Drugs 101 Midterm 1 Notes

Life expectancy
- Approx 30-35 yrs for most recorded hx → lasted 6000 yrs
- Approx 30-35 yrs through the stone age → 500,000 – 6000 yrs ago
- In Canada 82 yrs in 2009 -
- Most improvements in life span and increase of life expectancy happened over last 150
years
- 150 years ago, life expectancy was same as that of the stone age
- Canada has one of the highest standards of living in the world number of 35 years is an
estimate made by combining data from various sources - numbers may vary depending
on source used - range is more appropriate
- Even with doctrine of humor and doctrine of signatures, life expectancy was the same
until about 150 years ago when we started to use science
- Even though sx was available before, life expectancy remained the same because
people could die from shock during sx, infections, etc.
- Discoveries such as antisepsis and that bacteria causes disease happened about 150
years ago and its about 150 years ago life expectancy started to change
- Modern drug industry starts about 150 years ago which has contributed to the increase
in lifespan in humans starting in about 1850

Life Conditions Before

- Not only was life expectancy about 30-35 years but we would expect to endure illness an
endure a lot of hardships
- Life was harsh, cruel and short and disease was common and dangerous - 200 years
ago in Canada you would expect to have illness the vast majority of the time from birth
till death and people “soldiered on” through it
- Threat of disease was different back then, certain diseases that do not affect us greatly
today would have affected us greatly back then ex: cutting our finger back then can end
up killing you whereas today we can just put a band aid on it
- Lice and fleas back in the day the majority of the population would have them -
- Life with worms:
- Hookworm
- Tapeworm – can lay 1,000,000 eggs per day
- Tapeworm eggs
- Roundworm max size 50 cm lay 200,000 eggs/day
- Pinworms – migrates out of colon and lays eggs in anus – itching

Improved Quality of Life in Canada:

- 1900 (44 yrs) → Main causes of death were pneumonia, TB, influenza (lasted until
1950s)
 - 2004 (82 yrs) → Main causes of death are heart disease, cancer, stroke, lower
respiratory infections, traffic accidents, diabetes
- Causes of death have shifted from infectious disease to “wear and tear”
- Historically people lived entire lives in an unhealthy state

Main reasons for improved health

- All came into play in about the last 150 years due to development of the scientific
approach/ method to the world
- Science has given us all the 5 above, and is the reason behind our current long life
expectancy and high quality of living

1) Improved Sanitation
- Purpose of a toilet is to help separate people from the cause of disease (waste)
- Human waste carries disease
- About 100 yrs ago outhouses were common in cities = Waste was not separated from
you as it is today in a toilet
- In larger cities where outhouses were not available due to ex: space, chamber pots were
used
- Do business in bucket and when full is dumped into street, ditch, carts (that were carried
to cesspits that were in cities)
- Closed sewers is a relatively new innervation and became widespread inside cities about
200 years ago
- Populations used to be exposed to the dead and the dying
- Now is common people die in the hospital and health officials deal with the
people who have died
- About 200 years ago it was very common to be exposed to dead people: carrying
dead body into cart, people dying in the street, people died at home and family
looks after body and remains

2) Clean drinking water

- In Canada we have some of the safest water in the world
- Nature does not make pure water → Things live in the water in nature that can cause
infection or illness if drinking water in nature
- Guinea worm (dracucculiasis)
- Microscopic animal that lives in the water, affects people that live in tropical Africa
- When people ingest water containing this worm it starts to change
- Once in digestive tract, transforms into worm that live in the muscles inside the
persons body
- As worm multiplies and grows it uses resources from inside the persons body In
order to complete the water cycle it needs to leave the persons body and get
back into the water to infect other people – does this by creating hole and
creating discharge which causes a burning sensation
 - Major improvement is chlorination → Extremely important to do because filters aren’t fine
enough to get everything that’s in water
- Chlorination purposes: used to completely sanitize the water and ensure
remnants of any microscopic animal are not present acts as a preservative -
ensures there is a trace of sanitizer in water and protects/preserves it from water
plant, through pipes and to our homes safely

3) Refrigeration
- Food spoilage was common before refrigeration = you would have to eat rotten food/ cut
off the rotten part as much as you can because you had no choice
- Seasonal availability Refrigeration has given us the best food supply and also variety of
food that we want Ex: strawberries before were only seasonal because of lack of
refrigeration/storage and preservation potential

4) Vaccination
- Pharmaceuticals improve health
- Greatest achievement in medicine has had the most positive impact on human health
than any other kind of medical advancement
- Immunization (vaccination)
- Very successful for viral diseases
- Smallpox
- Eliminated in 1977, Only exists in labs and biological weapons,
- Used to kill 1000s people/year, 100 years ago you used to fear getting
disease
- Polio
- Eradicated from North America 1991, can only be found in 2 countries, >
300,000 cases in 1998, major eradication barrier Is politics

5) Antibiotics
- For bacterial infections
- Penicillin reduced maternal mortality
- Before, due to tearing from childbirth becoming infected can result in the woman
dying a few days or weeks after giving birth

Notable People
Jakob Bohme: shoemaker, philosopher (1575-1624). Believed that god left clues to tell us how
to use things and that disease and cure were linked. Example) walnuts look like brains, so.
Therefore, they are good for brain health. Boneset has to deal with bones

Sir Humphry Davy: discovers nitrous oxide (around 1850), which was the first anesthetic, now
known as laughing gas; nitrous oxide is also a propellant, used in the cool whip or as a way to
get high
William T.G. Morton: discovered that ether was a much better anesthetic than nitrous oxide
(1846), beginning of modern surgery, a person would not feel pain

Joseph Lister: uses phenol as antiseptic in 1867. Believed that bacteria could cause disease
and that if you could decrease the bacteria by poisoning them you could increase the survival
rates during surgery. Chose phenol bc/ that is what was used to clean sewars. Invented the
carbolic acid sprayer. This sprayer did not affect patients but did affect doctors. Also created
Listerine.

Thomas Roddick: brought antisepsis to Canada (1877). Changed cleaning techniques to be

more sterile, wore white to be sure that the area was clean.

William Perkin: first artificial dye that was mauveine and was created with coal (1856). These
dye companies later became drug companies (1897) because the chemical structure of coal
could be transferred to become drugs. The first artificial drug was aspirin (1897).

