DRUGS 101 Midterm #1

Lice and fleas on humans, common in powdered wig, save from itches and cover ugly scalp (pirates of the carribean wigs)

Life with worms and parasites- rare today- olivia knows, ****ing disgusting, trust her
Deworming was a thing before

Disease- effects quality of life, constant quality

Chronic infection- fungal infection present all the time

Malnutrition- food spoilage was common, was often rotten, ate what had, seasonal foods

Main reasons for improved health (5)Improved sanitation, clean drinking water, refrigeration, vaccination, antibiotics- both came with drug introductionSanitationFirst- toilets, what a great thing passed 100 years, waste now carried away, stopped carrying diseases before we had outhouses (shitty shed) even in cities waste was closer to you, human waste is source of disease we had chamber pots and communal cesspits "Tibor" waste transported in morning to sewers, because we drank water or you empty it out the window Open vs closed sewers- pits, didn't separate wastes, open sewers associated with lower life expectancies (poor countries still use) Living in close proximity, this created unhealthy situations, always germs, bacteria etc... up until 100 years ago Always exposed to death and dying, common to touch a dead body (disease) people would die in your house, you'd have to carry out...GROSSClean Drinking WaterCanada has some of the best water in the world, contributes to good health In history, villages didn't have clean water, villages upstream would contaminate your water; poop water Also, nature does NOT make clean water, even natural spring water is not clean, it is DANGEROUS Animals living in water such as water fleas and guinea worms can live inside your body Guinea worm: waterborn infection, drink water, worms burst out of body- secretes chemicals that create extreme pain Filter water through cheese cloth filters- would filter water fleas, can also boil water. No way of knowing if microscopic organisms lived in water, chlorine helped this chlorine disinfects water and preserves it Water pipes are long, can get holes- chlorine protects water from getting contaminatedRefrigerationUsing an ice house, extended the life of food but still rotted quickly Ice houses only reliable in northern climate, harvested in spring melt by summer Today, we can get food that we want all the time and well preserved strawberries- year round even though seasonalVaccinationPharmaceuticals Criticize companies because they know if something won't sell they simply make it Immunization biggest science invention. EX: small pox gone in 1977 (only exists in labs and bio weapons today) Eat away at skin, disfigured Vaccination scar before 1972- not case anymore because smallpox is gone Polio- paralyzes you- less then 1000 cases today through 10 or 11 countries major eradication barrier is politics, not technology eliminated in NA in 1991AntibioticsUsed for bacterial infections 50 years ago, could die from small cut on arm No penicillin back then Reduces maternal mortality Before 1940, when it was created- birth was a dangerous thing if mother had infection during birth she had 30% chance of dying tears were also common back then and would kill the motherWhat are two main markets for drugsPrescription-$300 billion in US, yearly, 10x more expensive because insurance pays for drugs Over the Counter (OTC) $25 billion, walk in pharmacy and buyTwo largest drug marketsUS. 50% of drugs- make most money selling to FDA Japan #2 Canada, 3.8%, still in top 7 top 7 make 90% of marketAncient medicationNo effect, or harmful- made up cures/magic Better by getting treatment (chicken noodle soup) Small number of treatments were successful, even fewer are still used today Came from plants Turn to plants for materials - readily available biochemical differences between plants and animalsDrugsProduce desired beneficial biological effectPoisonProduce undesired, harmful biological effect Poison kills, potion curesDrug vs PoisonDoseDosagesAssumed low dose produce beneficial effects- drug High dose- harmful- poison this is not always true, sometimes it's vice versa EX: diabetes: low insulin is bad, high is good Dose is key, change the dose, change the effect Ex: to much water, electrolyte imbalanceDiscovery of drugs: two waysObservation and Philosophy. OP Observation: people observe effect of drug, strong poison in large doses- this makes it a drug best way to develop a drug is experiments and observations IF made properly Philosophy: based on belief, more COMMON