scholarly journals Ubrogepant: a new era in migraine treatment

2020 ◽  
Vol 9 (5) ◽  
pp. 819
Author(s):  
Sangeeta Bhanwra ◽  
Kaza Ahluwalia
Keyword(s):  
Pain Perception ◽  
Migraine Treatment ◽  
New Era ◽  
Calcitonin Gene ◽  
United States Food ◽  
Cgrp Receptor Antagonists ◽  
Inflammatory Drugs ◽  
States Food ◽  
Acute Attacks ◽  
Good Oral Bioavailability

Migraine is the most common neurological disorder that leads to incapacitating neurological symptoms. Acute attacks of migraine have been dealt with effectively with non-steroidal anti-inflammatory drugs (NSAIDs), ergot derivatives and triptans since long, but their use is limited by various adverse effects. Recent studies have shown that a neuropeptide, calcitonin gene related peptide (CGRP) plays a major role in pathophysiology of migraine by increasing the pain perception, both at the peripheral and central nervous system levels. So, in the last few years, some CGRP antagonists have found their way in the treatment of both episodic and chronic migraine. Ubrogepant is the first oral CGRP antagonist, that was approved by USFDA (United States food and drug administration) in December 2019, for the acute treatment of migraine with or without aura. It is more potent than the earlier CGRP receptor antagonists, has a good oral bioavailability and the risk of hepatotoxicity is also lesser than the previous Gepants.

scholarly journals Effect of Calcitonin Gene-Related Peptide Receptor Antagonists on Migraine Treatment: A Meta-Analysis

2021 ◽  
Author(s):  
Jiyoung Kim ◽  
Kyoungjune Pak ◽  
Gha-Hyun Lee ◽  
Jae Wook Cho ◽  
Hyun-Woo kim
Keyword(s):  
Meta Analysis ◽  
Calcitonin Gene Related Peptide ◽  
Migraine Treatment ◽  
Acute Migraine ◽  
Cgrp Receptor ◽  
Receptor Antagonists ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Cgrp Receptor Antagonists ◽  
Acute Migraine Treatment

Abstract Background: The pathophysiology of migraine has been researched incessantly, and it has been suggested that calcitonin gene-related peptide (CGRP) is associated with migraine attacks. CGRP receptor blockers are attracting attention for migraine prevention and treatment of acute episodes, and CGRP receptor antagonists have been shown to be effective in treating acute migraine headaches. This meta-analysis aimed to assess the effect of available CGRP receptor antagonists, focusing on their therapeutic doses for acute migraine treatment.Methods: We performed a systematic search of MEDLINE (from inception to March 2021) and EMBASE (from inception to March 2021) for English publications using the keywords “migraine” and “Calcitonin gene-related peptide,” limited to human studies.Results: Five studies that focused on examining the effects of CGRP receptor antagonists on acute migraine treatment met the eligibility criteria for this meta-analysis. The pooled analysis demonstrated that the CGRP receptor antagonist improved freedom from pain (OR=2.066, 95% confidence interval [CI] 1.766–2.418, I2=0%), absence of bothersome symptoms (OR=1.606, 95% CI=1.408–1.830, I2=0%), pain relief (OR=1.791, 95% CI=1.598–2.008, I2=0%), and freedom from nausea (OR=1.361, 95% CI=1.196–1.548, I2=0%), significantly more than the placebo. Conclusions: CGRP receptor antagonists are effective for acute migraine treatment and are expected to be used clinically as emerging therapeutic agents.

scholarly journals Recent Advances in the Management of Cluster Headache

2020 ◽  
Vol 22 (12) ◽  
Author(s):  
María Dolores Villar-Martínez ◽  
Francesca Puledda ◽  
Peter J. Goadsby
Keyword(s):  
Cluster Headache ◽  
Serotonin Receptor ◽  
Critical Role ◽  
Therapeutic Approaches ◽  
New Era ◽  
Novel Treatments ◽  
Difficult Condition ◽  
Calcitonin Gene ◽  
Cgrp Receptor Antagonists ◽  
Autonomic Reflex

