Paikon noticed me im going to fucking ace this test

Question 1

What is the first step of drug discovery?

Answer 1

Testing toxicity and dosage with various perspectives to see if risks are all necessary

Question 2

What is metastatic cancer

Answer 2

Cancer that leaves the origin through lymph or blood and grows

Question 3

What are some problems and benefits of immunotherapy?

Answer 3

It didn’t work for many patients but can get rid of a tumor completely. Immunotherapy is not like chemo, the cells will stay in your body after treatment

Question 4

What are standard treatments for leukemia?

Answer 4

Bone marrow transplant and chemo

Question 5

How does re-engineering the immune system work for Bo?

Answer 5

Remove T-cells by aphoresis, leukemia cells are marked on the surface with proteins, which is used by modified T-cells to recognize and attach to the proteins on leukemia. These new cells are called chimeric antigen t-cells, or CAR-T

Question 6

How are CAR-t cells similar to normal cells?

Answer 6

They divide in the body. However, they also consume leukemia and you end up with a shit ton

Question 7

What is a side effect of destroying leukemia in the lungs and what was this solved by?

Answer 7

It compromises the lungs and this was solved by steroids that temporarily supress immune cells but may also stop the modified ones

Question 8

What is leukemia

Answer 8

A cancer that originates from interior of bones that produce blood (bone marrow). It is essentially cancer of blood cells, includes lymphatic system

Question 9

What does getting sick from the CAR-t treatment indicate?

Answer 9

That immune cells are fighting infection, releasing cytokines (proteins that fight infection) and that the treatment is still alive. This is called a cytokine storm, and it can be dangerous with flu-like symptoms, fever, low blood pressure

Question 10

What is remission? How is it determined in Bo’s case

Answer 10

All leukemia cells are gone, even one cell could multiply and overtake bone marrow. It is determined for Bo with a bone marrow biopsy

Question 11

How was melanoma attempted to be cured?

Answer 11

They attempted to extract immune cells from tumors and to grow them into billions. Immunotherapy is high risk high reward. Inside the tumors are cells that can cure cancer

Question 12

What is TIL and how is it used to cure cancer

Answer 12

Tumor infiltrating lymphocytes, which are from tumor. They are grown into millions and infused back. The more inflamed, the better. The most active TIL are infused back. TIL are a type of white blood cell. However, in the case tumors did not shrink from TIL

Question 13

What is Job’s Syndrome caused by and what effects does it have

Answer 13

Single mutation causes inability to heal wounds, staph, yeast. The immune system is not very well understood actually

Question 14

Why is lung damage threatening with Job’s

Answer 14

Pneumonia caused a large cyst in the lung which causes risk of infection even with antibiotics.

Question 15

How does a bone marrow transplant help Job’s

Answer 15

It creates a new immune system that makes red and white blood cells, and if the transplant is early, the lung can be remodelled, healed, and no need to remove. This is because Job’s is not limited to the immune system

Question 16

Where does chemo originate from?

Answer 16

Mustard gas in WW1, it attacked bone marrow and killed white blood cells.

Question 17

What was done to prepare for bone marrow transplant for Job’s, what were the complications

Answer 17

Chemo, which caused white blood cell inflammation that was solved by steroids and breathing treatment.

Question 18

How did the bone marrow transplant help Lucy’s recovery of her lung

Answer 18

Doctors took her infected lung out because you will not get rid of infection unless you remove root of problem. Removing cavity and having a healed lung was due to the transplant giving her new immune system

Question 19

What is the problem with using chemo on sickle cell disease

Answer 19

Chemo and radiation are needed to kill bone marrow, but you cannot do this without normal organ function. The goal is to get bone marrow in without too much toxicity. Chemo cannot be done with damage from sickle cell. So you only remove part of bone marrow

Question 20

Why does sickle cell cause pain

Answer 20

Cells don’t get oxygen, and they die. Pain indicates organ damage.

Question 21

How did they prep for sickle cell bone marrow transplant

Answer 21

Low doses of radiation to eliminate bone marrow. This destroys the immune system temporrarily and it is based on how well patients tolerate

Question 22

What does chemo do for bone marrow transplant?

