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Biomolecules Dec 2023Chronic neuropathic pain (NP) is an increasingly prevalent disease and leading cause of disability which is challenging to treat. Several distinct classes of drugs are... (Review)
Review
Chronic neuropathic pain (NP) is an increasingly prevalent disease and leading cause of disability which is challenging to treat. Several distinct classes of drugs are currently used for the treatment of chronic NP, but each drug targets only narrow components of the underlying pathophysiological mechanisms, bears limited efficacy, and comes with dose-limiting side effects. Multimodal therapies have been increasingly proposed as potential therapeutic approaches to target the multiple mechanisms underlying nociceptive transmission and modulation. However, while preclinical studies with combination therapies showed promise to improve efficacy over monotherapy, clinical trial data on their efficacy in specific populations are lacking and increased risk for adverse effects should be carefully considered. Drug-drug co-crystallization has emerged as an innovative pharmacological approach which can combine two or more different active pharmaceutical ingredients in a single crystal, optimizing pharmacokinetic and physicochemical characteristics of the native molecules, thus potentially capitalizing on the synergistic efficacy between classes of drugs while simplifying adherence and minimizing the risk of side effects by reducing the doses. In this work, we review the current pharmacological options for the treatment of chronic NP, focusing on combination therapies and their ongoing developing programs and highlighting the potential of co-crystals as novel approaches to chronic NP management.
Topics: Humans; Neuralgia; Drug Therapy, Combination; Combined Modality Therapy
PubMed: 38136672
DOI: 10.3390/biom13121802 -
Current Opinion in Ophthalmology May 2015Emerging developments and research for drug delivery to the posterior segment offer a promising future for the treatment of vitreoretinal disease. As new technologies... (Review)
Review
PURPOSE OF REVIEW
Emerging developments and research for drug delivery to the posterior segment offer a promising future for the treatment of vitreoretinal disease. As new technologies enter the market, clinicians should be aware of new indications and ongoing clinical trials.
RECENT FINDINGS
This review summarizes the advantages and shortcomings of the most commonly used drug delivery methods, including vitreous dynamics, physician sustainability and patient preferences. Currently available, intravitreal, corticosteroid-release devices offer surgical and in-office management of retinal vascular disease and posterior uveitis. The suprachoroidal space offers a new anatomic location for the delivery of lower dose medications directly to the target tissue. Implantable drug reservoirs would potentially allow for less frequent intravitreal injections reducing treatment burdens and associated risks. Newer innovations in encapsulated cell technology offer promising results in early clinical trials.
SUMMARY
Although pars plana intravitreal injection remains the mainstay of therapy for many vitreoretinal diseases, targeted delivery and implantable eluting devices are rapidly demonstrating safety and efficacy. These therapeutic modalities offer promising options for the vitreoretinal therapeutic landscape.
Topics: Drug Carriers; Drug Delivery Systems; Drug Implants; Humans; Intravitreal Injections; Molecular Targeted Therapy; Retinal Diseases
PubMed: 25759965
DOI: 10.1097/ICU.0000000000000143 -
The International Journal of... Feb 2019Several shortcomings with currently available pharmacotherapy of epilepsy necessitate the search for new drug targets. Paroxysmal depolarization shifts (PDS) represent... (Review)
Review
Several shortcomings with currently available pharmacotherapy of epilepsy necessitate the search for new drug targets. Paroxysmal depolarization shifts (PDS) represent the cellular correlates of electrographic (e.g. interictal) spikes. While the ionic basis of PDS is understood in great detail, controversy exists regarding their proposed implication in epilepsy. To address this issue and to consider potential targetability, this mini-review gives an overview of the ionic conductances contributing to PDS and reflects on the hypotheses of their potential pro-epileptic (epileptogenic) and anti-epileptic roles.
