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Biomedical subjects

Nabih M Ramadan

Publications and source records attributed to Nabih M Ramadan.

12 recordsLinked to original sources
PubMed2006

New and future migraine therapy.

Modern neuroscience advanced our understanding of putative migraine mechanisms, which led to improved therapeutics. Indeed, mechanism-based acute migraine therapy gained steam in the early 1990s after the introduction of the triptans (5-HT1B,D agonists). Post-triptans, novel targets such as calcitonin gene-related peptide (CGRP) antagonists, inhibitors of excitatory glutamatergic receptors, and nitric oxide synthase (NOS) inhibitors are leading the pack in this exploding field of discovery research. In contrast, novel therapeutic targets for migraine prevention are lacking despite a hugely unmet need. To date, migraine prophylactic drugs are advanced based on expanded indications for already approved pharmaceuticals (e.g., topiramate, valproate, propranolol, and timolol). An improved understanding of the predisposition to an attack, genomic discoveries, valid and reliable biomarkers and surrogates, and predictive preclinical models likely will unravel the neuronal substrates for central hyperexcitability and nociceptive dysmodulation, hopefully leading us to better mechanism-based targets for prevention, and ultimately yielding drugs with optimal therapeutic ratios or indices.

Humans↗
PubMed2006

Migraine headache prophylaxis: current options and advances on the horizon.

Migraine is increasingly recognized as a disorder of altered neuronal excitability, in part based on genetically mediated and environmentally modified aberrations of ionic exchange across the brain neuronal membrane. To this end, migraine pharmacotherapy aids in restoring the abnormally low threshold for neuronal excitation. Indeed, modulation of neuronal excitability is a common property of several established migraine preventive drugs such as propranolol, valproate, amitriptyline, and topiramate. Future migraine preventive pharmacologic therapies likely will aim at restoring the neuronal threshold for excitation by targeting such processes as cortical spreading depression and intracellular calcium influx. Also, strategies aimed at enhancing descending antinociceptive inhibition will yield effective antimigraine drugs.

Guidelines as Topic↗
PubMed2006

Classification of headache disorders.

Clinical diagnostic classifications are critical when clear biological markers are not available. Such is the case in many headache disorders and mental disorders. Also, it is crucial that the classification is widely accepted and utilized. A main goal of classification is to be a universal language for categorizing a disease or a set of disorders, establishing diagnostic criteria, and promoting unity in treatment. The International Headache Society published its first Classification of Headache Disorders in 1988 and its second edition in 2004. The first classification paved the way for a better understanding of the epidemiology, mechanisms, and treatment of headache disorders, and the second edition likely will magnify our knowledge. This article provides an overview of the classification system and outlines some of the major changes in the revised edition.

Diagnosis, Differential↗
PubMed2006

Prophylactic pharmacotherapy for migraine headaches.

Migraine therapeutics are pharmacological, including acute and preventive, nonpharmacological and/or both. Preventive pharmacological strategies serendipitously were discovered to be effective and include drugs from various pharmacological classes (e.g., beta-adrenergic blocker, anticonvulsant, tricyclic antidepressants, serotonin receptor antagonist). Converging level I evidence and clinical experience support the use of the antidepressant amitriptyline, the anticonvulsants divalproex and topiramate, and the beta-adrenergic blockers propranolol, timolol, and metoprolol in migraine prevention. Other options for migraine prophylaxis exist, but the level of evidence in support of their use is not as robust. All of these drugs have varying degrees of adverse effects, some of which can limit their use. Balancing potential efficacy with risk of adverse effects, addressing patients' expectations and desires, complying with management recommendations, adequate follow up, and accurate assessment of treatment goals are key to migraine prevention. Finally, future migraine-preventive drugs likely will target migraine mechanisms more specifically, which undoubtedly will enhance the therapeutic index.

Adrenergic Agents↗
PubMed2004

Sports-related headache.

Sports-related or sports-associated headaches are common. They can be benign as in primary exertional headache or may signal serious pathology as in headache associated with traumatic subdural hematoma. Specific sports activities are associated with unique headache conditions such as decompression sickness headache or high-altitude headache, which mountain climbers experience along with other symptoms of chronic mountain sickness. The management of sports-related headaches requires an adequate understanding of its underlying etiology with subsequent cause-directed treatment plan.

Female↗
PubMed2004

Prophylactic migraine therapy: mechanisms and evidence.

