RESUMEN
Ophthalmic timolol solution is increasingly being repurposed as a topical therapeutic for a variety of dermatologic diseases, including pyogenic granulomas, infantile hemangiomas, and chronic wounds. There are no published guidelines or protocols for use in these indications in adults, and the dermatologic community may not be familiar with adverse events that have been extensively documented relating to its ophthalmic use. We review the evidence available relating to adverse events to topical timolol use to evaluate its safety in dermatologic applications and to alert clinicians to screening and monitoring that is needed when repurposing this drug for dermatologic use. The majority of serious adverse events associated with ophthalmic timolol were reported in the first 7 years of use, between 1978 and 1985, of which most common were cardiovascular and respiratory events, but also included 32 deaths. The available evidence suggests that ophthalmic timolol safety profiling may have been incomplete prior to widespread use. Recent clinical trials for dermatologic indications have focused on documenting efficacy and have not had rigorous monitoring for potential adverse events. Topical timolol may be safe and effective for the treatment of various dermatologic conditions in patients whose medical histories have been carefully reviewed for evidence of pre-existing cardiac or pulmonary disease and are monitored for potential adverse events. Despite the wide use of timolol in ophthalmologic practice, safe dermatologic repurposing requires recognition of the potential for facilitated systemic absorption though the skin and appreciation of its history of adverse events.
Asunto(s)
Antagonistas Adrenérgicos beta/efectos adversos , Enfermedades Cardiovasculares/inducido químicamente , Reposicionamiento de Medicamentos/historia , Hemangioma/tratamiento farmacológico , Trastornos Respiratorios/mortalidad , Timolol/efectos adversos , Absorción Fisiológica , Administración Cutánea , Antagonistas Adrenérgicos beta/administración & dosificación , Antagonistas Adrenérgicos beta/historia , Enfermedades Cardiovasculares/mortalidad , Historia del Siglo XX , Humanos , Soluciones Oftálmicas/administración & dosificación , Soluciones Oftálmicas/efectos adversos , Soluciones Oftálmicas/historia , Trastornos Respiratorios/inducido químicamente , Piel/metabolismo , Timolol/administración & dosificación , Timolol/historiaRESUMEN
Heart failure remains the main cause of death in children with heart disease. In USA and Europe hospital mortality of children with heart failure is about 7% of children, nearly twice as high as in adults. In this review a group of authors report about their experience with beta-blockers in childhood heart failure. Most of them start to treat children with severe heart failure at a time - 20 years ago - when beta blockers seem to be contraindicated in this situation. The physicians and their patients and/or parents all are aware of the risk of this decision. However, unproven medical therapies for heart failure are the most important therapeutical dilemma in pediatric cardiology. The authors carefully observed a highly selected group of patients with the highest risk to die and had the patience to wait for the longtime follow up. Today - based upon this experience -we know that beta blockers are safe and may save the lives of many children with heart disease all over the world. Together with young colleagues who enthusiastically support this idea the authors now intend to break down the "wall of ignorance" for this promising therapy in pediatric cardiology.
Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Antagonistas Adrenérgicos beta/historia , Niño , Cardiopatías/complicaciones , Insuficiencia Cardíaca/complicaciones , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Inducción de RemisiónAsunto(s)
Antagonistas Adrenérgicos beta/administración & dosificación , Antagonistas Adrenérgicos beta/historia , Enfermedades Cardiovasculares/prevención & control , Complicaciones Posoperatorias/prevención & control , Guías de Práctica Clínica como Asunto , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Cuidados Preoperatorios , Ensayos Clínicos Controlados Aleatorios como Asunto/historia , Factores de RiesgoAsunto(s)
Antihipertensivos/historia , Hipertensión Renal/historia , Sistema Renina-Angiotensina , Renina/historia , Antagonistas Adrenérgicos beta/historia , Angiotensina II/sangre , Inhibidores de la Enzima Convertidora de Angiotensina/historia , Antihipertensivos/uso terapéutico , Historia del Siglo XX , Humanos , Hipertensión Renal/tratamiento farmacológico , Hipertensión Renal/metabolismo , Antagonistas de Receptores de Mineralocorticoides/historia , Renina/antagonistas & inhibidoresRESUMEN
James Black has many claims to pharmacological fame as the creator of two new classes of drugs (beta-blockers and H2 antihistamines) and as a tireless innovator in drug discovery strategies and analytical procedures. The latter attributes in particular assisted Black in the invention of the prototypes for the two major classes of drugs for which he is best known, propranolol and cimetidine. The clinical impact of these drugs on both morbidity and mortality has been profound. In addition, the application of his analytical approach to drug discovery and pharmacology led others in the field to create many other new classes of drugs. Shortly before he died in 2010, Black wrote a retrospective review of his research career that provides insight into his innovative thinking and career success. This overview affords readers a very personal picture of the man, his ideas and his contributions.
Asunto(s)
Antagonistas Adrenérgicos beta/historia , Descubrimiento de Drogas/historia , Antagonistas de los Receptores H2 de la Histamina/historia , Farmacología/historia , Antagonistas Adrenérgicos beta/farmacología , Cimetidina/historia , Cimetidina/farmacología , Descubrimiento de Drogas/métodos , Antagonistas de los Receptores H2 de la Histamina/farmacología , Historia del Siglo XX , Humanos , Farmacología/métodos , Propranolol/historia , Propranolol/farmacología , Investigación/historiaAsunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Benchmarking , Evaluación de Procesos y Resultados en Atención de Salud , Indicadores de Calidad de la Atención de Salud , Procedimientos Quirúrgicos Vasculares/normas , Antagonistas Adrenérgicos beta/historia , Competencia Clínica/normas , Bases de Datos como Asunto , Medicina Basada en la Evidencia , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Atención Perioperativa , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina/normas , Medición de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Procedimientos Quirúrgicos Vasculares/efectos adversos , Procedimientos Quirúrgicos Vasculares/historia , Procedimientos Quirúrgicos Vasculares/mortalidadRESUMEN
The history of glaucoma pharmacology begins in 1862 with the isolation of physostigmine from the calabar bean. The discovery of epinephrine's intraocular pressure lowering capacity came along some 40 years later. During the 20th century, drug discovery and development accelerated, with the introduction of carbonic anhydrase inhibitors, beta blockers, and prostaglandin analogs. This survey of the history of glaucoma medications reviews some of the pivotal stories behind the development of the drugs that we use daily to manage our patients with glaucoma. In addition, some unmet needs that persist in glaucoma pharmacology are discussed.
Asunto(s)
Glaucoma/historia , Agonistas Adrenérgicos/historia , Agonistas Adrenérgicos/uso terapéutico , Antagonistas Adrenérgicos beta/historia , Antagonistas Adrenérgicos beta/uso terapéutico , Inhibidores de Anhidrasa Carbónica/historia , Inhibidores de Anhidrasa Carbónica/uso terapéutico , Glaucoma/tratamiento farmacológico , Glaucoma/fisiopatología , Historia del Siglo XIX , Historia del Siglo XX , Historia Antigua , Humanos , Presión Intraocular/efectos de los fármacos , Mióticos/historia , Mióticos/uso terapéutico , Prostaglandinas/historia , Prostaglandinas/uso terapéuticoAsunto(s)
Antagonistas Adrenérgicos beta/historia , Cardiopatías/historia , Antagonistas de los Receptores H2 de la Histamina/historia , Hepatopatías/historia , Farmacología/historia , Propranolol/historia , Antagonistas Adrenérgicos beta/uso terapéutico , Investigación Biomédica/historia , Industria Farmacéutica/historia , Cardiopatías/tratamiento farmacológico , Antagonistas de los Receptores H2 de la Histamina/uso terapéutico , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Hepatopatías/tratamiento farmacológico , Premio Nobel , Úlcera Péptica/tratamiento farmacológico , Úlcera Péptica/historia , Propranolol/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , EscociaRESUMEN
During the past three decades, every aspect of cardiomyopathy has undergone dramatic change. When examining the literature on the physiological aspects of the failing heart, one immediately recognises that South Africa has made a contribution: Brink, Bester and Lochner evaluated the possible therapeutic aspects of the Bowditch phenomenon and myocardial energetics in cardiomyopathy almost four decades ago, at a time when the condition even had another name, myocardiopathy.
