CHEM 183 Midterm Review PDF

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Drug History A CHEM 180

Lecture

The Year in New Drugs - 2020 34 drugs have been approved in 2020 On average over the last decade 3040 drugs have been approved per year

Recent Issues Guy who raised price of Daraprim from 13.5 to 750 Sacklers vs. States: the Sackler family who owned Purdue Pharma gave up the company because they pushed opioids on doctors which has resulted in the opioid crisis J&J Baby powder causes cancer

Media False misconception that in the good old days there weren't that many health problems Medical practice back then were not exactly effective Old uroscopy wheels diagnosed problems by urine colour

Life Expectancy Over 80 years on average in most modern countries Maternal mortality has improved thanks to the creation of antibiotics 2 years for women 2 years for men World average is 72 years Oldest person in history lived to 122 years old Currently oldest person is 113 years old 1918 Pandemic Influenza/Bacterial Pneumonia) created a dip in life expectancy 550 000 died in the US, atm COVID has had 1/3 that many deaths Killed 3050 million across the world, atm COVID has almost killed 1 million

Drug History B CHEM 180

Lecture

Eradication of Disease - Through Non-Drug and Drug Methods Smallpox Eradicated through vaccination Queen Mary 2 died of smallpox WHO thinks vaccines have saved 40 million ppl

Polio Eradicated in 1991 in the Americas

Leprosy Now known as Hansens disease Solved by multi-drug therapy and anti-leprosy agents Around 200k/year down from 12 million in the 80s

Guinea Worm Disease Prevalent in hot and humid area of Africa, carried by a flea

People drink water with the flea in it and the disease appears 1 year later Can be prevented by filtering water through cheesecloth 3.5 mil cases in 1986 and 14 in 2020

Chagas Disease Introduced in the body by a parasite Symptoms occur 1020 years after infection Treated with medications These parasite/bugs are increasing due to climate change Has been reduced to 8 mil cases from 16 mil

What is a drug? A chemical agent that effects living matter, any preparation which in a persons mind has a beneficial effect on their well-being

History highlights The Sumerians had 16 beer recipes (will be on exam)

Egyptian tablet depicts a poppy, the oldest pain killer (opium/morphine) Morphine has been known for 200 years, discovered by Friedrich Serturner Hippocrates wrote the hippocratic oath, and made an effort to exclude superstition in his work His cures included: Using poppy juice to sooth crying babies LOL no shit they're opioids) Night blindness can be cured by Ox Liver Galen Born

Monks of the middle ages helped further the science of the age because they made alcohol and medicine Mandrake has hallucinogenic properties and looks like a human when pulled out of the ground Blood transfusions were attempted but usually failed bc they didn't know about compatibility and bacterial infections

Testing - FDA Clinical Trials, The "Gold Standard" Gold standard is a double blind study, but the first clinical trials were described in the Bible.

Dioscorides He depicted many plants such as opium, strawberry, bull rush etc and gave descriptions and the effects that they had.

Pharmakon The word pharmakon/pharmakeutes means drug in greek.

Paracelcus Lived until 50 y/o in the Medieval times He spoke against in the doctrine of humors which taught that 4 basic elements comprised all matter: fire, water, air and earth. Advocated for the scientific method and chemical treatments for disease

Ex. Of all drugs are poison.... applies to aspirin bc it can help headaches and heart attack but a big dose can be lethal

Drug History C CHEM 180

Lecture

Jakob Bhome Shoemaker but had a thesis of "the signature of all things"

The signature of all things implies that god has marked everything he created with a sign. The sign was an indication of the purpose of their creation

Ex. Walnuts look like brains and they're good for the brain Ex. Carrots look like eyes and they're good for the eyes Bezoar:

William Withering 1700s, discovered Foxglove which was thought to improve congestive heart failure (aka Dropsy) His paper on its side effects and effectiveness is regarded as one of the first scientific papers Erasmus Darwin was a competitor of Withering and insisted his son get credit for the discovery He published a work on the botanical arrangement of all vegetables, a real plant expert

Result Reporting - Journals First journal was published in 1797, discussed the Plague of Athens, remarks on manure

