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Lecture 15

BPS1101 Lecture 15: BPS1101 – Drugs 101

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University of Ottawa
Biopharmaceutical sciences
William Ogilvie

BPS1101 – Drugs 101 Topic 1 intro and history Class 1 Rank Country Years of - World life span much lower than in Canada, but Life still almost double that throughout most of human history 1 Macau 84.4 - in some countries in the world, life span is 2 Andorra 82.5 actually lower than life expectancy in the stone age 3 Japan 82.1 4 Singapore 82.0 - Life span is an educated guess – written records and archaeology 5 San Marino 82.0 - important to remember that only “important” people make it into historical records, life 6 Hong Kong 81.9 expectancy is mostly the “ordinary” people 7 Australia 81.6 - Most improvements in life span have happened 8 Canada 81.2 over last 150 years 9 France 81.0 - Variations smoothed out as records are not precise 159 World Average 66.6 - number of 35 years is an estimate made by 224 Swaziland 31.9 combining data from various sources - numbers may vary depending on source used - range is more appropriate - Data for united states - 150 years ago, life expectancy was same as that of the stone age - - special time in history to be living now fleas, always sick, worms (types of worms ) - 1 – hookworm - 2- tapeworm – can lay 1,000,000 eggs per day, - 3 – tapeworm eggs - 4- roundworm max size 50 cm lay 200,000 eggs/day - 5 pinworms – migrates out of colon and lays eggs in anus - itching Improved quality of life - Data for Canada - life expectancy has doubled in last 100 years - changes also in quality of life - causes of death have shifted from infectious disease to “wear and tear” - historically people lived entire lives in an unhealthy state - constantly sick (parasites) - this condition still exists in many developing countries Main reasons for improved health • Improved sanitation • Outhouses were common until recently • Chamber pot used when cesspits were available and in close contact • Open vs closed sewers (exposed to it) • Populations exposed to dead and dying • Clean drinking water • Safe water supply (in Canada, best that has ever existed) • Nature does not make pure water ➢ Guinea worm – dracucculiasis life depends on being ingested by other animals, ; consequence from contaminated water • Major improvement was chlorination • Refrigeration • Food spoilage was common before refrigeration • Seasonal availability • Modern food storage year round Pharmaceuticals improve health • Vaccination • Immunization • Very successful for viral diseases (ex. Smallpox eliminated entirely in 1977, Eradicated Polio from north America in 1991, less than 1000 cases worldwide) • Antibiotics • Penicillin reduced maternal mortality Improved health using the scientific method • Sanitation • Clean drinking water • Refrigeration – United States – 49.1 % • Vaccination • Antibiotics – Japan – 14.1 % Modern Drugs work – Germany – 7.7 % • Each starts with a scientific idea • Each is optimized using scientific – France – 7.1 % methods • Each is tested scientifically – United Kingdom – 4.2 % North American drug market (2009) – Canada – 3.8 % • Prescription drugs – $ 300 billion – Italy – 3.8 % • Over-the-counter (OTC) drugs – $25 billion – All Others – 10.3 % Modern pharmaceutical industry is young - only came around in the last 150 years (ish) - Started in 1856 - Uses scientific methods - Chemistry - Biology - Molecular biology - Epidemiology - Works hard to remove bias - Regulated by government Most ancient medications were useless • “Made-up” cures • People believe in magic • Feel better just by getting treatment • Only a small number of treatments actually worked • A few of these are still used today Drugs, Poison, and Plants • Most ancient drugs from plants • Why? Plants are poison (defense mechanism) • i.e. Drugs are poison • Drugs Produce desired (beneficial) biological effect • Poisons Produce undesired (harmful) biological effect • Difference between poison and drugs is DOSAGE “Sola dosis facit veneum” Poison – kill. Potion – cure Dosage Only the dose makes the poison • Normally we assume – low doses produce beneficial effects (drug) – high doses produce harmful effects (poison) Sometimes, the opposite problem occurs ex. Insulin if the body does not get enough it become dangerous. • Ask “how much”? • Works for lots of things – Drugs – Pollution – Finances – Everyday issues How were drugs discovered? • Observation (rare) – People observed the effect of the drug – Strong poisons • Philosophy (very common) – Based on belief – Cure arrived at by reasoning – Healing often connected with superstition, magic, religion Papyrus Ebers • Mostly wrong, occasionally found cures that are still used today • Egyptian medial document 1500 BC • Scroll about 20 meters long • Thousands of medical treatments – Most useless – A few are still used today • Ex. Opium (extracted from poppy seeds) • Narcotic painkiller • Sedative • Toxic in high doses • Drug in low doses Opium is basis of modern painkillers Modern anesthetics designed from cocaine • Anesthetics – Reduces sensation • Novocaine • Procaine • Lidocaine • Benzocaine Class 2 Problems with observation • Human brain searches for patterns – Even when they are not there • Ancients did not use experiments or statistics • Did not run tests after finding solution, leading to coincidences being thought as cures, and placebo affects. (ex. Mustard plaster) • Relied on their own experience • Anecdotal – Drug and effect may be coincidence – Perceptions subject to placebo effects – People lie • Once “evidence” is available, hard to contradict – Many harmful remedies retained because of this – Parent’s cold remedies Brain searches for patterns • Apophenia : Seeing patterns or connections in random or meaningless data o Even when they are not there • Pareidolia : Perceiving sounds or images as something else • Anecdotal : ( the one off, chance encounter, not reliable, rare) evidence unreliable (ex tomatoes are poisonous(1 person may have gotten sick hasty conclusion that tomato was the cause) Experimental evidence • Make a measurement • Measure properly • Measure accurately o Collect data from large number of experiment, o Look for averages and trends Traditional remedies • Things in nature have poor control over their doses (i.e. poison vs. drug) • Preparation changes chemical composition • No standardization o No instructions ▪ People couldn’t read, hard to keep and share information o Information passed verbally ▪ Game of broken telephone, information changes over time o Imprecise o Poor reproducibility Philosophy to identify cures • Cure arrived at by reasoning (make it up) • Search for “proof” afterward • Healing often connected with superstition, magic, religion Hippocrates develops doctrine of humors Said universe is made of 4 elements • Earth - dry • Air - cold • Fire - hot • Water - wet Hence body was made of 4 humors • Blood - cold • Phlegm – wet • Yellow bile – hot • Black bile – dry o 4 humors are normally in balance o Too much or not enough of a humor causes disease o Cure by re-balancing the humors o Diagnose using the properties of the humors Although bloodletting often killed the patient, the information out in the public that was shared was that it worked – once out there, hard to take back. Doctrine of Signatures • Jakob Bohme, shoemaker and philosopher (1575-1624) – God left clues to tell us how to use things • Cures that were left for us and we have to figure out how to develop it. Ex. 1 Eating walnuts is good for the brain because they look like brains (no factual correlation) 2 sharks don’t get cancer, sharks don’t have bones they have cartilage– so shark cartilage is a cure to human cancer. – Disease and cure were linked – This approach is/was used by almost all cultures • Most remedies developed this way were harmful • At best were harmless – Denied the patient proper treatment • Lack of rationality or evidence – Based on appearance or location – Required imagination to see connections Surgery - At the start no anesthetic - Started with amputations – rid of the problem (infection) entirely • Had to be done quickly • Trial and error (cut in V for amputations) • Sir Humphry Davy discovers nitrous oxide • William T.G. Morton discovered ether 1846 o Would put patient to sleep, take away pain during surgery. o Anesthetics made modern surgery possible • Less than 30% survived surgical treatment – main cause, infection. No knowledge on sanitation and cleanliness (wipe off scalpel between patients) • Joseph Lister uses phenol as antiseptic 1867 o First thought of sanitization to prevent infections o Phenol kills bacteria Phenol = good for patients = Bad for doctors (dosage) Washing and using gloves was safer for doctors and patients - No longer doing surgeries in living rooms and people’s homes, decided cleanliness was necessary - William Perkin first synthetic dye – 1856 o The start of colored clothes, and paint on the walls o Dye companies began - dye companies became pharmaceutical companies Aspirin is the first artificial drug – 1897 o Better and Cheaper than naturel drugs o Naturel drugs are really natures poison to defend themselves (*importance of dosage) Patent medication in the 1800’s • No regulation – Industrialization created big markets (fast quantities) – Lots of opportunity for fraud • All these problems had/have always existed, but there was a dramatic increase in the 19 century • The emergence of science made people trust claims – “scientifically proven” *lies – “patented” *** ALL AFFECTIVE DRUGS WILL HAVE SIDE EFFECTS *** Board of Food and Drug Inspection • Formed in 1907 – First government regulations for medicines – Labeling only – No regulation of therapeutic claims – No safety testing Lecture 5 Cephalalgia or Headaches - 90% of population get them - originally thought of demon inside head • had to rid the demon - head in oven (no logic) - Metallic tractor - Magic pulls out the pain - Surgical cures - Trepanation (cut hole in skull, escape hole for demons or relief of pressure feeling) • Brain does not feel pain, thin tissue that surrounds brain is what feels the pain, gives the illusion that it’s coming from center of head (brain) 12 types of headaches • Muscular headache, muscle band around • Muscular headache caused by stressed 