168-553: Wyeth Pharmaceuticals Inc. was a pharmaceutical company until it was purchased by Pfizer in 2009. The company was founded in Philadelphia, Pennsylvania , in 1860 as John Wyeth and Brother. Its headquarters moved to Collegeville, Pennsylvania , and Madison, New Jersey , before its headquarters were consolidated with Pfizer's in New York City after the 2009 merger. Wyeth manufactured over-the-counter (OTC) drugs Robitussin and
336-502: A benzodiazepine , in order to ameliorate alcohol withdrawal syndrome 's adverse impact. The addition of phenobarbital improves outcomes if benzodiazepine administration lacks the usual efficacy, and phenobarbital alone might be an effective treatment. Propofol also might enhance treatment for individuals showing limited therapeutic response to a benzodiazepine. Individuals who are only at risk of mild to moderate withdrawal symptoms can be treated as outpatients. Individuals at risk of
504-458: A coma (unconsciousness), life-threatening respiratory depression and possibly fatal alcohol poisoning . With all alcoholic beverages, drinking while driving , operating an aircraft or heavy machinery increases the risk of an accident; many countries have penalties for drunk driving. Having more than one drink a day for women or two drinks for men increases the risk of heart disease, high blood pressure , atrial fibrillation , and stroke . Risk
672-514: A sedative -hypnotic mechanism, such as barbiturates and benzodiazepines , withdrawal from alcohol dependence can be fatal if it is not properly managed. Alcohol's primary effect is the increase in stimulation of the GABA A receptor , promoting central nervous system depression. With repeated heavy consumption of alcohol, these receptors are desensitized and reduced in number, resulting in tolerance and physical dependence . When alcohol consumption
840-435: A vasodilator for treatment of angina , Dryvax , a freeze-dried smallpox vaccine, and Ovral, a combined oral contraceptive pill . Pharmaceuticals were generating an ever-increasing percentage of Wyeth's sales. Wyeth became a leading US vaccine producer after supplying polio vaccine for Salk trials. The corporate headquarters were moved to Radnor , Pennsylvania, where they remained until 2003. William F. Laporte became
1008-492: A 20% drop in those for which antibiotics were not effective. The report concluded that "it appears that the use of antibiotics, early diagnosis, and other factors have limited the epidemic spread and thus the number of these diseases which have occurred". The study further examined mortality rates for eight common diseases for which antibiotics offered effective therapy (syphilis, tuberculosis, dysentery, scarlet fever, whooping cough, meningococcal infections, and pneumonia), and found
1176-550: A 2014 report in the National Survey on Drug Use and Health found that only 10% of either "heavy drinkers" or "binge drinkers" defined according to the above criteria also met the criteria for alcohol dependence, while only 1.3% of non-binge drinkers met the criteria. An inference drawn from this study is that evidence-based policy strategies and clinical preventive services may effectively reduce binge drinking without requiring addiction treatment in most cases. The term alcoholism
1344-517: A 56% decline over the same period. Notable among these was a 75% decline in deaths due to tuberculosis. During the years 1940–1955, the rate of decline in the U.S. death rate accelerated from 2% per year to 8% per year, then returned to the historical rate of 2% per year. The dramatic decline in the immediate post-war years has been attributed to the rapid development of new treatments and vaccines for infectious disease that occurred during these years. Vaccine development continued to accelerate, with
1512-411: A Japanese biochemist working for the pharmaceutical company Sankyo, identified mevastatin (ML-236B), a molecule produced by the fungus Penicillium citrinum , as an inhibitor of HMG-CoA reductase, a critical enzyme used by the body to produce cholesterol. Animal trials showed very good inhibitory effect as in clinical trials , however a long-term study in dogs found toxic effects at higher doses and as
1680-687: A clinical context. Alcohol is addictive , and heavy long-term alcohol use results in many negative health and social consequences. It can damage all the organ systems , but especially affects the brain, heart, liver, pancreas and immune system . Heavy alcohol usage can result in trouble sleeping , and severe cognitive issues like dementia , brain damage , or Wernicke–Korsakoff syndrome . Physical effects include irregular heartbeat , an impaired immune response, liver cirrhosis , increased cancer risk , and severe withdrawal symptoms if stopped suddenly. These health effects can reduce life expectancy by 10 years. Drinking during pregnancy may harm
1848-414: A compound is identified as a potential drug in order to establish its suitability as a medication. Objectives of drug development are to determine appropriate formulation and dosing , as well as to establish safety . Research in these areas generally includes a combination of in vitro studies, in vivo studies, and clinical trials . The cost of late stage development has meant it is usually done by
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#17328524289122016-657: A conclusion comes from low to moderate certainty evidence "so should be regarded with caution". Others include LifeRing Secular Recovery , SMART Recovery , Women for Sobriety , and Secular Organizations for Sobriety . Manualized Twelve Step Facilitation (TSF) interventions (i.e. therapy which encourages active, long-term Alcoholics Anonymous participation) for Alcohol Use Disorder lead to higher abstinence rates, compared to other clinical interventions and to wait-list control groups. Moderate drinking amongst people with alcohol dependence—often termed 'controlled drinking'—has been subject to significant controversy. Indeed, much of
2184-510: A dedication of the food business, the PAM trademark becomes part of American Home Foods. Premarin becomes the most prescribed drug in the US in 1993. Effexor ( venlafaxine HCl), the first serotonin-norepinephrine reuptake inhibitor (SNRI), is introduced for the treatment of clinical depression and is later indicated for generalized anxiety disorder and social anxiety disorder . In 1993, Wyeth founded
2352-465: A drug could be sold, and explicitly prohibited false therapeutic claims. The aftermath of World War II saw an explosion in the discovery of new classes of antibacterial drugs including the cephalosporins (developed by Eli Lilly based on the seminal work of Giuseppe Brotzu and Edward Abraham ), streptomycin (discovered during a Merck-funded research program in Selman Waksman's laboratory ),
2520-440: A few recognizable effects on the body, including: With regard to alcoholism, BAC is useful to judge alcohol tolerance , which in turn is a sign of alcoholism. Electrolyte and acid-base abnormalities including hypokalemia , hypomagnesemia , hyponatremia , hyperuricemia , metabolic acidosis , and respiratory alkalosis are common in people with alcohol use disorders. However, none of these blood tests for biological markers
2688-503: A fire destroyed the brothers' original Walnut Street store, and they sold the retail business and focused on mass production. John Wyeth died in 1907 and his only son, Stuart, became the company's president. The Whitehall building in downtown Manhattan became the corporation's first headquarters. Global sales increased due to the sales of Wyeth's Kolynos brand of toothpaste. In 1929, Stuart Wyeth died and left controlling interest to Harvard University . In 1930, Wyeth purchased Anacin ,
2856-540: A heart attack were reduced by 42%. In 1995, Zocor and Mevacor both made Merck over US$ 1 billion. Endo was awarded the 2006 Japan Prize , and the Lasker-DeBakey Clinical Medical Research Award in 2008. For his "pioneering research into a new class of molecules" for "lowering cholesterol," Since several decades, biologics have been rising in importance in comparison with small molecules treatments. The biotech subsector, animal health and
3024-402: A higher mortality rate from alcoholism than men. Examples of long-term complications include brain, heart, and liver damage and an increased risk of breast cancer . Additionally, heavy drinking over time has been found to have a negative effect on reproductive functioning in women. This results in reproductive dysfunction such as anovulation , decreased ovarian mass, problems or irregularity of
3192-501: A highly toxic solvent that is now widely used as antifreeze. Under the laws extant at that time, prosecution of the manufacturer was possible only under the technicality that the product had been called an "elixir", which literally implied a solution in ethanol. In response to this episode, the U.S. Congress passed the Federal Food, Drug, and Cosmetic Act of 1938 , which for the first time required pre-market demonstration of safety before
3360-564: A lower weight and higher percentage of body fat and therefore a lower volume of distribution for alcohol than men. Long-term misuse of alcohol can cause a wide range of mental health problems. Severe cognitive problems are common; approximately 10% of all dementia cases are related to alcohol consumption, making it the second leading cause of dementia . Excessive alcohol use causes damage to brain function , and psychological health can be increasingly affected over time. Social skills are significantly impaired in people with alcoholism due to
3528-444: A medical condition, to display their drinking publicly, and to drink in groups. This pattern, in turn, leads family, physicians, and others to be more likely to suspect that a man they know is someone with an alcohol use disorder. Screening is recommended among those over the age of 18. Several tools may be used to detect a loss of control of alcohol use. These tools are mostly self-reports in questionnaire form. Another common theme