cure arrived from own reasoning healing related to superstition, magic, religion EX: Papyrus Ebers: talks about thousands of cures, mostly junk, small % work the ones that do were very strong poisons very little used todayStrong vs Weak poisonsStrong: easy identified, low dose makes into drug Weak: large quantity for effect Ex: almonds- cyanide, if you eat too many you die FUN FACT. Dose mattersHippocrates 460-370 BCFather of medicine Promoted experimental methods over philosophy tried to reject religion and superstition from medicine ox liver for night blindness poppy juice for crying babies (opium) animal fat- baldnessOpium- PainExtracted from poppies narcotic painkiller, a sedative around for 10,000 years toxic in high doses, drug in low dose Became very popular pharmaceutical didn't work,, just made you feel good/high Narcotic laws, 1910-1915 to stop people from taking so much morphineCocaine as a stimulantFound from observation, not philosophy, extracted from cocoa leaves, used as topical painkiller (on body, not in) Indians in peru consume it instead of coffee Classic coke- cocaineQuinineFrom plant, treats malaria Peruvian bark of south american tree was more valued then gold most effective treatment for malaria prevent dying with just this British army used in India to protect from malaria Gin & Tonic has quinine in it- to get them to drink it they would mix tonic water with gin because it tasted really bad. Tonic water still contains this substance and glows under UV lightProblems w/ Observation3 Main 1: brain searches for patterns even when not there, this is known as Apophenia Perceiving sounds or images as other things- PareidoliaAnecdotal evidenceMay be unreliable Drug may have different effects on different people May also just be a coincidence relied on own experience and chance only experimental evidence is reliable, look for trends, collect stats For example- tomatoes once thought to be poisonous Once it's "evidence" it's hard to contradict 500 years ago didn't do experiments correctly , many harmful remedies retained because of this (family traditions) chicken soup for exampleProblems with traditional remediesCan't control concentration of dose- no standardization no way of telling plant has what % of whatever in drugs we can measure Variation in preperation and administration. Preparing different can alter effects food for example, gives different effects if cooked or not No standardization or instructions "telephone game", people would pass on medicines, they would become lostPhilosophy to identify curesThe cure was arrived at by reasoning, we made it up, search for proof afterwards Often connected with magic, easier Info needed to be somewhat goodHippocrates develops Doctrine of:Doctrine of Humours (HH)- theory of what illness is about This persisted until about 150 years ago He said the universe was made of four elements (earth-dry air-cold water-wet fire-hot) this is the earth Body is made of four humours (4-4) Blood- Cold Phlegm- Wet Yellow bile- hot Black bile-dry this is us Believed they were balanced, inbalances would cause sickness diagnose using properties of the humours for example fever- hot and dry cure- cold and wetBloodlettingTechnique of Doctrine of Humours Goal was to re-balance blood humour For example, someone was sick you would rebalance blood humour by cutting them and allowing them to believe. They uncovered where to do this through astrology, had different tools for different cuts and sizes- books and stuff Based on what you had this often killed the patient and was worse then infection For example: George Washington died from this after he got an infection and tried this method Emetics- to throw up or purges- to poop force to vomit to reduce puss, phlegm and bile poop to reduce bile Indoctrine completely made upDoctrine of SignaturesCreated by Jakob Bohme was a shoemaker and philosopher believed that god left clues to tell us how to use things Thought disease and cure were linked This approach is/was used by all cultures This existed everywhere, he gave named to it Walnuts- look like brains, good for brain health bone stems- look like bones- good for bones Ex: sharks don't get cancer, they have cartilage where we have bones, thought this meant shark cartilage could cure cancer..sharks do get cancer Parsley- parsley green, chlorophyl- fresh breath, last ingredient, least amount Just candy, does nothing, artificial flavour masks aroma, after gone you get bad breath. Mandrake roots look like people- used for magical uses, demonic