Making-A-Pressor by Tom Latosek

Whether you are a brand-new paramedic or nurse or a seasoned critical care provider, chances are you have started or maintained a patient on vasopressors.  They are considered to be one of the hallmark drugs of resuscitation and what we consider to be “life support” drugs.  There are a few key drugs on the market that have fallen into/out of favor over the years for various reasons but there remains a significant amount of controversy on what the “best” agent is to use in a given situation. 
In this article, we step out of the clinical context of what the preferred vasopressor is for a given clinical situation, but instead take a look at the scientific concepts underlying their administration and efficacy as key players in resuscitation.  Specifically, we will look at those vasopressors derived from tyrosine and phenylalanine, though many of the biological concepts presented here extend to many other drugs as well.  It is my hope that by reading on you gain a better understanding of these agents to better apply them in your clinical practice, and that you learn or refresh your knowledge of biology and chemistry along the way.
Let’s dive in…
The Making of a Vasopressor
Above is what looks like a complicated synthesis pathway, a dreaded topic among many students in organic chemistry courses.  In this context, our goal is just to understand how our vasopressors are made in the body, and we can break down this complex pathway into more digestible components. 
First, looking at the picture above we can see that the process of forming the vasopressors: dopamine, noradrenaline (norepinephrine), and adrenaline (epinephrine).
Phenylalanine and tyrosine are both amino acids that are considered to be a part of the 20 essential amino acids the body requires to carry out many of our necessary reactions, and as the building blocks for other compounds (like nerdy legos). 
Both tyrosine and phenylalanine fall into the class of amino acids referred to as aromatics (literally because these enzymes have a sweet odor..).  Let’s talk a little bit of painless organic chemistry and the concept of an aromatic structure.
Aromatic ring structures are considered to be a very versatile form of an organic molecule. One of the most common structures is benzene, an aromatic ring of six carbons forming a hexagon.  The intersecting lines of the hexagons above each represent a carbon
Anytime you observe a second line, it indicates that there are two bonds attaching the carbons.  On most organic structures you will not see hydrogens, but they exist to satisfy a total of 4 bonds made by each carbon.  In this case, there is 1 additional H assumed to be attached to each carbon.
Why do we care so much about this?
It is a basic building block for adding things and moving other groups around, or forming new compounds. This is what makes these aromatic rings so versatile.  Ok, now let’s address how they apply to our vasopressors above.
If we start at tyrosine and we want to get to the compound L-Dopa, we need the compound tyrosine hydroxylase (the finger below) to make that happen.  If we break down the words, anything that contains “-ase” is an enzyme, and hydroxyl groups are the -OH groups you see on many of the molecules above. Legos don't build themselves. You need an enzyme to stack those puppies up!
The basic concept here, to go from tyrosine to L-Dopa we need to add a hydroxyl group (an -OH) to tyrosine.  Once that happens the new compound has different biological characteristics than the previous compound.  Because of the chemistry of the -OH group on L-Dopa it can now bind receptors differently and it reacts differently at physiological conditions inside the body.  
For example, Parkinson’s patients are often administered L-Dopa as part of their treatment regimen to replace needed dopamine in the brain.  L-Dopa can cross the blood brain barrier more readily, so it is administered in the L-Dopa form and converted to dopamine once inside the brain.   Another important point to consider is what we consider “vasopressors” derived from tyrosine, are also neurotransmitters that function within the brain carrying out other functions.
Back to the chemistry… to get from L-Dopa to dopamine, we need to do some rearrangement, and, in the process, we get rid of carbon dioxide. There is a loss of 1 carbon molecule and 2 oxygen molecules and we move the NH2group, called an amino group, to the end of the molecule.  Again, this rearrangement changes how this molecule will interact at different pH levels, with different receptors, and with different membranes.  The molecules are very similar, but the groups attached to them (NH2, OH, etc) change their functional abilities.  
In going from dopamine to noradrenaline (norepinephrine) and from noradrenaline to adrenaline (epinephrine) take a look above to see what’s added and what is re-arranged.  Then look at the arrows and see if you can make sense of the names of the enzymes, or reaction intermediates, that were needed to make those changes occur.  I would explain them here, but I think it would be more beneficial for you to see for yourself how that change occurs now that you have the education to decipher what just a few minutes ago may have looked extremely complex.
Now that the molecule is made, let’s discuss how they work in Part 2! Stay Tuned..
-Tom Latosek

Tom is a practicing paramedic and EMS educator who is interested in EMS research, and advancing the profession of EMS through education.  Tom has practiced in a variety of EMS clinical settings and teaches a variety of courses for a healthcare education company.  Tom holds an MS in neuroscience and a bachelor’s degree in biology and psychology and is currently a first-year medical student.


