A look at STEM: What is ADME/Drug Metabolism?

“If you swallow a pill and it simply sits in your stomach, and then passes out through your feces, it technically wasn’t absorbed into your body.”

Similar to the fields of Pharmacology and Toxicology, ADME/Drug Metabolism is a well-established field dating back to the nineteenth century, and it is very complex with respect to the wealth and depth of information available.  It is still evolving today.  The goal of this post is not to address every detail of the field, but instead to give readers a basic introductory understanding of the discipline.  Further details about the many aspects of ADME/Drug Metabolism can be accessed online, or in scientific journals.

In my Pharmacology and Toxicology posts, I briefly discussed Pharmacokinetics, Toxicokinetics, and the Absorption, Distribution, Metabolism and Excretion (ADME) of drugs and other xenobiotics.  These areas collectively comprise the exciting field of “Drug Metabolism”.   Whenever a new drug or industrial chemical is produced, several key aspects of the chemical must be characterized; how much of it gets absorbed into the body, where it goes in the body, and how long it stays there.  The answers to these questions are collectively known as the molecule’s “ADME” profile, and a tremendous amount of work goes into this type of research.  It’s very critical information as it helps characterize the chemical’s subsequent pharmacological or toxicological effectiveness and properties.  As you read through this post keep a couple of key questions in mind.  How much of the molecule gets absorbed into the body?  Where does it go once absorbed?  How long does it stay in the body?  Is it transformed into something new?  How does it leave the body?

Before walking through the ADME acronym in greater detail lets first talk about the three organs that impact a chemical’s ADME profile the most: the Liver, the Kidneys and the Small Intestine.  As described later in this post, other organs can impact a chemical’s ADME profile but these are the three major players.  I will try to explain these organs in the context of this post in the simplest way possible.

“If you take a pill and it simply sits in your stomach for a brief period of time, and then passes out through your feces, then it technically wasn’t absorbed into your body,” said the same professor from my Pharmacology post who distinguished the discipline of Pharmacology from Pharmacy.  This anecdote described how drugs and man-made industrial chemicals in the classic sense must be absorbed into the blood stream to actually have been absorbed into your body.  There are other ways a chemical can get into the body (inhalation and dermal exposures), but for this post I’m focusing only on oral absorption.

If absorbed in the small intestine, the molecule of interest then passes through the “Hepatic Portal Vein” into the liver where any number of things can happen to it (described in greater detail below).  After leaving the liver and entering the general circulation, the molecule is for the most part cleared through the kidneys via the urine, but in some cases it can be deposited back into the GI-Tract and leave the body through the feces.  Molecules can also be exhaled depending upon what they’re transformed into once absorbed.  Any molecule not absorbed by the small intestine leaves the body through the feces.

I can’t emphasize enough the importance of the liver and kidneys which both perform numerous critical functions in the body.  For this particular context, the normal function of both, are critical to the body’s handling of both endogenous and exogenous chemicals which is why physicians, nurses and pharmacists inquire about their function early on when patients are admitted for care in clinical settings.  With that in mind, I’ll now break down the ADME acronym and why these skill sets are so valuable for scientists who gain an expertise in them:

