Trends in COX-2 Inhibitor Research


Book Description

Cox-2 Inhibitors are newly developed drugs for inflammation that selectively block the Cox-2 enzyme. Blocking this enzyme impedes the production of the chemical messengers (prostaglandins) that cause the pain and swelling of arthritis inflammation. Cox-2 inhibitors are a new class of non-steroidal anti-inflammatory drugs (NSAIDS). Because they selectively block the Cox-2 enzyme and not the Cox-1 enzyme, these drugs are uniquely different from traditional NSAIDS. This book explores new research in the field.




Improved Non-Steroid Anti-Inflammatory Drugs: COX-2 Enzyme Inhibitors


Book Description

In 1971, Vane proposed that the mechanism of action of the aspirin-like drugs was through their inhibition of prostaglandin biosynthesis. Since then, there has been intense interest in the interaction between this diverse group of inhibitors and the enzyme known as cyclooxygenase (COX). It exists in two isoforms, COX-l and COX-2 (discovered some 5 years ago). Over the last two decades several new drugs have reached the market based on COX-l enzyme screens. Elucidation of the three-dimensional structure of COX-l has provided a new understanding for the actions of COX inhibitors. The constitutive isoform of COX, COX-l has clear physiological functions. Its activation leads, for instance, to the production of prostacyclin which when released by the endothelium is anti-thrombogenic and anti-atherosclerotic, and in the gastric mucosa is cyto protective. COX-l also generates prostaglandins in the kidney, where they help to maintain blood flow and promote natriuresis. The inducible isoform, COX-2, was discovered through its activity being increased in a number of cells by pro inflammatory stimuli. A year or so later, COX-2 was identified as a distinct isoform encoded by a different gene from COX-I. COX-2 is induced by inflammatory stimuli and by cytokines in migratory and other cells. Thus the anti-inflammatory actions of non-steroid anti-inflammatory drugs (NSAIDs) may be due to the inhibition of COX-2, whereas the unwanted side-effects such as irritation of the stomach lining and toxic effects on the kidney are due to inhibition of the constitutive enzyme, COX-I.




COX-2 Inhibitors


Book Description

COX-2 inhibitors are important drugs with analgesic and anti-inflammatory effects. The discovery of COX-2, the evolution of drug development in this field and the implications of these developments in patient therapy are topics of this volume. This book presents both pre-clinical and clinical information and is important for clinicians interested in the latest information about this class of drugs, for researchers and for students in the field.




COX-2 Blockade in Cancer Prevention and Therapy


Book Description

The revelation that aspirin and aspirin-like compounds have notableantineo plastic properties has revolutionized cancer research. COX-2 Blockade in Cancer Prevention and Therapy chronicles the evidence and presents exciting new op portunities for the use of cyclooxygenase-2 (COX-2) blockade in the prevention and treatment of cancer. The text is divided broadly into five areas. First, an historical overview documents the scientific discovery ofCOX-2 and the pharma ceutical development of nonsteroidal anti-inflammatory drugs (NSAIDs) designed for selective COX-2 inhibition. The process by which essential poly unsaturated fatty acids (PUF As) stimulate prostaglandin biosynthesis and cancer development, and its interruption by COX-2 inhibition, is elucidated. This is followed by a section on the epidemiology of NSAIDs and cancers of the colon and breast, and other anatomic sites. These chapters reflect significant cancer protection owing to the regular use of common NSAIDs such as aspirin and ibuprofen. A section on animal models of carcinogenesis presents comprehensive evidence that general NSAIDs inhibit a variety of malignant neoplasms in vivo, and highlights recent findings which show that COX-2 blocking agents produce striking chemopreventive effects against colon cancer and breast cancer as well as other malignancies. Genetic models are presented confirming the critical role of COX-2 in carcinogenesis. Section IV then discusses the molecular biology of COX -2 vis-a-vis the role of COX -2 and, to a lesser extent, COX -1, in modulating a number of important processes in molecular carcinogenesis such as mutagen esis, cell division, angiogenesis, cell differentiation, and apoptosis.