Sir William Osler 6413966 Teacher at McGill in 1874, went to John Hopkins Propagated the idea of medical theaters so everyone see's the examination table when the teacher is demonstrating Has a journal named after him at JH and Lib at McGill Controversy: Osler said that old people were useless and should be chloroformed (on exam) William Osler

https://en.wikipedia.org/wiki/William_Osler#Controversy

Osler goes viral: "The Fixed Period" revisited

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413966/

Said that desire to study medicine is the difference between man and animals but theres evidence of animals (monkeys) eating certain plants when they're sick

Malaria A parasitic disease that affects 50% of children in Africa it affects the brain Slows economic growth of Africa(kids) by over 1% per year, 1 million deaths per year The early cure for malaria was Quinine. 6% of the bark of the plant are alkaloids and 70% of Quinine comes from the bark DDT was used to get rid of malaria mosquitoes therefore reducing transmission of the disease. DDT is thought to be toxic but it is effective at killing the bugs. The problem with DDT is that it affects birds. Interferes with their ability to have strong egg shells so when they sat on the egg they'd break. This

reduced bird populations. Not harmful to humans tho

Joseph Lister Discovered phenol, which allowed women to better survive child birth Phenol killed bacteria, but he later realized that just washing hands would be sufficient and prevent the spread of infection and sepsis. Studied with Roddick of Roddick Gates Listerine was named after him and the active ingredient in it was Thymol (antiseptic) What was listerine used for in the 1950s? Dandruff control Bad breath

Drug History D CHEM 180

Lecture

Patent Medicines (1850s-1906) + FDA Regulations About 110120 years ago people started trying to discover which compounds actually cured disease. Aspirin was discovered that way.

1938 - The Federal Food, Drug and Comestics Act was made law. It introduced  Proof of safety  Regulations for cosmetics  Food standards be set Amendment to the act set out that there would be 2 categories of sale for drugs: 1. OTC and 2. Prescription Prior to this amendment prescriptions were only needed for narcotics and cocaine

Classic Problems in Drug Testing When a drug does something good in one hand but bad in testing

ex. Thalidomide - helped morning sickness in pregnant women but caused birth defects (showed us German singer and guy who can play guitar with his toes) Found out that it was not tested on women by Frances Kelsey, a McGill grad and thats why they didn't know if would cause birth defects FDA thinks it can be used for other treatments but still isnt legal

New Drugs Takes 1015 years to bring to market

Roughly takes $2.5 B for 1 drug over 12 years of development

Kaplan-Meier Plot Standard plot used by drug scientists to discover if its useful or not Ex. BiDil, which blended 2 drugs together and it was super complicated to test

New Drug Origins  Dart frogs

 Periwinkle - anti-cancer  Native medications through Shaman/Extracting from plants  Molecular modeling - modeling the compound itself or the organic compound on a screen, put it in 3D bla bla bla  Using AI to predict the effectiveness of drugs  Fragment Based Lead Discovery - putting together sections of atoms that are effective in hopes to create a really effective atom

Sale of Drugs Cancer is a big reason for the development of drugs

Big companies in pharm $ value in billions)

Sales around the world (still accurate)

This equation applies to any % increase

Answer is 4.

FDA Drug Cataloguing By chemical type:  New molecular entity  New derivative  New formulation (old drug in a skin patch)  New combo 2 drugs not marketed before)  Already marketed drug product but the patents expired  New use for a drug product  Excipients (fillers, binders, antioxidants, pigments...)

Excipients are the materials in the pill that is not medicine. There are 40 categories of this

Other problems Side effects Placebo effect

COVID A CHEM 180

Lecture

Epidemics and Pandemics Epidemic occurs when an infectious disease spreads rapidly to many people.