  • Absorption: As described earlier, the “Absorption” aspect deals with how much of the chemical is absorbed into the body following oral ingestion, passage into the small intestine, the liver, and finally into the blood stream. The properties of the chemical itself can dictate how much of it is absorbed – particularly its size and for simplicity whether it’s charged (+ or -) or neutral.  As described in my Pharmacology post, pharmaceutical companies designate molecules as either “small” or “large”, and many large molecules can only be administered by injection into the bloodstream.  While there are several experiments that can help characterize a molecule’s oral absorption, “Pharmacokinetic” and “Biliary Excretion” studies (discussed below) are the most specific.  Just briefly, by treating animals (usually rodents) with radio-labelled compound, the amount of compound absorbed can be determined by quantifying the amount of radioactivity in the blood, urine and feces over time telling scientists how quickly the molecule was absorbed in addition to the amount absorbed and if these two metrics change with increasing dose.
  • Metabolism: Once in the body, molecules can undergo “Biotransformation” – that is, classes of proteins called “Enzymes” can transform the structure of a given molecule by breaking it down into multiple pieces or adding on new “Functional Groups”, altering its properties so that it’s more readily eliminated from the body (discussed below).  In some instances, this biotransformation turns the molecule into something toxic which can cause injury to the liver or other tissues in the body.  The Metabolism aspect of ADME, involves a separate discipline called “Enzymology” which focuses just on the enzymes themselves; their levels in cells (Protein Expression), the rates of their reactions (Kinetics), their structures, etc.  There are actually multiple classes of drug metabolizing enzymes but the most prevalent class at least as it relates to the liver, is the “Cytochrome-P450s”.  Pharmaceutical companies pay particular attention to this class of enzyme (and a host of others) as they greatly impact the “Bioavailability” of the drug.  The “First Pass Effect” or “First Pass Metabolism” occurs when a drug is significantly metabolized before it gets into the general circulation due to metabolism by liver enzymes.  Some of the clinical aspects of metabolism will be further discussed later in this post.  By the way, while Cytochrome P450s were classically associated with the liver, we now know that they are expressed throughout the human body as well as all plants and animals.
  • Distribution: Once in the body’s general circulation, the molecule can travel to many of the tissues of the body and can accumulate there for short- or long-periods of time depending upon the tissue and the properties of the molecule itself.  If the molecule is particularly non-polar (neutral), it can accumulate in fatty tissues or for pregnant females, it can partition into breast milk and be transfered to nursing offspring.  Molecules can also bind reversibly to blood plasma allowing for an increased internal dose.
  • Excretion: Excretion refers to how the molecule is eliminated from the body.  Typically the urine and the feces are measured to determine how the molecule is eliminated.  Detection in the urine indicates that the molecule was absorbed to some degree into the bloodstream as the kidneys filter out aqueous waste from the blood.  Poor kidney function can actually lead to a prolonged bioavailability and subsequent toxicity which is why clinicians always inquire about it as described earlier.  Not all of the absorbed chemical exits the body through the urine though.  It turns out that absorbed chemicals can empty out back into the GI-Tract from the liver via the bile and then be eliminated through the feces.
  • Drug Transport: This aspect doesn’t traditionally fall under the ADME acronym, but it’s an important field that is now being actively researched in academia and industry.  It deals with how cells may concentrate the chemical in tissues or remove the molecule from the target tissue before it can exert its function.
  • Pharmacogenomics/Toxicogenomics: These new and exciting fields look at the genetics unique to individuals to determine the best treatments and dosages for that individual. Genetic differences in levels in the drug metabolizing enzymes mentioned above can result in drastically different effects of treatment with a given dose of a drug depending on the individual.  The same is true for an individual’s reaction to a toxicant.

So why is all of this important?  Whether in a hospital setting, a pharmacy, or in the chemical industry creating a new food additive, pesticide, or cosmetic, it’s important to have as clear an understanding as possible of where the molecule goes in the body and what its fate is following ingestion.  As described above, physicians, whether in general practice or in the emergency room, have to gauge a patient’s liver and kidney function as those two organs will dictate how long the pharmaceutical stays in circulation – again, its “Bioavailability”.  Even a pharmaceutical designed to be therapeutically beneficial can be toxic if it remains in the body too long, if its levels exceed a certain dose level, if it’s transformed into something toxic, or if there is a drug-drug interaction.  “Drug-Drug Interactions” are typically the result of one drug causing an increased internal dose of another drug due to inhibiting or preventing metabolism by the enzymes described in the metabolism bullet above.  In graduate school we learned about the classic case of Terfenadine causing abnormal heart rhythms that could lead to death by increasing the amounts of circulating Erythromycin – both of these drug molecules normally work by with non-cardiac mechanisms. Terfenadine was removed from the market once it’s ability to cause this deadly drug-drug interaction was recognized.

Chemical, food and beverage, and pharmaceutical companies all have to know what happens to their molecules in the body for several reasons.  A drug can be highly effective at preventing cancer cells from multiplying in a laboratory setting in dishes and flasks, but unless it is readily absorbed in the intestines and can actually get to its target tissue in the body as its untransformed structure, it’s useless.  In some instances, a drug can get to its site of action, but the cells of that tissue can adapt and effectively expel the molecule before it gets a chance to exert its function as described earlier.  Pesticides which are sprayed on agricultural commodities often make it to our dinner tables in low levels where we do ingest them to some degree.

Another very important context for ADME/Drug Metabolism is actually “Food Safety” which is a key consideration for food and beverage companies like Pepsico and Quaker Oats.  As a matter of fact, at a family dinner earlier this year, a discussion of about Trisodium Phosphate (TSP), a preservative used in “Cap’n Crunch” cereal which had other industrial uses, caused a stir amongst my relatives.  I had to remind them that both the ADME and toxicity profiles of this preservative had already likely been characterized and cleared through extensive studies by the company and the Food and Drug Administration (FDA).

