molecules of life standard set 3

What two industries could be considered the precursors to the pharmaceutical industry as we know it today?

Apothecaries (Pharmacists) transitioned into the wholesale production of drugs derived from natural products, such as morphine, quinine, and strychnine; Dye/chemical manufacturing industries began exploring the medicinal properties of their chemical compounds, leading to the creation of research labs that eventually merged into the pharmaceutical sector.  

What is the difference between the "mission" of drug discovery in the early days of the pharmaceutical industry compared to today?

the early days focused on treating common diseases, relieving symptoms, using natural sources, trial and error experimentation, and mass production of useful compounds. drug discovery today aims to invent medicines for ailments prevalent in the U.S., Europe, and Japan, while the absence of cures or affordable treatments for diseases prevalent in developing countries, especially HIV/AIDS and malaria, opens pharmaceutical firms to criticism.

What are some of the historical events that led to the regulation of drug discovery and development by the FDA?

During the HIV/AIDS crises patients pushed for faster access to experimental treatments; Accelerated approval pathways and expanded access to investigational drugs. Thalidomide was a sedative and treatment for pregnancy related nausea in the 1950s that was linked to birth defects in thousands of children worldwide. This tragedy underscored the need for rigorous clinical testing and regulatory oversight of new drugs. Led to the Kefauver-Harris amendments: manufacturers were required to substantiate the claims about the effectiveness of their products.

Explain why drug discovery is often slow, costly, and complex.

safety controls, regulations on drug labelling, and the establishment of clear distinctions between prescription and over-the-counter medications; Regulatory measures have been put in place by governments to control the growing volume of vaccines and antitoxins to establish stricter qualifying examinations and create a registry of chemists and druggists. It can take a drug around 15 years to get approval.

Explain how scientific and technological advances can influence drug development.

accelerates development by using AI to identify druggable targets and predict compound efficacy or toxicity without extensive experimentation; also, DNA sequencing and liquid biopsies enable precision medicine, allowing for personalized treatments based on genetic variations

Describe how economic factors, including cost and profitability, can affect which drugs are pursued and made available.

Pharmaceutical companies increasingly focused on developing prescription drugs, which offered greater profitability; Because a new drug is extremely expensive and time consuming to develop, companies tend to prioritize treatments that are likely to generate high returns such as diabetes rather than rarer diseases that affect fewer patients.

Describe how drugs may be developed for one purpose and later used for another (repurposing), and provide examples.

Unexpected side effects, improved understanding of disease biology, or systematic testing of existing drugs. example: Piperazine became widely used in the 1950s as an anthelmintic for treating roundworm infections in animals, Thiabendazole initially for treatment veterinary parasites then for gastrointestinal infections caused by parasitic worms in humans.

Explain why both pre-clinical and clinical trials are necessary.

Pre-clinical trials identify initial safety concerns and potential toxicity in laboratory models, preventing dangerous compounds from reaching humans. This involves both living and microorganism studies to evaluate efficacy and safety. Clinical trials then verify these findings in people, establishing efficacy and optimal dosage for human physiology.

Explain why the approval of AZT was considered both important and controversial (e.g., urgency, side effects, cost, limited alternatives).

Azidothymidine: Nucleotide analog that resembles a thymine base in a nucleotide, which gets in the way of viral replication. It is a reverse transcriptase inhibitor, blocking the reverse transcriptase enzyme and preventing RNA from being converted into DNA. It was the first drug approved for the treatment of HIV, and there were no other known HIV treatments in the 80s. The approval process of it was controversial because it got pushed through before the clinical trials were finished. The approval of the drug was necessary because of the limited alternatives to the cure for HIV at the time. Side effects include gastrointestinal distress and damage to the immune system.

Define and apply the concept of risk vs. benefit in drug use. Evaluate real-world drugs (e.g., OTC meds, antidepressants, anti-anxiety drugs) using cost–benefit reasoning.