3 types of vascular headaches (involves blood circulation, blood vessels are getting larger to allow more blood flow affects the tissue surrounding it because its pushing in their space) • Toxic Gives headaches o Histamine (found in grapes, red wine) o Tyramine (found in aged cheese) o Phenylethylamine (found in chocolate) o Nitrites (preservatives in processed meats) ▪ Nitroglycerine (a potent vasodilator) o Seaweed on its own doesn’t have much flavor but adds lots of flavor when cooked with other things – origin of MSG o Discovered that MSG gave headaches o Jk they proved that wrong again o MSG is in everything bagged, canned, and boxed • Migraine • Cluster • toxic Brain freeze Not from cold stuff in your stomach, actually occurs in mouth – when ice hits the soft palette (roof of the mouth that separates mouth from nose) Migraines are not common • Only 18% of women get them • Only 6% of men 4 phases of migraines • Prodrome phase (mood swings) (only affects 30-40% of people) • Aura, visual disturbances, flashes of lights (only affects 20-3-% of people) • Pain • Postdrome Triptans can prevent migraines Ideal drug • Easy to use • Provides beneficial effect – Specific • Limited side effects – Low incidence – Low severity • Cheap to manufacture • Patentable Lecture 6 COLDS • Most common infection • No difference between sinus cold and regular cold • Caused by viruses o More than 200 different viruses cause colds (cause the same results) o not the cold that causes the symptoms, but the body fighting it that does • viruses destroy tissues in airway • no cure for common cold o only relieve symptoms o no medication will prevent cold • common cold research Unit o studied people to find cause and cures of the cold o advertised it as a free vacation o was not free, experimented on its guests • sneezing does not spread colds • being cold does not cause colds • wet hair does not cause colds • direct exposure to virus does not always cause cold what does cause colds? • Direct contact with mucus • People touch face and then touch other objects which passes the virus around • Transferred by touching • Commonly touched objects • Colds are more common in crowds • School season is cold season Reducing colds • Washing hands • Touch face less • Don’t over wash, causes skin damage, destroys oil layer of skin that keeps it hydrated • Sneeze and cough into elbow Incidences of colds decrease with age • Except for the average age of new parents, kids give their parents colds • Children are more social • Can only contract virus once, then immune o As a child have experienced less viruses, more viruses to catch o As an adult have already contracted and become immune to many viruses Medication • Read back of box not front of box o Front not accurate, back has real info. • What to look for? o Think of symptoms, which would you like to do something about? o Look at active ingredients o Sinus = Pseudoephedrine o menthol very mild, artificial flavoring for mint o stimulates nerve endings for cold, what causes that cool feeling in the mouth o cough drop better than liquid medicine as it is more likely to have more contact with throat runny nose ? • 2 options o Pseudoephedrine o Phenylephrine (does not work!!) • Snot is mostly water with a little mucin • Vessels widen allowing water (snot) to flow o Decongestants tighten up those vessels • Amphetamine – the original decongestant • Phenylpropanolamine, used as a decongestant o Caused appetite suppression o Once discovered, was used as a diet medication o Overuse caused hallucinations o Worst conditions – caused strokes (blood vessels would burst) ▪ Overdose of product was main cause (easy to lose first 10 pounds afterwards body’s metabolism changes = people take more pills) • Heroin is best cough syrup • Dry cough = not productive, not good want to get rid of it • Wet cough = productive, thick mucus is tough to remove, meds to help soften it up and clear the throat • Drink lots of water, helps loosen up mucus  Beware multi-symptom medications ▪ When medications made for different symptoms are mixed together, can alter the affects. Flu outbreaks Past 100 years – 1918 20,000,000 deaths – 1957 1,000,000 deaths – 1968 700,000 deaths – virus carries a piece of human membrane around it – Hemagglutinin (viral entry into cell) important for infection – Neuraminidase (viral exit from cell) important for reinfection Brand doesn’t matter, all products will have the same ingredients: – Pain and fever – Acetaminophen 500 mg – Ibuprofen 200 mg – Decongestant – Pseudoephedrine 30 mg – Phenylephrine 10 mg – Antihistamine – Chlorpheniramine 2 mg – Antitussive – Dextromethorphan 15 mg – Expectorant – Guaifenesin 200 mg Lecture 7 • Cancer: part of your body that is out of control, an uncontrollable growth. Body normally stays the same because cells stop dividing. Cancer is the opposite • Malignant growths are much more aggressive and can spread to various tissues. • Biggest killer in Canada, around a third of deaths in Canada are caused from cancer. • Most cases of cancer are found in people over the age of 55. With age, cancer becomes more common. “if you were to live forever you would be likely to get cancer