We’ve discussed what ADME/Drug Metabolism is, but where do these scientists work and where do they receive their training?  ADME/Drug Metabolism scientists work in Pharmaceutical and Chemical companies, and in government performing “Regulatory” functions (visited in an upcoming post).  They receive their training for the most part in academic settings in labs specializing in Pharmacology and Toxicology, both of which have ADME/Drug Metabolism as a major component.  There are some labs that strictly study one of the many aspects of ADME/Drug Metabolism but they are in the minority of the research groups in the biomedical sciences.

“Scientists with training in Drug Metabolism will almost never be with jobs,” said one of the professors in my graduate department at the University of Michigan.  While we know that there is no job that is 100% secure, this particular professor was stressing that ADME/Drug Metabolism scientists are critical parts of most companies.  The divisions of those companies responsible for these types of studies are typically titled Drug Metabolism and Pharmacokinetics (DMPK).  No matter what disease the company is interested in (Diabetes, Cancer, HIV, etc.), it is essential that they understand the chemical’s ADME/Drug Metabolism profile for their own purposes and when submitting packages for approval by the Food and Drug Administration and other regulatory agencies.  The same is true for chemical companies.

There are numerous scientific tools and technologies that ADME/Drug Metabolism scientists use, but I’ll mention two of them briefly.  The first is the Mass Spectrometer also known as the “Mass-Spec”.  Mass-Specs are not used solely in ADME/Drug Metabolism studies, but they’re very important to the field because they can detect and identify molecules in whole blood, blood plasma, tissue samples, urine, and fecal samples at very, very low levels.  More importantly they can detect changes in the structure and identity of molecules once they have gone through the body and can help to predict a drug/industrial chemical’s efficacy or toxicity.

Technologies and methods are always changing and evolving but the Mass-Spec is currently a very important tool for ADME/Drug Metabolism.  Currently, Pharmacology and Toxicology scientists in industry are moving towards decreasing animal usage and towards more in vitro and in silico methods which are giving rise to the use of Physiologically Based Pharmacokinetic Models (PBPK) where the fate of molecules can be predicted using various constants and inputs into computational models.  We’re currently in the early era of these methods.

If you are interested in learning more about the exciting field ADME/Drug Metabolism, I suggest that you visit the website of the American Society for Pharmacology and Experimental Therapeutics (ASPET).  You can then click on the link titled Education & Careers.  In the right hand column, there is a link titled About Pharmacology, that provides a great deal of interesting information.  Speaking of ASPET, all scientific disciplines have their own professional societies with annual meetings that are held in various cities (eg. Boston, San Francisco, Chicago, San Diego, Washington,etc.) every year, and where scientists gather to show their results and network.  The two major professional societies for ADME/Drug Metabolism scientists are ASPET, and the International Society for the Study of Xenobiotics (ISSX).

Thank you for taking the time to read this post, and I hope I was able to shed some light onto what ADME/Drug Metabolism is as a field.  The next post in this series will discuss the field of Inhalation Toxicology.  If you enjoyed this post, you may also enjoy:

A special thank you is extended to Dr. Paul Hollenberg and Dr. Chester Rodriguez for their contributions to this post.  I also want to acknowledge Dr. Yoichi Osawa of the University of Michigan’s Department of Pharmacology for the picture of the Mass Spectrometer used in this post.

If you’ve found value here and think it would benefit others, please share it and or leave a comment.  To receive all of the most up to date content from the Big Words Blog Site, subscribe using the subscription box in the right hand column in this post and throughout the site.  Lastly follow me on Twitter at @BWArePowerful, and at the Big Words Blog Site Facebook page.  While my main areas of focus are Education, STEM and Financial Literacy, there are other blogs/sites I endorse which can be found on that particular page of my site.

 

Chris Herren discusses his journey, drug addiction, substance abuse and wellness

“Look at the first day, and not the worst day.”

The first principle of my blog is “Creating Ecosystems of Success” of which health and wellness are major aspects.  Personal stories also fall under this principle as they are one of the most powerful means of teaching individuals about success and failure.  Recently, three high schools in Northern Virginia hosted a very special guest who shared his life journey starting from his days as a high school basketball standout, to his college basketball stardom, to his ascension to the National Basketball Association (NBA), and then his personal struggles with drug addiction and substance abuse along the way.