Asunto(s)
Antagonistas Adrenérgicos beta/historia , Cardiomiopatías/historia , Frecuencia Cardíaca , Miocardio/metabolismo , Antagonistas Adrenérgicos beta/uso terapéutico , Animales , Cardiomiopatías/tratamiento farmacológico , Cardiomiopatías/fisiopatología , Metabolismo Energético , Historia del Siglo XX , Humanos , SudáfricaAsunto(s)
Antagonistas Adrenérgicos beta/historia , Antagonistas Adrenérgicos beta/farmacología , Antagonistas Adrenérgicos beta/uso terapéutico , Enfermedades Cardiovasculares/tratamiento farmacológico , Catecolaminas/antagonistas & inhibidores , Historia del Siglo XX , Historia del Siglo XXI , HumanosRESUMEN
beta-Adrenoceptor blocking agents (beta-blockers) that at low concentrations antagonize cardiostimulant effects of catecholamines, but at high concentrations also cause cardiostimulation, have been appearing since the late 1960s. These cardiostimulant beta-blockers, coined non-conventional partial agonists, antagonize the effects of catecholamines through a high-affinity site (beta(1H)AR), but cause cardiostimulation mainly through a low-affinity site (beta(1L)AR) of the myocardial beta(1)-adrenoceptor. The experimental non-conventional partial agonist (-)-CGP12177 increases cardiac L-type Ca(2+) current density and Ca(2+) transients, shortens action potential duration but augments action potential plateau, increases heart rate and force, as well as causes arrhythmic Ca(2+) transients and arrhythmic cardiocyte contractions. Other beta-blockers, which do not cause cardiostimulation, consistently have lower affinity for beta(1L)AR than beta(1H)AR. These sites were verified and the cardiac pharmacology of non-conventional partial agonists confirmed on recombinant beta(1)-adrenoceptors and on beta(1)-adrenoceptors overexpressed into the heart. A targeted mutation of Asp138 to Glu138 virtually abolished the pharmacology of beta(1H)AR but left intact the pharmacology of beta(1L)AR. Non-conventional partial agonists may be beneficial for the treatment of peripheral autonomic neuropathy but probably due to their arrhythmic propensities, may be harmful for the treatment of chronic heart failure.
Asunto(s)
Agonistas Adrenérgicos beta/farmacología , Antagonistas Adrenérgicos beta/farmacología , Receptores Adrenérgicos beta 1/efectos de los fármacos , Agonistas Adrenérgicos beta/efectos adversos , Agonistas Adrenérgicos beta/historia , Antagonistas Adrenérgicos beta/efectos adversos , Antagonistas Adrenérgicos beta/historia , Animales , Sitios de Unión , Catecolaminas/antagonistas & inhibidores , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Historia del Siglo XX , Humanos , Receptores Adrenérgicos beta 1/metabolismoRESUMEN
The development and subsequent clinical application of the beta-adrenergic receptor blocking drugs over the past 50 years represent one of the major advances in human pharmacotherapy. No other class of synthetic drugs has demonstrated such widespread therapeutic utility for the treatment of so many cardiovascular and noncardiovascular diseases. In addition, these drugs have proven to be molecular probes that have contributed to our understanding of disease, and on the molecular level, both the structure and the function of the 7 transmembrane G protein receptors, which mediate the actions of many different hormones, neurotransmitters, and drugs. The evolution of beta-blocker drug development has led to refinements in their pharmacodynamic actions that include agents with relative beta1-selectivity, partial agonist activity, concomitant alpha-adrenergic blockers activity, and direct vasodilator activity. In addition, long-acting and ultra-short-acting formulations of beta-blockers have also demonstrated a remarkable record of clinical safety in patients of all ages. Indeed, the beta-adrenergic blockers have provided us with a great clinical legacy for now and in years to come.