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#17328524289123696-522: A misdiagnosis such as schizophrenia . Panic disorder can develop or worsen as a direct result of long-term alcohol misuse. The co-occurrence of major depressive disorder and alcoholism is well documented. Among those with comorbid occurrences, a distinction is commonly made between depressive episodes that remit with alcohol abstinence ("substance-induced"), and depressive episodes that are primary and do not remit with abstinence ("independent" episodes). Additional use of other drugs may increase
3864-469: A number of companies developed products based on adrenal extracts containing varying purities of the active substance. In 1897, John Abel of Johns Hopkins University identified the active principle as epinephrine , which he isolated in an impure state as the sulfate salt. Industrial chemist Jōkichi Takamine later developed a method for obtaining epinephrine in a pure state, and licensed the technology to Parke-Davis . Parke-Davis marketed epinephrine under
4032-479: A number of firms generating dyestuffs derived from coal tar on a large scale, sought out new applications of their artificial materials in terms of human health . This trend to increased capital investment occurred in tandem with the scholarly study of pathology as a field advancing significantly, and a variety of businesses set up cooperative relationships with academic laboratories evaluating human injury and disease. Examples of industrial companies with
4200-444: A parent or sibling with an alcohol use disorder is three to four times more likely to develop an alcohol use disorder themselves, but only a minority of them do. Environmental factors include social, cultural and behavioral influences. High stress levels and anxiety, as well as alcohol's inexpensive cost and easy accessibility, increase the risk. People may continue to drink partly to prevent or improve symptoms of withdrawal. After
4368-492: A person stops drinking alcohol, they may experience a low level of withdrawal lasting for months. Medically, alcoholism is considered both a physical and mental illness. Questionnaires are usually used to detect possible alcoholism. Further information is then collected to confirm the diagnosis. Treatment of alcoholism may take several forms. Due to medical problems that can occur during withdrawal, alcohol cessation should be controlled carefully. One common method involves
4536-770: A pharmaceutical firm specializing in infant formulas. Wyeth also made its first licensing deal, acquiring an antibiotic for arthritis vaccine research. In 1941, the US entered World War II , and Wyeth shipped typical wartime drugs such as sulfa bacteriostatics, blood plasma , typhus vaccine, quinine , and atabrine tablets. Wyeth was later rewarded for its contribution to the war effort. During this time, Wyeth launched its penicillin research facility with G. Raymond Rettew. In 1943, Wyeth purchased G. Washington Coffee Refining Company , an instant coffee company created by early 20th century Belgian inventor George Washington . In 1943, Wyeth merged with Ayerst, McKenna and Harrison, Ltd. of Canada. With this merger came Premarin ,
4704-493: A pharmaceutical focus that have endured to this day after such distant beginnings include Bayer (based out of Germany) and Pfizer (based out of the U.S.). The modern era of pharmaceutical industry began with local apothecaries that expanded for their traditional role of distributing botanical drug s such as morphine and quinine to wholesale manufacture in the mid-1800s, and from discoveries resulting from applied research. Intentional drug discovery from plants began with
4872-411: A product for tension headaches which quickly became the company's flagship product. One year later, Harvard sold Wyeth to American Home Products for US$ 2.9 million. In 1935, Alvin G. Brush, a Certified Public Accountant , became CEO of the organization and served for 30 years. Under Brush's leadership, 34 new companies were acquired in 15 years, including Chef Boyardee and the S.M.A. Corporation ,
5040-499: A protocol to discontinue their use. A series of experiments performed from the late 1800s to the early 1900s revealed that diabetes is caused by the absence of a substance normally produced by the pancreas. In 1869, Oskar Minkowski and Joseph von Mering found that diabetes could be induced in dogs by surgical removal of the pancreas. In 1921, Canadian professor Frederick Banting and his student Charles Best repeated this study and found that injections of pancreatic extract reversed
5208-463: A push for revisions of the FD&;C Act emerged from Congressional hearings led by Senator Estes Kefauver of Tennessee in 1959. The hearings covered a wide range of policy issues, including advertising abuses, questionable efficacy of drugs, and the need for greater regulation of the industry. While momentum for new legislation temporarily flagged under extended debate, a new tragedy emerged that underscored
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5376-444: A reduced risk of developing alcoholism. Native Americans , however, have a significantly higher rate of alcoholism than average; risk factors such as cultural environmental effects (e.g. trauma ) have been proposed to explain the higher rates. The aldehyde dehydrogenase allele ALDH2*2 greatly reduces the rate at which acetaldehyde, the initial product of alcohol metabolism, is removed by conversion to acetate; it greatly reduces
5544-504: A reduction in initial public offerings being floated. A 2022 article articulated this notion succinctly by saying "In the business of drug development, deals can be just as important as scientific breakthroughs", typically referred to as pharmaceutical M&A (for mergers and acquisitions). It highlighted that some of the most impactful of the remedies of the early 21st Century were only made possible through M&A activities, specifically noting Keytruda and Humira . Drug discovery
5712-400: A result mevastatin was believed to be too toxic for human use. Mevastatin was never marketed, because of its adverse effects of tumors, muscle deterioration, and sometimes death in laboratory dogs. P. Roy Vagelos , chief scientist and later CEO of Merck & Co , was interested, and made several trips to Japan starting in 1975. By 1978, Merck had isolated lovastatin (mevinolin, MK803) from
5880-431: A series of such compounds, and was found to exhibit partially selective toxicity. Arsphenamine proved to be the first effective treatment for syphilis , a disease untl then had been incurable and led inexorably to severe skin ulceration, neurological damage, and death. Ehrlich's approach of systematically varying the chemical structure of synthetic compounds and measuring the effects of these changes on biological activity
6048-697: A severe withdrawal syndrome as well as those who have significant or acute comorbid conditions can be treated as inpatients. Direct treatment can be followed by a treatment program for alcohol dependence or alcohol use disorder to attempt to reduce the risk of relapse. Experiences following alcohol withdrawal, such as depressed mood and anxiety, can take weeks or months to abate while other symptoms persist longer due to persisting neuroadaptations. Various forms of group therapy or psychotherapy are sometimes used to encourage and support abstinence from alcohol, or to reduce alcohol consumption to levels that are not associated with adverse outcomes. Mutual-aid group-counseling
6216-557: A sleep aid beginning in 1904. Systematic investigations of the effect of structural changes on potency and duration of action led to the discovery of phenobarbital at Bayer in 1911 and the discovery of its potent anti-epileptic activity in 1912. Phenobarbital was among the most widely used drugs for the treatment of epilepsy through the 1970s, and as of 2014, remains on the World Health Organizations list of essential medications. The 1950s and 1960s saw increased awareness of
6384-489: A small fraction are eventually approved in most nations by government-appointed medical institutions or boards, who have to approve new drugs before they can be marketed in those countries. In 2010 18 NMEs (New Molecular Entities) were approved and three biologics by the FDA, or 21 in total, which is down from 26 in 2009 and 24 in 2008. On the other hand, there were only 18 approvals in total in 2007 and 22 back in 2006. Since 2001,
6552-558: A third of the global pharmaceutical market, with $ 340 billion in annual sales followed by the EU and Japan. Emerging markets such as China, Russia, South Korea and Mexico outpaced that market, growing a huge 81 percent. The top ten best-selling drugs of 2013 totaled $ 75.6 billion in sales, with the anti-inflammatory drug Humira being the best-selling drug worldwide at $ 10.7 billion in sales. The second and third best selling were Enbrel and Remicade, respectively. The top three best-selling drugs in
6720-586: A total of $ 1,228.45 billion in 2020. The sector showed a compound annual growth rate (CAGR) of 1.8% in 2021, including the effects of the COVID-19 pandemic . In historical terms, a pharmaceutical industry as an intellectual concept arose within the middle to late 1800s inside of certain nation-states with developed economies such as Germany , Switzerland , and the United States given that multiple businesses engaging in synthetic organic chemistry , such as
6888-470: A two-hour period. According to the NIAAA, men may be at risk for alcohol-related problems if their alcohol consumption exceeds 14 standard drinks per week or 4 drinks per day, and women may be at risk if they have more than 7 standard drinks per week or 3 drinks per day. It defines a standard drink as one 12-ounce bottle of beer, one 5-ounce glass of wine, or 1.5 ounces of distilled spirits. Despite this risk,
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7056-429: Is a score or tally that sums up the general severity of alcohol use. The CAGE questionnaire , named for its four questions, is one such example that may be used to screen patients quickly in a doctor's office. Two "yes" responses indicate that the respondent should be investigated further. The questionnaire asks the following questions: Other tests are sometimes used for the detection of alcohol dependence, such as