William J.A. Bailey: makes Radithor (water that contains radioactive water) … told people that
this water could make them smarter.

Eben M. Byers: a believer in the products that bailey sold. Had the product every day for 2
years. After these 2 years, he had extensive damage to his face and had to remove the bottom
half.

Reverend Edward Stone (1702-1768): described treatment for ague (fever) in 1763. He
realized that willow bark and quinine had a similar taste, finding out that willow bark has medical
properties. He applied the doctrine of signatures.

Felix Hoffmann (1868-1946): his father had arthritis, and he took salicylic acid for pain, but this
caused him stomach issues. Hoffmann planned to get rid of the stomach pain. He chemically
changed the salicylic acid to remove the OH and gain O-CH3. This caused the drug to have a
less bitter flavour and no stomach irritation, but it was not effective for pain. Ended up finding the
right combination on August 10th,1897. He turned salicylic acid into acetylsalicylic acid (the
world’s first artificial drug).

Carl Duisberg: needed to dispose of 50 tons of aminophenol, wanted it to look like Antikamnia,
created phenacetin with waste plus more.

Arthur Stoll: isolates ergotamine in 1918. Easy way to control dose using purified substances.

Albert Hoffman: discovered LSD by accident. While trying to find a drug that could treat mental
illness. He was experimenting with ergotamine… ended up giving himself hallucinations by
accident.
Edward Jenner: was a doctor who wanted to learn about smallpox. Observed that milkmaids
did not get smallpox. Milkmaids who didn’t get smallpox had cowpox.

Louis Pasteur: wanted to protect livestock from illness. Was looking at anthrax. He attenuated
anthrax bacteria by heating. Had to use a 2nd booster shot.

Ander Breivik: made his own explosive to blow up city hall and used A.S.A. to make the
explosives.

Acient Drug Industry

- Most ancient medications were useless
- “Made-up” cures→ People believe in magic
- Feel better just by getting treatment → Humans have strong tendency to believe in what
they want to believe and in feeling better with tx of something
- ex: eating chicken soup makes you feel better when you have a cold
- Only a very small number of tx actually worked A few of these are still used today
- ex: opium, drugs from different plants, etc.
- Many treatments were harmful due to the substance being poisonous or due to getting
incorrect tx = no access to correct tx = making the situation worst
- Most ancient drugs were from plants. Why plants?
- Animals have defense ex: horns, plants are rooted in the same spot and can’t
runaway so their defense is poison
- Plants produce poisons – poisons are the source of early drugs
- Drugs are poisons
- Drugs → Produce desired (beneficial) biological effect
- Poisons → Produce undesired (harmful) biological effect
- Sola dosis facit veneum
- Poison → Kill
- Potion→ Cure
- Only the dose makes the poison→ How much material = something is beneficial
or harmful ex: too much of water in short amount of time = poison
- Dosages → Normally we assume:
- Low doses produce beneficial effects (drug)
- High doses produce harmful effects (poison)
- Sometimes → low doses produce harmful effects (poison) AND higher doses
produce beneficial effects (drug)
- Ex: insulin in diabetics – not enough = harmful effect to diabetic and we
have to inject a little bit larger amounts to produce the beneficial effects
Majority of drugs → make sure you don’t have too much or too little

Doctrine of Signatures
- Jakob Bohme did not invent it he just gave it a name
- God left clues to tell us how to use things
 - Disease and cure were linked
- ex: disease acquired in forest = cure in forest, disease acquired from water =
cure in water
- This approach is/was used by almost all cultures going back 1000s of years
- Most remedies developed this way were harmful
- Lack of rationality or evidence → based on appearance or location, required imagination
to see connections
- Example of this doctrine beliefs:
- Eating walnuts is good for brain health because they look like brains –
they’re good for nutrients but wont restore brain tissue/health
- Boneset stems grow through leaves like bone = good for promoting bone
health
- Sharks don’t get cancer because skeleton is made of cartilage and we
have bones = they do get cancer
- Chlorophyl freshens breath because its green like parsley which freshens
breath chlorophyl makes no chemical reaction to actually freshen your
breath
- Mandrake roots look like people and used for many medicinal and
magical purposes ex: primary use was for demonic possession →
Believed that if plant screamed when harvested = the scream would harm
the person harvesting it = why they used dog to harvest it
- Rhino horn is a phallic symbol → powdered and used in Chinese
medicine as aphrodisiac - Rhino horn is made up of same material as our
nails and has no link to creating sexual libido
- Mercury is heavy liquid = People drink mercury as a purgative – idea that
heavy mercury is going to push out all the toxins down through body and
well flush toxins out

Modern Drug Industry:

1) Each start with a scientific idea.
2) Each is optimized using scientific methods.
3) Each is tested scientifically.
4) Manufacturing is standardized.
5) The drug industry is tightly regulated (must provide scientific proof)

- North America (US) drug market 2016

- Rx drugs - $470 billion OTC drugs
- $35 billion Rough scaling factor of about 10:1 between the 2
- US market by far the largest market in the world and is responsible for half of the
drug/pharmaceutical market of the world
- Modern pharmaceutical industry is young
- Started in 1856 ~ 150 years ago
- Uses scientific methods → Chemistry, Biology, Molecular biology (biochemistry),
Epidemiology
 - Regulated by government most heavily regulated industry in the world = high
quality products that have been extensively tested to ensure they work
- Effective due to being:
- Developed using scientifically tested
- Developed in non bias environment – tries to ensure honesty
- Everything is done under microscope/ observation

Regulation
- Industry regulation important to ensure safe products, good manufacturing quality, and
that products work downside = regulation increases costs
- Before 1907 there were no rules
- ANYBODY could make and sell drugs→ No proof that anything worked, No
safety testing/ testing of any kind
- Most drugs were “made-up” ex: Put some leaves in a bottle with water or alcohol
- Rise of patent medicine in late 1800s
- Patent medicine is a term for a series of medications that came out in 1800s, is
another word for “fake medicine”
- A bunch of companies put it on their medicine because people would associate
patented with quality
- A patent is a legal document that prevents someone from using your idea, it does
not say anything about the quality or validity of the idea or product. A patent just
protects the idea.

