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Drugs 101 notes first 4 lectures

40 Pages

Biopharmaceutical sciences
Course Code
William Ogilvie

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DRUGS 101 MIDTERM 1 NOTES History We are living in a time and place where you will have the maximum life expectancy for a human being: • Canada has the 8 highest life expectancy worldwide • About 82 years old • Swaziland life expectancy is lower than the life expectancy of the stone age ~32 Throughout most of recorded history you could expect to live to be about 30-35 years old. Improvements in the last 150 years have drastically increased life expectancy (connecting scientific principles to human health; experiments to determine why people die and get sick) In 1900 everyone was sick all of the time: • Life expectancy was 44 years • Main causes of death were disease o Pneumonia, tuberculosis,influenza • This lasted until the 1950’s In 2004 life expectancy was 82 years: • Statistically you won’t die from disease, your body will wear out o Heart disease, cancer, stroke, lower respiratory infection, traffic accidents, diabetes Ailments Throughout History: Problem: Description: Disease Affects the quality of life > 150 years ago disease was a constant quality Lice and fleas were very common Most people would have worms and parasites Chronic Infection Fungal infection was with people all of the time Today you get an infection, go to the doctor, get treatment Malnutrition Food spoilage was very common Everything was rotten and eating spoiled food could not be avoided Main Reasons for Improved Health: Reason Description Improved sanitation i. Toilet -Only exists in the developed world for the past 100 years -Outhouses used to be common in cities; human waste is a source for disease -Chamber pots and communal cesspits – sitting next to your bed, pot emptied out of the window ii. Living in close proximity -Creates unhealthy situations ~100 years ago iii. Exposure to dead bodies -Dead people were a source of disease; people died at home and had to be carried out Clean drinking water -Contributes to overall healthiness -Water supply we have in Canada is extremely safe and an important part of our health - In history, villages didn’t have clean water; nature doesn’t make clean water and villages upstream would pollute -Animals living in water such as water fleas and guinea worms can live inside your body -Filtering water through a cheese cloth filters water fleas -Boiling water also prevents disease - There was no way of knowing if microscopic organisms were living in the water -Chlorination sterilizes water by killing bacteria Refrigeration -Most people would eat spoiled food -Using an ice house extended the life of the food but it still rotted quickly -Ice houses were only reliable in the northern climate; ice was harvested in the spring and would melt usually by summer -Today you can get food that you want all the time -Food is well preserved -Example: you can obtain strawberries in the winter Vaccination -Very successful for viral diseases -Example: small pox eliminated in 1977 -Smallpox disfigured people who survived it – smallpox vaccine scar in people born prior to 1972 -Example: Polio was eradicated from North America in 1991; currently less than 1000 cases worldwide in 10/11 countries -The major problem preventing worldwide elimination of disease is politics Antibiotics -Used for bacterial infection -50 years ago pre-antibiotic infection was a major concern; you could die from a little cut on your arm -Penicillin significantly reduces maternal mortality; before the advent of penicillin in around 1940 a mother had a 30% survival rate if she contracted an infection during childbirth North American Drug Market (2009): There is a very large industry in North America for pharmaceuticals: World Drug Markets United States 49.1% Germany 7.7% France 7.1% United 4.2% Kingdom Canada 3.8% Italy 3.8% All others 10.3% • Prescription drugs: require a doctors permission o Approximately 10x more expensive o $300 billion • Over-the-counter drugs: you can walk into a pharmacy and buy o $25 billion Types of Medical Treatment: • Surgical o Removal of affected body part (traditional) o Modification of effected body part (modern, due to drug; anesthetics allow modification of body parts) • Medicinal o Use of chemical compounds to treat disease Plants as a Source of Drugs: • Medication has existed since the beginning of time – people chewed things for medicinal purposes • Plants have been the primary source of our medications since the beginning of recorded history; what plants are useful, how to obtain and use them • Biochemical difference between plants and animals – the production of poisons – provides opportunity to produce medicine • If a poison kills you it is because it is interacting with something in your body and may be altered to be beneficial Early Drugs were Poisons: • Drugs: produce desired (beneficial) biological effect • Poisons: produce undesired (harmful) biological effect • The only