7224-406: Is a very large study of efficacy in the intended patient population. Following the successful completion of phase III testing, a New Drug Application is submitted to the FDA. The FDA reviews the data and if the product is seen as having a positive benefit-risk assessment, approval to market the product in the US is granted. A fourth phase of post-approval surveillance is also often required due to
7392-417: Is an approach used to facilitate relapse prevention. Alcoholics Anonymous was one of the earliest organizations formed to provide mutual peer support and non-professional counseling, however the effectiveness of Alcoholics Anonymous is disputed. A 2020 Cochrane review concluded that Twelve-Step Facilitation (TSF) probably achieves outcomes such as fewer drinks per drinking day, however evidence for such
7560-544: Is as sensitive as screening questionnaires. The World Health Organization , the European Union and other regional bodies, national governments and parliaments have formed alcohol policies in order to reduce the harm of alcoholism. Increasing the age at which alcohol can be purchased, and banning or restricting alcohol beverage advertising are common methods to reduce alcohol use among adolescents and young adults in particular. Another common method of alcoholism prevention
7728-620: Is associated with loss of employment , which can lead to financial problems. Drinking at inappropriate times and behavior caused by reduced judgment can lead to legal consequences, such as criminal charges for drunk driving or public disorder, or civil penalties for tortious behavior. An alcoholic's behavior and mental impairment while drunk can profoundly affect those surrounding him and lead to isolation from family and friends. This isolation can lead to marital conflict and divorce , or contribute to domestic violence . Alcoholism can also lead to child neglect , with subsequent lasting damage to
7896-400: Is characterized by an increased tolerance to alcohol – which means that an individual can consume more alcohol – and physical dependence on alcohol, which makes it hard for an individual to control their consumption. The physical dependency caused by alcohol can lead to an affected individual having a very strong urge to drink alcohol. These characteristics play a role in decreasing
8064-474: Is commonly used amongst laypeople, but the word is poorly defined. Despite the imprecision inherent in the term, there have been attempts to define how the word alcoholism should be interpreted when encountered. In 1992, it was defined by the National Council on Alcoholism and Drug Dependence (NCADD) and ASAM as "a primary, chronic disease characterized by impaired control over drinking, preoccupation with
8232-441: Is detoxification followed by a combination of supportive therapy, attendance at self-help groups, and ongoing development of coping mechanisms. Much of the treatment community for alcoholism supports an abstinence-based zero tolerance approach popularized by the 12 step program of Alcoholics Anonymous ; however, some prefer a harm-reduction approach. Medical treatment for alcohol detoxification usually involves administration of
8400-739: Is disagreement on the definition of the word alcoholism, it is not a recognized diagnosis, and the use of the term alcoholism is discouraged due to its heavily stigmatized connotations. It is classified as alcohol use disorder in the DSM-5 or alcohol dependence in the ICD-11 . In 1979, the World Health Organization discouraged the use of alcoholism due to its inexact meaning, preferring alcohol dependence syndrome . Misuse, problem use, abuse, and heavy use of alcohol refer to improper use of alcohol, which may cause physical, social, or moral harm to
8568-500: Is due to neuroadaptations which occur as a result of periods of abstinence followed by re-exposure to alcohol. Individuals who have had multiple withdrawal episodes are more likely to develop seizures and experience more severe anxiety during withdrawal from alcohol than alcohol-dependent individuals without a history of past alcohol withdrawal episodes. The kindling effect leads to persistent functional changes in brain neural circuits as well as to gene expression . Kindling also results in
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#17328524289128736-473: Is greater with binge drinking , which may also result in violence or accidents. About 3.3 million deaths (5.9% of all deaths) are believed to be due to alcohol each year. Alcoholism reduces a person's life expectancy by around ten years and alcohol use is the third leading cause of early death in the United States. Long-term alcohol misuse can cause a number of physical symptoms, including cirrhosis of
8904-450: Is not associated with cancer in people. Other notable new vaccines of the period include those for measles (1962, John Franklin Enders of Children's Medical Center Boston, later refined by Maurice Hilleman at Merck), Rubella (1969, Hilleman, Merck) and mumps (1967, Hilleman, Merck) The United States incidences of rubella, congenital rubella syndrome, measles, and mumps all fell by >95% in
9072-409: Is often used for self-medication of conditions like anxiety temporarily, prevention of alcoholism may be attempted by reducing the severity or prevalence of stress and anxiety in individuals. Treatments are varied because there are multiple perspectives of alcoholism. Those who approach alcoholism as a medical condition or disease recommend differing treatments from, for instance, those who approach
9240-565: Is stopped too abruptly, the person's nervous system experiences uncontrolled synapse firing. This can result in symptoms that include anxiety , life-threatening seizures , delirium tremens , hallucinations, shakes and possible heart failure . Other neurotransmitter systems are also involved, especially dopamine , NMDA and glutamate . Severe acute withdrawal symptoms such as delirium tremens and seizures rarely occur after 1-week post cessation of alcohol. The acute withdrawal phase can be defined as lasting between one and three weeks. In
9408-428: Is taxation of alcohol products – increasing price of alcohol by 10% is linked with reduction of consumption of up to 10%. Credible, evidence-based educational campaigns in the mass media about the consequences of alcohol misuse have been recommended. Guidelines for parents to prevent alcohol misuse amongst adolescents, and for helping young people with mental health problems have also been suggested. Because alcohol
9576-677: Is the abstinence based mutual aid fellowship Alcoholics Anonymous (AA). A 2020 scientific review found that clinical interventions encouraging increased participation in AA (AA/twelve step facilitation (AA/TSF))—resulted in higher abstinence rates over other clinical interventions, and most studies in the review found that AA/TSF led to lower health costs. Many terms, some slurs and some informal , have been used to refer to people affected by alcoholism such as tippler , drunkard , dipsomaniac and souse . The risk of alcohol dependence begins at low levels of drinking and increases directly with both
9744-430: Is the core guide for pharmacists and clinicians. In many non-US western countries, a 'fourth hurdle' of cost effectiveness analysis has developed before new technologies can be provided. This focuses on the 'efficacy price tag' (in terms of, for example, the cost per QALY ) of the technologies in question. In England and Wales NICE decides whether and in what circumstances drugs and technologies will be made available by
9912-645: Is the most available, widely consumed, and widely misused recreational drug . Beer alone is the world's most widely consumed alcoholic beverage ; it is the third-most popular drink overall, after water and tea . It is thought by some to be the oldest fermented beverage . Based on combined data in the US from SAMHSA 's 2004–2005 National Surveys on Drug Use & Health, the rate of past-year alcohol dependence or misuse among persons aged 12 or older varied by level of alcohol use: 44.7% of past month heavy drinkers, 18.5% binge drinkers, 3.8% past month non-binge drinkers, and 1.3% of those who did not drink alcohol in
10080-498: Is the most important risk factor for cardiovascular morbidity and mortality , in industrialized countries . Prior to 1940 approximately 23% of all deaths among persons over age 50 were attributed to hypertension. Severe cases of hypertension were treated by surgery. Early developments in the field of treating hypertension included quaternary ammonium ion sympathetic nervous system blocking agents, but these compounds were never widely used due to their severe side effects, because
10248-595: Is the process by which potential drugs are discovered or designed. In the past, most drugs have been discovered either by isolating the active ingredient from traditional remedies or by serendipitous discovery. Modern biotechnology often focuses on understanding the metabolic pathways related to a disease state or pathogen , and manipulating these pathways using molecular biology or biochemistry . A great deal of early-stage drug discovery has traditionally been carried out by universities and research institutions. Drug development refers to activities undertaken after
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#173285242891210416-415: Is the value of the publicly traded companies. Small Molecules modality had 58.2% of the valuation share down from 84.6% in 2003. Biologics was up at 30.5% from 14.5%. The valuation share of Chinese Pharma grew from 2003 to 2021 from 1% to 12% overtaking Switzerland who is now ranked number 3 with 7.7%. The United States had still by far the most valued pharmaceutical industry with 40% of global valuation. 2023