of some sort. • Very rare for children to get cancer, uncommon. • Cancer is very painful, treatments are painful, not enjoyable. Drugs and chemo, cancer itself is painful. • Little evolution in cancer cures, nearly the same death rate from 1950 to now. • Much easier to survive cancer when young. Takes a harder toll on body with age. Best way to beat cancer is to avoid it altogether. • Men are more likely to die from cancer. Lung cancer is the most dangerous and common form of cancer in America. Has increased in the past 40 years, women tend to smoke less than men. Lung cancer is the reason for the difference in death rates between men and women • Normally our cells don’t divide, but cancer cells do. A cell will change slightly and become cancerous, and continue to divide uncontrollably. Causes a growth, essentially a parasite that can interfere with main organ function which causes death (ex. Heart pumping, brain cancer) • Normal cells have a maximum lifespan of 50 cell divisions. Cells must be touching similar cells, of the same tissue, if removed from body they will die. Normal cells will only divide on command. Only does its division when it is instructed to do so. Cells are not allowed to move from one place in the body to another, can survive within its designated tissue. • Cancer cells can live forever, do not have a limit amount of divisions they can make, they can live forever and travel in the body, are designated to only one type of tissue. o HeLa cells (Henrietta Lacks) removed tumor cells from her, as she had cervical cancer and they continued to divide and thrive outside the human body, something that does not happen with normal cells. • How does a normal cell turn into a cancerous cell? o Requires 8-10 mutations in the same cell, normally requires 20 years to develop. • Every cancer is different, every tissue can spawn o More than 100 forms o Each tumor is unique • Biological signals are cascading processes o Ex. Message from brain to foot to move o Cascading chemical reaction is a chain of events, one action creates another which creates another... etc. (ex. Game of mouse trap) • Cell division is regulated in 2 ways o Stimulations (accelerator) what tells the cells to divide o Repression (brakes) what tells the cells to stop dividing. ▪ In the human body the acceleration and brakes are being used at the same time, working simultaneously • Cancer mutations involves loss of function o Impossible to repair the function with small molecules o Easier to break something than to fix it o Cannot repair the damage with today’s technology o Genetic repair expensive, difficult and unreliable o Cancer cell means “off” switch is broken, cells don’t know when to stop multiplying. • P53 is important “breaking’ protein, if this protein stops working highly increases chances of cancer. • Apoptosis – programmed cell death o Cells programmed for a Controlled death. Without p53, cells lose the ability to self-destruct highly increases the chances of cancer. • Chromosomes have tip which controls the information, with every cell division, part of that tip is removed (shoelace aglet reference) eventually over time chromosomes become frayed. • A Gene is a set of instruction on how to make a protein o Gene mutation occurs when there is an error in the DNA coding, incorrect amino acids. A typo can throw of the entire coding. • Genetic susceptibility o Some individuals are more susceptible to cancer than others ▪ Oncogenes • Instructions are easier to change • Most cancer deaths are caused by controllable factors • Tobacco Diet and Obesity Viruses Everything else (in order of prevalence) alcohol lack of exercise UV radiation environmental exposure (2 - 4 %) genetics medical procedures (X-rays and chemotherapy) strong correlation between cancer and diet and obesity. Not meat that’s dangerous, as rumors have it, but the way its cooked that causes dangers Meat spoils quickly, must be cooked. Fruits and vegetables are better because they are prepared differently, cooked less often than meat, also have beneficial elements that protect the human body. Contains loss of fiber, which helps the body pass waste, helps flush out harmful materials. Obesity has reached epidemic proportions in the United States. The percentage of adults age 20 to 74 who are obese increased from 1960 to 2000 with the largest increases occurring in the 1990s. Similar trends were observed among men and women. • Obesity increases risks of diseases • Increase in obesity is due to eating habits, not genetic changes o Processed food taste better, are not healthy o Fast food is unhealthy but people would rather eat faster than eat healthy. o Change in portion size, (Americans want maximum value for money, things are created for quantity not quality) humans can eat nearly double what is needed to survive • Viruses are responsible for 15% of cancer death, p53 is a high risk virus target. • Viruses have learnt to protect themselves, have figured out how to stop the destruction process of cells. • Alcohol increases risk for cancer, acetaldehyde causes the headache feeling of being hungover, also is a leading
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