The concept of risk vs. benefit in drug use is weighing the potential positive effects of the medication against the possible harms to decide whether it should be used. Ibuprofen, for example, has Clear benefits of pain and inflammation relief with minimal risk when used as directed, but can cause kidney issues if overused.

Describe the role of social factors, public opinion, and activism in drug approval and access.

In cases like the HIV/AIDS crises, patient advocacy groups demanded faster drug approvals and broader access to experimental medications, leading to major changes in clinical trial policies. Income, race, education, and geographic location also affect access, as some populations may face barriers like high drug costs, limited health care coverage, or lack of nearby providers.

Explain, at a basic level, how vaccines stimulate the immune system and lead to immune memory.

they imitate an infection using harmless parts or weakened versions of a germ (antigens). This triggers the body to produce specific antibodies and specialized memory cells without causing the disease itself.

Distinguish between vaccines as preventative interventions and therapeutic treatments used after infection.

Vaccines prevent disease by training a healthy immune system to recognize and fight pathogens before exposure, creating long-term immunity (ex. polio). therapeutic vaccines are given during an existing disease to induce a stronger cellular response (ex. HIV)

live attenuated vaccine

a version of a pathogen that’s sub-cultured in a lab, usually against a viral infection. When its grown over and over, it is pampered so that it propagates, which makes it lose its ability to spread disease. It is Strong and long lasting because it triggers both antibody and cellular immune response, and usually requires fewer doses or boosters. It is not safe for immunocompromised people and requires careful storage. Minimal risk of reverting to a harmful form. (very rare). Examples are the MMR (measles, mumps, rubella), and varicella (chickenpox).

Explain why some vaccines may require multiple doses or boosters.

Initial doses alert the immune system, while subsequent doses establish strong immune memory. A gap between doses often allows the immune system to build a stronger response. They train the immune system through repeated exposure, or boosters to restore protection that wanes over time.

Explain why vaccines are considered a major tool in public health.

They prevent disease before it starts, create herd immunity, help eradicate diseases, reduce healthcare costs, and they control outbreaks and pandemics.

Identify the type of pathogen that antibiotics target.

Antibiotics specifically target bacterial pathogens, which are prokaryotic, single-celled organisms. The antibiotics target Bacterial pathways like cell wall synthesis, protein synthesis, nucleic acid (DNA/RNA) synthesis, and metabolic pathways.

Provide examples of bacteria that have become resistant to many types of antibiotics and explain why this is a problem (more detail than simply saying the infections are harder to cure).

MRSA causes skin infections, pneumonia, and bloodstream infections. This requires Doctors to use more dangerous or toxic medicines for a patient that would usually be a last resort. Routine procedures such as surgery depend on antibiotics, making said procedures much more risky when bacteria become resistant to this vital antibiotic.

Describe some of the reasons for the prevalence of antibiotic-resistant bacteria.

People overuse or incorrectly use their antibiotics; you need finish your dose when prescribed so that the bacteria doesn’t mutate and survive in your body. The traits of surviving bacteria also get passed onto others, called mating.

Explain why it is incorrect to state that people become resistant to antibiotics.

resistance is a property of bacteria, not human cells. Antibiotics are designed to target bacterial cell walls or specific enzymes, which human cells do not have, meaning the infection becomes hard to treat, not that the person's body has developed immunity

Explain why antibiotic resistance is a major public health concern.

it renders standard treatments ineffective, leading to higher mortality rates, prolonged illnesses, and increased healthcare costs. They spread rapidly.

Describe the purpose and methods for the experiment “The Evolution of Bacteria on a ‘Mega-Plate’ Petri Dish (Kishony Lab)”

displays the movement of bacteria (E. Coli) through different amounts of antibiotic to show how bacteria can mutate and continue to multiply and evolve resistance to even extreme concentrations of antibiotic in a short period of time.

Propose one change to policy or behavior that could stop or slow down the spread of antibiotic resistance in bacterial populations / communities.

Implementing mandatory rapid diagnostic testing—such as molecular bedside tests to differentiate bacterial from viral infections—before prescribing antibiotics can significantly slow the spread of resistance.