possession. believed they made screeching noise- used dogs to pull out of ground for dogs- no noise to keep screaming Rhino horn- phallic symbol- powder rhino horn in China Mercury- heavy liquid- purging- detox intestines Doctrine bad and harmful, at BEST did nothing Lack of rationality and evidence, based on appearance and location, required imagination, highly subjective imaginationSurgerySome conditions can't be fixed with drugs these affected areas had to be removed or cut off no anaesthetics at one point amputation to be done quickly 5 or 6 people hold down- bones sawed off must be cut off at apex at v shape, they didn't know this back then v shape- exposed bone and tissue be coveredHumphrey DaveyDiscovery: Nitrous Oxide (laughing gas) 1850s, noticed chemical compounds could be used to reduce pain during surgery Forge what happened in procedures- still used todayWilliam T.G. MortonEther: 1846 effective, patient didn't move, or feel pain held jar over patients mouth, very dirty allowed modern surgery to be more complex because procedure could be done without patient moving around, still less then 30% died This was because there was no info on what caused disease, and how to prevent infection The tools weren't changed, wore street clothes, didn't wash handsJoseph ListerPhenol- Antiseptic First, Louis Pasteur discovered bacteria and pasteurization caused by microscopic organism that got into body Lister developed chemical that would kill bacteria He came up with Phenol/carbocylic acid sprayer Candle at bottom would heat, cause mist, sprayed on patient to remove bacteria and clean acids. 70-80% survival rate, he decided to wash hands, change clothes, tools etc Phenols had toxic effects on doctors because they always breathed it in Listerine had phenol at first- was all around cleaning product and dan drift control Today, thymol is substituted Don't think he made but there was carbolic smoke ball for home use- to be a cure for influenza and number of things because it killed bacteriaWashing and Glove useIdea of cleanliness produced same effects of phenol, but no toxic effects 100 years ago room was white, dirt was easy to spot, surgical gouns and gloves Thomas Roddick in 1877m antisepsisProblem in 1800 with medicationNo regulation, industrialization created large market, didn't have to prove it worked, large amounts of fraud Have always existed but increased in 19th century because drug industry thrived in 1850s and big chance to make money. FRAUDSScience and fraudEmergencies of science gained peoples trust Scientifically proven or patented to get people to buy product legallly had to have this Patent is right to make product, no credibility at all, first one to come up with or release it Alcohol and opium common because people felt good, used science to market things Late became easier to identify fraud, with science Kickapoo indian oil- cures everything- no side effects..NOT TRUE, not a drug if it does nothing Radium spring water for wellness cure-radioactive water Experiments on humans common until WW2 After WW2, regulations for working on humans arose MengalayWilliam J.A BaileyRadi-Thor Kill cancer cells in lab, but many cells can kill in lab without real effect Twisted science, water increased intellectual ability Byers was a believer, a golf pro, had lower jaw removed because it was so badly destroyed by radiation in water, then died Needed government to regulate what could be sold or notBoard of Food and Drug Inspection- 1907Created MINIMAL regulations, had to list everything in it could use anything in drug as long as you listed it No safety testing, controlled most patent medicines because they didn't want to say what was in it, but some still exist today (buckley's- just menthol)MassengilSulphanillamide Elixir antibiotic powder- first one EVER Dangerous product- cannabis, chloroform, morphine Created good tasting liquid which had ethylene glycol- anti-freeze Reason why is that it was destroying peoples kidneys Company didn't stop because there was no laws against killing people with toxic drugs- label was incorrect Said it was an elixir which is mixed with alcohol and water, but they didn't do this Recovered most of that was sold 107 dead, 260 permanently disabledFDA Created-1932In response to ^ to ensure safety of drugs Animal testing now required for safety only Clinical trials were done to follow safety in humans- directions required on labels Thalidomide- pregnant women- 1957- sedative Teratogen- birth defects- "monster" caused something called