Answer 22

It prevents original red blood cells from recovering so quickly and taking over the immune system again. It kills fast growing cells. They are powerful and old drugs that will kill healthy cells

Question 23

What are first in class and me too drugs

Answer 23

First in class are the first to target certain proteins. Mee too drugs target same protein but with a different way or method.

Question 24

What is in the preclinical testing/discovery phase

Answer 24

It in the lab with animal testing, can be in universities and takes about 6.5 years. It tests safety, finds suitable formulas with a shit ton of molecules (biological activity). 5000 molecules evaluated

Question 25

How many compounds after filing IND at the FDA

Answer 25

5

Question 26

What is on the WHO list of essential medicines

Answer 26

Commonn diseases that are serious have drugs. Effective, safe, and cost effective drugs

Question 27

What is a drug target

Answer 27

Usually a protein the drug binds to inactivating it (could be other molecules, but rarer)

Question 28

What is tested in phase 1

Answer 28

Safety, not effectiveness, with 2 animal species, 1 rodent one non rodent. Start low, 100 times less and you need consent. Also testing dosage

Question 29

What is the surveyed population for phase 2

Answer 29

People with certain illnesses and of a smaller age range. This tests preliminary efficacy, and clinical and control groups are tested to prevent expected effect. It also looks for side effects aside from effectiveness

Question 30

What is tested in phase 3 and how many people

Answer 30

effectiveness, adverse reactions from long term use. you need 1000-5000 people

Question 31

How was the first vaccine developed

Answer 31

Cowpox being used to protect against smallpox

Question 32

WHat was the difference between polypharmacy and monopharmacy

Answer 32

Polypharmacy was by Galen and co who believed disease is internal and made a shit ton of complicated cures. Monotherapy is in alchemy, where you make minerals and metals. Paracelsus founded monotherapy

Question 33

What are the plants that actually have medicinal value

Answer 33

Opium, quinine, and digitalis. Respectively painkiller, malaria, and heart failure

Question 34

What was the first true drug

Answer 34

Morphine

Question 35

How does the dye industry contribute to drug discovery

Answer 35

Arsenic was used in dye and led to the discovery of atoxyl. It followed atom and matter theory’s development, which allowed for the analysis of atoxyl’s structure

Question 36

How is modern and previous drug discovery different

Answer 36

Modern drug discovery linked chemical structure and biological properties. Back then, only the dye industry made new compounds. Intermediates can be tailored to deal with different diseases

Question 37

What does malignant mean in cancer

Answer 37

Can get to other body parts

Question 38

What are two ways to organize cancer

Answer 38

By tissue or organ of origin, or mechanism of growth. Different location but same mechanism could be treated in the same way

Question 39

What causes mutations and what do mutations cause

Answer 39

DNA copying mistakes or damage from UV, chemicals, genetics, smoking, viruses. Causes RNA problems and protein problems

Question 40

What are inherited and acquired mutations, where does cancer come from

Answer 40

Acquired mutations cause most cancer. Inherited mutations are in gametes, acquired not passed down.

Question 41

What does targeted therapy in cancer try to do? What is an example

Answer 41

Herceptin, it binds to cancer only and stops the chain of signalling. It focuses on proteinns in cancerous cells. Targeted therapy is aimed at proteins in abundance in cancer cells and focuses drugs to type of cancer

Question 42

What are the two types of white blood cells, what do they do

Answer 42

Blood and lymphatic system. T-cells bind to foreign particles and eat it, B cells create antibodies that prevent surface mutation.

Question 43

How does cancer evade detection

Answer 43

Turns off immune system, can’t be seen by immune system, immune system deals differently

Question 44

Why are nonprotein targets rare

Answer 44

DNA and RNA are not potent (do not bind well). Lipids and fats too wiggly and flexible. Sugars and starches fuck with drug safety. Half of drugs work with proteins, half with receptors

Question 45

What are enzyme reactions? How do they interact with substrates

Answer 45

Amino acid structure of protein factory allow substrate to fit.