What is the blood-brain barrier? How does it function to protect the central nervous system?

it protects the brain from outside substances allowing only small molecules, fat soluble molecules, and pre-existing transport protein through.

also maintains cerebral spinal fluid for neuronal function.

What is a neuron? How do signals travel from one neuron to another?

The fundamental cell of the nervous system. It’s specialized for receiving, processing, and transmitting electrical signals throughout the body, allowing for rapid communication. If the next signal is strong enough, the next neuron fires an action potential, continuing the message.

What happens at a synapse that allows signals to travel?

Signal goes down axon, neurotransmitters are synthesized, when action potential arrives, the vesicles start to move towards synapse, as electrical signal arrives, voltage gate calcium channels open to allow calcium in, calcium allows vesicles docking, releasing the neurotransmitter into the synapse. Neurotransmitters bind to receptors causing channels to open/close. Then excitatory or inhibitory postsynaptic potential is generated. It’s then reuptook by glial

Be able to predict side effects based on a class of drug

Describe the historical trajectory of ketamine "from battlefield to psychiatry" and how it could be useful under different circumstances.

Began as a safer alternative to PCP during the Vietnam war, recreational use led to it being classified as a scheduled III controlled substance in 1999, in the 2000s research identified its ability to rapidly alleviate treatment resistant depression often within hours rather than weeks. 2019 FDA approval of esketamine nasal spray.

inactivated (killed) vaccine

the bacteria in the vaccine is “killed” preventing them from propagating. it’s cultured in the lab then inactivated by heat or chemicals. it’s a mostly humoral response and may require boosters. The risk is a compliance issue—it may need multiple doses. an example is polio or hepatitis a.

toxoid vaccine

the known toxin is extracted form the organism and administered in a small dose to mount an immune response. The molecule still elicits an immune response but an adjuvant is often needed . the response is targeted. The risks are anaphylaxis and local and systemic allergic reactions (in the tetanus vaccine). Examples are tetanus and diphtheria.

subunit/conjugate vaccine

A component of the cell/virus is extracted from the pathogen and included in the vaccine to elicit an immune response. you don’t have the entire cell/virus, just a component of it, which causes an immune response. May need immune boosters, often requires multiple doses, and immune response may be less robust. Examples are meningococcus and pertussis.

mRNA vaccine

contains nucleic acid (mRNA) that can be translated by the ribosome. It is developed fast, there is no live virus, and has a strong immune response with both the antibody and the t cell. It’s limitations are its ultra cold storage, temporary side effects, and its novelty that limits its long-term data. examples are the Moderna and Pfizer covid 19 vaccines and the Ebola vaccine

viral vector vaccine

viral nucleic acid is delivered to cells via weakened adenovirus. It elicits a strong immune response, has no need for live target pathogen, and is more stable than mRNA vaccines. Limitations include pre-existing immunity to the vector which can reduce effectiveness, rare side effects, and a decline in booster effectiveness if the body attacks the vector. An example is the Johnson and Johnson covid-19 vaccine.

beta lactams

targets beta lactamase. gets in the way of peptidoglycan synthesis (bacteria cell wall), which makes for good selectively toxic antibiotics. examples include Penicillins, Cephalosporins, Vancomycin

polymixins

target the outer cell membrane of bacteria. binds to and disrupts lipopolysaccharides, leading to increased permeability and leaking inner contents, thereby killing the bacterial cell

tetracycline

targets the 30s ribosomal subunit in protein synthesis to stop protein production

macrolides

target the 50s ribosomal subunit in protein synthesis to inhibit synthesis and growth

rifampin

targets RNA polymerase and halts the synthesis of RNA

quinolones

target DNA gyrase to prevent DNA replication, transcription, and repair

sulfonamide

targets folate synthesis, which is essential for dna synthesis

Cell Wall Synthesis Resistance

bacteria modify their target enzymes, such as penicillin-binding proteins, reduce membrane permeability, or produce enzymes like beta-lactamases to break the beta lactam ring and destroy antibiotics. renders penicillins useless