Pandemic affects a wider geographical area, often worldwide and infects a greater number of people than an epidemic

Past Epidemics Typhus Caused by a bacteria called rickettsia... and is spread to ppl through contact with ppl infected by body lice Discovered by Charles Nicolle and Henry Rickett Could be prevented by DDT, an insecticide Big epidemic of typhus in the Warsaw Ghetto and doctors slowed its spread by isolating the sick people

SARS Was a severe acute respiratory syndrome Killed 800 ppl

Past Pandemics Black Plague AKA the bubonic plague and killed 1/3 of the european population Named after the swelling of the lymph glands and these swellings were called buboes Caused by bacteria yersinia... which was carried by fleas that lived on rats Officials in Venice controlled the spread by not allowing sailors off their ships immediately until it was certain they weren't sick or carrying the disease Also believed people got sick because they sinned and would flagellate themselves Cholera Dr. John Snow took a map and marked all the houses that were affected by cholera and what he found was that these houses all got their water from a pump that was being contaminated by sewage Cholera is an acute, diarrheal illness caused by infection of the intestine with the bacteria Vibrio ... and is spread by the ingestion of contaminated food or water HIV The human immunodeficiency virus, attacks cells that help the body fight infection No vaccine for it

1919: Spanish Flu Basically COVID but way back in the day

2550 million deaths Dr. Thomas Tuttle Recommended:  Keep away from crowds  Go outside  Walk instead of public transit  Use lysol His instructions for spanish flu are very similar to todays recommendations but not everyone believed him

COVID-19 End of december we start hearing about it Due to wet markets where they sell live animals and butcher them on the floor so the floor has to be washed all they time They sell all these random animals bc TCM believes that certain foods and animal byproducts have unique health effects China is being criticized because they weren't fully transparent with the rest of the world Cause Bat poop contaminates Pangolin which is a delicacy in China and so they ate infected pangolins 3000 in COVID video 1 explains the chem of the virus

Testing Several kinds  Nucleic acid test: detets the virus' genetic material to confirm that a person is currently infected

 Only reliable about a week after the virus has entered the body but even after that theres 20% false positives  Antigen test: detects fragments of viral protein to confirm if someone is infected  Antibody test: tells you if you have been exposed to the virus in the past  Helpful for information for epidemiologists Antigen vs. Antibody

Antigen: substance that can induce an immune response

Antibody: proteins that can recognize and bing to antigens

Accuracy Sensitivity: correct production of positive results Specificity: correct production of negative results

Transmission RT is a measure of how fast the disease in spreading. A value higher than one means infections are increasing, lower than one means they're decreasing

Air ventilation is so important in the reduction of the transmission of the virus

Surface Transmission Mass disinfectant: calcium hypochlorite BUT its not very effective UV light is a good disinfectant for phones and surfaces Cooper is good to reduce transmission, has an antimicrobial effect Implementing cooper door knobs bc they have such a high touch rate

COVID B CHEM 180

Lecture

Prevention Techniques:  Taking temperature  Social distancing (time of exposure is important)  Wearing a mask (prevents for user and others)

Treatments  Bunch of quackery  Lavender  Silver  Pendant  Injecting disinfectant  Copper zap  Herbal supplements  "Boosting immune system"

 Your body is made up of cells and the immune system is a very complex system and yes healthier people might have better ones but no foods actually boost it  Questionable ones  Hydroxychloroquine  Oleandrin  Acai berry  Quercetin (but they're lab trials not randomized human trials)  Cannabis  Zinc  Vitamin C  Significant Evidence  Dexamethasone (steroid with anti-inflammatory properties will reduce length of stay in hospital)  Remdesivir (fewer days in hospitals)  Anticoagulants (aspirin) to reduce micro blot clots caused by COVID  Vitamin D at 1000 IU (plays a role in many bodily functions, especially the immune system)

 Convalescent plasma (not a new idea but it seems very promising, but its not recommended by the gov't)

 Monoclonal antibody

Vaccine We want to force the body to produce antibodies that will interact with the virus and then neutralize the virus

Types:  We want to inject an attenuated of inactivated virus/weakened version of SARSCoV2  Important to know the genome of the virus bc with the sequence of the virus, a spike protein can be made synthetically in a test tube This will generate subunit protein vaccines that contains the spike protein

3. Viral Vector Vaccines contain a different virus that is genetically engineered to carry the gene for the SARSCoV2 Spike Protein 4. Nucleic Acid Vaccines contain DNA or RNA with genes for the SARSCoV2 Spike Protein delivered into cells which will force the body to make antibodies

Worries that vaccine generation is being sped through and the phases are being skipped

Phase 1 and 2 can be skipped because side effects are felt very quickly...