10584-537: The Alcohol Dependence Data Questionnaire , which is a more sensitive diagnostic test than the CAGE questionnaire . It helps distinguish a diagnosis of alcohol dependence from one of heavy alcohol use. The Michigan Alcohol Screening Test (MAST) is a screening tool for alcoholism widely used by courts to determine the appropriate sentencing for people convicted of alcohol-related offenses, driving under
10752-508: The Nobel Prize in Medicine for this discovery. Nonetheless, the dramatic decrease in deaths from infectious diseases that occurred prior to World War II was primarily the result of improved public health measures such as clean water and less crowded housing, and the impact of anti-infective drugs and vaccines was significant mainly after World War II. In 1928, Alexander Fleming discovered
10920-540: The Women's Health Research Institute , the only institute in the pharmaceutical industry entirely dedicated to research in women's health. The Institute conducted trials in menopausal issues, endometriosis , contraception , and more. In 1994, Wyeth acquired American Cyanamid and its subsidiary Lederle Laboratories. This acquisition brought the Lederle Praxis vaccines, new research and development capacity, and Centrum ,
11088-489: The analgesic Advil ( ibuprofen ) as well as prescription drugs Premarin and Effexor . In 1860, pharmacists John (1834–1907) and Frank Wyeth opened a drugstore with a small research lab on Walnut Street in Philadelphia. In 1862, on the suggestion of doctors, they began to manufacture large quantities of commonly ordered medicines. They were successful, and in 1864 they began supplying medicines and beef extract to
11256-577: The birth control movement and the efforts of activists Margaret Sanger , Mary Dennett , and Emma Goldman . Based on fundamental research performed by Gregory Pincus and synthetic methods for progesterone developed by Carl Djerassi at Syntex and by Frank Colton at G.D. Searle & Co. , the first oral contraceptive, Enovid , was developed by G.D. Searle & Co. and approved by the FDA in 1960. The original formulation incorporated vastly excessive doses of hormones, and caused severe side effects. Nonetheless, by 1962, 1.2 million American women were on
11424-416: The central nervous system and peripheral nervous system can occur from sustained alcohol consumption. A wide range of immunologic defects can result and there may be a generalized skeletal fragility, in addition to a recognized tendency to accidental injury, resulting in a propensity for bone fractures. Women develop long-term complications of alcohol dependence more rapidly than do men, women also have
11592-428: The menstrual cycle , and early menopause . Alcoholic ketoacidosis can occur in individuals who chronically misuse alcohol and have a recent history of binge drinking . The amount of alcohol that can be biologically processed and its effects differ between sexes. Equal dosages of alcohol consumed by men and women generally result in women having higher blood alcohol concentrations (BACs), since women generally have
11760-477: The opportunity cost of investing capital many years before revenues are realized (see Time-value of money ). Because of the very long time needed for discovery, development, and approval of pharmaceuticals, these costs can accumulate to nearly half the total expense. A direct consequence within the pharmaceutical industry value chain is that major pharmaceutical multinationals tend to increasingly outsource risks related to fundamental research, which somewhat reshapes
11928-454: The Center for Drug Evaluation and Research has averaged 22.9 approvals a year. This approval comes only after heavy investment in pre-clinical development and clinical trials , as well as a commitment to ongoing safety monitoring . Drugs which fail part-way through this process often incur large costs, while generating no revenue in return. If the cost of these failed drugs is taken into account,
12096-593: The Chairman and President of AHP in 1965, and served until 1981. The World Health Organization initiated the Global Smallpox Eradication Program in 1967, and approached Wyeth to develop a better injection system for smallpox vaccines which could be used in the field. Wyeth waived patent royalties on its innovative bifurcated needle , aiding in the delivery of over 200 million smallpox vaccines per year. Wyeth's oral contraceptives became popular in
12264-489: The Chinese pharmaceutical sector have also grown substantially. On the organisational side, big international pharma corporations have experienced a substantial decline of their value share. Also, the core generic sector (substitutions for off-patent brands) has been downvalued due to competition. Torreya estimated the pharmaceutical industry to have a market valuation of US$ 7.03 trillion by February 2021 from which US$ 6.1 trillion
12432-509: The Institute of Experimental Therapy in Berlin. The drug was given the commercial name Salvarsan. Ehrlich, noting both the general toxicity of arsenic and the selective absorption of certain dyes by bacteria, hypothesized that an arsenic-containing dye with similar selective absorption properties could be used to treat bacterial infections. Arsphenamine was prepared as part of a campaign to synthesize
12600-806: The NHS, whilst similar arrangements exist with the Scottish Medicines Consortium in Scotland, and the Pharmaceutical Benefits Advisory Committee in Australia. A product must pass the threshold for cost-effectiveness if it is to be approved. Treatments must represent 'value for money' and a net benefit to society. There are special rules for certain rare diseases ("orphan diseases") in several major drug regulatory territories. For example, diseases involving fewer than 200,000 patients in
12768-785: The Orange Book site. In the UK, the Medicines and Healthcare products Regulatory Agency approves and evaluates drugs for use. Normally an approval in the UK and other European countries comes later than one in the USA. Then it is the National Institute for Health and Care Excellence (NICE), for England and Wales, who decides if and how the National Health Service (NHS) will allow (in the sense of paying for) their use. The British National Formulary
12936-605: The Pyramid vaccine line, Quest Gel, and EtoGesic Tablets. Prenatal Infant Toddler Pre-school Special Feeder A "whistleblower suit" was filed against Wyeth in 2005 alleging that the company illegally marketed their drug Rapamune . Wyeth is targeted in the suit for off-label marketing , targeting specific doctors and medical facilities to increased sales of Rapamune, trying to get current transplant patients to change from their current transplant drugs to Rapamune and for specifically targeting African-Americans. According to
13104-458: The US market. The FDA received authority to regulate advertising of prescription drugs and to establish good manufacturing practices . The law required that all drugs introduced between 1938 and 1962 had to be effective. An FDA - National Academy of Sciences collaborative study showed that nearly 40 percent of these products were not effective. A similarly comprehensive study of over-the-counter products began ten years later. In 1971, Akira Endo ,
13272-602: The US. John W. Culligan, after becoming Chairman and CEO in 1981, spun off less profitable lines and focused resources on consumer and prescription drugs. Wyeth made history in 1984 with the introduction of Advil , the first nonprescription ibuprofen in America, as well as the most famous prescription-to-OTC switch in history. John R. Stafford became CEO and Chairman in 1986. He completed the divestiture of non-core businesses such as household products, foods, candy ( Brach's Candy ), and medical devices (e.g., its Sherwood-Medical Company
13440-733: The Union army during the Civil War . In 1872, Henry Bower, an employee of Wyeth, developed one of the first rotary compressed tablet machines in the United States . This enabled the mass production of medicines with unprecedented precision and speed. It was successful, and the Wyeth brothers won multiple awards at the Centennial Exhibition . In 1883, Wyeth opened its first international facility in Montreal , Canada, and began vaccine production. Six years later
13608-537: The United States in 2013 were Abilify ($ 6.3 billion,) Nexium ($ 6 billion) and Humira ($ 5.4 billion). The best-selling drug ever, Lipitor , averaged $ 13 billion annually and netted $ 141 billion total over its lifetime before Pfizer's patent expired in November 2011. Alcoholism Alcoholism is the continued drinking of alcohol despite it causing problems. Some definitions require evidence of dependence and withdrawal. Problematic use of alcohol has been mentioned in
13776-679: The United States, or larger populations in certain circumstances are subject to the Orphan Drug Act. Because medical research and development of drugs to treat such diseases is financially disadvantageous, companies that do so are rewarded with tax reductions, fee waivers, and market exclusivity on that drug for a limited time (seven years), regardless of whether the drug is protected by patents. In 2011, global spending on prescription drugs topped $ 954 billion, even as growth slowed somewhat in Europe and North America. The United States accounts for more than
13944-535: The United States, the Diagnostic and Statistical Manual of Mental Disorders (DSM) is the most common diagnostic guide for substance use disorders, whereas most countries use the International Classification of Diseases (ICD) for diagnostic (and other) purposes. The two manuals use similar but not identical nomenclature to classify alcohol problems. Attitudes and social stereotypes can create barriers to
14112-417: The ability to stop drinking of an individual with an alcohol use disorder. Alcoholism can have adverse effects on mental health, contributing to psychiatric disorders and increasing the risk of suicide. A depressed mood is a common symptom of heavy alcohol drinkers. Warning signs of alcoholism include the consumption of increasing amounts of alcohol and frequent intoxication, preoccupation with drinking to