difference between a drug and a poison is the doseage!!! • “Sola dosis facit veneum” Dosage: • Normally we assume that low doseage produces beneficial effects and high dosage produces harmful effects • However, sometimes low doses produce harmful effects and higher doses produce beneficial effects • Example: in a person with diabetes, when insulin level is too low it is poisonous • Everything is toxic if it is not given in the appropriate amount • Example: too much water can affect electrolyte imbalance and kill you How were Drugs Discovered? • Observation and experiment o People observed the effect of the drug o Strong poisons given in low doses o In history best way to develop a drug; experiments have to be done and observations made properly • Philosophy o Cure arrived at by reasoning o Method requires good information (Garbage in, garbage out) o Healing was often connected with superstition, magic, religion o Can work provided that basis of information is correct Drugs from Observation and Experiment: • Strong poisons o Easily identified o Low dose makes it a drug • Weak poisons o Large quantity or effects • Easy to identify – affect is easily observable • Example: almonds contain cyanide and if you eat a large number of them you can die. The difference between the pure material and the almonds is the dose. The chance of identifying the effects of cyanide by eating almonds is improbable Hippocrates 460-370 BC • Father of medicine o Promoted experimental methods o Rejected superstition and religion from healing o EX: large amounts of vitamin A for good eyesight from ox liver o Opium for crying babies Identification of Opium for Pain: • Opium was extracted from poppy seeds o Narcotic pain killer o Sedative • Toxic in high doses • Drug in low doses • Narcotics laws were put in place in 1910/1915 • It used to be used in a lot of medications because when you consume opium you feel good; you’re not really cured, you just feel better Identification of Cocaine as a Stimulant: • From observation o Extracted from coca leaves and used as a topical pain killer and a stimulant o Indians in peru consumes coca-leaves to get a “pick-me-up” because of the low oxygen levels in the air Quinine as a Malaria Treatment: • Present in the bark of a south American tree; most effective treatment for malaria • Peruvian bark was once more valuable than gold for its medicinal properties Problems with Observation: 1. The human brain searches for patterns; we see patterns even when they don’t exist 2. Anecdotal evidence may be unreliable; the drug and resulting effect may be a coincidence ⇒ Relies on chance; medication and cure may not be connected ⇒ Poison and harm may not be connected ⇒ Only experimental evidence is reliable; you must take proper evidence, rely on statistical significance and look for averages and trends while collecting data from a large populatio 3. Once “evidence” is available it is hard to contradict. • 500 years ago, people didn’t necessarily do the experiments correctly • Patterns are a survival mechanism • As soon as you find something is medicinal it is hard to disprove even if it is false Problems with Herbal Remedies: • Poor control over dose o Plants produce variable amounts of the active ingredient o There is no standardization • Variation in preparation and administration o Preparing the ingredient differently provides different results o I.e cooking affects the chemical composition of the material (raw carrots have more vitamin A) • No instructions o Information was passed verbally, was often imprecise and reproduced poorly o Most people throughout history were illiterate Philosophy to Identify Cures: • Cure arrived at by reasoning • Method requires good information • If you base your philosophy on something wrong, your conclusion will be wrong Hippocrates Develops Doctrine of Humors: • Common belief that the universe was made of four elements: o Earth (dry) o Air (cold) o Fire (hot) o Water (wet) • Thus belief that humans were made of four humours o Blood (cold) o Phlegm (wet) o Yellow bile (hot) o Black bile (dry) • It was believed that illness was a result of the humours being out of balance • To cure illness you had to renew balance by removing or adding the property • The four properties were used to look for things in the four elements that would cure disease • Example: fever associated with hot and dry to be cured using elements that are cold and wet Bloodletting • Re-balance blood humour • If somebody was sick you would rebalance their blood humour by cutting them open and allowing them to bleed • Old medical texts specify the different locations on the body, different tools to be used, the shape of the hole, and how much blood to take out • Emetics were also used to renew phlegm and possibly bile humour by forcing you to vomit; purgatories were used to empty the lower bowel The doctrine of humours was based on an incorrect idea; it was made up. Treatments developed using it were harmful and painful; this was state of the art medicine for up to 2000 years. Doctrine