Topics: Disease Progression; Electrophysiological Phenomena; Epilepsy; Humans; Molecular Targeted Therapy
PubMed: 30557621
DOI: 10.1016/j.biocel.2018.12.006 -
Expert Opinion on Pharmacotherapy May 2020Opioid use disorder (OUD) and alcohol use disorder (AUD) are two highly prevalent substance-related disorders worldwide. Co-use of the substances is also quite... (Review)
Review
Opioid use disorder (OUD) and alcohol use disorder (AUD) are two highly prevalent substance-related disorders worldwide. Co-use of the substances is also quite prevalent, yet there are no pharmacological treatment approaches specifically designed to treat co-morbid OUD and AUD. Here, the authors critically summarize OUD, AUD and opioid/alcohol co-use and their current pharmacotherapies for treatment. They also review the mechanisms of action of opioids and alcohol within the brain reward circuitry and discuss potential combined mechanisms of action and resulting neuroadaptations. Pharmacotherapies that aim to treat AUD or OUD that may be beneficial in the treatment of co-use are also highlighted. Preclinical models assessing alcohol and opioid co-use remain sparse. Lasting neuroadaptations in brain reward circuits caused by co-use of alcohol and opioids remains largely understudied. In order to fully understand the neurobiological underpinnings of alcohol and opioid co-use and develop efficacious pharmacotherapies, the preclinical field must expand its current experimental paradigms of 'single drug' use to encompass polysubstance use. Such studies will provide insights on the neural alterations induced by opioid and alcohol co-use, and may help develop novel pharmacotherapies for individuals with co-occurring alcohol and opioid use disorders.
Topics: Alcohol Deterrents; Alcoholism; Animals; Brain; Comorbidity; Disease Models, Animal; Humans; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Prevalence
PubMed: 32103695
DOI: 10.1080/14656566.2020.1732349 -
Pharmacology & Therapeutics Sep 2018Typical and atypical antipsychotics are the first-line treatments for schizophrenia, but these classes of drugs are not universally effective, and they can have serious... (Review)
Review
Typical and atypical antipsychotics are the first-line treatments for schizophrenia, but these classes of drugs are not universally effective, and they can have serious side effects that impact compliance. Antipsychotic drugs generally target the dopamine pathways with some variation. As research of schizophrenia pathophysiology has shifted away from a strictly dopamine-centric focus, the development of new pharmacotherapies has waned. A field of inquiry with centuries-old roots is gaining traction in psychiatric research circles and may represent a new frontier for drug discovery in schizophrenia. At the forefront of this investigative effort is the immune system and its many components, pathways and phenotypes, which are now known to actively engage the brain. Studies in schizophrenia reveal an intricate association of environmentally-driven immune activation in concert with a disrupted genetic template. A consistent conduit through this gene-environmental milieu is the gut-brain axis, which when dysregulated can generate pathological autoimmunity. In this review, we present epidemiological and biochemical evidence in support of an autoimmune component in schizophrenia and depict gut processes and a dysbiotic microbiome as a source and perpetuator of autoimmune dysfunction in the brain. Within this framework, we review the role of infectious agents, inflammation, gut dysbioses and autoantibody propagation on CNS pathologies such as neurotransmitter receptor hypofunction and complement pathway-mediated synaptic pruning. We then review the new pharmacotherapeutic horizon and novel agents directed to impact these pathological conditions. At the core of this discourse is the understanding that schizophrenia is etiologically and pathophysiologically heterogeneous and thus its treatment requires individualized attention with disease state variants diagnosed with objective biomarkers.
Topics: Animals; Antipsychotic Agents; Autoimmunity; Drug Therapy, Combination; Humans; Phenotype; Schizophrenia
PubMed: 29742478
DOI: 10.1016/j.pharmthera.2018.05.005 -
European Radiology Experimental Jul 2020More than 1,200 active or recruiting clinical trials for novel coronavirus disease 2019 (COVID-19) treatments and vaccines are registered. Many drugs have shown promise... (Review)
Review
More than 1,200 active or recruiting clinical trials for novel coronavirus disease 2019 (COVID-19) treatments and vaccines are registered. Many drugs have shown promise for treatment of COVID-19. Nevertheless, up to date, no drugs have been confirmed as a definitive treatment for COVID-19. Trials such as the SOLIDARITY and RECOVERY are ongoing, and first results were announced in favour of therapy with dexamethasone with a significant trend showing greatest benefit among those patients requiring ventilation. The drawbacks of these trials include exposing the patients to drugs with well-documented systemic adverse effects or unknown complications of novel therapies without proof of clinical benefit. We present here the hypothesis that bronchial artery infusion could be an alternative for systemic drug infusion in COVID-19 trials with superadded benefits of high drug concentration and low systemic adverse effects. The concept of this idea has many uncertainties and no current clinical data to support. Perhaps, the technique should be first applied in animal models to determine its safety and calculate the effective dose of the drugs. Guidelines and reviews of pharmacotherapy for COVID-19 should be implemented for this fiction to come true.