This article focuses on the scientific evidence for pharmacotherapy for migraine prevention. Non-pharmacologic approaches are not discussed. However, it is important to remember the complementary value of some of these strategies (eg, biofeedback) to migraine treatment.

Analgesics↗
PubMed2004

Future pharmacologic targets for acute and preventive treatments of migraine.

Advances in investigative research (e.g., functional magnetic resonance imaging) have made it possible to study putative migraine processes and better understand the pathophysiology of the disorder. Consequently, the apparent opposing vascular and neuronal theories of migraine are now reconciled into a neurovascular hypothesis that pieces together migrainous events and allows us to better target such events in the hope of providing safe and effective therapies. Parallel discoveries in the fields of pharmacology, physiology, genetics and other biomedical disciplines will lead to the development of optimal migraine therapeutics. Such discoveries have already yielded some major enhancement in acute migraine treatment with the development of sumatriptan (Imitrex, GlaxoSmithKline) and other triptans and the trajectory is likely to be exponential. Novel targets, such as calcitonin gene-related peptide antagonists and inhibitors of excitatory glutamatergic receptors, are leading the pack but many other promising targets are in development. The post-sumatriptan decades will witness treatment strategies that will improve the therapeutic index of acute therapies and others which will effectively and safely prevent migraine attacks.

Acute Disease↗
PubMed2004

Functional and anatomical correlates of impaired velocity storage.

Velocity storage (VS), a brainstem function, extends the low-frequency response of the vestibular system. To better understand VS mechanisms and characteristics in humans, we analyzed retrospectively functional measures of gait, electrophysiological measures of vestibular function, and imaging studies in an attempt to determine clinical, electrophysiological, and anatomical correlates of abnormalities in VS. Two cohorts of patients referred to our Risk of Falls Assessment Clinic participated in this investigation. Group 1 (control) patients demonstrated normal caloric and rotary chair tests. Group 2 patients with impaired velocity storage (experimentals) differed clinically from Group 1 only by demonstrating abnormal multifrequency vestibulocular reflex phase measures on rotational testing. Results showed that Group 2 patients had greater impairments in postural stability and gait than Group 1 patients. Additionally, 80% of patients in Group 2 and none in Group 1 showed pontine hyperintense lesions on MRI.

Aged↗
PubMed2003

The link between glutamate and migraine.

Migraine pain-relay centers, including the trigeminal ganglion, trigeminal nucleus caudalis, and thalamus, contain glutamate-positive neurons, and glutamate activates the trigeminal nucleus caudalis. Glutamate is implicated in cortical spreading depression, trigeminovascular activation, and central sensitization. Glutamate receptor-subtype antagonists are effective in preclinical models of migraine, and in the clinic. These preclinical and clinical observations argue for a strong link between migraine and the glutamatergic system, a link that is important to further characterize in an effort to better understand migraine mechanisms and deliver effective therapies.

Glutamic Acid↗
PubMed2002

Assessing the efficacy of drugs for the acute treatment of migraine: issues in clinical trial design.

Clinical trials of therapies for acute migraine attacks have evolved over the years from open-label, small observational studies to highly structured randomised, controlled trials. The International Headache Society Committee on Clinical Trials in Migraine developed a tool to guide in designing scientifically sound trials. The proof of effect is best achieved in a clinical trial with: clearly defined objectives;a well-characterised study population, identified using well-validated diagnostic tools;proper randomisation and blinding;inclusion of a placebo arm, with proper balancing of patients receiving placebo and those receiving active drug;adequate study power; and appropriate statistical methods. Both parallel and crossover studies may be suitable in clinical trials of antimigraine agents, although the latter are a better choice in patient preference and bioequivalence studies. Although various efficacy measures are used to assess treatment effect, the 2-hour pain free rate (total resolution of pain within 2 hours after an initial moderate to severe headache) is preferred because it is clinically relevant and is relatively 'placebo-insensitive'. Various migraine surveys have indicated that a rapid onset of therapeutic effect is a highly desirable attribute of an antimigraine drug. Therefore, accurate measurements of treatment effect before 2 hours are becoming increasingly emphasised. Consistency of effect across multiple attacks adds to the understanding of the therapeutic efficacy of a test drug. Finally, preference and satisfaction studies allow us to assess patients' global impression of a particular treatment, weighing the positive effects on pain and associated symptoms of migraine against potential adverse effects.

Clinical Trials as Topic↗