Asunto(s)
Antagonistas Adrenérgicos beta/historia , Antagonistas Adrenérgicos beta/uso terapéutico , Historia del Siglo XX , Historia del Siglo XXI , HumanosAsunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Infarto del Miocardio/tratamiento farmacológico , Evaluación de Resultado en la Atención de Salud/métodos , Indicadores de Calidad de la Atención de Salud , Antagonistas Adrenérgicos beta/historia , Historia del Siglo XX , Humanos , Programas Controlados de Atención en Salud/normas , Infarto del Miocardio/historia , Evaluación de Resultado en la Atención de Salud/historia , Indicadores de Calidad de la Atención de Salud/historia , Estados UnidosRESUMEN
Beta-adrenoceptor blockers belong to the most successful drug classes of medicine. Mainly they are used in internal medicine. 40 years ago beta-adrenoceptor blockers have occasionally been used in psychiatry for the treatment of anxiety disorders. Over the past four decades, the effects of beta-adrenoceptor blockers in the treatment of schizophrenic and manic psychoses, withdrawal syndromes and aggressive behaviour with temper outbursts has been investigated. Beta-adrenoceptor blockers are also used in the treatment of side-effects of psychopharmacological agents like neuroleptic or antidepressant-induced tachycardias, lithium-induced tremor, antipsychotic-induced akathisia or tardive dyskinesia as well. Since the mid-nineties it has been attempted to improve the efficacy of antidepressant agents by means of the 5-HT-(1a)-receptorantagonist pindolol. Presumedly memory consolidation of traumatic events can be enhanced by adrenergic activation. Therefore some open clinical trials investigated the effects of propranolol, a lipid soluble drug, which crosses the blood-brain barrier easily, to reduce the manifestation of PTSD. The present review presents the results of the literature with respect to the indications for beta-blockers in psychiatry. Considering evidence-based-medicine criteria beta-blockers are indicated to treat lithium-induced tremor, antipsychotic-induced akathisia and to reduce aggressive behavior of patients with brain-injuries.
Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Trastornos Mentales/tratamiento farmacológico , Antagonistas Adrenérgicos beta/historia , Agresión/efectos de los fármacos , Trastorno Bipolar/tratamiento farmacológico , Quimioterapia Combinada , Historia del Siglo XX , Humanos , Trastornos Mentales/historia , Psicotrópicos/uso terapéutico , Esquizofrenia/tratamiento farmacológicoRESUMEN
This article analyses how practolol, the first British drug disaster of the modern, post-thalidomide regulatory period, related to the pharmaceutical industry, the medical profession and government regulation of patients' health. Drawing on comparison with the USA, it argues that, contrary to public expectation and perception, the aftermath of thalidomide did not give rise to strident British drug control, imposing the highest possible safety standards on the pharmaceutical industry. Rather, there existed a culture of reluctant regulation that was characterised by continued optimism about, and trust in the purported benefits of new drugs among manufacturers and regulators in the United Kingdom, together with commitment to the protection of the industry and its institutional support for the medical profession. In particular, British regulators were willing to allow new drugs on to the market, fully aware of uncertainty about their safety, but unwilling to be pro-active in issuing warning letters about risks and requiring 'certainty' before acting to withdraw a product. Even after the practolol disaster, the British system was unable to reform itself to construct more rigorous and pro-active monitoring of drug risks. This was because of conflicts with industry interests.