Pharmacology Phridays: A "Quick and Dirty" Guide to Sympathomimetics

Congratulations folks, it’s Friday!  Granted, for those of us in EMS, weekends do not really mean that much.  However, it’s an important milestone none-the-less, if for no other reason than trying to keep up with the rest of society.  If you’re a reader here, you have another reason to be happy, because today marks the start of “Pharmacology Phridays.”  I’ve decided that I’ll try to profile a different medication you’re likely to encounter in the field every Friday.  These drugs will probably be the ones you’re likely to be using, but I’ll also throw in the odd prescription or OTC medication for giggles once in awhile as well.

Our first Pharmacology Phriday will be a bit of a twofor; you have my partner at work to thank for that.  As we were waiting to pick up a patient from one of our local ICU’s the other day, he began quizzing me on how dopamine works, and why we would find ourselves giving it.  I wasn’t able to answer him with the level of confidence I wanted, so decided it was probably time to hit the books (again) myself.  The more I studied, the more I realized that I should first do a “quick and dirty” look at the sympathetic nervous system and sympathomimetics in general, and then hit dopamine, specifically.  So you’re welcome.

Gotham’s “Quick and Dirty” to the Sympathetic Nervous System

Batman vs. Joker, Parasympathetic vs. Sympathetic...seems about right.

The nervous system is made up of two major parts, the Sympathetic and the Parasympathetic nervous systems.  The parasympathetic nervous system controls most of the things that happen when your body is relaxed, such as digestion, excretion, etc.  You could call it the “feed and breed” system.  On the other hand, the sympathetic nervous system controls all the things that happen when your body is stressed, like increasing your heart rate, increasing respiratory rate, etc; its the "fight or flight" side of the nervous system.  The parasympathetic and sympathetic systems oppose each other, like Batman and the Joker.  If one is being stimulated, the other is being repressed.  We're not going to worry about the parasympathetic system right now, just know that it's there.

The sympathetic nervous system is also called the adrenergic system.  The adrenergic system passes information from the brain to target organs (such as the heart, lungs, and muscles) using cells called neurons, and chemicals called neurotransmitters.  Neurotransmitters pass information from neuron to neuron, and from neuron to target organ by bonding to, or interacting with, small structures in cells called receptors.  When a neurotransmitter binds to a receptor, it causes a biological effect to take place.  So, for example, if the body wants to increase its heart rate due to being pursued by the Joker’s minions, an impulse would be sent from the brain to the heart via the sympathetic nervous system’s neurons.  Neurotransmitters would be released from the neurons which would bind to receptors in the heart muscle myocardium.  That interaction would cause a series of changes which would cause the heart to beat faster.  

In the adrenergic system the primary neurotransmitter, also called a catecholamine, is a chemical called Norepinephrine.  As for receptors, we’ve classified six different types of receptors in the adrenergic system, each of which have different effects when stimulated.  The six kinds of adrenergic receptors are:

1. Alpha 1 Receptors:  When stimulated, cause the blood vessels in the extremities to constrict (the professional way to put this is “peripheral vasoconstriction”).
2. Alpha 2 Receptors:  When stimulated, cause the adrenal glands to stop producing norepinephrine.
3. Beta 1 Receptors:  When stimulated, cause the heart to beat more rapidly, with greater force, with more automaticity, and conduction.
4. Beta 2 Receptors:  When stimulated, cause the blood vessels in the extremities to get bigger (“peripheral vasodilation”).
5. Beta 3 Receptors:  When stimulated, causes body fat to be broken down, and body heat to be produced.
6. Dopaminergic Receptors:  When stimulated, cause dilation of the renal, coronary, and cerebral arteries.  

Weren't You Going to Talk about Sympathomimetics?

Right.  So how does this affect us in EMS?  First of all, its pronounced "sym-path-o-my-met-ics."  As medics, we are able to give a variety of drugs which either simulate the effects of of the sympathetic nervous system on target organs, or directly stimulate the sympathetic nervous system (or the adrenergic system, whichever works better for you) to signal to target organs.  Drugs which either directly cause an effect similar to a catecholamine like norepinephrine, or stimulate the production of catacholamines which then go on to cause the effect are called sympathomimetics (because they “mimic” the “sympathetic” system).  The most commonly used sympathomimetics are epinephrine, norepinephrine (Levophed), isoproterenol (Isuprel), dopamine (Intropine), and dobutamine (Dobutrex).  

We're going to get to know this one very well...

Sympathomimetics are usually used in EMS to treat shock by improving systemic blood pressure.  Recall that shock is hypoperfusion of tissues due to loss of blood volume (hypovolemic shock), problems with the heart, such as the heart not beating at all, not beating fast enough, or not beating with enough force (cariogenic shock), and problems with the vascular container, such as the blood vessels becoming leaky or too dilated either due to massive bacterial infection or nervous damage (distributive shock, with anaphylactic shock and septic shock).  

A quick glance at the various types of receptors will show you that if we stimulate the right receptor, we have our choice of how to raise a patient’s blood pressure because, luckily for us, some sympathomimetics target vein and artery size, while others target the heart itself.  Of those that target the heart, we say that some are positive Chronotropic Agents (which means they cause an increase in heart rate), others are positive Inotropic Agents (which means they cause an increase in the force of cardiac contraction), and others are positive Dromotropic Agents (which means they cause an increase in speed of conduction through the heart’s AV node, which in turn increases heart rate).  

So, to treat a patient who is experiencing shock (with the exception of hypovolemic shock—more on that later):  Option one is to increase systemic blood pressure by increasing peripheral vasoconstriction by stimulating alpha 1 receptors (making the blood’s container smaller).  Option two is we could increase systemic blood pressure by  increasing cardiac output using positive chronotropic/inotropic/dromotropic agents which stimulate beta one receptors (improving the pump).  

The various sympathomimetics (epinephrine, norepinephrine, isoproterenol, dopamine, and dobutamine) all have slightly different properties, which means that they all target a slightly different combination of adrenergic receptors.  So a doctor can fine-tune a patient’s drug therapy depending on a great number of factors.  For those of us who ride ambulances, the options are somewhat more limited.  In my system, we carry dopamine or norepinephrine (Levophed), which we use for all patients who need any kind of sympathomimetic drug therapy.  

Stay tuned—we will dig a little deeper into a specific sympathomimetic tomorrow.

Sources:

Bledsoe, BE and Clayden, DE.  Prehospital Emergency Pharmacology, 7th ed.  Pearson, New York New York, 2012.