On Oct. 2 Chris Herren visited Northern Virginia to talk to students and families about his basketball journey and his lifelong struggle with drug addiction and substance abuse.  In the first of many local stops, Herren spoke at Fairfax High School to an audience of all students in the morning, and then to adults, families and the general public in the evening.  I first heard part of Chris’s story years ago on the Jim Rome Show, and then I watched ESPN’s powerful documentary on his life and journey, Unguarded.  I learned about his visit a couple of weeks ago by chance after Tweeting to Chris’s foundation ‘The Herren Project’.  I told them that I would’ve definitely attended one of his talks in Massachusetts if I lived there.  They shared that he would be making an appearance in early October in the DC area, and as a lover of sports stories, I knew that I had to attend.

Chris Herren was one of the top 20 high school basketball players coming out of Durfee High School in 1994 with multiple offers to some of the nation’s top college basketball programs.  It was in high school where he first experimented with alcohol – something he had seen his father do growing up.  After playing just a little bit for Boston College, he failed a drug test which almost ended his career.  He received a second chance from a legendary coach who had given numerous young men second chances throughout his career – legendary coach Jerry Tarkanian also known as “Tark the Shark”, who had taken over as head coach at Fresno State University where I first saw Chris play on television.  There he played his way into being the 33rd overall pick for the Denver Nuggets in the 1999 NBA Draft.  He was later traded to the Boston Celtics where his drug problems escalated, and then went on to play overseas in Italy where his life further spiraled downwards before setting off on his road to recovery years later.

“The kids across the room who didn’t do anything, they had something I didn’t have,” Chris said in his strong New England accent, describing one of the high school parties he attended where he and his friends consumed alcohol underage, while another set of kids across the room didn’t consume anything and were fine with it.  During his talk, Chris told many stories about his journey which involved experimentation and addiction to Cocaine, OxyContin, and finally Heroin – all while becoming a father and a professional basketball player.  This particular story was significant because it touched on something many young people struggle with well into adulthood; personal contentment and self-esteem.

The significance of Chris’s opening quote of this post is to get people to note where our personals problems start and their root causes, as opposed to focusing solely on the end results – substance abuse, drug overdoses, suicides, and many others.  His just happened to be his father’s struggle with alcoholism, his mother’s resulting pain, and then the experimentation with drugs and alcohol amongst his peers early on as teens.  Chris’s other over-arching message was about “Wellness”, and how both parents and schools need to be more vigilant and aware of the struggles of young people which can lead to any number of injurious outcomes later in life if not caught early and addressed.

“Over the last seven years I’ve had the responsibility of sharing my story in front of a million kids.  I truly believe in my heart that I’ve made a difference for some, and I do this for many reasons,” Chris Herren said opening up his talk.  “When it comes to addiction, I think we’ve gone horribly wrong.  I think we put way too much focus on the worst day, and we forget about the first day.

“It’s safe as parents to show our children pictures of drug addicts and how to watch a movie and at the end explain to them what happened.  It’s hard to sit them down at 15 years old and say honestly, ‘Please tell me why you’re letting this begin.’

After telling his story, Chris took questions from the audience – parents and teens, whom he also makes himself available to through email.  Afterwards he graciously took pictures with those of us in the audience and took further questions individually.  I seized the opportunity to ask him one to two more.

“He’s one of the people that I will unconditionally love for the rest of my life.  I did the eulogy at his funeral at the Thomas and Mack Center in front of 12,000 people.  What I told everyone that night is that he meant the world to me.  He changed me,” Chris reflected afterwards when I asked him to say a few words on Jerry Tarkanian.  “I do what I do today because he did that for me.”

“He gave me a second chance and I truly believe people are worth second chances.  If we didn’t give second chances to people in recovery, we’d be much worse off.  He instilled that in me and it continues in my life today.”

Thank you for taking the time out to read this post.  If you’ve found value here and think it would benefit others, please share it and or leave a comment.  To receive all of the most up to date content from the Big Words Blog Site, subscribe using the subscription box in the right hand column in this post and throughout the site.  Lastly, follow me on Twitter at @BWArePowerful, and the Big Words Blog Site Facebook page.  While my main areas of focus are Education, STEM and Financial Literacy, there are other blogs/sites I endorse which can be found on that particular page of my site.

A look at STEM: What is Toxicology?

Similar to Pharmacology, the field of Toxicology is centuries old and is very complex regarding the wealth and depth of information available.  It is also still evolving today.  The goal of this post is not to address every detail of the field, but instead to give readers a basic introductory understanding of the discipline.  Further details about the many aspects of Toxicology can be accessed online, or in scientific journals.