Nucleic Acid Synthesis Resistance

Bacteria commonly modify enzymes like DNA gyrase or RNA polymerase to prevent fluoroquinolones from binding. Permeability is reduced to deny entry of drugs into the cell. efflux pumps also eject quinolones from the cell and expel drugs or plasmid-mediated protection of target enzymes

protein synthesis resistance

Methylation of the ribosomal RNA (rRNA) changes the structure of the target site, preventing macrolides from binding. Bacteria produce enzymes (e.g., aminoglycoside-modifying enzymes) that chemically modify the antibiotic (e.g., phosphorylation, acetylation), preventing it from acting on the ribosome. Specialized efflux pumps actively transport tetracycline out of the cytoplasm.

peripheral nervous system

All nerves outside the brain and spinal cord which functions to connect the central nervous system with the rest of the body. Carries signals to and from the central nervous system.

autonomic nervous system

controls involuntary functions. the Sympathetic part is the “Fight or flight”, which increases heart rate, dilates pupils, and prepares body for stress. The parasympathetic is “Rest and digest”, which slows heart rate, conserves energy, and promotes digestion.

somatic nervous system

Controls voluntary systems like walking and sends sensory information to the central nervous system. detects stimulus like heat and sends commands to muscles or glands

Dendrites

branch-like extensions from the cell body that receives the signals from other neurons or sensory cells

axon

Long, thin fiber that carries signals away from the cell body.

axon terminal

small branches at the end of the axon that releases neurotransmitters to communicate with the next neuron or a muscle/gland.

Excitatory neurotransmitters

excites or activates the next cell. Stimulates the next neuron to fire an action potential. Glutamate

Inhibitory neurotransmitters

“inhibits” or dampens neural activity by preventing the next neuron from firing. Glycine

Modulatory neurotransmitters

“modifies” the activity rather than directly exciting or inhibiting how neurons respond to other neurotransmitters. Serotonin.

How is it possible for dopamine to be all 3 types of neurotransmitter

Dopamine can be all three because its role depends on the neural context, making it a classic neuromodulator. It can either increase or decrease the likelihood of neuronal firing. It can also regulate entire neural circuits, influencing motivation, reward, attention, and motor control.

antagonists

bind in neurotransmitter receptors blocking actual neurotransmitters, thus preventing their effect with greater affinity than endogenous (body’s natural) transmitter ideally.

Reuptake inhibitors

can act on both neuronal auto reuptake or glial cell reuptake (usually meds don’t do both)

agonists

bind to the same receptors as neurotransmitter and mimic their effects

enzyme inhibitors

decrease breakdown of neurotransmitters in synaptic cleft to prolong activity; block active site of enzyme

stimulants

Increases concentration of excitatory neurotransmitters. Like dopamine and norepinephrine. side effects include insomnia, increased heart rate and blood pressure, anxiety, appetite suppression.

antidepressants

Increases likelihood of neurotransmitter binding. side effects include Nausea and sexual dysfunction

anxiolytics

increases GABA levels having a calming effect. side effects include Drowsiness/sedation, impaired coordination, memory problems, dependency.

antipsychotics

dopamine/serotonin receptor antagonists and modulators. Decreases dopamine. side effects include motor spasms

analgesics

“pain management” enhances dopamine's inhibitory effect. Decreases pain signaling. Side effects include Constipation, nausea

anti epileptics

enhance GABA to prevent overexcitation. Decrease neuronal excitability. Side effects include tremors, dizziness.

Pharmacogenomic 

the study of how an individual's genetic makeup affects their response to drugs, optimizing medication safety and efficacy by predicting reactions and allowing for personalized dosing

psychedelic therapy 

combines controlled administration of substances like psilocybin or MDMA with psychotherapy to treat mental health conditions such as PTSD, depression, and addiction. It works by increasing neuroplasticity and fostering new cognitive perspectives

precision medicine

trying to get meds exactly where you want them to work.