of Signatures: • Jakob Bohme was a showmaker and philosopher in 1575-1624 • He believed that God left clues to tell us how to use things in nature • Disease and cure were linked • This approach is/was used by almost all cultures • God has left clues and if we can decode the signatures we can figure out how to use them • EX: walnuts look like brains so eating walnuts is good for brain health • EX: boneset has leaves that are side by side and the stem goes up the middle which was connected to bone being surrounded by tissue; people believed this plant was good for bones • EX: sharks don’t get cancer, sharks have cartilage, so shark cartilage can be used to treat cancer (sharks can have induces tumors though…) • EX: Fresh breath  parsley  green  chlorophyll  fresh breath (chlorophyll in clorets, last ingredient) • EX: mandrake roots look like people and were thus used for many medicinal and magical purposes o Used for demonic possessions; believed they made a screeching noise so would use dogs to pull mandrakes out of the ground • EX: Rhino horn is a phallic symbol and is powdered and used in Chinese medicine as an aphrodisiac • Most remedies developed this way were harmful, harmless AT BEST • There is a lack of rationality or evidence, based on appearance or location, imagination was required to see connections Some Problems Require Surgery: • Throughout history, problem areas were just cut off because there was no way to anesthetize the patient • Strong people would strap them down and amputation would happen as quickly as possible • Anybody could complete an amputation; had to cut off the tissue as quickly as possible and saw off the bones o Amputations had to be made using a V-shaped cut so that the exposed bone and tissue could be covered Sir Humphrey Davy Discovered Nitrous Oxide: • In around the 1850’s he noticed that chemical compounds can be used to reduce pain during surgery • Nitrous oxide is laughing gas; still used today medicinally and recreationally William T.G Morton and Ether in 1846: • Used ether as an anesthetic • It would put the patient completely to sleep and they would not feel any pain • Held a jar of ether over a patient’s mouth; no cleanliness • Allowed surgery to become more complex because now procedures could be done and the patient wouldn’t move/try to run away Only less that 30% of people survived surgical treatment. There was no information about what caused disease and after surgery most died of infection. Tools weren’t changed after use . Joseph Lister used Phenol as Antiseptic: • Pasteur: disease was caused by some sort of microscopic organism that was getting into your body • Lister developed a chemical that would kill bacteria • Phenol / Carbolic Acid sprayer: candle at the bottom of the contraption would heat the solution causing a mist which would be sprayed onto the patient to prevent growth of bacteria • Increased survival rate of surgery from 30% to 70-80% • Phenol had toxic effects on the doctors because they were exposed to it all day long • Listerine, a spinoff product, originally contained phenol and was a all around cleaning product. Now they use thymol Washing and use of Gloves was Safer: • Idea of cleanliness achieves almost same effects of carbolic acid sprayer without the toxic effects on the doctor • Room was white so dirt was easy to spot • Antisepsis brought to Canada by Thomas Roddick, a student of Lister in 1877 Problems with Drugs in the 1800’s • No regulation o Industrialization created big markets o Lost of opportunity for fraud • All of these problems have always existed but there was a dramatic increase in the 19 century o Opportunity to make big money Science and Fraud: • The emergence of science made people trust claims like “patented” and “scientifically proven” o Fraudsters used science to market things • It became easier to identify fraud; before science there was no way to identify fraud o It became easier to tell people when they were being ripped off  Analysis of sugar content in wine - 1862  Morphine content in opium - 1873  Pesticide tests on humans – 1874 Experiments on humans were common until World War II • Mengalay – dentist at a concentration camp who used humans as experimental animals with experiments that amounted to torture • After WWII first regulations for experimenting on humans arose Rise of Patent Medicine in Late 1800’s: • A patent is a right to manufacture a product; does not give you reliability or credibility it just means you were the first person to come up with the idea • Alcohol and opium are common ingredients in patent medicine because they make you feel good • Danger signal when products will be good for everything, they have no side effects or are listed as “absolutely harmless” • EX: radium spring waters, original bottled water, was radioactive water William J.A Bailey makes Radithor • Water which contained radium; medical reports showed that radioactivity could kill cancer cells and thus it has a beneficial effect • Water increases you intellectual activity • Eben M Byers was a