-
Discovery Medicine Jun 2014Acromegaly is a disease characterized by growth hormone (GH) excess originating, in approximately 95% of cases, from a somatotroph pituitary adenoma. Symptomatology and... (Review)
Review
Acromegaly is a disease characterized by growth hormone (GH) excess originating, in approximately 95% of cases, from a somatotroph pituitary adenoma. Symptomatology and clinical features are due to GH and insulin-like growth factor 1 excess; unfortunately, for most patients diagnosis is delayed by several years. Acromegaly patients' morbidity and mortality are higher than those of the normal population. However, with adequate biochemical control mortality rates can be restored to normal. Tumor size and location, symptoms, comorbidities, and lastly, but not least, patient preference, are all important aspects in treatment decision making, and treatment approach should be individualized. Current therapy includes medical, surgical, and radiation. This review focuses on recent significant developments in medical therapy. There are three major therapeutic drug classes: somatostatin receptor ligands (SRLs), which represent the mainstay of medical therapy, GH receptor blockers, and dopamine agonists. Multi-ligand receptor SRLs such as pasireotide, should increase therapeutic choices for acromegaly patients currently uncontrolled on available SRLs. Furthermore, significant research has been focused in the development of novel delivery modalities (e.g., oral and long acting subcutaneous administration).
Topics: Acromegaly; Dopamine Agonists; Drug Therapy; Drug Therapy, Combination; Human Growth Hormone; Humans; Receptors, Somatostatin
PubMed: 24979253
DOI: No ID Found -
Journal of Neurology Jul 2011We review current pharmacological treatments for peripheral and central vestibular disorders, and ocular motor disorders that impair vision, especially pathological... (Review)
Review
We review current pharmacological treatments for peripheral and central vestibular disorders, and ocular motor disorders that impair vision, especially pathological nystagmus. The prerequisites for successful pharmacotherapy of vertigo, dizziness, and abnormal eye movements are the "4 D's": correct diagnosis, correct drug, appropriate dosage, and sufficient duration. There are seven groups of drugs (the "7 A's") that can be used: antiemetics; anti-inflammatory, anti-Ménière's, and anti-migrainous medications; anti-depressants, anti-convulsants, and aminopyridines. A recovery from acute vestibular neuritis can be promoted by treatment with oral corticosteroids. Betahistine may reduce the frequency of attacks of Ménière's disease. The aminopyridines constitute a novel treatment approach for downbeat and upbeat nystagmus, as well as episodic ataxia type 2 (EA 2); these drugs may restore normal "pacemaker" activity to the Purkinje cells that govern vestibular and cerebellar nuclei. A limited number of trials indicate that baclofen improves periodic alternating nystagmus, and that gabapentin and memantine improve acquired pendular and infantile (congenital) nystagmus. Preliminary reports suggest suppression of square-wave saccadic intrusions by memantine, and ocular flutter by beta-blockers. Thus, although progress has been made in the treatment of vestibular neuritis, some forms of pathological nystagmus, and EA 2, controlled, masked trials are still needed to evaluate treatments for many vestibular and ocular motor disorders, including betahistine for Ménière's disease, oxcarbazepine for vestibular paroxysmia, or metoprolol for vestibular migraine.
Topics: Drug Therapy; Humans; Nystagmus, Pathologic; Ocular Motility Disorders; Vestibular Diseases
PubMed: 21461686
DOI: 10.1007/s00415-011-5999-8 -
International Journal of Molecular... Jun 2020The Special Issue entitled "New Strategies in Cancer Pharmacotherapy: Development of Hormonal Antineoplastic Drugs, Cytotoxic Drugs and Targeted Therapies" was conceived...
The Special Issue entitled "New Strategies in Cancer Pharmacotherapy: Development of Hormonal Antineoplastic Drugs, Cytotoxic Drugs and Targeted Therapies" was conceived with the idea of compiling information on the latest advances in the treatment of both hormone-dependent and hormone-independent cancers [...].
Topics: Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Disease Susceptibility; Drug Development; Humans; Molecular Targeted Therapy; Neoplasms
PubMed: 32521599
DOI: 10.3390/ijms21114081 -
Molecular Aspects of Medicine Feb 2013The increase in obesity in the Unites States and around the world in the last decade is overwhelming. The number of overweight adults in the world surpassed 1 billion in... (Review)
Review
The increase in obesity in the Unites States and around the world in the last decade is overwhelming. The number of overweight adults in the world surpassed 1 billion in 2008. Health hazards associated with obesity are serious and include heart disease, sleep apnea, diabetes, and cancer. Although lifestyle modifications are the most straightforward way to control weight, a large portion of the population may not be able to rely on this modality alone. Thus, the development of anti-obesity therapeutics represents a major unmet medical need. Historically, anti-obesity pharmacotherapies have been unsafe and minimally efficacious. A better understanding of the biology of appetite and metabolism provides an opportunity to develop drugs that may offer safer and more effective alternatives for weight management. This review discusses drugs that are currently on the market and in development as anti-obesity therapeutics based on their target and mechanism of action. It should serve as a roadmap to establish expectations for the near future for anti-obesity drug development.