Board of Food and Drug Inspection

- Modern FDA regulates drugs, regulates medical devices and regulates procedures
- Formed in 1907 → First ever government regulations for medicines
- Labeling only – had to make sure it was accurate
- No regulation of therapeutic claims and No safety testing
- 1938 created Food, drug and cosmetic act
- 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 label

Modern Drugs
Aspirin:
- Salicylic acid and Acetylsalicylic acid were given a trade name (Aspirin)
- First sold as a powder than tablets (more drug-like)
- Benefits: pain (muscle not visceral), fever, inflammation, reduce heart attack risks
- Side effects: tinnitus, stomach irritation, interference with blood clotting, death of more
than 60 tablets at once
- One of the world's most popular drugs
Acetaminophen:
- Side effects: death (more than 60 tablets, #1 suicide drug in England), stomach irritation
(weak), liver toxicity, never take for hangovers (alcohol stimulates liver function),
poisoning is very common, no risk of rye syndrome.
- Benefits: Pain relief raises pain threshold, good for muscle and visceral pain
- It is an antipyretic, not for inflammation (it doesn’t inhibit prostaglandins).

Ibuprofen:
- Developed In 1961
- Originally by prescription only
- OTC use was approved in 1984
- Inhibits cyclooxygenase (blocks the enzyme)

Naproxen:
- Aleve
- Very good for inflammation
- Generic now available
- Relatively expensive

Prostaglandins:
- Are local hormones
- Produced and used in the same cell
- Exist for short times
- Made by cyclooxygenase
- Help to protect the stomach (decrease HCL, increase mucus)

COX1 and COX2

- Different molecular versions of the same enzyme
- Both carry out the same reactions such as creating prostaglandins and creating pain,
fever, and inflammation
- Both are distributed unequally throughout the body and are found in different locations. If
we inhibit one or the other, there will be different effects because of location
- COX -1 inhibition (HARMFUL EFFECTS)
- Found in the Stomach → HCl production increases and Mucus production
decreases
- Also found in Platelets → Clotting is inhibited
- Long-term COX-1 inhibition = Ulcers in the stomach can bleed severely -
- COX -2 inhibition (BENEFICIAL EFFECTS)
- Reduces pain, inflammation, and fever
- Current arthritis tx inhibit both COX-1 & COX 2
- Selective COX-2 inhibitor for arthritis
- Invention was very beneficial for those with arthritis
Bufferin:
- Contains an antacid (counteracts HCL acid)
- Pills dissolve quickly.

Disulfiram (Antabuse):
- To treat alcoholics
- Blocks aldehyde dehydrogenase

Headaches:
- Experienced by 90% of the population
- Once believed they were caused by demons led to putting head into oven to “lose
demons/ headache”
- Surgical cures for headaches → cut into the head in certain ways to relieve pain.
Possible belief pressure of the headache would be gone with incision or give place of
demon to escape from
- Trepanation as cure for headache → cut different holes in skull, High possibility of dying
from sx or from post sx infection
- Brain is incapable of feeling pain → pain is in thin tissue surrounding skull (gets
compressed = headache)
- 12 types of headaches → 60 subtypes
- Headache grouped into 2 classes:
1) Muscular
- Constriction of muscle band around skull
- If muscle stays contracted for long period of time = pressure of surrounding
tissues
- Caused by stress
- Tx → A.S.A., acetaminophen, Ibuprofen, Naproxen
2) Vascular
- Involves blood circulation
- 3 major types:
a) Toxic
- caused by poison
- pain caused by vasodilation (occurs to flush out poison faster)
- Tx → A.S.A., ibuprofen, naproxen, don’t use acetaminophen due to toxic
pathway it can go down, and it can lead to liver damage, Caffeine can
cause toxic headaches or help them
- Hangover (most common type) – metabolism of alcohol contributes or
helps
- Aging of alcohol adds to the pain of hangover – wood barrel =
materials/congeners dissolved in alcohol = stronger hangover you feel
- Other things that cause toxic headaches – histamine (grape skin/red wine
& fermented foods), tyramine (cheese), phenylethylamine (chocolate),
nitrates (hotdogs or other smoked meats), nitroglycerin (potent
vasodilator)
 - Monosodium glutamate (MSG) discovered by Kikunae Ikeda in 1907
- oriental styled cooking started incorporating MSG in their recipes to
enhance flavor
- ppl started realizing they started getting headaches in restaurants (mostly
Chinese) using MSG, is disguised as “hydrolyzed vegetable protein”
- MSG DOES NOT CAUSE HEADACHES - - Its only when people know or
think food has MSG that they report headaches
- MSG is a normal human metabolite % of our protein, produced
constantly in body and used everyday
- Caffeine
- Caffeine causes vasoconstriction
- Body compensates for heavy caffeine use by trying to initiate vasodilation
- Reducing caffeine intake results in vasodilation because our body gets
accustomed to drinking caffeine
- Brain Freeze
- When we drink something cold it is being pushed up against the palate
and cold sensation is interpreted by the brain = body immediately dilates
blood vessels in head = compression on head/ headache
b) Migraine
- Affects smaller population – 18% women and 6% men
- Starts with serotonin → NT in brain seem to be involved in initial stages of
migraine 2 stage process:
- 1) Vasoconstriction
- 2) Vasodilation → This stage is where you feel the pain of the headache
- Triggers – tension, lack of sleep, menstruation, foods, relaxation, too much sleep,
pregnancy, drugs, strong smells
- Tx family of drugs called triptan ex: sumatriptan, rizatriptan, naratriptan, etc.
Follow 4 phases after trigger starts
- 1) Prodrome Phase → gives warning 1-2 days in advance but varies,
30-40% of sufferers, characterized by mood swings
- 2) Aura → 20-30% of sufferers, 1-2 hrs before pain phase, characterized
by scotomas(visual disturbances), olfactory and auditory hallucinations,
vertigo, reduced sensation, hypersensitivity, nausea, GI disturbances.
Serotonin levels drop in this phase
- 3) Pain→ involves ½ of head (why phase is unique), lasts 1-72 hrs,
characterized by nausea, GI disturbances, makes movements worst,
sensitivity to light/ sound/ smell
- 4) Postdrome → may take hours or days, hung over experience,
exhaustion, poor concentration, depression or euphoria
- Tx – pain meds and ride it out ex: A.S.A, acetaminophen,
ibuprofen, naproxen, rx pain meds
- Triptans can abort migraines → Need to have a type of warning
(first 2 phases) because once in pain phase it is less effective,
 does not cure but prevents c) Cluster (less understood, more
common in your 50s)
Serotonin
- Chemical secreted at the base of the brain
- Levels change during migraine, amounts drop during aura, you can
prevent a migraine by replacing missing serotonin with a drug),
- Nerve signals are cascading chemical reactions, signals travel along the
outside of the cell membrane, they do not touch each other as the
messages are carried by neurotransmitters in the synapse
- Serotonin is a poor drug (used in many parts of the brain but the drug can
only affect the migraine, it doesn’t pass easily from blood to brain
because of the blood brain barrier but the drug must travel from stomach
to brain in the blood) so want to make an artificial neurotransmitter
- You can engineer it for the effect you want (reduced amounts trigger
migraine), take something that can fit into a variety of shapes and alter it
- Came up with sumatriptan (selectively targets migraine), must take it
before the pain phase starts (i.e. during prodrome and aura)
- Want to have choices for meds
- Market competition
- Some works better than others on different people
c) Cluster (less understood, more common in your 50s)