phochomelia (born without limbs) never marketed in the US, discovered when FDA approval was given Tested in rats, but rats don't give birth to deformed pups- they re absorb damaged embryo Humans doModern Safety StandardsHad to be done in a t least two species now at least one had to be a primate must show drug is bio available- gets into body muse use relevant doses must be good when you use large or small dosesWilliam PerkinFirst synthetic dye-1856 Coloured clothes purple- didn't have coloured clothes, cheap to make, first industry of dye companies these became pharm companies Bayer started as a dye company for example First artificial drug in 1897, better, cheaper, plant drugs don't produce chemicals for us Genetically engineered drugs use the softest source of proteinWhere do we get drugs?Get most drugs from synthetic, more then 50% semi-synthetic biologic-gmo natural-5% used to be only sourceTopic Two-PainMost commonly used drugOTC are cheaper because of no insuranceTop OTC medicines1: Cough & Cold 2: Pain Relief Imortant to think of when buying: Safety- dosage is key to size of body OTC, safe, regulated Prescription dangerous- irregular dosageSide EffectsALL drugs have side effects-if not, not a drug A- effect- what is it? B- Incidence, how common is the symptoms? difficult to find, evaluate risksIndicationsWhat to use a drug for: many people take wrong drugs (won't work for them) some people take drugs without needing (laxative)Counter-indicationsWhen to not use drug: pregnancy, sick, drug combos, food and drug combosPricePain reliever, one of the most common OTC medsCommon drugAlcohol, caffiene, aspirin- first artificial drug most commonSalixThis is a drug that comes from genus- salix includes willow, poplar, beach, winter-grain Salicalates in willow is effective pain treatment Summarions use willow leaves for pain from long ago, Egyptians used it for inflammation, Hippocrates- willow for child birth Not natural- does reduce inflammation (Egyptians right) Knowledge of herbs were lost in dark ages of Europe because church said not to believe in herbal remedies (magic, witchcraft) Reverand Edward Stone- described medicine for fever he used doctrine of signatures to associate between cure and disease "People who live near swamps get malaria, people with malaria have a fever, treated with quinine, quinine is bitter, willow is bitter, willow grows in swamp, willow will cure fever" Actually cures fever- take willow bark for fever out of dry bark pound it to a powder or tea and give it to reduce pain and feverSalicinActive ingredient in willow Henri Leroux, in 1829, was able to extract active ingredient from willow bark- salicin. from 1.5kg of willow bark would only create a small amount of salicylic acid 1.5kg-30 grams of salicin, 14g of salicylic acid Bad because supply of willow was limited, had to pay to get them there, only rich could getSalicylic acidMade from salicin, Rafeal Piria made this acid. Has all same properties of salicin. Exists in wintergreen tree, better drug because active in lower dose and has same effect( give less) Anti-inflammatory Made from existing compound already in nature Semi-synthesis, made from coal tar, waste product in 1800s treat coal with steam to produce natural gas- now we could make coal tar into same substance, but it more practical because it was waste and produced much better, 1 Kilogram of coal made 300 grams salicylic acid William Perkin- converted coal tar into dye first to use this Used as a painkiller with two side effects- bitter taste, stomach irritationFelix Hoffman-1868-1946Father had arthritis, got stomach ulcers and problems from taking salicylic acid Made better drug by chemically transforming drug slightly Process of drug optimization Make it better but not effective for pain added CH-3-methyl to get rid of the side effects One problem without side effects, no pain relief August 10, 1897- Acetasalicylic acid This is what we know as A.S.A.