believer and had to get his lower jaw removed because it was so badly destroyed by the radiation • Patent medicines were dangerous sometimes toxic materials; there was an outcry from the public to make the government do something about it  government made rules for medication; what you can and cannot sell Board of Food and Drug Inspection • Formed in 1907 o Labelling only o No regulation of therapeutic claims o No safety testing o You just had to list the stuff properly on the label in order to control some of the patent medicines – they mostly went away o You can still buy patent medicine today – buckleys original contains no medicinal ingredients whatsoever Massengill Sells Sulfanilamide Exilir: • Started selling a particularly dangerous product: cannabis, chlorophorm, and morphine • Sold sulfanilamide (an antibiotic) as a powder • They created a good tasting liquid form to market for children which contained ethylene glycol (antifreeze!) It was sold as a treatment for strepp throat • Children were dying from the Sulfanilamide elixir. The company wouldn’t stop selling the material because there was no law against killing people with toxic drugs • The company was finally forced to stop selling the product because the label was incorrect; an exilir is alcohol and water o Government inspectors recovered 234/240 gallons that were sold o 107 died o 260 were permanently disabled Food and Drug Administration (FDA) Created: • In response to Massengill tragedy • Ensure the safety of drugs • Animal testing was now required (safety only) • Clinical trials were done to follow safety in humans • Directions for proper use were required on the labels Thalidomide: • In 1957 it was developed as a sedative and appeared to have very few side effects • By 1962 it was recognized as a teratogen (causes birth defects) o Caused Phocomelia (babies born without limbs) o Never marketed in the US  Tetragenocity was discovered before FDA approval was given • Thalildomine was tested in rats o Rats do not give birth to deformed pups; the uterus will reabsorb the embryo o Humans miscarry or give birth to babies with defects Modern Safety Standards: • Safety testing must be done on at least 2 species • At least one species must be a primate • Must be able to show that the drug is bioavailable • Must use relevant doses in testing Genetic Engineering Changes Drug Discovery: • Replaces many animal experiments • Because of genetic modification you can do different tests that were previously done on animals • You can look at the genetic makeup instead of testing it; see how the drug interacts with your body at a molecular level o Humulin: genetically modified human insulin o Safest source of human protein Drug Discovery Today: • Each new drug costs more than 1 billion dollars to develop • From idea to market requires 8 years • High risk/high profit • Worldwide only about 25-30 drugs are released each year Sources of Drugs Today Biologic 14% Genetically engineered Vaccine 4% ?? Natural product 5% Found in nature Semi-synthetic 23% Using as naturally occurring chemical as the start-point Synthetic 54% Produced entirely in a laboratory; new drugs are designed on the computer with random screening Less than 1/10 drugs survive clinical trials and reach market. More than 10000 compounds are tested to find each new drug. Process requires 8-12 years. Each new drug costs $1 billion Pain Relievers The most common reason people take medication is to cure pain • We spend billions of dollars on pain medications • Prescriptions – 300 billion $ / year (US) o Cost usually hidden because of insurance • OTC – 25 billion $ / year (US) o Instructions on the label, do not require permission o You consume more but they are less expensive o Cost is visible o Most commonly used Top OTC Meds (North America, 2008) Cough and Cold 4.1 Billion Pain Reliever 2.7 Billion Antacid 1.4 Billion Toothpaste 1.2 Billion Laxative 0.8 Billion Important considerations when buying: 1. Safety ⇒ It is assumed that people will take them incorrectly so there is a lot of leeway ⇒ Information located on the label. One capsule for a smaller person and two capsules for a larger person ⇒ Dose makes the drug! 2. Indications 3. Counter-indications 4. Cost** ⇒ Buy the cheapest stuff Side Effects: • All drugs have side effects: unwanted effects of the drug, not necessarily bad • Effect – what is it? • Incidence – how common is it? o Difficult information to find; have to dig through scientific literature • You need to know both effect and incidence to evaluate risk Indications: • What to use the drug for? • Many people take the wrong drug • Many people take drugs unnecessarily Counter-Indications: • When you should NOT use the drug o Conditions: may counteract the drug o Drug combinations o Foods: certain foods will inactivate any drug that you take – may result in a loss of effect or an amplified effect o “natural” remedies: may contain substances that interfere with the drug or which create toxic situations Worlds most popular drugs are: alcohol, caffeine, aspirin, and