Colds
- Most common infection → outnumber all others by 25 to 1 -
- More than 200 ciruses cause colds ex: rhinovirus, coronavirus, influenza, adenovirus,
enterovirus, HMPV, bocavirus
- Colds are not a single disease they are a collection of a bunch of diseases with the
same symptoms
- Virus destroys tissue (usually upper part of resp. system) and immune system makes
symptoms ex: runny nose, runny eyes, aches and pains, etc.
- No cure for common cold
- Average cold lasts a week
- Some cold medications relieve symptoms
- Many remedies do nothing → Doing something makes you feel better
- No medication will prevent colds → We rely on immune system to recover us
- Vitamin C will not prevent or cure a cold or reduce symptoms of colds
- Research unit in Salisbury, England
- A lot of info we know today about colds ex: spread, tx, comes from research
conducted by this group in England
- Offered free vaccination to bring in volunteers even though wasn’t exactly free
(had to be tested on)
- Test subjects in extreme comfort
- Sneeze does not spread colds → discovered by using sneeze collector
 - Artificial sneeze→ They took the liquid from sneeze collector and then gave it to
people who didn’t have colds and tested if the sneeze put into someone would
cause a cold
- Being cold does not increase chances of causing colds
- Wet hair does not cause colds
- Direct exposure to virus does not always cause cold → bit less than 50% of the
time when they administered virus to person did they actually catch a cold
- Cold virus in nasal secretions → Nose/ nasal secretions contain large amounts of
the virus and spread easily
- Colds are primarily transferred by touching→ You touch a surface, then touch
your face and then it’s transferred to you
- Colds are common in crowds
- School season is cold season
- Tristan ca Cunha → most isolated place on earth. Incident of colds was when ships
arrived
Colds decrease with age
- one reason is behavior ex: children are more social and touchy
- second reason as you age you acquire immunity by being infected
- Exposure to virus causes illness Immune response is too slow and weak to prevent -
Body makes large amounts of antibodies only during infection - After each infection you
build up “memory” cells
- Later exposure to the same virus does not make you sick Rapid and strong immune
response
Cold medicine
- Active ingredients will tell you what the product does, not the front of the box
- $4.1 billion on colds each year (North America)
- Cold remedy ingredients:
a) Pain reliever or fever reducer→ acetaminophen is used, ibuprofen becoming
common replacement
- Menthol – is a weak analgesic = comes into contact with tissue and can
reduce a bit of pain, used to alleviate sore throat
- Cepacol - contains topical anesthetic = reduces sensation
b) Decongestant
- Snot is mostly water with a little mucin→ produced by tissue in nose and
water is supplied by blood vessels in nose due to vasodilation (= leaky
vessels)
- Are vasoconstrictors → jams cells together and they don’t leak as much =
little to no water to create mucus
- Nasal sprays contain decongestant
- All decongestants are members of the amphetamine (stimulant) family
- 2 drug ingredients used:
1) Pseudoephedrine – this one works
2) Phenylephrine – this one doesn’t work - Only tiny amount of
drug makes it from stomach into the blood = not a big effect
 - Amphetamine has ability to dry up nasal secretions → no longer used in
cold medications and instead is replaced with pseudoephedrine
- Drug dealers used to buy pseudoephedrine → Up to 50 % of
pseudoephedrine used to make methamphetamine
- Dealers turned to smurfing → getting drug addicts to buy all
pseudoephedrine products off the shelves and bring it to the drug lab
- Pseudoephedrine only by rx now → Still available OTC but is always
bundled with pain reliever
c) Antihistamine → for sneezing, runny nose, watery eyes, reduce nausea, side
effect = drowsiness
- Dimenhydrinate – active ingredient in benedryl. This is a combination of:
- Diphenhydramine (anithistamine) AND 8-chlorotheophyliine
(stimulant, similar to caffeine)
- Combination relieves nausea without making you sleepy
- Chlorpheniramine is most common antihistamine for colds side effect
drowsiness
- Diphenhydramine is most common antihistamine for allergies side effect
drowsiness
d) Antitussive → used for Dry Cough = cough but with no feeling of ex: mucus
moving around
- Morphine was known to be effective for a cough but was very addictive
- Bayer company invented heroin and was first sold as non addictive cough
medicine
- Heroin although highly addictive is probably one of the best cough
suppressants
- Dextromethorphan used today - Supresses cough reflex
e) Expectorant → used for Productive cough = a lot of mucus in throat and you can
feel it when you cough
- Thick mucus is difficult to remove/dislodge - antitussive will not work
- Guaifenesin makes mucus watery but never has been clinically proven to
work
- Drink liquids with expectorants - Helps the effect much better in
loosening/ dislodging mucus = relief from cough. This is more effective
than the ingredient guaifenesin
Multi-symptom Medication -
- Drug companies don’t necessarily sell things that are good for you but rather what
people want to buy
- Why are all-in-ones not the greatest choice?
- here, we have antitussive and expectorant, which can be dangerous
- ex: in children, if they have a productive cough, the expectorant will help
them dislodge the mucus, but the antitussive will take away the cough
reflex. This can create a dangerous situation.
- Daytime and nighttime version are identical. Only difference is that night time includes
histamine
 - No cold meds for children under 6 → because multisystem medications can be harmful
to the child, parents don’t know how to choose medication and that can be harmful ex:
acetaminophen overdose from being in lots of OTC medications
Influenza Virus
- Flu can be more severe than a cold
- Not much difference between colds and flus
- We get flus on average 2-3x a year - 5-15% of population affected with colds due to flu
- New virus formed every year
- Most forms not dangerous → Very young and very old are at risk - Occasional severe
pandemics arise
- Virus contains an outer envelope
- 2 proteins of viruses:
1) Hemagglutinin (helps viral entry into cell)
2) Neuraminidase (helps viral exit from cell)
- Flu virus classified using envelope proteins → Harder to measure proteins on the inside
of a virus and easier to measure proteins on the outside of the virus