- Aspirin He used fish gills as our stomach model to test stomach irritation- thought what irritated fish irritated us- this was wrong, but it still worked The trade name made can ONLY be used by Bayer, Aspirin ASA is generic nameA.S.A BenefitsPain, fever, inflammation, muscle pain, heart attack, not visceral painSide effectsTinniuts (ringing in ear) stomach irritation reduce blood clotting Rye syndromeProstaglandinsThese are local hormones produced and used in same cell. exists for short times- signal molecules for short distances Help to protect the stomach and control much us level, decreases acid production, increases mucus production so that aspirin can increase acid production and decrease mucus production...Ulf Von Euhler- 1934Associated with intense muscle contraction and induce pain Aspirin blocks prostaglandins from being produced Body does note store it, but produces when necessaryCyclooxygenseArachadonic acid to prostaglandin aspirin blocks part of cyclooxy which blocks part of prostaglandin formation 1 aspirin every 2 days for 5 years reduces risk of heart attack by half, but only if you're at risk for a heart attack Some people think it's associated with cancer, for that, you need to take about 14 per week for 10 years and only get smaller effect. has more dangerous side effects then cancer ASA in news- homemade explosivesBufferinASA + Anti acid Magnesium sulfate MgSO4 dissolve quickly and have plastic coating to be degraded in small intestine. to avoid stomach irritation take with glass of water, can get stuck in intestine wrinklesRye Syndrome and InfluenzaChildren suffering from influenza took aspirin to reduce fever- caused rye syndrome, that's why it's associated don't give to children also got brain damage still applied precautionary principle removed children's aspirin from market because risk outweighed benefitsRegular vs extra strength ASADose is only difference, 325mg vs 500mg sell more extra (bigger is better) Gell caps absorb slightly faster (12 vs 15 min) pretty green colorName Brand Vs GenericNo difference- only associate quality with name brand, same chemical substance, same dosage, must have equivalent bioavailability Company must show that same amount of drug enters bodyA Cahn and P HeppExperiment to find vermifuge- tried to cure intestine worm Gave patients Naphthalene (mothballs) by accident Actually worked, reduced fever because it contained acetanillideAntikamnia (antifebrin)Good for fever, made from coal tarCarl DuisbergChemist at bayer had to dispose of 150 tons of amino thymol created phenacetin dissolved alternate form of drug because he worried about toxicity of OH group which is a hydroxide, makes it an alcohol started to sell this made APC tablet- had aspirin, phenacetin and caffeine in itD. Lester and L.A. GreenbergAcetaminophen- correlated with antikamnia and phenacetin these three correlate- intermediate Both be converted by body to make the same substance- acetaminophen (most popular pain medication) Lester thought it would be toxic because it's original structure looked like a toxic oneAcetaminophen for pain reliefActive ingredient in tylenol less sensitive to pain muscle and visceral pain as well (unlike aspirin) Raises pain threshold By interfering with way you transmit pain signals from body to brain Does not inhibit prostaglandin synthesis-wont reduce swelling like ASA Works for arthritis but not always (works better ostioarthirits) No problem with stomach irritation- for instance- ASA has strong only happens on purpose (more then 60 pills) sweet tasting version called children's tylenol- small dose so children don't all- expensive not good for hangover alcohol stimulates liver function, increases toxicity of the drug you can triple dose yourself if mixed wronglyOstioarthirtisIn bonesRheumeutoidInvolves inflmattionBenefits of tylenolPain relief, muscle AND visceral, fever NO FEVER, NO reduce of heart attack No associated with ryeSide EffectsLiver toxcicity (no alc and tylenol) Activiates P450 Tylenol PM also adds in antihistamine makes sleepy (uses side effect as benefit)Tylenol and cynadieSeattle murders, Johnson and Johnson took all tylenol off, made safer- adding safety seal to OTC meds and made capsules more likelyIbuprofen1961, prescription only originally OTC approved in 1984 used in Advil and Motrin similar mechanisms to aspirin, does not prevent heart attack cyclooxygenase is inhibited with use Makes pain go away everywhere in body- drug just goes through whole body extra and super strrength- cost more because of nameBenefitsMuscle pain relief, reduce inflmattion, reduce feverSide effectsBlood clotting, stomach irruption with long term useNaproxenAleve: inflmattion, bit better then IBUTop pain relievers in NA43% tylenol (acetim ASA- 28% Ibu-26% Naproxed 3%Cox-1If you stop production of prostaglandin's you stop production of pain Found in stomach, 20,000 people die a year from this, hydrochloric acid increase, mucus decrease (you need protective mucus) to much stomach acid dangerous, platelets, blood clothing inhibited, stomach ulcers, bleeding sometimesCOX-2Reducs pain, inflmattion, fever