When I meet people outside of my scientific circles at career and STEM fairs, Toxicology doesn’t get confused with other disciplines the way Pharmacology and Pharmacy do – I thus won’t open with a story about misunderstandings.  I’ll simply say that Toxicology an exciting field with vast opportunities for individuals who are trained in it.  Following my principle of “Creating Ecosystems of Success”, I wanted to write an overview of the field – particularly for parents and young students who have an aptitude for science and may be interested in Toxicology as a career one day.  As you’ll see later on, Toxicology is an important component of numerous industries, and scientists with this training will never be without jobs.

“The dose makes the poison,” is the popular toxicology adage credited to the Swiss physician and alchemist Paracelsus.  Simply put, given the proper dose, even chemicals and substances considered harmless can be poisonous – too much sugar or water for example.  Dosage or the amount of a substance one is exposed to is a key component of Toxicology – keep this in mind as you read through this post.  Also keep in mind the route of exposure.  Toxicologists are always considering that an individual can be poisoned through oral ingestion, or through either dermal or inhalation exposures.

I think of Pharmacology and Toxicology as “sister” sciences – both dealing with the effects of xenobiotics on living systems.  While Pharmacology focuses more on the therapeutic effects of xenobiotics, Toxicology focuses on the harmful effects – in most cases humans but in some instances other mammalian and non-mammalian species.  These effects can occur on the molecular, cellular, tissue, and whole organism levels. While Pharmacology and Toxicology are separate disciplines, they have several overlapping principles and skill sets allowing individuals credentialed in one to work in the other.

I’ll start my discussion of why Toxicology is important with drugs.  Both biotechnology and large pharmaceutical compan9ies have to understand and report a drug’s toxicological profile to the federal government before selling it to the general public.  Many promising drugs actually never make it to market because they’re too toxic.  Some actually make it and are then recalled – Rezulin for example.

There are also both clinical and research contexts for Toxicology.  Similar to Pharmacology, all medical practitioners (Anesthesiologists, Physicians, Pharmacists, Nurses, Surgeons, etc.) must receive some toxicology training as they all need an understanding of the potential toxicities of the drugs they’ll ultimately prescribe.  They need to understand how much of a given pharmaceutical will be beneficial vs. harmful to patient – a drug’s “Therapeutic Index”.  If the patient is taking multiple medications, “Drug-Drug” interactions can result – toxicities and side effects resulting from one or more drugs being present in the body at the same time causing others be poisonous.  The patient’s current liver and kidney function are critical here as well as they will ultimately determine how long the drugs persist in the body.  In an emergency room, physicians must often determine what a patient may have been poisoned by in order make swift life-saving decisions.

Forensic Toxicologists are instrumental in solving crimes and deaths.  They’re masters of detecting chemicals in the body’s tissues and understanding how they may have led to a victim’s death.  Michael Jackson’s overdose on “Propofol” comes to mind, and is just one of many examples.

In the research context, think about experimentation in laboratory settings – well designed studies run by scientists asking questions and looking for specific answers.  Initial toxicological studies typically involve determining how a toxicant exerts its effect on the molecular and then on the tissue/organ levels – similar to how Pharmacologists identify new drug targets.  After determining a toxicant’s molecular mechanism, there is then the need to determine the toxic dose range of the chemical at the molecular, tissue and whole animal levels.  This is called a “Dose Response” – a critical tool of both Pharmacology and Toxicology where scientists look to determine if increasing the amount of the chemical in question, increases the amount of biological response.  This applies to a broad spectrum of chemicals – pharmaceuticals and industrial chemicals alike.

What am I referring to when I say industrial chemicals?  Simply look around your home at all of the products you use daily including: household cleaners, cosmetics, pesticides (Raid for example), and even additives and preservatives in some the foods we consume.  Thus when you think about Toxicology, think very broad in terms of scope.  For this reason, individuals with toxicology training will never be without jobs as everything we use must be screened for safety.  Toxicologists are currently in high demand.

Similar to Pharmacology, there are numerous sub-disciplines within Toxicology.  The following is a list of some of the major areas beyond what’s been described thus far.  These areas are heavily considered by government agencies and private sector companies who all need toxicologists to create new products, determine the safety of those products, and lastly determine the fate of those products once used:

  • Aquatic, Eco- and Environmental Toxicology: While these are distinct disciplines all in themselves, I’ve grouped them together for simplicity. They collectively consider toxicity to non-human life – aquatic, avian, other terrestrial life.  They consider what happens to ecosystems if a particular species is inadvertently killed off.  Some questions involve where the toxicant goes in our environment, how long it stays there, and if it breaks down into something else more or less toxic.
  • Computational (In silico) Toxicology: Uses computational models, to predict mammalian toxicities. “Tox21” is a current effort to minimize animal testing using computational and predictive models.
  • Entomotoxicology: Determines how a given chemical is toxic to insect species. This is very important for the creation of pesticides, and it’s also critical for Ecotoxicology as the chemical designed to control specific insects may easily kill something else unintended.

