Paikon noticed me im going to fucking ace this test Flashcards
What is the first step of drug discovery?
Testing toxicity and dosage with various perspectives to see if risks are all necessary
What is metastatic cancer
Cancer that leaves the origin through lymph or blood and grows
What are some problems and benefits of immunotherapy?
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
What are standard treatments for leukemia?
Bone marrow transplant and chemo
How does re-engineering the immune system work for Bo?
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
How are CAR-t cells similar to normal cells?
They divide in the body. However, they also consume leukemia and you end up with a shit ton
What is a side effect of destroying leukemia in the lungs and what was this solved by?
It compromises the lungs and this was solved by steroids that temporarily supress immune cells but may also stop the modified ones
What is leukemia
A cancer that originates from interior of bones that produce blood (bone marrow). It is essentially cancer of blood cells, includes lymphatic system
What does getting sick from the CAR-t treatment indicate?
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
What is remission? How is it determined in Bo’s case
All leukemia cells are gone, even one cell could multiply and overtake bone marrow. It is determined for Bo with a bone marrow biopsy
How was melanoma attempted to be cured?
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
What is TIL and how is it used to cure cancer
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
What is Job’s Syndrome caused by and what effects does it have
Single mutation causes inability to heal wounds, staph, yeast. The immune system is not very well understood actually
Why is lung damage threatening with Job’s
Pneumonia caused a large cyst in the lung which causes risk of infection even with antibiotics.
How does a bone marrow transplant help Job’s
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
Where does chemo originate from?
Mustard gas in WW1, it attacked bone marrow and killed white blood cells.
What was done to prepare for bone marrow transplant for Job’s, what were the complications
Chemo, which caused white blood cell inflammation that was solved by steroids and breathing treatment.
How did the bone marrow transplant help Lucy’s recovery of her lung
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
What is the problem with using chemo on sickle cell disease
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
Why does sickle cell cause pain
Cells don’t get oxygen, and they die. Pain indicates organ damage.
How did they prep for sickle cell bone marrow transplant
Low doses of radiation to eliminate bone marrow. This destroys the immune system temporrarily and it is based on how well patients tolerate
What does chemo do for bone marrow transplant?
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
What are first in class and me too drugs
First in class are the first to target certain proteins. Mee too drugs target same protein but with a different way or method.
What is in the preclinical testing/discovery phase
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
How many compounds after filing IND at the FDA
5
What is on the WHO list of essential medicines
Commonn diseases that are serious have drugs. Effective, safe, and cost effective drugs
What is a drug target
Usually a protein the drug binds to inactivating it (could be other molecules, but rarer)
What is tested in phase 1
Safety, not effectiveness, with 2 animal species, 1 rodent one non rodent. Start low, 100 times less and you need consent. Also testing dosage
What is the surveyed population for phase 2
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
What is tested in phase 3 and how many people
effectiveness, adverse reactions from long term use. you need 1000-5000 people
How was the first vaccine developed
Cowpox being used to protect against smallpox
WHat was the difference between polypharmacy and monopharmacy
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
What are the plants that actually have medicinal value
Opium, quinine, and digitalis. Respectively painkiller, malaria, and heart failure
What was the first true drug
Morphine
How does the dye industry contribute to drug discovery
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
How is modern and previous drug discovery different
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
What does malignant mean in cancer
Can get to other body parts
What are two ways to organize cancer
By tissue or organ of origin, or mechanism of growth. Different location but same mechanism could be treated in the same way
What causes mutations and what do mutations cause
DNA copying mistakes or damage from UV, chemicals, genetics, smoking, viruses. Causes RNA problems and protein problems
What are inherited and acquired mutations, where does cancer come from
Acquired mutations cause most cancer. Inherited mutations are in gametes, acquired not passed down.
What does targeted therapy in cancer try to do? What is an example
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
What are the two types of white blood cells, what do they do
Blood and lymphatic system. T-cells bind to foreign particles and eat it, B cells create antibodies that prevent surface mutation.
How does cancer evade detection
Turns off immune system, can’t be seen by immune system, immune system deals differently
Why are nonprotein targets rare
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
What are enzyme reactions? How do they interact with substrates
Amino acid structure of protein factory allow substrate to fit.
What is pharmacodynamics
how drugs interact with targets, drugs are similar to ligands and stop normal behavior
What is target identification
Finding proteins central to disease mechanism, which is different in healthy people
What is the difference between genomics and genetics
Genomics is studying all genes and interactions between gene and environment. Genetics is about a single gene.