Abstract Purpose of review Among the spectrum of pain conditions, cluster headache represents one of the most severe. Targeted therapies for cluster headache are evolving thus improving the available therapeutic armamentarium. A better understanding of the currently available therapies, as well as new and emerging options, may aide physicians to manage affected sufferers better by evolving treatment guidance. Recent findings While classic first-line medications are useful in some patients with cluster headache, they are often accompanied by significant side effects that limit their use. Recently, novel treatments with better tolerability and decreased medication interactions have proven to be effective. A remarkable example of this is the blockage of the calcitonin gene-related peptide pathway with monoclonal antibodies, which may be a key element in the future treatment of cluster headache. The sphenopalatine ganglion and vagus nerve perform a critical role in the regulation of pain and the trigeminal autonomic reflex. Neuromodulation therapies targeting these structures have shown excellent tolerability and few significant adverse events, constituting a promising form of treatment. Finally, several potential therapeutic targets are examined in this review, such as small molecule CGRP receptor antagonists, known as gepants, and serotonin receptor 5-HT1F receptor agonists: ditans. Summary In summary, a deepening of the understanding of cluster headache mechanisms in recent years has driven the evolution of sophisticated therapeutic approaches that could allow a new era in the treatment of this difficult condition.

scholarly journals Migraine therapeutics differentially modulate the CGRP pathway

Cephalalgia ◽  
2021 ◽  
Vol 41 (5) ◽  
pp. 499-514
Author(s):  
Minoti Bhakta ◽  
Trang Vuong ◽  
Tetsuya Taura ◽  
David S Wilson ◽  
Jennifer R Stratton ◽  
...  
Keyword(s):  
Small Molecule ◽  
Therapeutic Agents ◽  
Camp Signaling ◽  
Migraine Treatment ◽  
Cgrp Receptor ◽  
Calcitonin Gene ◽  
Migraine Pathogenesis ◽  
Cgrp Receptor Antagonists ◽  
Receptor Family

Background The clinical efficacy of migraine therapeutic agents directed towards the calcitonin-gene related peptide (CGRP) pathway has confirmed the key role of this axis in migraine pathogenesis. Three antibodies against CGRP – fremanezumab, galcanezumab and eptinezumab – and one antibody against the CGRP receptor, erenumab, are clinically approved therapeutics for the prevention of migraine. In addition, two small molecule CGRP receptor antagonists, ubrogepant and rimegepant, are approved for acute migraine treatment. Targeting either the CGRP ligand or receptor is efficacious for migraine treatment; however, a comparison of the mechanism of action of these therapeutic agents is lacking in the literature. Methods To gain insights into the potential differences between these CGRP pathway therapeutics, we compared the effect of a CGRP ligand antibody (fremanezumab), a CGRP receptor antibody (erenumab) and a CGRP receptor small molecule antagonist (telcagepant) using a combination of binding, functional and imaging assays. Results Erenumab and telcagepant antagonized CGRP, adrenomedullin and intermedin cAMP signaling at the canonical human CGRP receptor. In contrast, fremanezumab only antagonized CGRP-induced cAMP signaling at the human CGRP receptor. In addition, erenumab, but not fremanezumab, bound and internalized at the canonical human CGRP receptor. Interestingly, erenumab also bound and internalized at the human AMY1 receptor, a CGRP receptor family member. Both erenumab and telcagepant antagonized amylin-induced cAMP signaling at the AMY1 receptor while fremanezumab did not affect amylin responses. Conclusion The therapeutic effect of agents targeting the CGRP ligand versus receptor for migraine prevention (antibodies) or acute treatment (gepants) may involve distinct mechanisms of action. These findings suggest that differing mechanisms could affect efficacy, safety, and/or tolerability in migraine patients.

scholarly journals Calcitonin Gene-Related Peptide Targeting Therapies for Migraine: A New Era for Migraine Treatment

2020 ◽  
Vol 38 (2) ◽  
pp. 88-99 ◽  
Author(s):  
Hong-Kyun Park ◽  
Byung-Kun Kim
Keyword(s):  
Preventive Treatment ◽  
Calcitonin Gene Related Peptide ◽  
European Medicines Agency ◽  
Migraine Treatment ◽  
New Era ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
The Usa ◽  
Cgrp Receptor Antagonist ◽  
Peptide Targeting

Development of medications targeting the trigeminal sensory neuropeptide calcitonin gene-related peptide (CGRP) or its receptor has ushered in the new era for the treatment of migraine. Some of these drugs are approved by the USA Food and Drug Administration and European Medicines Agency since 2018, and others are in the process of approval. Since the CGRP-related therapies act directly on the migraine pathophysiology, they have advantages over conventional treatments not only in effect but also in terms of adverse effects. CGRP receptor antagonist have an effect on both acute and preventive treatment of migraine, while monoclonal antibodies for CGRP ligand (fremanezumab, galcanezumab, and eptinezumab) or receptor (erenumab) reduce migraine frequency and related disability. Galcanezumab was approved by the Ministry of Food and Drug Safety in Korea in September 2019. As of December 2019, it is available for use in adult patients with migraine. We describe the pathophysiology of CGRP in migraine, summarize the results of recent CGRP antagonism related clinical trials, and provide opinions about the use of CGRP-related therapies in clinical practice.