Cancer
- Cancer is an uncontrolled growth: our bodies grow but at some point they stop, although
we do get larger we hit an age where we are at maximum size and height, cells in cancer
do not stop growing (i.e. there is no max)
- Hyper-proliferative lesion (benign): usually not life threatening, but in parts of the
developing world a person’s life can be threatened by the uncontrolled growth o
- Hyper-proliferative lesion (malignant): basically consumes resources from the
body, may interfere with bodily function
- Cause of death Canada: #1 cause of death (2011), we pretty much failed in trying to
reduce the number of deaths by cancer (1950-2001), there is a difference is cancer
death in men and women (men get it more, because of the lifestyle of smoking, women
started smoking later and also a lot less than men)
- Since 1930, most cancer rates have stayed the same other than lung cancer
(increased significantly in men) and stomach cancer (decreased)- could be due
to increased quality of food nowadays
- Cancer is a disease of the aged: most of cases of cancer occur after the age of 55, as
we age we increase the likelihood that we get cancer, it is the same for death rate
because of cancer
- Children’s cancer is extremely rare: does happen but not often
- Cancer treatments are unpleasant (very painful, nausea, hair loss, can die from cancer
treatments- high mortality rate)
- Normal cells become cancerous: our cells normally just sit there and function but in the
case of a tumor some cell in your body has gone out of control and doesn’t stop growing
- One of the cells goes rogue and divides uncontrollably, it eventually becomes
large enough to take resources or interferes with organs in your body
 - Normal cell growth is closely regulated (cells divide only on command- have to
maintain a specific shape, maximum of 50 cell divisions- counted by a telomere,
cells must be touching similar cells- tissue)
- Cancer cell growth is uncontrolled (cells divide continuously, more than 50 cell
divisions- immortal, cells are mobile- metastasis, can detach and move around to
create other tumors all over the body, parasites everywhere)
- HeLa cells from Henrietta Lacks (1951): she had cervical cancer and her doctor
noticed that the cells would grow in a petrie dish outside her body, today they are all over
the world (used for research in universities)
- Cancer requires 20 years to develop
- Requires 8-10 mutations in the same cell
- Every cancer is different
- Every tissue can spawn (more than 100 forms, each tumor is unique)
- Basic processes are similar (4 or 5 systems that can be affected)
- Biological signals are cascading processes
- Cascading chemical reactions: signaling systems (like nerve signals), in cancer it
is a different reaction every time (instead of the same one over and over)
- Biological regulation is complex (like the game mouse trap)
- Cell division is regulated in 2 ways (both systems activated at the same time)
- Stimulation (accelerator): growth signal
- Repression (brakes): tell them not to grow
- Cancer mutations involve loss of function
- Impossible to repair the function with small molecules (easier to break something
than to fix it)
- Cannot repair the damage with today’s technology (generic repair expensive,
difficult and unreliable)
- The “off” switch for cell growth is broken (accelerator stays on), “stop growing”
signals are complex, cell’s “brakes” are broken (cut brake line)
- p53 is an important braking protein (when this goes wrong, the cell loses its
ability to switch off, more than 50% of cancers have this), it is also involved in
“suicide” aka apoptosis, if something goes wrong with this you’re kinda fucked
- Apoptosis: programmed cell death (can be important in embryo
developmenttadpole loses its tail, being selectively killed), used in wound healing
(damaged cells die when they are told), protects the body from viruses and
cancer
- Normal cells count cell divisions
- Molecular clock is the telomere: like the tips of a shoe lace, every time the cell
divides it chops a bit off the end and the chromosome unravels, telomerase
results in the repairing of the telomere making cancer cells immortal
- Tumor formation requires 8-10 mutations
- In the same cell
- Mutations happen continuously
- Damaged cells are eliminated from the body
- Several mutations within the same cell are rare
 - Accumulation of enough mutations for cancer requires more than 20 years
- Gene is a set of instructions to make proteins
- Codons specify an amino acid for the protein being built
- Sequence of amino acids determines protein structure
- A mutation is a typo in the gene (changes chemical property and shape)
- Deletion
- Addition
- Genetic susceptibility
- Some individuals are more susceptible to cancer than others
(oncogenesinstructions are easier to change)
- Some individuals are more susceptible to some cancer types than others (ex:
lighter skin color makes you more susceptible to skin cancer)
- Most cancer death is caused by controllable factors
- Tobacco: smoke contains over 4800 chemicals, 400 are toxic and 40 are
carcinogenic (officially listen but there are probably more)
- Nicotine is the addictive substance
- Carcinogens: polonium 210 (from fertilizer in plants-bird guana,
radioactive from birds eating fish containing uranium, alpha emitters are
safe i.e. you can touch polonium in solid form, sold in sparkplugs,
spinthariscope, antistatic brushes, was also used as a poison, not only is
it radioactive but also has a low vapor point so the smoker inhales it and it
becomes solid again once it cools in your body)
- Combustion products: benzopyrenes (the body chemically changes them
but the intermediate is a very powerful electrophile and makes a bond
with DNA and damages it), nitrosamines, ethylene oxide
- Use in the US: male lung cancer graph is exactly 20 years correlated to
cigarette consumption graph, female curve is much later as cigarettes
were only advertised to men and so in the 40s and 50s they changed their
marketing to appeal to women (Mommy it’s good for you)
- Diet and obesity: strong correlation, cooking for safety and flavour but it also
generates some nasty materials (similar to tobacco), careful not to overcook it,
food preparation creates carcinogens, beneficial foods protect us (fruits and
vegetables- very good for you, they contain foods that stimulate hydrolase 30
production to protect against DNA mutations, they also contain fiber (cellulose)
which promotes the passage of waste), there has been an increase in average
size of people living in 2017 vs 1975, obesity increases your risk for everything,
changes in eating habits (adds fat to processed food to improve flavor), changes
in portion size (much larger)
- Viruses (can’t control): responsible for about 15% of cancer death, high risk
viruses target p53 (apoptosis), when viruses infect your body they tend to be on
the inside and not the outside and they dramatically increase risk for getting
cancer, Guardasil for HPV induced cervical cancer (vaccine against virus that
transmits the cancer),
 - Alcohol: excess alcohol increases cancer risk, acetaldehyde is carcinogenic (very
powerful electrophile), see saw effect for risk
- Physical activity: increasing overall ability of your body decreases risk of getting
cancer, people with less than a high school education have a higher risk of
getting cancer
- UV Light: induces skin cancer, more common type in Canada, rarely fatal
- Environmental exposure: split between man-made and nature, strongest
carcinogens occur naturally (aflatoxin- in peanut butter)
- Medical procedures: x-rays and chemo (very powerful carcinogen)
- Treatment
- Very difficult to target selectively
- Abnormal human proteins (junk protein): non-functional enzymes,
nonfunctional protein
- Poor drug targets - drugs can block protein function, cannot restore
protein function
- Cancer cells are human cells
- Normal cells have 23000 genes
- Only 8-10 are changed in a cancer cell (changes very small, drug has to
“know” which cell to target)
- Major difference is cell division (cancer drugs are strong poisons, cancer
drugs target cell division, fast growing cells are killed first), not necessarily
targeting cancer cells, only targets ones that grow faster
- Strategy for chemotherapy
- Kill the cancer faster than you kill the patient
- Side effects are guaranteed
- Side effects are severe (death, cancer, extreme nausea, vomiting, hair
loss, immune suppression, sterility)
- Cancer drugs
- Nitrogen mustards in WW1: destroys tissue, designed to hurt the enemy in the
war, liberty ship was sunk and the mustard gas it was containing killed several
hundred servicemen when it exploded
- Survivors had fewer white blood cells
- Mustard gas becomes chemically linked to DNA, this changes it and leads
to damage or even death in certain situations
- Mustine was the first cancer drug, they changed the sulfur in the
mustard gas to a nitrogen and this made it a slower chemical reaction,
gave them a selectivity between normal cells and fast growing cells
- Sometimes the cells cannot repair themselves and now you’ve introduced
a mutation which can lead to cancer or cell death
- Cisplatin
- Effects on electric fields on bacteria, generated chemicals that stopped
bacterial growth (grow but would never divide)
- Current and oxygen corroded the electrode (caused the chemical to be
converted to Peyrone’s salt, damaged DNA in fast growing cells)
 - First synthesized in 1845, inhibition of cell division, anticancer actibity
discovered, approved for human use (1978), today is used in 40-80% of
all cancer patients 32
- It moves in and out of normal cells, the inactive version can move in and
out but when it is toxic it can’t get out which makes it very useful
- Taxol
- USDA searches for new poisons (poisons can be medications)
- Yew bark extract found to be cytotoxic (kills cancer cells)
- Taxol identified as a toxic substance (in the bark)
- Effective against breast cancer (30%)
- Impossible to make a synthetic version (complex molecule)
- Manufacture form yew trees (13000 kg of bark gave 1 kg of taxol), north
American demands 360000 trees per year
- Clear-cutting the entire pacific north west would only give a 5 year supply
of the drug, what do you do about it? Trees or people?
- Taxus baccata is the European yew, semi synthesis of taxol and
produces it in a renewable fashion (from the tree’s needles), can extract
the complex part from the needles and synthesize the rest
- Robert Holton, instead of publishing his research, made a bunch of
money because he made patents
- Taxol now manufactured using cell cultures (plant cells suspended in the
growth medium, genetically modified to maximize production)