  • Food Safety Toxicology: Looks at the potential toxicity of man-made or natural ingredients intentionally added to our food. Heat formed compounds are of particular concern – acrylamide and furan are examples which can spontaneously form during the cooking of certain precursor molecules.  Lastly the ingredients in food packaging are also considered as they can be ingested through the foods they are in contact with.
  • Forensic Toxicology: As described above, deals with the solving of crimes – often determining what a victim was poisoned with.
  • In vitro Toxicology: Characterizes how a toxicant works using cell models and protein systems as opposed to whole animals.

  • Mammalian Toxicology: Studies the effects of a given toxicant on mammalian systems – traditionally using animals to model to human toxicity. Experiments can be designed over multiple dose ranges and through any of the three routes of exposure – oral, dermal or inhalation.  Time of these studies can range from hours to days, to years.  Varying indices can be studied such as life-stage sensitivity, cancer potential, or the ability to inhibit one’s immune response.  Mammalian toxicology is very important in “Regulatory” settings described below.
  • Modes of toxic action: Characterizes how toxicants exert their action on the molecular, cellular and whole animal levels. This information can be used to design chemicals to control something like a pest, or to determine how a cancer tumor-type forms.
  • Medical Toxicology: As described above, deals with the prevention of patient poisoning in medical settings.
  • Occupational Toxicology: Involves potential toxicity to workers who are in contact with a given toxicant and may get exposed through their skin or through inhalation.

  • Regulatory Toxicology (Private Sector): When the private sector creates a product, it must work with federal and state government agencies to determine the safety of that product. The products can be: drugs, pesticides, cosmetics, food additives, paints – you name it.  Regulatory Toxicologists in the private sector must understand government laws and guidelines for the products they’re creating – knowing which animal and in vitro studies to run to get their product registered in the most cost efficient way.
  • Regulatory Toxicology (Public Sector): Involves government and state agencies determining the safety of products produced by private industry. This usually consists of considering real world human exposures, and looking at any pertinent data (animal, in vitro, exposure or physical chemical) that might help model those exposures to determine levels of safety or lack thereof.
  • Toxicogenomics: Similar to Pharmacogenomics, looks at the genetics unique to individuals to determine potential increased toxicity for that individual.
  • Toxinology: Deals specifically with animal, plant and microbial toxins.
  • Toxicokinetics: Similar to the description in my Pharmacology post, Toxicokinetics deals with how the body handles toxicants in terms of absorption (entry to the body), tissue accumulation (distribution), biotransformation (metabolism) of the molecule, and excretion (elimination). I will revisit Pharmacokinetics and Toxicokinetics in greater detail in a separate post.

So have I convinced you that toxicologists are literally everywhere?  Similar to pharmacologists, toxicologists can leverage their skill sets to work in other capacities besides academia, and the public and private sectors.  When combined with other fields such as law and business, toxicologists can start their own companies – consulting for example, and in some cases they can create new health-related technologies and innovations.

There are numerous avenues by which to pursue training in Toxicology.  According the website of the Society of Toxicology, training can start as early as high school and the amount of training one pursues (Bachelors, Masters, Ph.D.) will depend upon specific career goals.  As there is tremendous overlap in skill sets of scientists in the biomedical sciences, one need not have a degree in “Toxicology” per se to work in the field in most cases. An exception is the federal government which is very stringent in terms of matching one’s academic credentials exactly with job openings regardless of one’s actual scientific training and expertise.  An individual for example with a Masters or Ph.D. in another biological science, MD, or a DVM for example can receive training in Toxicology through postdoctoral fellowship.

Toxicology also has a unique certification – the Diplomate of the American Board of Toxicology (DABT).  Earning one’s DABT allows toxicologists to be nationally certified which is particularly important in the private sector, and in capacities such as serving as expert witnesses in litigations.  The European Union has a similar certification titled “European Registered Toxicologists” (ERT).

If you are interested in learning more about the exciting field of Toxicology, I suggest that you visit the website of the Society of Toxicology (SOT) – the major professional society for Toxicology.  Click on the “Careers” tab and scroll down to the “Becoming a Toxicologist” tab.  A wealth of information is available talking about numerous aspects of the field.  Similar to Pharmacology, Toxicology has its own annual meeting hosted by SOT where scientists gather to network, discuss their results, employers seek new job prospects, and companies show their latest devices and technologies.