Delirium Secondary to Lamotrigine Toxicity

2020 ◽  
Vol 15 (2) ◽  
pp. 156-159 ◽  
Author(s):  
Deborah L. Sanchez ◽  
Adam J. Fusick ◽  
Steven R. Gunther ◽  
Michael J. Hernandez ◽  
Gregory A. Sullivan ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Valproic Acid ◽  
Mental Status ◽  
The United States ◽  
Clinical Correlation ◽  
Medication Regimen ◽  
Medication Effects ◽  
United States Food ◽  
States Food ◽  
Rule Out

Background: Lamotrigine is a phenyltriazine medication that has been approved by the United States Food and Drug Administration as monotherapy and as an adjunctive agent for the treatment of seizure disorder. It was later approved by the FDA for the treatment of bipolar disorder. Lamotrigine is generally well tolerated by patients, but some serious symptoms can occur during treatment. These severe side effects include rashes and multi-organ failure. Lamotrigine has also been associated with the development of mental status changes, frequently when used concurrently with other medications that may impact the metabolism of lamotrigine. Objective: To present the case of a 65-year-old man being treated with lamotrigine and valproic acid who developed mental status changes after the addition of sertraline to his medication regimen, and to compare this case to existing cases reported in the literature. Discussion: Our case adds to the existing literature by demonstrating that patients may experience adverse medication effects despite lamotrigine levels that are normally considered to be in the therapeutic range, highlighting the importance of clinical correlation when obtaining medication levels. Conclusion: Clinicians should use caution interpreting lamotrigine levels when working up delirium, as normal levels may not rule out the development of lamotrigine toxicity.

scholarly journals D-Penicillamine: The State of the Art in Humans and in Dogs from a Pharmacological and Regulatory Perspective

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 648
Author(s):  
Michela Pugliese ◽  
Vito Biondi ◽  
Enrico Gugliandolo ◽  
Patrizia Licata ◽  
Alessio Filippo Peritore ◽  
...  
Keyword(s):  
Veterinary Medicine ◽  
State Of The Art ◽  
European Medicines Agency ◽  
Therapeutic Goals ◽  
First Choice ◽  
Regulatory Perspective ◽  
The World ◽  
United States Food ◽  
States Food ◽  
Food And Drugs Administration

Chelant agents are the mainstay of treatment in copper-associated hepatitis in humans, where D-penicillamine is the chelant agent of first choice. In veterinary medicine, the use of D-penicillamine has increased with the recent recognition of copper-associated hepatopathies that occur in several breeds of dogs. Although the different regulatory authorities in the world (United States Food and Drugs Administration—U.S. FDA, European Medicines Agency—EMEA, etc.) do not approve D-penicillamine for use in dogs, it has been used to treat copper-associated hepatitis in dogs since the 1970s, and is prescribed legally by veterinarians as an extra-label drug to treat this disease and alleviate suffering. The present study aims to: (a) address the pharmacological features; (b) outline the clinical scenario underlying the increased interest in D-penicillamine by overviewing the evolution of its main therapeutic goals in humans and dogs; and finally, (c) provide a discussion on its use and prescription in veterinary medicine from a regulatory perspective.

scholarly journals The Efficacy of Convalescent Plasma Use in Critically Ill COVID-19 Patients

Medicina ◽  
2021 ◽  
Vol 57 (3) ◽  
pp. 257
Author(s):  
Livius Tirnea ◽  
Felix Bratosin ◽  
Iulia Vidican ◽  
Bianca Cerbu ◽  
Mirela Turaiche ◽  
...  
Keyword(s):  
Pilot Study ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Therapeutic Option ◽  
White Blood Cells ◽  
The United States ◽  
Plasma Therapy ◽  
Reactive Protein ◽  
United States Food ◽  
States Food