Current arthritis treatments invoke both COX-2 beneficial, 1 is harmful Selective COX-2 for arthiritsi- benefits only, no side effects Example: VIOXX clinical trials Approx 60 studies- thousands of patients said no problem or side ffects no difference in placebo and drugs etc.. approved in 1999 huge sales, whole study released (only included first 10 months of study) last 8 moths full of side effects Increase risk of heart attack, .4 for vioxx, .1 for naproxen Got in trouble- FDA analyzed 1.4 mill patietns, said drug caused 88,000-140,000 heart attacks over 6 years MERCK voluntarly removed drug from market because lawsuits and money lost FDA wanted them to put it back on with improved labelling and MD education on how to use it BUT they refused because all lawsuits, another company called celebrex in same family of drugs are still selling today Some say it's cheap way- but it's the way it should be done, better safer packageCurrent arthritis treatment10-20,000 from current treatment death vioxx-18-28,000Topic 3-Heachache90% get headaches (cephelegia) Once believed headaches were caused by demons lose demon- lose headacheCuresStick head in oven to cook demon out metallic or magnetized needles or heated and stuck in ears to suck out pain Perform surgery to cure headache Trepenation- opening of whole in skull to relieve pressure 30% of surviving, harmful not beneficial Hole in head movement BUT neurons in brain aren't capable of feeling pain local anestheticHow we get headachesPain originiates in thin tissues surrounding skulls type of headaches 12 types of headaches, 60 sub-types all can be grouped into two main categories, muscular and vascular headachesMuscuularMusuclar band around skull contracts and squishes the tissue primarily caused by stressed- relax muscles Naproxen, ibuprofen, all pain medicationsVascularBlood circulation in tissue Three major types Toxic: caused by ingesting of a poison, drink, eat, environment. Pain is caused by vasodilatation (gets bigger) as they swell and press against skull and cause pain. This increased blood flow pushes on tissue and generates pain Hangovers are most common form Body tries to get rid of by metabolizing using enzymes proteins ends in ase is enzyme Two step system Acetadehyde nasty substance, contributes to hangover. body produces different amount of enzyme Alcohol D then other enzyme- less severe hangover vice versa most common in Asians Aging the alcohol adds flavours- congeners the darker the alc beverage- more severe hangover alters function of liver Some red wines have histamine, to much results in headache Aged cheese- tyramine Choclate triggers heaches in some people- phenolethalomine hot dogs and smoked meats- nitries- nitrous oxide- 9n the blood which is a potent vasodilator Nitrogylcerine produces nitrous oxide. an explosive and used as a heart medication because it billets blood vessels. heart attack prevention active ingredient in TNTMonosodium glutumateMSG- Soups made with seaweed tastes much better 1907 used in oriental cooking 1968 kwok syndrome letter to editor of new england journal of medicine- guy got headaches at some chinese places that uses MSG some people avoid because advertising, turns out no cause of headache unless you have a vast amount and know its in food in EVERYTHING packaged industrial food needs this at end Disguised as Hydroligzed vegetable protein Normal human metabolite (in body naturally) Constitutes about 5% of protein Msg does not cause headachessecond type of vascularMigraine Overused, only 18% of women, 6% of men First change- vasoconstriction constrics- blood vessels constrict second stage vasodilation Get small- then Get Big Blood vessels in head get larger because of this triggers, tension, lack of sleep, menstartion, relaxation, food,d drugs, strong smells Follows a progression Prodome: experience by 1/3 of people pre-signals, gives warning characterized by moodswings Aura- 1/3 of sufferers- 1-2 hours before pain phase Characterized by olfactory hallucinations audtiory hallucinations, vertigo, hypersentivity, tunnel vision Pain- different from normal headache- involves half of head- feels like someone is shoving spike in one year 1-72 hours nautious, sensitive to light sound and smell Postdome: After-effect- hungover- exhausted- euphoric, depressed, no concentration Treatment: pain meds, ride it out All the buddies or prescript has codeine Triptin- help migraine Ergot: powerful hallucinogen

DRUGS 101 Midterm #1

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