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BPS 1101 Topic 2 Pain.docx

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Biopharmaceutical sciences
William Ogilvie

Topic 2: Pain -pain medication was not easily available historically -prescription drugs make up a $300 billion market in the US -these drugs require a doctor's prescription -we have to be careful using them due to safety issues -we need permission from a doctor to use them -over-the-counter drugs -make up a $25 billion market (1/10 the size of the prescription drug market) -no prescription is required -OTC drugs are used more often -some OTC drugs are "behind the counter" drugs -we have to ask the pharmacist for these drugs -these drugs are controlled, but not necessarily due to safety -OTC drugs versus prescription drugs -OTC drugs are more common -OTC drugs are cheaper -the cost is visible for OTC drugs, since prescription drugs are usually paid for by insurance and not out of our own pocket -the top OTC drugs include: -cough / cold drugs ($4.1 billion) -pain relief drugs ($2.7 billion and the #1 consumed pills) -antacids ($1.4 billion) -tooth paste ($1.2 billion) -laxatives ($0.8 billion) -laxatives are usually unnecessary for most people -there are some important considerations when buying drugs: 1) Safety -dose makes the drug / poison -we should just read the label to ensure safety -the dose that we need is based on our body size (if we have a larger body mass, we need a larger dose) -labels give us an indication of what amount of the drug it takes to work and what amount of the drug is dangerous -side effects -all drugs have side-effects -the effect and the side-effects of the drug may be indicated on the box; information on the drugs and the effects is easy to find -we can use google to find information about drugs -incidence (how common does this side effect occur?) -this information is difficult to find -people tend to focus on the bad things and the side-effects, but not how common these side-effects are -we need to evaluate both in order to get the correct information / idea about the drug and its risks 2) Indications -what is the drug used for? -an indication is a valid reason to use a certain medication -many people take the wrong drug or they take a drug that doesn't alleviate their symptoms -many people take drugs unnecessarily; people take drugs even though there may be no benefit 3) Counter-Indications -counter indications are products that interfere with drugs -a counter indication is a condition or factor that serves as a reason to withhold a certain medical treatment -counter indications include: -conditions (i.e.: pregnancy) -drug combinations (that may lead to overdose) -foods (i.e.: grapefruits interfere with drugs) -"natural remedies" which may contain chemicals that interfere with other drugs -e.g.: St.John's worts inactivates drugs 4) Price Pain Relievers -pain relievers are the most common OTC drugs -makes up a $2.7 billion / year market -50 billion tablets / year -35 000 tonnes / year -1200 dump trucks of pills / year Aspirin -aspirin was one of the first pain relievers / first artificial drugs -it is the #1 pain reliever outside of North America -it is a relatively old drug -its structure is related to compounds found in the Salix family of plants (it is related to the willow plant) -the Salix family includes willow, poplar, beech, and wintergreen -these compounds are salicylates which are produced by the Salix plants as a defense mechanism -Sumerians used willow leaves for pain in 2200 BC -Egyptians used willow for inflammation -Hippocrates used willow for childbirth -knowledge of herbs was lost in the dark ages -the Church suppressed this information on herbs -witches were often seen as people with herbal knowledge -Revered Edward Stone (1702-1768) -he was the rector in the Church of England -he described a treatment for fever -he discovered pain relieving properties in willow bark -he did not discover aspirin but gets credit for discovering the compound leading to aspirin -willow bark has a bitter taste -it is similar to the taste of quinine (quinine is used to cure malaria) - the Doctrine of Signatures was used to discover the anti-pyretic properties of willow: -people who lived near swamps got malaria -people with malaria had fevers -people treated malaria with quinine -quinine was bitter -willow bark was bitter -willow bark grew in swamps -therefore, willow bark will cure fevers -willow bark was used to treat fevers -the bark was dried and ground to a powder, which was sometimes used to make a tea -people had to limit the amount of bark that was used since removing lots of bark from the trees would kill it -the active ingredient in willow bark is salicin -1.5 kg of willow bark yields 30g of salicin -30g of salicin is equivalent to 50 aspirin tablets -this yield is actually quite high -fossils provide evidence of past life -oil contains molecular fossils -bacteriophane is a molecular fossil -it is related to the modern compound produced by the bacteria bacteriophanetriol acetobacter -Rafaelle Piria (1838) -he finds a way to convert salicin to salicylic acid -salicylic acid reduces pain, fever, and inflammation (i.e.: it is a analgesic, antipyretic, and an anti-inflammatory) -salicylic acid is better than salicin -salicylic acid can be found in nature, but only in trace amounds -salicylic acid can be made from coal-tar -coal-tar is a waste product from oil -synthetic salicylic acid is made from oil and is easier to make compared to salicylic acid from a natural source -coal-tar was a waste product in the 1800s -coal, when treated with steam can be converted to natural gas -coal is hard to transport -gas is