14280-495: The addictive properties and abuse potential of barbiturates and amphetamines and led to increasing restrictions on their use and growing government oversight of prescribers. Today, amphetamine is largely restricted to use in the treatment of attention deficit disorder and phenobarbital in the treatment of epilepsy . In 1958, Leo Sternbach discovered the first benzodiazepine , chlordiazepoxide (Librium). Dozens of other benzodiazepines have been developed and are in use, some of
14448-401: The antibacterial effects of penicillin , but its exploitation for the treatment of human disease awaited the development of methods for its large scale production and purification. These were developed by a U.S. and British government-led consortium of pharmaceutical companies during the world war. There was early progress toward the development of vaccines throughout this period, primarily in
14616-556: The article Fenfluramine/phentermine . Pharmaceutical company The pharmaceutical industry is an industry involved in medicine that discovers, develops, produces, and markets pharmaceutical goods for use as drugs which are then administered to (or self-administered by) patients. These medications are created and put to market for the curing or preventing of disease , as well as alleviating symptoms of illness or injury . Pharmaceutical companies may deal in " generic " medications and medical devices without
14784-476: The biological effects of these structural changes. By the 1890s, the profound effect of adrenal extracts on many different tissue types had been discovered, setting off a search both for the mechanism of chemical signalling and efforts to exploit these observations for the development of new drugs. The blood pressure raising and vasoconstrictive effects of adrenal extracts were of particular interest to surgeons as hemostatic agents and as treatment for shock, and
14952-487: The child's health , and drunk driving increases the risk of traffic accidents. Alcoholism is also associated with increases in violent and non-violent crime. While alcoholism directly resulted in 139,000 deaths worldwide in 2013, in 2012 3.3 million deaths may be attributable globally to alcohol. The development of alcoholism is attributed to both environment and genetics equally. The use of alcohol to self-medicate stress or anxiety can turn into alcoholism. Someone with
15120-485: The classical disease model follows a progressive course: if people continue to drink, their condition will worsen. This will lead to harmful consequences in their lives, physically, mentally, emotionally, and socially. Johnson (1980) proposed that the emotional progression of the addicted people's response to alcohol has four phases. The first two are considered "normal" drinking and the last two are viewed as "typical" alcoholic drinking. Johnson's four phases consist of: In
15288-921: The complaint of poor health, with loss of appetite, respiratory infections, or increased anxiety. Drinking enough to cause a blood alcohol concentration (BAC) of 0.03–0.12% typically causes an overall improvement in mood and possible euphoria (intense feelings of well-being and happiness), increased self-confidence and sociability, decreased anxiety, a flushed, red appearance in the face and impaired judgment and fine muscle coordination. A BAC of 0.09% to 0.25% causes lethargy , sedation , balance problems and blurred vision. A BAC of 0.18% to 0.30% causes profound confusion, impaired speech (e.g. slurred speech), staggering, dizziness and vomiting. A BAC from 0.25% to 0.40% causes stupor , unconsciousness, anterograde amnesia , vomiting (death may occur due to inhalation of vomit while unconscious) and respiratory depression (potentially life-threatening). A BAC from 0.35% to 0.80% causes
15456-399: The condition as one of social choice. Most treatments focus on helping people discontinue their alcohol intake, followed up with life training and/or social support to help them resist a return to alcohol use. Since alcoholism involves multiple factors which encourage a person to continue drinking, they must all be addressed to successfully prevent a relapse. An example of this kind of treatment
15624-404: The cost of developing a successful new drug ( new chemical entity , or NCE), has been estimated at US$ 1.3 billion (not including marketing expenses ). Professors Light and Lexchin reported in 2012, however, that the rate of approval for new drugs has been a relatively stable average rate of 15 to 25 for decades. Industry-wide research and investment reached a record $ 65.3 billion in 2009. While
15792-590: The cost of research in the U.S. was about $ 34.2 billion between 1995 and 2010, revenues rose faster (revenues rose by $ 200.4 billion in that time). A study by the consulting firm Bain & Company reported that the cost for discovering, developing and launching (which factored in marketing and other business expenses) a new drug (along with the prospective drugs that fail) rose over a five-year period to nearly $ 1.7 billion in 2003. According to Forbes, by 2010 development costs were between $ 4 billion to $ 11 billion per drug. Some of these estimates also take into account
15960-451: The data supporting the safety of thalidomide was incomplete. The firm continued to pressure Kelsey and the FDA to approve the application until November 1961, when the drug was pulled off the German market because of its association with grave congenital abnormalities. Several thousand newborns in Europe and elsewhere suffered the teratogenic effects of thalidomide. Without approval from the FDA,
16128-499: The deal due to issues in the soon-to-be-combined boardroom. (Monsanto announced in December 1999 that it would merge with Pharmacia & Upjohn instead; the new conglomerate eventually unloaded Monsanto again, before being bought themselves by Pfizer in 2003.) Wyeth Consumer Healthcare (formerly Whitehall-Robins Consumer Healthcare) operated throughout the world. The consumer healthcare division had sales of $ 2.5 billion in 2004 and
16296-443: The detection and treatment of alcohol use disorder. This is more of a barrier for women than men. Fear of stigmatization may lead women to deny that they have a medical condition, to hide their drinking, and to drink alone. This pattern, in turn, leads family, physicians, and others to be less likely to suspect that a woman they know has alcohol use disorder. In contrast, reduced fear of stigma may lead men to admit that they are having
16464-409: The development of tricyclic antidepressants in the 1960s. In 1903, Hermann Emil Fischer and Joseph von Mering disclosed their discovery that diethylbarbituric acid, formed from the reaction of diethylmalonic acid, phosphorus oxychloride and urea, induces sleep in dogs. The discovery was patented and licensed to Bayer pharmaceuticals , which marketed the compound under the trade name Veronal as
16632-588: The drinker. The Dietary Guidelines for Americans , issued by the United States Department of Agriculture (USDA) in 2005, defines "moderate use" as no more than two alcoholic beverages a day for men and no more than one alcoholic beverage a day for women. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) defines binge drinking as the amount of alcohol leading to a blood alcohol content (BAC) of 0.08, which, for most adults, would be reached by consuming five drinks for men or four for women over
16800-550: The drug alcohol, use of alcohol despite adverse consequences, and distortions in thinking." MeSH has had an entry for alcoholism since 1999, and references the 1992 definition. The WHO calls alcoholism "a term of long-standing use and variable meaning", and use of the term was disfavored by a 1979 WHO expert committee. In professional and research contexts, the term alcoholism is not currently favored, but rather alcohol abuse , alcohol dependence , or alcohol use disorder are used. Talbot (1989) observes that alcoholism in
16968-424: The earliest historical records. The World Health Organization (WHO) estimated there were 283 million people with alcohol use disorders worldwide as of 2016 . The term alcoholism was first coined in 1852, but alcoholism and alcoholic are sometimes considered stigmatizing and to discourage seeking treatment, so diagnostic terms such as alcohol use disorder or alcohol dependence are often used instead in
17136-490: The emotional development of children of people with alcohol use disorders. For this reason, children of people with alcohol use disorders can develop a number of emotional problems. For example, they can become afraid of their parents, because of their unstable mood behaviors. They may develop shame over their inadequacy to liberate their parents from alcoholism and, as a result of this, may develop self-image problems, which can lead to depression. As with similar substances with
17304-469: The exclusion of other activities, promises to quit drinking and failure to keep those promises, the inability to remember what was said or done while drinking (colloquially known as "blackouts"), personality changes associated with drinking, denial or the making of excuses for drinking, the refusal to admit excessive drinking, dysfunction or other problems at work or school, the loss of interest in personal appearance or hygiene, marital and economic problems, and
17472-448: The extent that such laws did exist, enforcement was lax. In the United States, increased regulation of vaccines and other biological drugs was spurred by tetanus outbreaks and deaths caused by the distribution of contaminated smallpox vaccine and diphtheria antitoxin. The Biologics Control Act of 1902 required that federal government grant premarket approval for every biological drug and for the process and facility producing such drugs. This
17640-425: The fact that even the largest clinical trials cannot effectively predict the prevalence of rare side-effects. Postmarketing surveillance ensures that after marketing the safety of a drug is monitored closely. In certain instances, its indication may need to be limited to particular patient groups, and in others the substance is withdrawn from the market completely. The FDA provides information about approved drugs at