Thank you for taking the time to read this post, and I hope I was able to shed some light onto what Toxicology is.  If you enjoyed this post, you might also enjoy:

A special thank you is also extended to Dr. Chester Rodriguez for his contribution to this post, and sharing the importance of earning one’s DABT.

If you’ve found value here and think it would benefit others, please share it and or leave a comment.  To receive all of the most up to date content from the Big Words Blog Site, subscribe using the subscription box in the right hand column in this post and throughout the site.  Lastly follow me on Twitter at @BWArePowerful, and at the Big Words Blog Site Facebook page. While my main areas of focus are Education, STEM and Financial Literacy, there are other blogs/sites I endorse which can be found on that particular page of my site.

A look at STEM: What is Pharmacology?

The field of Pharmacology is centuries old and it is very complex with respect to the wealth and depth of information available.  It is still evolving today.  The goal of this post is not to address every detail of the field, but instead to give readers a basic introductory understanding of the discipline.  Further details about the many aspects of Pharmacology can be accessed online, or in scientific journals.

I earned my Ph.D. in Pharmacology from the University of Michigan.  I admittedly didn’t understand the field initially, although I did know that it dealt with drugs and hoped that a degree in it would one day secure a position for me in the Pharmaceutical industry.  Since starting my studies in 1999, completing my degree in 2005, and starting my current career as a Regulatory Scientist, I’ve gotten the same question over and over again, “You have a background in Pharmacology?  Are you a Pharmacist?”  At Career and STEM Fairs, I get this question a lot, and thus following my principle of “Creating Ecosystems of Success“, I wanted to write a brief overview of the field – particularly for parents and young students who have an aptitude for science and may be interested in Pharmacology as a career one day.

“Simply put, Pharmacy is the study of what drugs do to man, and Pharmacology is the study of what man does to drugs,” said one of the Cancer Pharmacology faculty in our Principles of Pharmacology course during my first year of graduate school.  This statement explained in a very simple way some of the differences between the two disciplines.  Pharmacy is the study of the actual drugs administered to patients as therapeutic agents and its practitioners work at various institutions including hospitals, medical centers, and drug stores – CVS for example.  Pharmacists are health professionals, earn Doctor of Pharmacy degrees (Pharm Ds), are experts on medications, and are responsible for dispensing medicines.  Pharmacology is a basic research science that studies the mechanisms underlying the therapeutic effects of pharmaceuticals and potential drug candidates with the goal of developing and testing of new drugs.

All medical practitioners (Anesthesiologists, Physicians, Pharmacists, Nurses, Surgeons, etc.) must take Pharmacology courses as they all need some understanding of the mechanisms of the drugs they ultimately prescribe.  Pharmacologists are the actual researchers performing experiments trying to create new drugs and identify new drug targets.  They further seek to characterize how mammalian systems (in most cases human although they are also involved in developing veterinary drugs) handle molecules at the molecular, cellular, tissue and whole organism levels.  It’s a vast field with many areas of specialization that I’ll discuss in the remainder of this post.

Pharmacology classically can be divided into two parts; Pharmacokinetics, which deals with how the drug is absorbed and eliminated by the body, and Pharmacodynamics, which deals with how the drug exerts its medicinal effect mechanistically.  The following sub-disciplines within Pharmacology generally fall under one of these two umbrellas or, in most cases, are a mixture of the two.  Each of us or someone we know has taken a drug or a treatment which has been impacted by one of these areas.  Any pharmacologist reading this can easily further parse this list out into greater detail, but again this was written for a general audience:

