulatory framework needs thorough introspection, debate, reconsideration and strict implementation. These guidelines should not only be recommendatory but mandatory in nature and those who indulge in violations, shall be punished as per the law of the land effectively. How to cite this article Gautam CS, Aulakh R, Cheema PS. Clinical Drug Trials on Human Beings viz-a-viz Sanctions related to Animal Experimentation: Need to do Introspection? J Postgrad Med Edu Res 2012;46(3):113-116.

Alcohol and Drug Withdrawal Syndromes and Their Clinical Management

2021 ◽  
Author(s):  
Alexander Thompson ◽  
Andrea Weber
Keyword(s):  
Alcohol Withdrawal ◽  
Psychiatric Hospitalization ◽  
Psychiatric Symptoms ◽  
Signs And Symptoms ◽  
Opioid Withdrawal ◽  
Sustained Remission ◽  
Opioid Agonist ◽  
Dsm 5 ◽  
Cannabis Withdrawal ◽  
Withdrawal Syndromes

Withdrawal syndromes are clusters of signs and symptoms that occur with cessation or decrease in use of a substance. All substance withdrawal syndromes are classified and diagnosed based on criteria published in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). All withdrawal syndromes range in their ability to cause significant medical and/or psychiatric consequences. Alcohol withdrawal remains a medically serious syndrome that can occur within hours to days of decreased use and result in hallucinations, delirium, seizures, and death. Despite increasing research into the type, frequency, dose, and route of administration, benzodiazepines remain the first-line treatment in preventing alcohol withdrawal complications. Although typically not medically severe, opioid withdrawal is often associated with relapse even after successful detoxification. Opioid-agonist therapy, including methadone and buprenorphine, remains the treatment of choice for both opioid withdrawal and relapse prevention. Stimulant withdrawal from cocaine or amphetamines can cause significant psychiatric symptoms within minutes to hours of cessation and may require psychiatric hospitalization for suicidal ideation or attempts. There are no current medications approved by the Food and Drug Administration (FDA) for treatment of stimulant withdrawal. Cannabis withdrawal, although not medically dangerous, has recently been adopted as a discrete syndrome in the DSM-5. Its severity correlates significantly with the amount of cannabis used, functional impairment, and ability to achieve sustained remission. There are no current medications approved by the FDA for treatment of cannabis withdrawal. This review contains 6 figures, 13 tables, and 101 references. Key words: alcohol, amphetamine, benzodiazepines, buprenorphine, cannabis, clonidine, cocaine, dexmedetomidine, methadone, opioid, phenobarbital, stimulant, withdrawal 

Neuroendocrinology of Stress and Addiction

2021 ◽  
Author(s):  
Steven Kinsey ◽  
Olivia Vanegas ◽  
Kristen Trexler ◽  
Floyd Steele ◽  
Matthew Eckard
Keyword(s):  
Stress Response ◽  
Psychotropic Drugs ◽  
Drug Exposure ◽  
Drugs Of Abuse ◽  
Drug Withdrawal ◽  
Host Organism ◽  
Repeated Use ◽  
Drug Abstinence ◽  
Withdrawal Syndromes ◽  
Development Of Tolerance

The stress response evolved as a series of neural and endocrine mechanisms that protect the host organism from threats to homeostasis. Repeated use of psychotropic drugs can lead to the development of tolerance (i.e., decreased drug activity at a given dose) and drug dependence, as indicated by withdrawal syndromes following drug abstinence. Drug withdrawal is often overtly stressful, although acute drug exposure may also represent a threat to homeostasis. This article explores the neuroendocrine effects of drugs of abuse and some of the ways in which stress and appetitive mechanisms interact.

scholarly journals Comprehensive physicochemical, pharmacokinetic and activity profiling of anti-TB agents

2014 ◽  
Vol 70 (3) ◽  
pp. 857-867 ◽  
Author(s):  
Suresh B. Lakshminarayana ◽  
Tan Bee Huat ◽  
Paul C. Ho ◽  
Ujjini H. Manjunatha ◽  
Véronique Dartois ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Volume Of Distribution ◽  
Metabolic Stability ◽  
New Drugs ◽  
Pharmacokinetic Parameters ◽  
Lipinski’S Rule ◽  
Drug Classes ◽  
Human Pharmacokinetic

Abstract Objectives The discovery and development of TB drugs has met limited success, with two new drugs approved over the last 40 years. Part of the difficulty resides in the lack of well-established in vitro or in vivo targets of potency and physicochemical and pharmacokinetic parameters. In an attempt to benchmark and compare such properties for anti-TB agents, we have experimentally determined and compiled these parameters for 36 anti-TB compounds, using standardized and centralized assays, thus ensuring direct comparability across drugs and drug classes. Methods Potency parameters included growth inhibition, cidal activity against growing and non-growing bacteria and activity against intracellular mycobacteria. Pharmacokinetic parameters included basic physicochemical properties, solubility, permeability and metabolic stability. We then attempted to establish correlations between physicochemical, in vitro and in vivo pharmacokinetic and pharmacodynamic indices to tentatively inform future drug discovery efforts. Results Two-thirds of the compounds tested showed bactericidal and intramacrophage activity. Most compounds exhibited favourable solubility, permeability and metabolic stability in standard in vitro pharmacokinetic assays. An analysis of human pharmacokinetic parameters revealed associations between lipophilicity and volume of distribution, clearance, plasma protein binding and oral bioavailability. Not surprisingly, most compounds with favourable pharmacokinetic properties complied with Lipinski's rule of five. Conclusions However, most attempts to detect in vitro–in vivo correlations were unsuccessful, emphasizing the challenges of anti-TB drug discovery. The objective of this work is to provide a reference dataset for the TB drug discovery community with a focus on comparative in vitro potency and pharmacokinetics.

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