nicotine (?, suppressed by tobacco companies) • Aspirin is the first artificial drug created Salix • Genus: willow, poplar, beech, wintergreen • Salicylates in willow is an effective treatment for pain o Sumerians used willow leaves for pain in 2200 BC o Egyptians used willow for inflammation o Hippocrates used willow bark for childbirth Knowledge of herbs lost in the dark ages in Europe because the church didn’t like natural and herbal remedies; they were associated with witchcraft Reverand Edward Stone 1702-1768 • Rector in Church of England • Described treatment for ague (fever) in 1763 o Gets credit for discovering aspirin but he did not – he rediscovered how willow could be used for pain relief • Used doctrine of signatures to associate between the disease and cure o People who live near swamps get malaria  people with malaria have a fever  malaria is treated with quinine  quinine is bitter  willow bark is bitter  willow grows in swamps  willow will cure fever! o Luck! Salicin • Henri Leroux 1829 • Able to extract the active ingredient from willow bark  Salicin • Salicin from willow bark 30g is enough for 50 doses ; you need a lot of bark for a little bit of salicin which is not effective Salicylic Acid made from Salicin: • Rafaelle Piria 1838 • Salicylic acid has all the properties of salicin: analgesic, antipyretic, anti- inflammatory • It was active in a lower dose and gave the same effect • This material was made from an existing compound exitsting in nature = semi- synthesis • Salicin was a neturl substance but if you started with willow bark you must use large amounts of material to make the substance • Salicylic acid was made from coal tar (oil) using the Kolbe-Schmitt reaction o Coal tar is a waste product of treating coal with steam to produce natural gas • William Perkin- 1856 found a way to convert coal tar into dye. Dye industry became the parent industry of the drug industry as they were looking for more ways to use the coal tar o Bayer started as a dye company • Salicylic acid had two side effects: bitter taste and stomach irritation Felix Hoffmann was a chemist who’s father suffered from arthritis and got stomach ulcers from salicylic acid; came up with the idea of chemically transforming the drug slightly • Process of drug optimization o Added a CH g3oup got rid of the irritation and bitter taste but also the pain relief • On August 10,1897 salicylic acid was optimized into acetasalicylic acid o Known today as aspirin o Does not irritate the stomach as much as the original substance o Substance is artificial – completely man made o Chemically modified into a drug-like substance Hoffmann used a biological assay (animal testing). He substituted fish gills for the stomach because they are as sensitive as a stomach; thinking that if the drugs irritated the gills they would irritate the stomach • Hoffmann trademarked the name Aspirin • Bayer’s first drug sales were heroin; aspirin was marketed initially with heroin • Aspirin was initially sold as a powder • Aspirin tablets became more popular Aspirin A.S.A Brand name, only the bayer company can Generic name use the name The structure is identical! Only difference is the price Benefits: pain, fever, inflammation, reduce heart attack risk Adverse side effects: tinnitus, stomach irritation, reduced blood clotting [depend on the dose!!] • A.S.A is effective for muscle pan • A.S.A is not effective for visceral pain (i.e. will not help with the pain of internal organs) Prostaglandins are local hormones • They are produced and “used” in the same cell • They exist for short times • They are associated with intense muscular contractions and cause pain • Aspirin blocks prostaglandin biosynthesis • Your body does not store prostaglandins, it only produces them as necessary • Cyclooxygenase is the enzyme that makes prostaglandins o Aspirin blocks part of the cyclooxygenase which prevents prostaglandin formation Aspirin and Heart Disease: One aspirin every 2 days for 5 years the chance of heart attack decreases by half • Available OTC; ¼ of a dose daily is highly protective against heart attack A.S.A and Cancer? • Does protect against cancer but ou have to take >14 aspirins per week for more than 10 years which has much more dangerous side effects than cancer Side Effects of A.S.A Death More than 60 tablets at once; fairly popular suicide method but not 100% effective Tinnitus Ringing in the ears, when consume more than 10 tablets. Warning sign of salicylism (poisoning) Stomach Irritation Excess of HCL. Prostaglandins lowers HCL production and increases mucous production so aspirin in the stomach can inhibit prostaglandins and increase acid production = ulcer.Pill may get caught in a wrinkle in the stomach – generally gets absorbed in the small intestine Bufferin is A.S.A plus an antacid • Doctrine of sigantures: irritation is because aspirin is an enzyme not because it is an acid Plastic coating on A.S.A tablets designed to be degraded in the small intestine; if pill transit slowly it may get degraded in the stomach anyways * To avoid stomach irritation take your aspirin with a glass of water to expand the stomach and get rid of the wrinkly parts Reye Syndrome and Influnza • Children suffering from influenza took childrens aspirin to reduce fever • Caused brain damage? • Never proven whether aspirin caused it or not; only saw association with children who got Reye syndrome and took aspirin getting brain damage • Applied the pre-cautionary principle o Removed childrens aspirin from the market o Risk outweighed the benefits A.S.A is not recommended in the last 3 months of pregnancy because prostaglandins are important for birth. Regular Vs. Extra Strength • Difference is the dose: 325mg vs 500mg • Sell a lot more extra strength because of mentality that it will be better, therefore it is stronger Tablets and Gelcaps and Caplets • Technically a gel cap will dissolve faster but it doesn’t matter because it all gets absorbed in the small intestine Anacin has 35 mg caffeine for headaches, a cup of coffee will have the same effect Generic drugs are the same quality as name brands • Thy are the same chemical substance • They have the same doseage • They have equivalent bioavailability o Same amount of drug enters the body {similar, not precisely the same} A. Cahn and P. Hepp 1886 • Experimenting to find a vermifuge (expels intestinal worms) o Gave patient naphthalene (mothballs) o Noticed fever reduction o Bottle was mislabeled o Acentanilide Antikamnia (antifebrin) • Extracted directly from coal tar and was a successful treatment for fever Carl Duisberg • Chemist at bayer who needed to dispose of 50 tons of aminophenol and created phenacetin o APC tablet  Aspirin  Phenacetin  Caffeine D. Lester and L.A. Greenberg 1947 • Acetaminophen is an intermediate between antikamnia and phenacetin • Thought it would be toxic because chemical structure ressembeled original toxic antiseptic (lister) Acetaminophen • Raises pain threshold by interfering with the way you transmit pain signals from your body to your brain • Good for muscle pain • Good for visceral pain • Will work to reduce fever • Not for inflammation; does not inhibit prostaglandin synthesis • Not always effective for arthritis use; better benefit for osteoarthritis because rheumatoid involves inflammation • No association between rye syndrome and Tylenol • Much weaker to no irritation on stomach • Children’s Tylenol is sweet tasting and low doseage can become dangerous but are put in small bottles so that even if children have all of it the medication will not be harmful. • In certain cases cytochrome can metabolize acetaminophen into a toxic substance which can harm the liver • Never take for hangover! Alcohol stimulates liver function and increases toxicity of acetaminophen • Tylenol migraine includes caffeine which is good for headaches – not a large enough dose to be very effective • Arthritis and muscle and body are identical • Migraine also available, essentially extra strength with added caffeine • Tylenol PM contains drug that will help you sleep, contains some good and some bad side effects Excedrin • Mixes Acetomenophin ASA and caffeine (not available in Canada Tylenol and Cyanide 1982 • Substance in capsule was replaced by cyanide; 7 people were killed • Every capsule of Tylenol was recalled by Johnson and Johnson o As a result Tylenol capsules were replaced by caplets o Safety seal packages were added to the OTC meds Ibuprofen • Similar to aspirin, it inhibits cyclooxygenase • Benefits pain, fever, and inflammation • Side effects of reduced blood clotting and stomach irritation • Pain relief lasts longer! • Advil, motrin (regular 200mg, extra 300mg, and super 400mg) • Always read the back of the box not the front Naproxen: • Aleve • Very good for inflammation • Related to ibuprofen • Basically works the same as ibuprofen COX-1 and COX-2 • Effect of COX1 inhibition o HCL production increases o Mucous production decreases o Clotting is inhibited o Ulcers in stomach • Effect of COX2 Inhibition o Reduced pain o Reduced fever o Reduced inflammation • Current arthritis treatment inhibit both COX1 and COX2 • Selective COX2 inhibitor for arthritis o VIOXX clinical trials - approved o Full VIGOR data released to FDA – increased risk of heart attack 0.4% for Vioxx, 0.1% for naproxen. No difference in mortality o Approx 60 studies were done, more than 5000 patients found no serious side effects, no difference in cadivascular disease vs placebo. o Media made it look like the drug was extremely dangerous o Company removed drug from market because they were losing money o However, benefit outweighs risk: current arthritis treatment 10-20000 deaths/year from GI bleeding, vioxx 18-28000 heart attacks/ year o Celebrex is the same but did not make the same mistakes as Vioxx • Current arthritis treatment o FDA estimates 10,000 to 20,000 deaths/year from gastrointestinal bleeding VIOXX as an arthritis treatment o FDA estimates 18,000 – 28,000 heart attacks/year o Risk of heart attack similar to ibuprofen
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