Question 46

What is pharmacodynamics

Answer 46

how drugs interact with targets, drugs are similar to ligands and stop normal behavior

Question 47

What is target identification

Answer 47

Finding proteins central to disease mechanism, which is different in healthy people

Question 48

What is the difference between genomics and genetics

Answer 48

Genomics is studying all genes and interactions between gene and environment. Genetics is about a single gene.

Question 49

What are genome wide association studies, example

Answer 49

Compare genomes of healthy and affected groups to see differences in chromosomes. Cancer genome studies compare sequenced tumors and metastasises

Question 50

What is the goal of target validation

Answer 50

To see if the protein matters to the mechanism, and does the loss of protein cause problems. They use model organisms as we are genomically very similar

Question 51

What is a SNP and how common

Answer 51

Single nucleotide polymorphism. We have a shit ton of them

Question 52

What is the difference between single gene disorders and multiple gene disorders. Name a few single gene disorders

Answer 52

Cystic fibrosis, sickle cell, taysacks. If you have the mutation, you have it fr. Multiple gene disorders have a genetic and environment interaction that increase risk as SNP amount increases

Question 53

What did organoids tell us about human brain tissue

Answer 53

That there was no need for feedback from other parts of the nervous system and uterus to develop neural tissue.

Question 54

How are brain waves formed? What is true about organoid brain wave, and what are the types of brain waves

Answer 54

Brain waves are formed from random firing of neurons, and can be detected bt EEGs. The organoid has delta waves, similar to newborn and deep sleep states. Alpha waves are when you fall asleep, beta waves are when you think hard

Question 55

Why are organoids not conscious? How many cells are there

Answer 55

Sea slug amount of cells. The reticular formation is used to wake up. Organoids need bigger structures to arouse into consciousness

Question 56

What drugs can be tested on organoids, how

Answer 56

Drugs that require analysis of brain activity, like Alzheimer’s and schizophrenia

Question 57

What is the importance of animal testing

Answer 57

You can reproduce cause of disease, and to create a computer model, you need basic knowledge of the disease. You can recreate diseases and test accordingly

Question 58

What is ALS and how is it inherited

Answer 58

A disease that begins in adulthood characterized by loss of motor neurons which cause paralysis and death if it gets to the lungs. It is sometimes genetic

Question 59

Explain ALS in terms of cell body activity

Answer 59

Proteins in cytoplasm reproduce incorrectly, may damage mitochondria and cause oxidative stress and DNA Repair problems. Also can cause neurotransmitter vescicles to not work and axon retraction

Question 60

What do oligodendrocytes do

Answer 60

Insulate axon to support motor neuron. Does not work in ALS

Question 61

What is the stone man syndrome

Answer 61

Disease caused by mutated gene with tumors in brainstem that cannot be removed. Chemo does not work

Question 62

How do people look for cures for stone man

Answer 62

Transplant tumors into mice. Mutant cells don’t respond to activin A, which inflame muscles

Question 63

Explain how altering genes of a model organism could help drug development

Answer 63

Focus on proteins as a result of altering that gene

Question 64

How are human cells used to test drugs?

Answer 64

Removing proteins to see respective effects/genetic engineering. Organoids can see cell types and interactions. Microphysiological systems allow you to have dedicated compartments

Question 65

What do you need to do before human research

Answer 65

Identify and validate targets, efficacy and safety of the drug must be confirmed

Question 66

What is translational medicine

Answer 66

Preclinical and mechanistic systems going to the clinic. Making diagnostic tests, drugs and therapies for a clinical impact

Question 67

What are the 3 R’s in animal research

Answer 67

Replacement (computer models, invertebrates). Reduction (less animals). Refinement (minimizing distress, better living environment).

Question 68

What is a xenograph

Answer 68

Putting human tumors into immunocompromised mice to measure efficacy of treatment

Question 69

What does mutant ACVR signalling do and what indicates an effective treatment in mice

Answer 69

It increases signalling, which is blocked selectively by drugs. If the tumors shrink and activity is lessened, then the treatment works

Question 70

What does the open field and light dark test say about mice behavior

Answer 70

Anxious mice hangs out in the dark part of light dark test, less anxious in the middle of open field

Question 71

What is COVID tested on?