17808-670: The firm distributed Kevadon to over 1,000 physicians there under the guise of investigational use. Over 20,000 Americans received thalidomide in this "study," including 624 pregnant patients, and about 17 known newborns suffered the effects of the drug. The thalidomide tragedy resurrected Kefauver's bill to enhance drug regulation that had stalled in Congress, and the Kefauver-Harris Amendment became law on 10 October 1962. Manufacturers henceforth had to prove to FDA that their drugs were effective as well as safe before they could go on
17976-418: The first vaccine against Japanese Encephalitis . Hilleman later moved to Merck , where he played a key role in the development of vaccines against measles , mumps , chickenpox , rubella , hepatitis A , hepatitis B , and meningitis . Prior to the 20th century, drugs were generally produced by small scale manufacturers with little regulatory control over manufacturing or claims of safety and efficacy. To
18144-407: The form of academic and government-funded basic research directed toward the identification of the pathogens responsible for common communicable diseases. In 1885, Louis Pasteur and Pierre Paul Émile Roux created the first rabies vaccine . The first diphtheria vaccines were produced in 1914 from a mixture of diphtheria toxin and antitoxin (produced from the serum of an inoculated animal), but
18312-520: The fungus Aspergillus terreus , first marketed in 1987 as Mevacor. In April 1994, the results of a Merck-sponsored study, the Scandinavian Simvastatin Survival Study , were announced. Researchers tested simvastatin , later sold by Merck as Zocor, on 4,444 patients with high cholesterol and heart disease. After five years, the study concluded the patients saw a 35% reduction in their cholesterol, and their chances of dying of
18480-465: The general population, which can lead to higher instances of psychiatric disorders and greater dependence on alcohol. Serious social problems arise from alcohol use disorder; these dilemmas are caused by the pathological changes in the brain and the intoxicating effects of alcohol. Alcohol misuse is associated with an increased risk of committing criminal offences, including child abuse , domestic violence , rape , burglary and assault . Alcoholism
18648-490: The general public. In 1945, Wyeth acquired the Fort Dodge Serum Company, entering the animal health field. In 1951, Wyeth launched Antabuse , a drug for the treatment of alcoholism , as well as the antihistamine Phenergan . Ansolyen was launched the next year as a high blood pressure medication. The anticonvulsant Mysoline was introduced in 1954. Other drugs introduced during this time include Isordil ,
18816-626: The genetics of alcohol consumption and alcohol dependence, although the two are to some degree related. Alcohol-induced DNA damage , when not properly repaired, may have a key role in the neurotoxicity induced by alcohol. Metabolic conversion of ethanol to acetaldehyde can occur in the brain and the neurotoxic effects of ethanol appear to be associated with acetaldehyde induced DNA damages including DNA adducts and crosslinks. In addition to acetaldehyde, alcohol metabolism produces potentially genotoxic reactive oxygen species , which have been demonstrated to cause oxidative DNA damage. Because there
18984-401: The immediate aftermath of widespread vaccination. The first 20 years of licensed measles vaccination in the U.S. prevented an estimated 52 million cases of the disease, 17,400 cases of mental retardation , and 5,200 deaths. Hypertension is a risk factor for atherosclerosis, heart failure , coronary artery disease , stroke , renal disease , and peripheral arterial disease , and
19152-907: The industry ecosystem with biotechnology companies playing an increasingly important role, and overall strategies being redefined accordingly. Some approved drugs, such as those based on re-formulation of an existing active ingredient (also referred to as Line-extensions) are much less expensive to develop. In the United States, new pharmaceutical products must be approved by the Food and Drug Administration (FDA) as being both safe and effective. This process generally involves submission of an Investigational New Drug filing with sufficient pre-clinical data to support proceeding with human trials. Following IND approval, three phases of progressively larger human clinical trials may be conducted. Phase I generally studies toxicity using healthy volunteers. Phase II can include pharmacokinetics and dosing in patients, and Phase III
19320-513: The influence being the most common. The Alcohol Use Disorders Identification Test (AUDIT), a screening questionnaire developed by the World Health Organization , is unique in that it has been validated in six countries and is used internationally. Like the CAGE questionnaire, it uses a simple set of questions – a high score earning a deeper investigation. The Paddington Alcohol Test (PAT)
19488-596: The intensification of psychological symptoms of alcohol withdrawal. There are decision tools and questionnaires that help guide physicians in evaluating alcohol withdrawal. For example, the CIWA-Ar objectifies alcohol withdrawal symptoms in order to guide therapy decisions which allows for an efficient interview while at the same time retaining clinical usefulness, validity, and reliability, ensuring proper care for withdrawal patients, who can be in danger of death. A complex combination of genetic and environmental factors influences
19656-471: The involvement of intellectual property , in " brand " materials is specifically tied to a given company's history, or in both within different contexts. The industry's various subdivisions include distinct areas, such as manufacturing biologics , which are all subject to a variety of laws and regulations that govern the patenting , efficacy testing, safety evaluation , and marketing of these drugs. The global pharmaceuticals market produced treatments worth
19824-505: The isolation between 1803 and 1805 of morphine – an analgesic and sleep-inducing agent – from opium by the German apothecary assistant Friedrich Sertürner , who named this compound after the Greek god of dreams, Morpheus . Multinational corporations including Merck , Hoffman-La Roche , Burroughs-Wellcome (now part of Glaxo Smith Kline ), Abbott Laboratories , Eli Lilly and Upjohn (now part of Pfizer ) began as local apothecary shops in
19992-436: The isolation of tuberculosis-infected people were an ubiquitous feature of cities in developed countries, with 50% dying within 5 years of admission. A Federal Trade Commission report issued in 1958 attempted to quantify the effect of antibiotic development on American public health. The report found that over the period 1946–1955, there was a 42% drop in the incidence of diseases for which antibiotics were effective and only
20160-462: The larger pharmaceutical companies. The pharmaceuticals and biotechnology industry spends more than 15% of its net sales for Research & Development which is in comparison with other industries by far the highest share. Often, large multinational corporations exhibit vertical integration , participating in a broad range of drug discovery and development, manufacturing and quality control, marketing, sales, and distribution. Smaller organizations, on
20328-413: The law to prosecute manufacturers for making unsupported claims of efficacy were undercut by a Supreme Court ruling restricting the federal government's enforcement powers to cases of incorrect specification of the drug's ingredients. In 1937 over 100 people died after ingesting " Elixir Sulfanilamide " manufactured by S.E. Massengill Company of Tennessee. The product was formulated in diethylene glycol ,
20496-568: The leading US multivitamin . Wyeth's sales topped US$ 13 billion in 1995; two years later, Premarin became the company's first brand to reach US$ 1 billion in sales. In 1995, Wyeth acquired the animal health division of Solvay , which was folded into Fort Dodge Animal Health. The acquisition gave Fort Dodge Animal Health strong market presence in Europe and Asia as well as expanding its product portfolio to include swine and poultry vaccines. In 1996, American Home Products spun off its food unit as International Home Foods . International Home Foods
20664-407: The liver, pancreatitis , epilepsy , polyneuropathy , alcoholic dementia , heart disease, nutritional deficiencies, peptic ulcers and sexual dysfunction , and can eventually be fatal. Other physical effects include an increased risk of developing cardiovascular disease , malabsorption , alcoholic liver disease , and several cancers such as breast cancer and head and neck cancer . Damage to
20832-513: The long-term health consequences of high blood pressure had not yet been established, and because they had to be administered by injection. In 1952 researchers at Ciba discovered the first orally available vasodilator, hydralazine . A major shortcoming of hydralazine monotherapy was that it lost its effectiveness over time ( tachyphylaxis ). In the mid-1950s Karl H. Beyer, James M. Sprague, John E. Baer, and Frederick C. Novello of Merck and Co. discovered and developed chlorothiazide , which remains
21000-401: The mergers and acquisitions game for AHP. In 1999, another American Home Products merger fell through, this time a proposed $ 34 billion merger-of-equals with chemical and biotech manufacturer Monsanto Company . Though the companies issued a combined statement saying the breakup was mutual "because (the deal) was not in the best interests of shareholders," rumors circulated that AHP had canceled
21168-453: The mid-1800s. By the late 1880s, German dye manufacturers had perfected the purification of individual organic compounds from tar and other mineral sources and had also established rudimentary methods in organic chemical synthesis . The development of synthetic chemical methods allowed scientists to systematically vary the structure of chemical substances, and growth in the emerging science of pharmacology expanded their ability to evaluate