What are genome wide association studies, example
Compare genomes of healthy and affected groups to see differences in chromosomes. Cancer genome studies compare sequenced tumors and metastasises
What is the goal of target validation
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
What is a SNP and how common
Single nucleotide polymorphism. We have a shit ton of them
What is the difference between single gene disorders and multiple gene disorders. Name a few single gene disorders
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
What did organoids tell us about human brain tissue
That there was no need for feedback from other parts of the nervous system and uterus to develop neural tissue.
How are brain waves formed? What is true about organoid brain wave, and what are the types of brain waves
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
Why are organoids not conscious? How many cells are there
Sea slug amount of cells. The reticular formation is used to wake up. Organoids need bigger structures to arouse into consciousness
What drugs can be tested on organoids, how
Drugs that require analysis of brain activity, like Alzheimer’s and schizophrenia
What is the importance of animal testing
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
What is ALS and how is it inherited
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
Explain ALS in terms of cell body activity
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
What do oligodendrocytes do
Insulate axon to support motor neuron. Does not work in ALS
What is the stone man syndrome
Disease caused by mutated gene with tumors in brainstem that cannot be removed. Chemo does not work
How do people look for cures for stone man
Transplant tumors into mice. Mutant cells don’t respond to activin A, which inflame muscles
Explain how altering genes of a model organism could help drug development
Focus on proteins as a result of altering that gene
How are human cells used to test drugs?
Removing proteins to see respective effects/genetic engineering. Organoids can see cell types and interactions. Microphysiological systems allow you to have dedicated compartments
What do you need to do before human research
Identify and validate targets, efficacy and safety of the drug must be confirmed
What is translational medicine
Preclinical and mechanistic systems going to the clinic. Making diagnostic tests, drugs and therapies for a clinical impact
What are the 3 R’s in animal research
Replacement (computer models, invertebrates). Reduction (less animals). Refinement (minimizing distress, better living environment).
What is a xenograph
Putting human tumors into immunocompromised mice to measure efficacy of treatment
What does mutant ACVR signalling do and what indicates an effective treatment in mice
It increases signalling, which is blocked selectively by drugs. If the tumors shrink and activity is lessened, then the treatment works
What does the open field and light dark test say about mice behavior
Anxious mice hangs out in the dark part of light dark test, less anxious in the middle of open field
What is COVID tested on?
Cell cultures, animals, people. ACE 2 allows virus to infect us with molecular handshake, mice with humanized protein lets us test
How is thalidomide an example of drug development fuck ups
You need adequate info from animal tests, it caused limb formation problems. People thought placenta are barriers to block drug passage but not true
How long does drug exposure for animal testing have to be
6 months to a year
What is toxicity in cells
Death of cells in proportion, the unit is mg/kg to kill 50% of cells
What is in vivo and in vitro
Respectively in living organism and in glass (lab, cell culture).
What are to ways drugs can cause toxicity
Binding to receptor or to a new molecule which could be from drug metabolizing enzyme (metabolite, any substance produced during metabolism of drug)
How is mutagenicity observed in bacteria
Bacteria need histadine, if there is a strain that grows without histadine, then it is mutated
How do toxicologists check for toxicity
In every organ because design is unrelated to real effects. Cardiotoxicity causes heart problems which is the primary cause of drug recall.
What is stem cell testing
Turns normal cells into embryo cells then brain liver and heart cells
What are biomarkers of toxicity and indirect markers
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
What are ethics and values
Ethics determine moral duties and values of human conduct. Values are more specific, include justice nonmaleficience, beneficience, nonexploitation, respect, autonomy
What did the nuremberg code and declaration of helsinki say
Respectively about sterilization, free will and filling in gaps of nuremberg code with stuff about risk-benefit
What is clinical equipoise
Drugs might be better or worse for treatment, we don’t know. People need to know the drug may not help
What is value in clinical research
To investigate important generalizable things with a good hypothesis, practical intervention. Communicate results. This is due to finite resources (including people) and nonexploitation
What is scientific validity
Having a good design that’s practical with clean conduct and enough subjects
What is fair subject selection
Exclusion and inclusion is reasonable, target different groups and don’t recruit based purely on ease. Speed is not as important as fairness
What is favorable risk benefit ratio
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)
What does independent review do
Prevent inference of researcher’s interests. Research ethics board checks recruitment, consent, risk benefit, confidentiatlity, fairness, conflicts of interest
What is informed consent and what ethical principles is it related to
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)
What is an example of lack of respect for subjects
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
What does respect for subjects include
Info privacy, allowing subjects to change their mind, monitoring patients, acknowledge contributions
Where do clinical trials happen and who is it by
At universities and hospitals or private organizations. It is sponsored by company making drugs. A doctor suprevises
How to participate in clinical trials
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
How are phase 1 trials performed
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