Answer 71

Cell cultures, animals, people. ACE 2 allows virus to infect us with molecular handshake, mice with humanized protein lets us test

Question 72

How is thalidomide an example of drug development fuck ups

Answer 72

You need adequate info from animal tests, it caused limb formation problems. People thought placenta are barriers to block drug passage but not true

Question 73

How long does drug exposure for animal testing have to be

Answer 73

6 months to a year

Question 74

What is toxicity in cells

Answer 74

Death of cells in proportion, the unit is mg/kg to kill 50% of cells

Question 75

What is in vivo and in vitro

Answer 75

Respectively in living organism and in glass (lab, cell culture).

Question 76

What are to ways drugs can cause toxicity

Answer 76

Binding to receptor or to a new molecule which could be from drug metabolizing enzyme (metabolite, any substance produced during metabolism of drug)

Question 77

How is mutagenicity observed in bacteria

Answer 77

Bacteria need histadine, if there is a strain that grows without histadine, then it is mutated

Question 78

How do toxicologists check for toxicity

Answer 78

In every organ because design is unrelated to real effects. Cardiotoxicity causes heart problems which is the primary cause of drug recall.

Question 79

What is stem cell testing

Answer 79

Turns normal cells into embryo cells then brain liver and heart cells

Question 80

What are biomarkers of toxicity and indirect markers

Answer 80

Biomarkers of toxicity are things like liver enzymes in blood from burst cells. Indirect markers are characteristics that can be measured in the body objectively like blood glucose, blood oxygen

Question 81

What are ethics and values

Answer 81

Ethics determine moral duties and values of human conduct. Values are more specific, include justice nonmaleficience, beneficience, nonexploitation, respect, autonomy

Question 82

What did the nuremberg code and declaration of helsinki say

Answer 82

Respectively about sterilization, free will and filling in gaps of nuremberg code with stuff about risk-benefit

Question 83

What is clinical equipoise

Answer 83

Drugs might be better or worse for treatment, we don’t know. People need to know the drug may not help

Question 84

What is value in clinical research

Answer 84

To investigate important generalizable things with a good hypothesis, practical intervention. Communicate results. This is due to finite resources (including people) and nonexploitation

Question 85

What is scientific validity

Answer 85

Having a good design that’s practical with clean conduct and enough subjects

Question 86

What is fair subject selection

Answer 86

Exclusion and inclusion is reasonable, target different groups and don’t recruit based purely on ease. Speed is not as important as fairness

Question 87

What is favorable risk benefit ratio

Answer 87

Connecting benefit of people to community, risks in diagnosis and treatment. To communicate potential benefit. Benefits cannot be extraneous medical services and evaluate ratios of hazards and what hazards are. If no benefit, there needs to be societal benefit. (This emphasizes nonmaleficience, beneficience, nonexploitation)

Question 88

What does independent review do

Answer 88

Prevent inference of researcher’s interests. Research ethics board checks recruitment, consent, risk benefit, confidentiatlity, fairness, conflicts of interest

Question 89

What is informed consent and what ethical principles is it related to

Answer 89

Participation only when a study is in line with morals. Ethical principles include autonomy, knowing side effects, and quizzing people to see if they know their shit (people can say no even if they will die)

Question 90

What is an example of lack of respect for subjects

Answer 90

People using placebo for anti-vomiting med test, when placebo isn’t the status quo. They should recieve old and new drug and compare instead of having to suffer. They had rescue meds did not use them

Question 91

What does respect for subjects include

Answer 91

Info privacy, allowing subjects to change their mind, monitoring patients, acknowledge contributions

Question 92

Where do clinical trials happen and who is it by

Answer 92

At universities and hospitals or private organizations. It is sponsored by company making drugs. A doctor suprevises

Question 93

How to participate in clinical trials

Answer 93

Family doctors provide info, then phone interview with eligibility and includsion criteria. A screening visit to measure blood sugar and pressure, with a questionaire. Tell lifestyle and health changes, known risk benefit. If decide to join, can ask people who have been in trial

Question 94

How are phase 1 trials performed

Answer 94

Dosing guided by animal studies, then test in ascending order. A single dose first is called single ascending. Then you increase in amount. For multiple ascending, you take same dose on many days for long term effects. People are healthy unless drug is too risky, then cancer patients