21336-524: The more popular drugs being diazepam (Valium), alprazolam (Xanax), clonazepam (Klonopin), and lorazepam (Ativan). Due to their far superior safety and therapeutic properties, benzodiazepines have largely replaced the use of barbiturates in medicine, except in certain special cases. When it was later discovered that benzodiazepines, like barbiturates, significantly lose their effectiveness and can have serious side effects when taken long-term, Heather Ashton researched benzodiazepine dependence and developed
21504-448: The most notable achievement of the period being Jonas Salk 's 1954 development of the polio vaccine under the funding of the non-profit National Foundation for Infantile Paralysis . The vaccine process was never patented but was instead given to pharmaceutical companies to manufacture as a low-cost generic . In 1960 Maurice Hilleman of Merck Sharp & Dohme identified the SV40 virus, which
21672-439: The most widely used antihypertensive drug today. This development was associated with a substantial decline in the mortality rate among people with hypertension. The inventors were recognized by a Public Health Lasker Award in 1975 for "the saving of untold thousands of lives and the alleviation of the suffering of millions of victims of hypertension". A 2009 Cochrane review concluded that thiazide antihypertensive drugs reduce
21840-457: The need for more comprehensive regulation and provided the driving force for the passage of new laws. On 12 September 1960, an American licensee, the William S. Merrell Company of Cincinnati, submitted a new drug application for Kevadon ( thalidomide ), a sedative that had been marketed in Europe since 1956. The FDA medical officer in charge of reviewing the compound, Frances Kelsey , believed that
22008-479: The neurotoxic effects increases impulsive behaviour, which may contribute to the development, persistence and severity of alcohol use disorders. There is evidence that with abstinence, there is a reversal of at least some of the alcohol induced central nervous system damage. The use of cannabis was associated with later problems with alcohol use. Alcohol use was associated with an increased probability of later use of tobacco and illegal drugs such as cannabis. Alcohol
22176-815: The neurotoxic effects of alcohol on the brain, especially the prefrontal cortex area of the brain. The social skills that are impaired by alcohol use disorder include impairments in perceiving facial emotions, prosody , perception problems, and theory of mind deficits; the ability to understand humor is also impaired in people who misuse alcohol. Psychiatric disorders are common in people with alcohol use disorders, with as many as 25% also having severe psychiatric disturbances. The most prevalent psychiatric symptoms are anxiety and depression disorders. Psychiatric symptoms usually initially worsen during alcohol withdrawal, but typically improve or disappear with continued abstinence. Psychosis , confusion , and organic brain syndrome may be caused by alcohol misuse, which can lead to
22344-500: The other hand, often focus on a specific aspect such as discovering drug candidates or developing formulations. Often, collaborative agreements between research organizations and large pharmaceutical companies are formed to explore the potential of new drug substances. More recently, multi-nationals are increasingly relying on contract research organizations to manage drug development. Drug discovery and development are very expensive; of all compounds investigated for use in humans only
22512-429: The pH of the extract allowed a relatively pure grade of insulin to be produced. Under pressure from Toronto University and a potential patent challenge by academic scientists who had independently developed a similar purification method, an agreement was reached for non-exclusive production of insulin by multiple companies. Prior to the discovery and widespread availability of insulin therapy the life expectancy of diabetics
22680-735: The past month met the criteria for alcohol dependence or misuse in the past year. Males had higher rates than females for all measures of drinking in the past month: any alcohol use (57.5% vs. 45%), binge drinking (30.8% vs. 15.1%), and heavy alcohol use (10.5% vs. 3.3%), and males were twice as likely as females to have met the criteria for alcohol dependence or misuse in the past year (10.5% vs. 5.1%). However, because females generally weigh less than males, have more fat and less water in their bodies, and metabolize less alcohol in their esophagus and stomach, they are likely to develop higher blood alcohol levels per drink. Women may also be more vulnerable to liver disease. There are genetic variations that affect
22848-401: The period of 3–6 weeks following cessation, anxiety, depression, fatigue, and sleep disturbance are common. Similar post-acute withdrawal symptoms have also been observed in animal models of alcohol dependence and withdrawal. A kindling effect also occurs in people with alcohol use disorders whereby each subsequent withdrawal syndrome is more severe than the previous withdrawal episode; this
23016-401: The pill, and by 1965 the number had increased to 6.5 million. The availability of a convenient form of temporary contraceptive led to dramatic changes in social mores including expanding the range of lifestyle options available to women, reducing the reliance of women on men for contraceptive practice, encouraging the delay of marriage, and increasing pre-marital co-habitation. In the U.S.,
23184-451: The risk for alcoholism. A genome-wide association study (GWAS) of more than 100,000 human individuals identified variants of the gene KLB , which encodes the transmembrane protein β- Klotho , as highly associated with alcohol consumption. The protein β-Klotho is an essential element in cell surface receptors for hormones involved in modulation of appetites for simple sugars and alcohol. Several large GWAS have found differences in
23352-555: The risk for alcoholism. Some of these variations are more common in individuals with ancestry from certain areas; for example, Africa, East Asia, the Middle East and Europe. The variants with strongest effect are in genes that encode the main enzymes of alcohol metabolism, ADH1B and ALDH2 . These genetic factors influence the rate at which alcohol and its initial metabolic product, acetaldehyde, are metabolized. They are found at different frequencies in people from different parts of
23520-486: The risk of death ( RR 0.89), stroke (RR 0.63), coronary heart disease (RR 0.84), and cardiovascular events (RR 0.70) in people with high blood pressure. In the ensuring years other classes of antihypertensive drug were developed and found wide acceptance in combination therapy, including loop diuretics (Lasix/ furosemide , Hoechst Pharmaceuticals , 1963), beta blockers ( ICI Pharmaceuticals , 1964) ACE inhibitors , and angiotensin receptor blockers . ACE inhibitors reduce
23688-683: The risk of depression. Psychiatric disorders differ depending on gender. Women who have alcohol-use disorders often have a co-occurring psychiatric diagnosis such as major depression , anxiety , panic disorder , bulimia , post-traumatic stress disorder (PTSD), or borderline personality disorder . Men with alcohol-use disorders more often have a co-occurring diagnosis of narcissistic or antisocial personality disorder , bipolar disorder , schizophrenia , impulse disorders or attention deficit/hyperactivity disorder (ADHD). Women with alcohol use disorder are more likely to experience physical or sexual assault , abuse, and domestic violence than women in
23856-473: The risk of new onset kidney disease [RR 0.71] and death [RR 0.84] in diabetic patients, irrespective of whether they have hypertension. Prior to the Second World war, birth control was prohibited in many countries, and in the United States even the discussion of contraceptive methods sometimes led to prosecution under Comstock laws . The history of the development of oral contraceptives is thus closely tied to
24024-440: The risk of the development of alcoholism. Genes that influence the metabolism of alcohol also influence the risk of alcoholism, as can a family history of alcoholism. There is compelling evidence that alcohol use at an early age may influence the expression of genes which increase the risk of alcohol dependence. These genetic and epigenetic results are regarded as consistent with large longitudinal population studies finding that
24192-634: The safety of the inoculation was marginal and it was not widely used. The United States recorded 206,000 cases of diphtheria in 1921, resulting in 15,520 deaths. In 1923, parallel efforts by Gaston Ramon at the Pasteur Institute and Alexander Glenny at the Wellcome Research Laboratories (later part of GlaxoSmithKline ) led to the discovery that a safer vaccine could be produced by treating diphtheria toxin with formaldehyde . In 1944, Maurice Hilleman of Squibb Pharmaceuticals developed
24360-647: The skepticism toward the viability of moderate drinking goals stems from historical ideas about 'alcoholism', now replaced with 'alcohol use disorder' or alcohol dependence in most scientific contexts. A 2021 meta-analysis and systematic review of controlled drinking covering 22 studies concluded controlled drinking was a 'non-inferior' outcome to abstinence for many drinkers. Rationing and moderation programs such as Moderation Management and DrinkWise do not mandate complete abstinence. While most people with alcohol use disorders are unable to limit their drinking in this way, some return to moderate drinking. A 2002 US study by
24528-528: The symptoms produced by pancreas removal. Soon, the extract was demonstrated to work in people, but development of insulin therapy as a routine medical procedure was delayed by difficulties in producing the material in sufficient quantity and with reproducible purity. The researchers sought assistance from industrial collaborators at Eli Lilly and Co. based on the company's experience with large scale purification of biological materials. Chemist George B. Walden of Eli Lilly and Company found that careful adjustment of