easier to transport (especially in pipes) -in turning coal to gas, coal tar was produced as a waste product -William Perkin (1856) -he took coal-tar and made synthetic dyes -his first dye was a mauve color (mauveine) -ordinary people could now afford coloured clothes -these dyes had chemical similarities to salicylic acid -the word "synthetic" = made from oil -we do not have to kill trees to make synthetic products -the majority of oil is used to make synthetic products -Bayer started as a dye company but is now known as the company that sells aspirin -salicylic acid had side effects -it did not taste good -it caused stomach irritation -Felix Hoffman (1868-1946) -his father had arthritis and consumed large amounts of salicylic acid for pain -his father then began to suffer from stomach ulcers -Hoffman changed the compound so that it had less bitter taste and stomach irritation; this new compound lost its pain relieving properties -later, he converted salicylic acid to acetylsalicylic acid -acetylsalicylic acid had pain relieving properties, did not taste bad, and caused less stomach irritation -acetylsalicylic acid (ASA / aspirin) = first artificial drug -synthetic = from oil -natural = occurs in nature -artificial = does not occur in nature -materials from nature are designed / engineered for the plant's protection -Hoffman used a biological assay (test) -he used the fish gill to test for stomach irritation -this isn't really the right approach to test for stomach ulcers because the fish gill is very anatomically and physiologically different from the stomach -Aspirin was trademarked -Aspirin was made into a brand name; this name was catchy and easy to remember -Aspirin was initially sold as a powder -Bayer company compressed them into tablets for sale -Aspirin = a brand name -only Bayer can call the drug aspirin -ASA = acetylsalicylic acid -this is the generic name for the drug -acetylsalicylic acid: -benefits include: -analgesic, anti-pyretic, anti-inflammatory, reduces risk of heart attack -side effects: -tinnitus (ringing in the ear); this is an early sign of poisoning by ASA -stomach irritation and blood clotting are the most common -ASA is effective for muscular pain -ASA is not effective for pain in the internal organs (i.e.: visceral pains) -ASA blocks the production of prostaglandins -proastaglandins are local hormones (they are produced and used in the same cell) and exist for short periods of time -prostaglandins are produced in muscles but not the organs -ASA blocks prostaglandin biosynthesis -arachadonic acid is converted to prostaglandin through the cyclooxygenase enzyme -ASA binds to the active site of the enzyme so arachadonic acid cannot by synthesized into prostaglandin, which is necessary for the sensation of pain, fever, and inflammation -ASA and heart disease -aspirin is only effective in reducing the risk of heart attack if it is taken 2 times a day for 5 years -prostaglandins and blood clotting -prostaglandins cause blood platelets to stick together and form a clot -by inhibiting prostaglandin producing, aspirin slows clot production -aspirin will thin the blood if taken over long periods of time -early ads claimed that aspirin did not affect the heart; aspirin is now advertised for heart protection -ASA and cancer -ASA protects against certain cancers -this protection only occurs if it is taken for 10 years, 14 times a week -ASA tablets were used to make bombs (Norway terrorist attacks) -picric acid is related to TNT and can be made using aspirin as a starting material -side effects of ASA -death (if you take more than 60 tablets at once) -if you survive from a major overdose, you get serious organ damage -salicylism (aspirin poisoning) -tinnitus is indicative of salicylism -stomach irritation -the stomach secretes a mucous layer to protect it from the HCl that it secretes -these processes are regulated by prostaglandins -prostaglandins regulate stomach acidity by increasing mucus production and decreasing HCl production -when no prostaglandins are present in the stomach: HCl secretion increases and mucous secretion decreases -aspirin blocks the functioning of cyclooxygenase which causes stomach damage -this usually occurs if ASA is taken for a long time -we can die from internal bleeding due to stomach ulcers and thinning blood (blood is not able to clot and stomach ulcers cause the person to slowly bleed out) -tablets / pills can get stuck in the stomach if it is taken on an empty stomach and this may cause problems -when the stomach is empty, there are many folds in it and the pill may get stuck there -bufferin -contains antacid (MgSO4) that was thought to counteract the acidity of ASA in order to stop stomach ulcers -this concept relies on the doctrine of signatures since counteracting the acidity of ASA will not necessarily prevent stomach ulcers -plastic coating on ASA tablets -this plastic coating dissolves only when it reaches the small intestine; normally it would dissolve when it enters the stomach, which may cause stomach ulcers -generally, we can avoid stomach irritation by filling the stomach to reduce the wrinkles so that pills will not get stuck -Reye syndrome and influenza -Reye syndrome involves acute brain damage and liver function problems -there is an association between Reye syndrome and ASA -only children who were given ASA developed Reye syndrome -children's aspirin is no longer available; there are other alternatives -ASA should not be used in the last 3 months of pregnancy -prostaglandins are important for fetal development and pregnancy -regular and extra strength pills -people prefer to buy extra strength -extra
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