  • ADME/Drug Metabolism: Deals with how the body handles the therapeutic molecules in terms of absorption (entry to the body), tissue accumulation (distribution), biotransformation (metabolism) of the molecule, and excretion (elimination). Another focus of ADME/Drug Metabolism is “Drug Transport” which focuses on how drugs are absorbed and effluxed from cells using membrane channels and transporters impacting their effectiveness.  I will revisit ADME/Drug Metabolism in greater detail in a separate post as me and some of my peers know it pretty well and find it to be a very exciting aspect of both Pharmacology and Toxicology.
  • Antimicrobial Pharmacology: Involves the control of bacteria, fungi, and viruses to fight off or prevent infections.
  • Autonomic Pharmacology: Deals with how the drug interacts with the Autonomic Nervous System (that part of the nervous system responsible for controlling bodily functions that are not consciously directed such as the heartbeat, breathing, and the digestive system) particularly through pathways involving epinephrine, norepinephrine, dopamine, and seratonin.
  • Cancer Pharmacology: Deals with drugs used in the treatment of cancer – usually some form of chemotherapy.
  • Cardiovascular Pharmacology: Deals with drugs used in treatment of heart disease and regulation of blood pressure.  A well-known class is the “Statins” – cholesterol lowering drugs such as “Lipitor“.
  • Endocrine and Receptor Pharmacology: Deals with how a given drug binds, interacts or even blockades a given cellular receptor, and then what the receptor does or doesn’t do to impact the homeostasis of that cell or tissue. The receptor can be membrane bound or cytosolic (many hormone receptors).
  • Drug Discovery: Typically associated with the private sector and deals with the identification of new drug entities and the identification of new drug targets. In industry, pharmacologists generally refer to drugs as either “small molecules” which are our classic drugs like Aspirin (~180 g/mol), or “large molecules” (as heavy as 150,000 g/mol) also known as “biologics” which are generally proteins which have therapeutic effects.  An example is Abbvie’sHumira”.  The units “g/mol” or grams per mole designate a chemical’s molecular weight and as you can see the size difference between the two classes is considerable.
  • Neuropharmacology: Similar to Autonomic Pharmacology but deals with all of the other parts of the nervous system such as pain responses – analgesics and anesthetics for example.
  • Pharmacogenomics: This new and exciting field looks at the genetics unique to individuals to determine the best treatments and dosages for that individual.

For each of these sub-disciplines there is a clinical side and a research side.  The clinical side is self-explanatory – it involves treating patients for various diseases as well as the prevention of illness by the above mentioned medical practitioners.  Think of the many medications you have been prescribed when you go to see medical doctors when you’re sick or for checkups, emergencies or surgeries.  But where do these medications come from originally?  Also, where will new medications come from in the future?

This is where the research side come comes into play.  At institutions like my alma mater, and in the private sector, there are scientists working year round on research projects asking questions about current medications in addition to trying to unlock the secrets of nature to create new therapeutics.  The investigations they perform involve testing molecules using whole animal models, cellular models, and in vitro systems to ask questions at the molecular level (proteins, lipids, DNA and RNA) about what the compound does.  It’s this research that can get very esoteric to the general public and that is published in academic journals including: Drug Metabolism and Disposition, the Journal of Pharmaceutical and Experimental Therapeutics, and Molecular Pharmacology.

Pharmaceutical companies like Merck and Pfizer conduct research as well but instead of doing it strictly to find new knowledge, it’s to create new drugs that they can sell.  The same is true for smaller Biotech companies like Biogen.  Both need scientists with backgrounds in Pharmacology.  The Federal Government also employs scientists with backgrounds in Pharmacology to determine the safety of new drugs before they can be prescribed to the general public.  The same is true for food products and chemicals used in those products, so Pharmacologists are literally everywhere.

Pharmacologists generally receive their training at major research universities.  While undergraduates can get training in Pharmacology – nursing students for example, degrees in Pharmacology are usually conferred at the Masters and Ph.D. levels and support for the student’s educational expenses as well as a modest salary are provided.  Upon attaining these degrees, scientists then determine which sector they want to pursue – academia, the private or public sectors, or nontraditional careers.  With the skills obtained in graduate school, scientists with these backgrounds have the flexibility to combine their knowledge sets with other disciplines to go into a wide variety of areas in addition to drug discovery in pharmaceutical companies and biotechs including: consulting, Toxicology, patent law and even starting their own companies.

If you are interested in learning more about the exciting field of Pharmacology, I suggest that you visit the website of the American Society for Pharmacology and Experimental Therapeutics (ASPET).  You can then click on the Education & Careers link near the top of the page.  In the right hand column, there is a link titled About Pharmacology, that provides a great deal of interesting information.  Speaking of ASPET, all scientific disciplines have their own professional societies with annual meetings that rotate cities every year, and where scientists congregate to show their results, and network.  The two major professional societies for pharmacologists are ASPET, and the International Society for the Study of Xenobiotics (ISSX).

Thank you for taking the time to read this post, and I hope I was able to shed some light onto what Pharmacology is.  If you enjoyed this post, you might also enjoy:

A special thank you is also extended to Dr. Paul Hollenberg, Chair of the Department of Pharmacology at The University of Michigan when I was a student, who graciously looked at this post and gave feedback prior my publishing it.

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