HIV Article
- In 2007, a campaign advertisement for the former mayor if NYC Rudy Giuliani said that
he had prostate cancer 5 or 6 years ago and compared his chances of surviving in the
- US → 82% to that of England→ 44% under socialized medicine
- Giuliani used these stats to argue that NYC is the best - this was a mistake
- In 1938 in World Brain (Methuen & Co.), English writer H. G. Wells argues that the
average citizen is taught reading and writing but not statistical thinking
- Misconceptions easily spread to the public
- Illusion of certainty in medicine
- Easily susceptible;e to political and commercial manipulation
- Result can be serious damage to physical and emotional wellbeing
- Treatment based on an ethic of personal trust as a posed to quantitative facts
- Facts were dismissed as impersonal or irrelevant to the individual
- Many doctors rely on intuition and faith rather than even asking for
data to analyze
- Much of the public harbours illusionary certainty about the reliability of screening tests
- Unsophisttacted patients and their doctors tend to wildly overestimate the
benefits of screening tests and are blind to their harm
- Ex. Mammography reduces the risk of a woman in her 50s dying from
breast cancer from about five to four in 1,000 over some 13 years, but 60
 percent of a random sample of U.S. women believed the benefit to be 80
times as high.
- A modern citizen in a technological society faces a bewildering array of medical
decisions
- If people want to make informed decisions, they need to understand health
statistics.
- In particular, they need to understand the difference between absolute and
relative risks and how to use natural frequencies to infer the true chances of
disease from a positive test result.
- Individuals should also know to trust mortality rates over five-year survival
statistics when evaluating screening tests that look for disease in healthy people.
- The practice of presenting health information in opaque forms (hard to understand) that
erroneously (incorrect way) suggest big benefits and small harms from interventions (but
smt it can be the opposite if you intervene it might cause smth bigger)
- But some citizens do not understand those stats so they refer to their mindset
and environment which can cause wrong influences and harm them and smt to
get the satisfaction of their feelings.
- Ex: covid-19 vaccine
- A few solutions to make a better understanding of those stats in med.
- 1. we argue that medical journals, the media and others should communicate risk
in more easily understood forms
- 2. we recommend introducing young children to statistical thinking and teaching
statistics as a way of solving real-world problems rather than as a purely
mathematical discipline.
- Trust your doctor? , treatment was based on an ethic of personal trust as
opposed to quantitative facts, which were dismissed as impersonal or irrelevant
to the individual
- Even today many doctors think of themselves as artists, relying more on
intuition and faith in their own judgment than on numbers many patients
prefer to trust their doctors rather than even asking for data to analyze.
- Ex: a 2008 unpublished survey by one of us (Gigerenzer) and his
colleagues, two-thirds of more than 100 American economists said
they had not weighed any pros and cons of getting a prostate
cancer screening test but simply followed their doctor’s
recommendation
- Individuals often shy away from statistics because they have an emotional need
for certainty ** when we arent certain we’re gonna use our emotional thoughts to
lead us of making a decision or certainty → concluded by tests with cancer and
HIV patients (. Much of the public harbors illusory certainty about the reliability of
tests such as those for cancers and HIV, suggests a survey Gigerenzer
conducted in 2006. )
- Statistically unsophisticated patients and their doctors tend to wildly overestimate
the benefits of screening tests and are blind to their harms.
 - Ex: mammography reduces the risk of a woman in her 50s dying from
breast cancer from about five to four in 1,000 over some 13 years, but 60
percent of a random sample of U.S. women believed the benefi t to be 80
times as high
- Americans are similarly overenthusiastic about total-body computed
tomographic scans: in a random sample of 500 Americans, nearly three
quarters said they would prefer a free total-body CT scan to $1,000 in
cash But the organizations dont offer those because they will penilized
since those ctscan are harmful if too many of them.
- Stats help ppl understand the outcomes of some medications etc
- Ex: Should a pregnant woman undergo prenatal screening for chromosomal
anomalies at age 35?
- Ex2: Should parents send their teenage daughters to be vaccinated against
human papillomavirus, to protect them against cervical cancer, despite a few
reports that the vaccine Gardasil could lead to paralysis
- It’s important people understand the probability of the outcome of the exposed group and
and how to use natural frequencies to infer the true chances of disease from a positive
test result.
- Individuals also should know to trust mortality rates over five-year survival
statistics when evaluating screening tests, which look for disease in healthy
people. We deal with each of these issues in turn
- Absolute Risks
- In 1995, the UK committee on safety of médecines discovered that
third-generation oral contraceptive pills increased blood clots in the legs or lungs
twofold
- That info passed by 190000 specialists and even the media. Ppl got
scared so women stopped taking the pill (cuz of babies) but 13K more
abortions the following year.
- For every abortion there was one extra brith including 800 girls under 16.
(abortions and pregnancies are associated with an increased risk of
thrombosis that exceeds that of the third-generation pills)
- BUT if it could have been avoided if the data was put there correctly
which was 1 in 7000 women who took the second-gen. pill had a blood
clot but in third gen it increased to 2 in 7000
- The absolute risk was the 1 in 7K even though the relative risk increase
was 100%
- Absolute risks are typically small number and relative changes tend to look big—
particularly when the base rate is low.
- “Absolute risks help put into perspective how much benefit an individual is
likely to have from a treatment or prevention. The relative risk can help us
find disparities, like if one group is having better outcomes than another.”
- So the relative risk is a comparison between two groups In this case 2nd gen. and
3rd gen. And absolute risk is the number of ppl experiencing it in a large
population like 1 in 7K
- So most ppl prefer to present tests and info in the relative risk “reduction”?
- Ex. In a 2007 review of experimental studies, for example, psychologist
Judith Covey of the University of Durham in England found that when the
benefit of a drug was presented in the form of relative risk reduction, 91
percent of Danish general practitioners would recommend it to their
patients. But when given the absolute risk reduction, only 63 percent
would recommend the same drug Brochures, news etc prefer it in the
relative change cuz big numbers attract the ppl. But it can be bad smt too
- Ex: HRT (hormone replacement therapy o ig the replacement of a
hormone) “has been proven to protect women against colorectal cancer
(by up to more than 50 percent),” whereas the risk of breast cancer “may
possibly increase by 0.6 percent (six in 1,000)”. The data revealed that
50% is the absolute number which is less than 6 in 1000→ HRT produces
more case of cancer then it prevents
- But in 2003 study, 60 to 80 women concluded the exact opposite
from the leaflet (the news thing)
- Absolute risks are more informative since they take account info. About background
rates Given the absolute risks a person can derive the relative risk but not vice versa.
- After all, a relative risk reduction of 50 percent could describe either a substantial
mortality reduction from 200 to 100 in 10,000 patients or a much smaller one
from two to one in 10,000 patients.
- Randomized trials provide some of the best information in med. but unless the results
are reported adequately, people will not be able to assess them