Topics: Anti-Obesity Agents; Appetite; Drug Delivery Systems; Humans; Life Style; Lipase; Neuropeptides; Obesity; Pancreatic Hormones; Synaptic Transmission; Weight Loss
PubMed: 23103610
DOI: 10.1016/j.mam.2012.10.005 -
Current Drug Delivery Dec 2021The recent increased interest in orodispersible films (ODF) stems from their ideal potential to circumvent several pharmacotherapy-related problems, such as improved... (Review)
Review
The recent increased interest in orodispersible films (ODF) stems from their ideal potential to circumvent several pharmacotherapy-related problems, such as improved medication compliance and adherence, especially in children, elderly and uncooperative patients. Their administration is well accepted by the majority of patients because ODF dissolve upon contact with the saliva in the oral cavity without the need for water intake. ODF application in personalized pharmacotherapy is currently being exploited. Moreover, innovative preparation methods and characterization technologies have been evolving in recent years, highlighting a promising future both from the technological and clinical standpoints. However, the key obstacles to the attainment of full potential of ODF in the pharmaceutical field is the lack of harmonized and well-defined quality characterization procedures, standard evaluation parameters, guidance on appropriate final product properties and specifications. This review provides an appraisal on the ODF characterization methods from slurries to the finished medicinal products with a specific focus on the technologies suitable for identification, quantification, and quality evaluation of extemporaneously prepared ODF on small batches in individualized pharmacotherapy. Generally, there is a paradigm shift from the use of the conventional quality evaluation tools and/or protocols for oral solid dosage forms to characterize ODF to more specific equipment and procedures that suit the peculiarities of the ODF.
Topics: Administration, Oral; Aged; Chemistry, Pharmaceutical; Child; Drug Compounding; Drug Delivery Systems; Humans; Pharmaceutical Preparations; Solubility
PubMed: 33305704
DOI: 10.2174/1567201818999201210212557 -
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 -
Expert Opinion on Therapeutic Targets Jan 2022In COVID-19 pneumonia, there is a massive increase in fatty acid levels and lipid mediators with a predominance of cyclooxygenase metabolites, notably TxB ≫ PGE > PGD... (Review)
Review
INTRODUCTION
In COVID-19 pneumonia, there is a massive increase in fatty acid levels and lipid mediators with a predominance of cyclooxygenase metabolites, notably TxB ≫ PGE > PGD in the lungs, and 11-dehydro-TxB, a TxA metabolite, in the systemic circulation. While TxA stimulates thromboxane prostanoid (TP) receptors, 11-dehydro-TxB is a full agonist of DP2 (formerly known as the CRTh2) receptors for PGD. Anecdotal experience of using ramatroban, a dual receptor antagonist of the TxA/TP and PGD/DP2 receptors, demonstrated rapid symptomatic relief from acute respiratory distress and hypoxemia while avoiding hospitalization.
AREAS COVERED
Evidence supporting the role of TxA/TP receptors and PGD/DP2 receptors in causing rapidly progressive lung injury associated with hypoxemia, a maladaptive immune response and thromboinflammation is discussed. An innovative perspective on the dual antagonism of TxA/TP and PGD/DP2 receptor signaling as a therapeutic approach in COVID-19 is presented. This paper examines ramatroban an anti-platelet, immunomodulator, and antifibrotic agent for acute and long-haul COVID-19.
EXPERT OPINION
Ramatroban, a dual blocker of TP and DP2 receptors, has demonstrated efficacy in animal models of respiratory dysfunction, atherosclerosis, thrombosis, and sepsis, as well as preliminary evidence for rapid relief from dyspnea and hypoxemia in COVID-19 pneumonia. Ramatroban merits investigation as a promising antithrombotic and immunomodulatory agent for chemoprophylaxis and treatment.
Topics: Animals; COVID-19; Carbazoles; Chemoprevention; Humans; Inflammation; SARS-CoV-2; Sulfonamides; Thrombosis; Post-Acute COVID-19 Syndrome; COVID-19 Drug Treatment
PubMed: 35068281
DOI: 10.1080/14728222.2022.2031975 -
Psychiatry and Clinical Neurosciences Nov 2015Well-organized clinical guidelines of pharmacotherapy for schizophrenia are not necessarily applicable to emergency and acute-phase situations. Thus, practical... (Review)
Review
Well-organized clinical guidelines of pharmacotherapy for schizophrenia are not necessarily applicable to emergency and acute-phase situations. Thus, practical pharmacotherapy for acute schizophrenia patients should be based on data from real clinical practice and be independent of pharmaceutical companies. This study investigated the current guidelines being used to determine the initially preferred antipsychotics, durations required before an antipsychotic is viewed as being ineffective, and the strategies utilized for early non-responders that include switching, high dose, and augmentation. In patients who develop side-effects to the preferred antipsychotic drug, continued use may depend on the specific characteristics of the side-effects. For acute-phase patients, antipsychotics with high efficacy and effectiveness may be chosen based on meta-analysis findings for not only double-blinded but also rater-blinded randomized controlled trials. Many previous studies have reported being able to make an early prediction at 2 weeks regarding the later response. These predictions were supported by the findings of a recent meta-analysis of 34 studies that examined 9975 participants. In early non-responders to the initial antipsychotic, the effectiveness of the switching strategy appears to depend on the initial antipsychotic administered and the antipsychotic the patient is subsequently switched to. Furthermore, the effectiveness of the strategy between switching and augmentation might also depend on the initial antipsychotic administered. The current findings might serve as the basis for the use of dosing above the licensed range versus continuing the use of conventional dosing in non-responders, provided there is close monitoring of the side-effects. Further research is required before any modifications of routine practices are undertaken regarding the direction of new potential treatments.
Topics: Acute Disease; Antipsychotic Agents; Drug Resistance; Drug Therapy, Combination; Humans; Practice Guidelines as Topic; Schizophrenia
PubMed: 26037685
DOI: 10.1111/pcn.12325 -
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 -
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