Making Your Presentations... Prolific!


If I click baited you into reading this with my cover art, I assume you are an educator looking to "spruce" up your presentation skills; or maybe you're a newbie looking to enter the world of teaching and education. I, too, was in the same spot, and while I think I still am a newbie, I have found many ways to improve my lectures and presentations over the years. I have been continuously trying to find ways to engage an audience, capture further and maintain their attention, and use visually pleasing slides, all while attempting to keep the information I relay easy to retain. That's where Prolific: The Speakers Atlas comes in.


Prolific: The Speakers Atlas is an online course directed at educators (or even soon to be educators) with intentions of elevating their lecture game and improving their presentations overall. Sam Ireland and Tyler Chrisitifulli are your instructors during this approximately 5-week long course, and you will find that they are handing out their "secrets" to education. 


Through emulation and a short stent through their course, I began revamping some of my content.

Lookie here:

(Slides from a capnography course I created; Eric Bauer’s “3 P’s of EtCO2) 

Not only did I improve the appearance of the slides, but through some constructive criticism from Sam and Tyler, I have learned to further appeal to the audience by using animations timed with my lecture to upgrade the entertainment value of my presentations.



As I nerd out on an almost daily basis -- and annoy the hell out of my wife --  over EMS related jumbo, I have co-workers and friends asking many questions about how I put some of my content together. I tell them about the Prolific course, of course. But I realize that it doesn't really answer the question. So here, I attempt to answer the questions I get the most often regarding the Prolific: The Speakers Atlas course. 



How do they do it?

As I mentioned… Through their course, Prolific: The Speakers Atlas. During that 5-weeks (5 online modules, at your own pace), Sam and Tyler take you through all you need to know to improve your presentations and lectures. This includes:


Content Development – This is the first module, where the course begins. The module includes material on content framework and storyboarding. You’ll learn to brainstorm ideas and allow natural progression for those ideas. You then start learning to develop a presentation and how to cater that presentation to specific time frames or different audience types. Sam and Tyler then teach you to build from your thoughts and organize the mess of ideas in your head. 

Graphic Design – In the second module, you get into my favorite part of the course: graphic design. You've watched many of the FOAMfrat presentations, I imagine. If you're anything like me, you've asked yourself, "how do they do that?"  Whether you use PowerPoint or Keynote, they got you covered.

Transitions and Builds – Imagining how your talk will go and how it actually goes when you are in front of an audience is often very different. Module three will dive into the speaker's mind and cover the avoidance of the audience divide through the clever use of transitions and builds within your presentation. You'll learn to avoid looking and feeling awkward in front of an audience.

Speaking and Drawing – Bueller? Bueller? Bueller? Module four concentrates on speech variability and avoiding that monotone voice everyone hates from presenters. You'll also dive into free drawing, memorization, and illustrations often seen on what many call, "whiteboard exercises."

Showing Up and Leaving Them Wanting More – How do we show up prepared? What awkward behaviors should we avoid? How do I keep the audience wanting more without looking like a douche? Module five covers these questions, without making you look… like a douche. Know your call to action and give the audience something to do when they leave.



Is the course stressful, is it graded?

Yes, to both, but in a good way! You’re getting two of the best speakers and educators in our industry giving you constructive criticism. Can that be stressful? Of course, but you have an opportunity only providers who take the course get; turn that stress into excitement.

You’ll have assignments, Q&A, and even a capstone project to show off all of the information you learned throughout the course. You'll be graded, but you won't fail. If you’re anything like me, you’ll be anxiously waiting for them to grade and critique your work.


While I thought this cover art was a masterpiece, following some criticism from Sam and Tyler, I learned quickly of some very common mistakes that educators make while creating their work. I’m gonna leave you wondering with this one. Take the course then come back and judge my work.




 Did you learn anything cool?

Hell yeah! I've used my obsession with memes and GIFs and found a way to include them in my presentations... THANKS, SAM!

 (Yes, they taught me to create these!)

Now, I could go on and on about the course… But I don’t want to bore you with a blog that’s too long (something they teach within the course). To summarize, take the course and let Sam and Tyler teach you some pretty rad things and improve your presentations/lectures. You’ll also gain access to an exclusive group on FB full of other EMS educators with similar passions.




Take The Course Now!




- Jared Patterson, CCP-C, One Rad Dude



Patterson, Jared M. (1989). Pretending to have an actual reference for this blog. Omaha: Nebraska. Patterson and Friends, LLC (Not really an LLC). #medicsagainst500and12. PROLIFIC2020 FOR 50% off.



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