- FAST FACTS
- Know Your Numbers
- 1>> Statistical illiteracy is rooted not in intellectual deficits but in the
doctor-patient relationship, the illusion of certainty in medicine, and the practice
of presenting health information in opaque forms that erroneously suggest big
benefits and small harms from interventions.
- 2>> Without understanding the numbers, citizens are susceptible to political and
commercial manipulation of their anxieties and hopes. The result can be serious
damage to physical health and emotional well-being.
- 3>> People need to understand the difference between absolute and relative
risks and how to use natural frequencies to infer the true chances of disease from
a positive test result. Individuals also should know to trust mortality rates over
five-year survival statistics when evaluating screening tests.
- 4>> To boost statistical literacy, we also recommend introducing young children
to statistical thinking and teaching statistics in school as a way of solving
real-world predicaments rather than as a purely mathematical discipline.
- Living with uncertainty
 - Risks is inevitable so in no matter what you do there will be risks and there is
certain questions one will ask when it comes to certain situations
- People end to take tests and treatments to apply a need of certainty but again it
goes back to being a risk sinc its never certain
- 1. Risk of what? Its to understand the outcome the risk refers too for
exemple is it the risk of dying froma disease or getting a dieases, etc
- 2. What is the time frame? So is it in the next 10 yrs or lifetime risks? Its
better to know a time frame snce risks change overtime so that time
frame can either decrease that risk (action can be taken) or it worsens
- 3. How big is the risk? Since there is no zero risk its measured in size in
absolute terms for exemple 13 out of 1000 50 yr old female smokers will
die of a heart disease within 10 yrs or comparing it to another risk
- Ex. a 50 yr old female smoker has the same chance of dying of
lung cancer as of heart disease in the next 10 yrs and these
chances are 7 times higher then dying in a car accident.
- 4. Does the risk apply to me? Find out if the risk is based on studies of
people like you- like same sex, health issues.
- 5. What are the harms of “finding out”? Smt they can be false alarms
when it comes to screening and it can cause useless anxiety and even
useless treatments
- Natural Frequencies (a positive mammogram may mean a mere one in 10 chance of
cancer)
- Research was made about breast cancer in 2007 and here’s the research A
women who tested positive in a mammogram asks her doctor if she has breast
cancer or the disease. Pursuing the education/questions, he asked 160
practitioners to answer that question based on given info:
- The probability that a woman has breast cancer (prevalence) is 1 percent.
- If a woman has breast cancer, the probability that she tests
positive (sensitivity) is 90 percent.
- If a woman does not have breast cancer, the probability that she
nonetheless tests positive (false-positive rate) is 9 percent
- Here are some answers
- A. The probability that she has breast cancer is about 81 percent.
- B. Out of 10 women with a positive mammogram, about nine have
breast cancer.
- C. Out of 10 women with a positive mammogram, about one has
breast cancer.
- D. The probability that she has breast cancer is about 1 percent
- Positive mammograms can cause considerable anxiety
- A positive result would be far less alarming; however, if women knew that,
it might mean a mere 10 percent chance of having breast cancer. In 10
years of testing, one in every two women without cancer can expect at
least one positive mammogram
 - Out of all of them the best answer is C why cuz all the other ones
are falsely alarming
- Only 21% answered the best Answer which is not good since it
can cause anxiety to the patient's
- Many physicians do not know the probabilities that a person has any disease given a
positive screening test that is—the positive predictive value of that test.
- Nor can they estimate it from conditional probabilities such as the test’s
sensitivity (the probability of testing positive in the presence of the disease) and
false positive rate.
- So technically they cant acc know the true diagnosis since positive tests can smt
be false positive rate which adds on to the stats of “positive” of the disease. And
obv they cant assume who’s gonna be positive and who’s gonna be negative
- All of that creates fears in women of mammogram as in they can’t trust it anymore etc
cuz it gave them false alarms of diseases.
- The stats need to be presented in a simple way to be easy to understand as well for
exemple:
- Ten out of every 1,000 women have breast cancer.
- Of these 10 women with breast cancer, nine test positive.
- Of the 990 women without cancer, about 89 nonetheless test positive
- Even tho 98% tested positive it's, only 9 that acc has it and the physicians (87%) were
taught how to read it and from there the Answer C came to be the best.