24696-418: The tetracyclines (discovered at Lederle Laboratories, now a part of Pfizer ), erythromycin (discovered at Eli Lilly and Co.) and their extension to an increasingly wide range of bacterial pathogens. Streptomycin, discovered during a Merck-funded research program in Selman Waksman's laboratory at Rutgers in 1943, became the first effective treatment for tuberculosis. At the time of its discovery, sanitoriums for
24864-494: The trade name Adrenalin . Injected epinephrine proved to be especially efficacious for the acute treatment of asthma attacks, and an inhaled version was sold in the United States until 2011 ( Primatene Mist ). By 1929 epinephrine had been formulated into an inhaler for use in the treatment of nasal congestion. While highly effective, the requirement for injection limited the use of epinephrine and orally active derivatives were sought. A structurally similar compound, ephedrine ,
25032-440: The use of benzodiazepine medications, such as diazepam . These can be taken while admitted to a health care institution or individually. The medications acamprosate or disulfiram may also be used to help prevent further drinking. Mental illness or other addictions may complicate treatment. Various individual or group therapy or support groups are used to attempt to keep a person from returning to alcoholism. Among them
25200-419: The volume of alcohol consumed and a pattern of drinking larger amounts on an occasion , to the point of intoxication, which is sometimes called binge drinking . Binge drinking is the most common pattern of alcoholism. It has different definitions and one of this defines it as a pattern of drinking when a male has five or more drinks on an occasion or a female has at least four drinks on an occasion. Alcoholism
25368-413: The whistleblowers, Wyeth also provided doctors and hospitals with kickbacks to prescribe the drug in the form of grants, donations and other money. As of 2010 a US House of Representatives committee, led by Rep. Edolphus Towns was investigating Wyeth for these abuses. Wyeth was sued for its marketing of Prempro, a hormone replacement therapy , which was implicated in the cancers of 14,000 patients. Wyeth
25536-413: The world's first conjugated estrogen medicine, which was a flagship product for Wyeth until 2002, when preliminary results from the Women's Health Initiative linked it to a number of negative effects, including increased risk for breast cancer. Sales subsequently fell off worldwide. Wyeth was one of 22 companies selected by the government in 1944 to manufacture penicillin for the military, and later for
25704-540: The world. The alcohol dehydrogenase allele ADH1B*2 causes a more rapid metabolism of alcohol to acetaldehyde, and reduces risk for alcoholism; it is most common in individuals from East Asia and the Middle East. The alcohol dehydrogenase allele ADH1B*3 also causes a more rapid metabolism of alcohol. The allele ADH1B*3 is only found in some individuals of African descent and certain Native American tribes. African Americans and Native Americans with this allele have
25872-453: The younger the age of drinking onset, the greater the prevalence of lifetime alcohol dependence. Severe childhood trauma is also associated with a general increase in the risk of drug dependency. Lack of peer and family support is associated with an increased risk of alcoholism developing. Genetics and adolescence are associated with an increased sensitivity to the neurotoxic effects of chronic alcohol misuse. Cortical degeneration due to
26040-439: Was a year of layoffs for at least 10,000 people across 129 public biotech firms globally, albeit most small firms; this was a significant increase in reductions versus 2022 was in part due to worsening global financial conditions and a reduction in investment by "generalist investors". Private firms also saw a significant reduction in venture capital investment in 2023, continuing a downward trend started in 2021, which also led to
26208-510: Was at the time the fifth largest over-the-counter health products company in the world. Wyeth Pharmaceuticals , formerly Wyeth-Ayerst Laboratories, is the original company founded by the Wyeth brothers, originally known as John Wyeth and Brother. They focused on the research, development, and marketing of prescription drugs. The pharmaceuticals division was further subdivided into five subdivisions: Wyeth Research, Prescription Products, Biotech, Vaccines, and Nutritionals. Fort Dodge Animal Health
26376-504: Was designed to screen for alcohol-related problems amongst those attending Accident and Emergency departments . It concords well with the AUDIT questionnaire but is administered in a fifth of the time. There are reliable tests for the actual use of alcohol, one common test being that of blood alcohol content (BAC). These tests do not differentiate people with alcohol use disorders from people without; however, long-term heavy drinking does have
26544-519: Was developed by Smith, Kline and French as a nasal decongestant under the trade name Benzedrine Inhaler. Amphetamine was eventually developed for the treatment of narcolepsy , post-encephalitic parkinsonism , and mood elevation in depression and other psychiatric indications. It received approval as a New and Nonofficial Remedy from the American Medical Association for these uses in 1937, and remained in common use for depression until
26712-454: Was followed in 1906 by the Pure Food and Drugs Act , which forbade the interstate distribution of adulterated or misbranded foods and drugs. A drug was considered misbranded if it contained alcohol, morphine, opium, cocaine, or any of several other potentially dangerous or addictive drugs, and if its label failed to indicate the quantity or proportion of such drugs. The government's attempts to use
26880-588: Was founded in 1912 by Daniel E. Baughman as "Fort Dodge Serum Company". The company was established in Fort Dodge, Iowa, to manufacture hog cholera serum. It became a division of American Home Products in 1945. It is a leading manufacturer of prescription and over-the-counter veterinary vaccines and pharmaceuticals. Its global headquarters are located in Overland Park, Kansas . Innovative Fort Dodge products include West Nile-Innovator, Duramune Adult, CYDECTIN Pour-on,
27048-476: Was identified by Japanese chemists in the Ma Huang plant and marketed by Eli Lilly as an oral treatment for asthma. Following the work of Henry Dale and George Barger at Burroughs-Wellcome , academic chemist Gordon Alles synthesized amphetamine and tested it in asthma patients in 1929. The drug proved to have only modest anti-asthma effects but produced sensations of exhilaration and palpitations. Amphetamine
27216-485: Was later shown to cause tumors in many mammalian species. It was later determined that SV40 was present as a contaminant in polio vaccine lots that had been administered to 90% of the children in the United States. The contamination appears to have originated both in the original cell stock and in monkey tissue used for production. In 2004 the National Cancer Institute announced that it had concluded that SV40
27384-421: Was left at the altar by British pharma powerhouse SmithKline Beecham , who pulled the plug on the estimated $ 70 billion merger. The deal was reportedly killed in response to British regulators who feared losing jobs to a proposed US headquarters location. (SmithKline Beecham merged with fellow Brit Glaxo Wellcome in 1999 to form the world's leading drug company.) This was the start of a three-year losing streak in
27552-448: Was only a few months. The development of drugs for the treatment of infectious diseases was a major focus of early research and development efforts; in 1900, pneumonia, tuberculosis, and diarrhea were the three leading causes of death in the United States and mortality in the first year of life exceeded 10%. In 1911 arsphenamine , the first synthetic anti-infective drug, was developed by Paul Ehrlich and chemist Alfred Bertheim of
27720-449: Was particularly criticised by observers for its use of 'ghostwriters' to put their names to research papers that Wyeth had paid a third party, DesignWrite, to prepare. The drug combination fenfluramine/phentermine , usually called "fen-phen," was an anti-obesity treatment. Fenfluramine was marketed by Wyeth as Pondimin, but was shown to cause potentially fatal pulmonary hypertension and heart valve problems. For more information refer to
27888-460: Was purchased by ConAgra Foods in 2000. Wyeth also purchases full ownership of Genetics Institute, Inc. after acquiring a majority interest in 1992. In 1997, the U.S. Food and Drug Administration (FDA) requested that Wyeth withdraw its controversial diet drug fenfluramine from the market by after several reports of deaths and other health problems associated with the drug combination known as fen-phen occurred. In 1998, American Home Products
28056-535: Was pursued broadly by industrial scientists, including Bayer scientists Josef Klarer, Fritz Mietzsch, and Gerhard Domagk . This work, also based on the testing of compounds available from the German dye industry, led to the development of Prontosil , the first representative of the sulfonamide class of antibiotics . Compared to arsphenamine, the sulfonamides had a broader spectrum of activity and were far less toxic, rendering them useful for infections caused by pathogens such as streptococci . In 1939, Domagk received
28224-622: Was sold to Tyco-Kendal in 1997). Wyeth and Ayerst merged to form Wyeth-Ayerst Laboratories, thus strengthening and consolidating Wyeth's pharmaceutical operations. In the late 1980s, Wyeth acquired the animal health businesses of Bristol-Myers and Parke-Davis . Wyeth also acquired A.H. Robins, makers of Robitussin , ChapStick , Dimetapp , and the Dalkon Shield merging it into its Whitehall unit to establish its Whitehall-Robins Division. In 1990, Reckitt & Colman (now Reckitt Benckiser ) acquired Boyle-Midway from American Home Products. After
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