Background and Objectives: On 24 March 2020, the United States Food and Drug Administration (FDA) announced the approval of convalescent plasma therapy for critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as an emergency investigational new drug. This pilot study from Romania aimed to determine if convalescent plasma transfusion can be beneficial in the treatment of selected critically ill patients diagnosed with a SARS-CoV-2 infection. Materials and Methods: Donor and receiver eligibility for critically ill coronavirus disease 2019 (COVID-19) patients was based on Romanian guidelines issued at the time of the study. Here, we describe the evolution of a total of five eligible patients diagnosed with COVID-19 who received convalescent plasma (CP) in Romania. Results: In spite of our efforts and convalescent plasma administration, three of the five patients did not survive, while the other two recovered completely. Over the course of our five-day laboratory record, the surviving patients had significantly lower values for C-reactive protein, interleukin-6, and white blood cells. Conclusions: This pilot study provides insufficient evidence to determine the efficacy of convalescent plasma use as a therapeutic option for critically ill COVID-19 patients.

scholarly journals Calcitonin Stimulation Tests: Rationale, Technical Issues and Side Effects: A Review

2021 ◽  
Vol 53 (06) ◽  
pp. 355-363
Author(s):  
Mara Băetu ◽  
Cristina Alexandra Olariu ◽  
Gabriel Moldoveanu ◽  
Cristina Corneci ◽  
Corin Badiu
Keyword(s):  
Side Effects ◽  
Stimulation Test ◽  
Cardiac Monitoring ◽  
Calcium Stimulation ◽  
United States Food ◽  
Stimulation Tests ◽  
Gender Specific Differences ◽  
Technical Issues ◽  
States Food ◽  
The Right

AbstractCalcitonin (CT) stimulation tests have great value and could help to: differentiate thyroid causes of elevated CT apart from non-thyroid sources, determine whether the patients with slightly elevated basal CT could/could not be candidates for surgery, and indicate the right moment for prophylactic thyroidectomy in children with MEN syndromes when with normal basal CT. This triggered the requests for development of CT stimulation tests, taking into consideration their safety and aimed us to write a systematic review of literature regarding the rationale, technical issues, and side effects of CT stimulating tests used for diagnosis of MTC. After a thorough review of the literature, we classified the reported side effects by severity, as defined by United States Food and Drug Administration. A statistical analysis was performed using IBM SPSS Statistics version 20. Various side effects were noticed during stimulation tests that differ by intensity, duration and severity, depending on types of substances and protocols used. The side effects after pentagastrin test were significantly more severe than those reported after calcium stimulation test (p=0.0396). There are also significant gender-specific differences in side effects induced by stimulation tests. In conclusion, we recommend performing Ca CT stimulation test when needed, considering preventive evaluation of some clinical, instrumental, and biochemical aspects of each patient. Precise instructions should be followed before a stimulation test and furthermore continuous cardiac monitoring is essential during and after the test to minimize the possibility of a serious event.

scholarly journals Review of COVID-19 mRNA Vaccines: BNT162b2 and mRNA-1273

2021 ◽  
pp. 089719002110096
Author(s):  
Shyh Poh Teo
Keyword(s):  
Vaccine Development ◽  
Safety Data ◽  
The United States ◽  
Virus Infections ◽  
Phase 3 ◽  
Vaccination Programs ◽  
Safety Surveillance ◽  
Mass Immunization ◽  
United States Food ◽  
States Food

The United States Food and Drug Administration recently issued emergency use authorization for 2 mRNA vaccines for preventing COVID-19 disease caused by SARS-CoV-2 virus infections. BNT162b2 from Pfizer-BioNTech and mRNA-1273 by Moderna are planned for use in mass-immunization programs to curb the pandemic. A brief overview of COVID-19 mRNA vaccines is provided, describing the SARS-CoV-2 RNA, how mRNA vaccines work and the advantages of mRNA over other vaccine platforms. The Pfizer-BioNTech collaboration journey to short-list mRNA vaccine candidates and finally selecting BNT162b2 based on safety data is outlined, followed by the Phase 3 study of BNT162b2 demonstrating 95% efficacy in preventing COVID-19 infections. Studies regarding mRNA-1273 (Moderna) are described, including extended immunogenicity data up to 119 days. The Phase 3 COVE study of mRNA-1273 eventually showed vaccine efficacy of 94.5%. Recommendations for future mRNA vaccine development are provided, including ongoing safety surveillance, evaluation in under-represented groups in previous studies and improving mRNA vaccine thermostability. Finally, further logistical considerations are required for manufacturing, storing, distribution and implementing mass vaccination programs to curb the pandemic.

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