ITS IMPORTANT TO INFORM PATIENTS NO TEST IS PERFECT

**the solution was found to redo a test**

- There has been similar situations as well like HIV in 1987

- Which ended in men committing suicide
- the base rate in a population determines the meaning of a positive test
result
- Forecasting Infections
- Natural frequencies gives us a better math of probabilities, its less complicated
- Mortality Matters
- When Giuliani applied for president he was using stats but he used it wrong
instead it was a large difference between the countries instead of the better
treatment - that means US prob have better treatment or just fewer people who
have it, etc
- To understand why, imagine a group of prostate cancer patients
diagnosed (by their symptoms) at age 67 in the U.K., all of whom die at
70. Each survived only three years, so the 5 yr survival is 0%
- So now imagine in the US, where doctors detect most prostate cancer by
screening for prostate-specific antigens (PSA). (The PSA test is not
routinely used in Britain.) These U.S. patients are diagnosed earlier, at
age 60, but they all die at age 70. All have now survived ten years, and
thus their five-year survival rate is 100 percent.
 - Even though the survival rate has changed dramatically. They still died.
The only diff it was diagnosed earlier, which can help them survive longer.
- THE PROBLEM IS
- it can be overdiagnosis so they can see, but it won't develop into anything, and it
can obv scare the person
- Ex: 1,000 men with progressive cancer do not undergo screening. After
five years, 440 are still alive, which results in a survival rate of 44 percent.
- Meanwhile, in another population of men, PSA screening detects
1,000 people with progressive cancer and 2,000 people with
nonprogressive cancer (who by definition, will not die of cancer in
five years).
- These nonprogressive cases are now added to the 440 who survived progressive
cancer, which inflates the survival rate to 81 percent.
- But the amount of ppl who die did not change at all.
- So whenever the new PSA was developed it increased more of diagnosis
in cancer then Britain so a it looked bad a bit yk so thsts why ppl survived
it more
- In the 5 year since more were diagnoses if that makes sense 91% US vs 71%
UK but the death is similar PSA test has needlessly flagged prostate cancer in
many American men, resulting in a lot of unnecessary surgery and radiation
treatment, which often leads to impotence or incontinence
- The 5 year survival rate is useless cuz it doesn’t predict anything since they still
die in a way, they still get diagnosed, etc and it can acc worry some ppl
- For exemple UK will move to US thinking its gonna help them or cure
them but they still fall into the 5 yr survival rate/death rate.
- They decided to change it to mortality rates instead of 5 yr since it wasn’t
enough of gap to know the full diagnosis In the end it doesn’t matter they
will stil die of the disease (cancer in that case)
- People commonly regard screening as a safeguard for their health, even if an illness is
rare.
- But additional testing may lead to unnecessary medical interventions that can
result in harm, whigh means theres nothing safe about this strategy.
- The equipment can be harmful like the radiation etc
- Solving problems
- It would be better if they use absolute risk instead of relative
- it would be better for natural frequencies instead of conditional probabilities
- Mortality rates instead of 5 yr survival rate
- Teach the young about science
- Now they teach the stats at school and the health too about the drugs
- The HIV exemple of the women who lost her job and jusit was positive
DOESNT mean she acc was cuz when she did it again and it was
negative If she was taught stats she would have known better lol