Topics: Antiviral Agents; Betacoronavirus; Bronchial Arteries; COVID-19; Catheterization, Peripheral; Coronavirus Infections; Drug Delivery Systems; Humans; Infusions, Intra-Arterial; Pandemics; Pneumonia, Viral; SARS-CoV-2
PubMed: 32632766
DOI: 10.1186/s41747-020-00171-4 -
The Oncologist 2010The definition of "polypharmacy" ranges from the use of a large number of medications; the use of potentially inappropriate medications, which can increase the risk for... (Review)
Review
The definition of "polypharmacy" ranges from the use of a large number of medications; the use of potentially inappropriate medications, which can increase the risk for adverse drug events; medication underuse despite instructions to the contrary; and medication duplication. Older adults are particularly at risk because they often present with several medical conditions requiring pharmacotherapy. Cancer-related therapy adds to this risk in older adults, but few studies have been conducted in this patient population. In this review, we outline the adverse outcomes associated with polypharmacy and present polypharmacy definitions offered by the geriatrics literature. We also examine the strengths and weaknesses of these definitions and explore the relationships among these definitions and what is known about the prevalence and impact of polypharmacy.
Topics: Aged; Aged, 80 and over; Humans; Neoplasms; Polypharmacy
PubMed: 20418534
DOI: 10.1634/theoncologist.2009-0290 -
Yakugaku Zasshi : Journal of the... 2018
Topics: AMP-Activated Protein Kinases; Cardiovascular Diseases; Drug Discovery; Drug Therapy; Energy Metabolism; Forecasting; Humans; Life Style; Sarcopenia
PubMed: 30270268
DOI: 10.1248/yakushi.18-00091-F -
The International Journal of... Jun 2004The introduction of the new-generation antipsychotics has changed the way we treat patients with schizophrenia. This article reviews these agents, focusing mainly on the... (Review)
Review
The introduction of the new-generation antipsychotics has changed the way we treat patients with schizophrenia. This article reviews these agents, focusing mainly on the published randomized controlled trials and meta-analyses in which the new-generation antipsychotics are compared with placebo, conventional antipsychotics or with one another. Agents included are risperidone, olanzapine, quetiapine, ziprasidone, sertindole, amisulpride and aripiprazole. Acute-phase and maintenance studies are reviewed, as well as randomized trials for pre-psychotic, first-episode schizophrenia and refractory schizophrenia. Finally, specific areas of current clinical interest are dealt with. These are: conventional vs. new-generation antipsychotics, head-to-head comparisons of new-generation antipsychotics, and side-effect profiles.
Topics: Antipsychotic Agents; Clinical Trials as Topic; Drug Resistance; Drug Therapy, Combination; Evidence-Based Medicine; Humans; Schizophrenia
PubMed: 15043765
DOI: 10.1017/S1461145704004171 -
Frontiers in Endocrinology 2021Obesity and Type 2 diabetes represent global health challenges, and there is an unmet need for long-lasting and effective pharmacotherapies. Although long-acting... (Review)
Review
Obesity and Type 2 diabetes represent global health challenges, and there is an unmet need for long-lasting and effective pharmacotherapies. Although long-acting glucagon-like peptide-1 (GLP-1) analogues are now in routine use for diabetes and are now being utilised for obesity , the need for ever better treatments has driven the development of co-agonists, with the theoretical advantages of improved efficacy by targeting multiple pathways and reduced adverse effects. In this review, we highlight the past and present progress in our understanding and development of treatments based on GLP-1/glucagon co-agonism. We also reflect on the divergent effects of varying the GLP-1:glucagon activity and ratio in the context of pre-clinical and human clinical trial findings. In particular, the multiple metabolic actions of glucagon highlight the importance of understanding the contributions of individual hormone action to inform the safe, effective and tailored use of GLP-1/glucagon co-agonists to target weight loss and metabolic disease in the future.
Topics: Drug Therapy, Combination; Glucagon-Like Peptide-1 Receptor; Humans; Obesity; Receptors, Glucagon
PubMed: 34566894
DOI: 10.3389/fendo.2021.735019