Selective COX-2 Inhibitors


Book Description

The mainstay of therapy for rheumatoid disease is the non-steroid antiinflammatory drugs (NSAIDs), despite their inherent gastrointestinal toxicity and ability to cause renal damage in susceptible patients. The theory that the beneficial and toxic effects of NSAIDs stem from a reduction in prostanoid production through inhibition of cyclooxygenase implied that particular toxicities were inevitable with NSAIDs and would always be correlated with efficacy. However, over the years, it became apparent that at therapeutic doses, some NSAIDs had greater toxic side-effects than others, a fact not explained by the general theory. A significant clarification arose from the discovery that there are two distinct isoforms of COX, a constitutive enzyme (COX-I) responsible for the production of prostanoids necessary for platelet aggregation and protection of the gastric mucosa and kidney; and an inducible enzyme (COX-2) that is newly synthesized at sites of tissue damage and produces prostaglandins that manifest pathological effects. It became clear that different NSAIDs had greater or lesser effects on COX-I when used in therapeutic doses, explaining the variation in side-effects. ' The elucidation of the crystal structure of these different enzymes and the skills of medicinal chemists have led to the synthesis of new chemicals with a selectivity for the inducible enzyme, and thus with therapeutic efficacy without those toxic effects result ing from inhibition of the constitutive enzyme.




COX-2 Inhibitor Research


Book Description

COX-2 Inhibitors are newly developed drugs for inflammation that selectively block the COX-2 enzyme. Blocking this enzyme impedes the production of the chemical messengers (prostaglandins) that cause the pain and swelling of arthritis inflammation. Cox-2 inhibitors are a new class of nonsteroidal anti-inflammatory drugs (NSAIDS). Because they selectively block the Cox-2 enzyme and not the Cox-1 enzyme, these drugs are uniquely different from traditional NSAIDS. This book explores new research in this field.




The $800 Million Pill


Book Description

"Goozner shows how drug innovation is driven by dedicated scientists intent on finding cures for diseases, not by pharmaceutical firms, whose bottom line often takes precedence over the advance of medicine. Stories of a university biochemist who spent twenty years searching for single blood protein that later became the best-selling biotech drug in the world, a government employee who discovered the causes for dozens of crippling genetic disorders, and the Department of Energy-funded research that made the Human Genome Project possible - these accounts illustrate how medical breakthroughs actually take place.".




Selected Health Conditions and Likelihood of Improvement with Treatment


Book Description

The Social Security Administration (SSA) administers two programs that provide disability benefits: the Social Security Disability Insurance (SSDI) program and the Supplemental Security Income (SSI) program. SSDI provides disability benefits to people (under the full retirement age) who are no longer able to work because of a disabling medical condition. SSI provides income assistance for disabled, blind, and aged people who have limited income and resources regardless of their prior participation in the labor force. Both programs share a common disability determination process administered by SSA and state agencies as well as a common definition of disability for adults: "the inability to engage in any substantial gainful activity by reason of any medically determinable physical or mental impairment which can be expected to result in death or which has lasted or can be expected to last for a continuous period of not less than 12 months." Disabled workers might receive either SSDI benefits or SSI payments, or both, depending on their recent work history and current income and assets. Disabled workers might also receive benefits from other public programs such as workers' compensation, which insures against work-related illness or injuries occurring on the job, but those other programs have their own definitions and eligibility criteria. Selected Health Conditions and Likelihood of Improvement with Treatment identifies and defines the professionally accepted, standard measurements of outcomes improvement for medical conditions. This report also identifies specific, long-lasting medical conditions for adults in the categories of mental health disorders, cancers, and musculoskeletal disorders. Specifically, these conditions are disabling for a length of time, but typically don't result in permanently disabling limitations; are responsive to treatment; and after a specific length of time of treatment, improve to the point at which the conditions are no longer disabling.




Hidden Costs, Value Lost


Book Description

Hidden Cost, Value Lost, the fifth of a series of six books on the consequences of uninsurance in the United States, illustrates some of the economic and social losses to the country of maintaining so many people without health insurance. The book explores the potential economic and societal benefits that could be realized if everyone had health insurance on a continuous basis, as people over age 65 currently do with Medicare. Hidden Costs, Value Lost concludes that the estimated benefits across society in health years of life gained by providing the uninsured with the kind and amount of health services that the insured use, are likely greater than the additional social costs of doing so. The potential economic value to be gained in better health outcomes from uninterrupted coverage for all Americans is estimated to be between $65 and $130 billion each year.