Ah, the exception to the rule. If you are on this page for the first time, go ahead and scroll down to the earlier posts so you know what the heck I’m talking about. If you get it already, then nevermind! Carry on!
First of all, I want you to dig back in that Rolodex of your mind and think about the nervous system. Remember that the Peripheral Nervous System (PNS) goes out into the body to send efferent signals, and receives afferent signals to bring back to the CNS. Well the PNS is full of alpha-1, beta-1, and beta-2 receptors. Alpha-2 receptors are there too, but their main function is to stop NE release presynaptically. We actually don’t have much therapeutic use for those particular PNS alpha-2 receptors, so generally we ignore them*.
The alpha-2 receptors we need to worry about are the ones in the Central Nervous System (CNS) and they are very important! There are two main functions of these important receptors:
1. Reduce the sympathetic efferent signals from the CNS (so reducing adrenergic response in the PNS)!
2. Reduce the perception of severe pain, especially neuropathic pain.
You may have noticed that these adrenergic receptors do not prepare you to run from tigers like the other ones do. The best way to remember this is that they are located in a different area. They still control sympathetic stimuli, but they do it higher up in the chain. Alpha-2 receptors in the CNS are the Dictators of the adrenergic receptors. “No, alpha-1, you SHALL NOT BE ACTIVATED!”. Or something like that.
*There are many MANY things that need to be learned about all receptors, so it’s handy to just acknowledge that PNS alpha-2’s are there on the synapses, just in case you decide on further research! For the purposes of common drugs, just put those guys on the back burner.
I know, breathing and babies sound kind of unrelated. But that’s what you have to remember about beta-2! Activation of this receptor does two major things:
1. Bronchodilation (Some people say “-dilitation” by the way. It’s the same thing so don’t sneer!). This is very useful for asthma, as it widens the airways and let’s you breathe easier.
2. Relaxation of uterine smooth muscle. Huh? No, for real. Beta-2 receptors are on the uterus! When they are activated, the uterus relaxes. Therefore, if you or someone you love is going into preterm labor, they might get a beta-2 agonist to stop that baby!
Now, I know that I’ve been breaking these receptors down for you one by one. Now that you’ve got the gist of it, here I am to break some news to you. First of all DON’T HAVE AN ADRENERGIC ATTACK. You okay? Okay.
Remember when I said that the BEST DRUG EVER would be totally selective? And that there is no BEST DRUG EVER? Yeah. Well, most drugs are not selective. That’s where side effects come from! Most adrenergic drugs affect more than one receptor. Like epinephrine, for example. It’s actually an alpha-1, beta-1, and beta-2 receptor agonist. Some beta blockers mostly block beta-1 but also block beta-2 a little bit. So, just keep that somewhere in the back of your mind as we move on to the drugs later. But also remember: No matter how many receptors a drug affects, if you know what the receptor does, you know what the drug will do!
When you think of Beta-1, always think of the HEART. Beta-1 receptors are all over the heart muscle. There just happen to be some fancy words, that you should DEFINITELY remember, associated with beta-1 affect on the heart.
Beta-1 effects are:
1. Positive Chronotropic: They cause the heart to beat faster.
2. Positive Inotropic: They cause the heart to pump harder
3. Positive Dromotropic: They increase the conductive ability of the heart.
These terms are important because when we get to the drugs, they can be very easily classified according to these characteristics!
As you may have guessed, beta-1 agonists can be used for all sorts of heart issues, including AV heart block (a conduction issue) and heart failure, among other things!
So, can you now think of some characteristics of a beta-1 antagonist (beta blocker)?
Yes! Negative Inotropic, Negative Chronotropic, Negative Dromotropic! So beta blockers make your heart slow down, let it not pump quite so hard, and chill out all of those nerve impulses that may be causing it to freak out a little bit.
Fun fact: There are a ton of auditioning musicians (especially Classical musicians!) that take beta-blockers for an off-label use. Can you figure out why?
Straightjacket, you ask? Yes! Because the number one thing you should remember about alpha-1 receptors is that their activation causes constriction. VASOCONSTRICTION, to be exact. As you may remember from physiology class, blood vessels are wrapped in a layer of smooth muscle. The alpha-1 receptors are all over this smooth muscle, and signal it to contract (thus constricting the blood vessel) when the brain says so.
A drug that is an alpha-1 agonist will cause vasoconstriction. How can this be used therapeutically? Glad you asked! Here are a few therapeutic uses for alpha-1 agonists:
1. Hemostasis. Yes, there are times that we want this to happen! Epinephrine is used topically during surgery to constrict blood vessels and reduce bleeding. Go team!
2. Hand-in-hand with local anesthesia. Vasoconstriction means that drugs can’t flow out of the area so quickly, so adding an alpha-1 agonist makes the anesthetic effect last longer!
3. Sniffle-bashing, AKA nasal decongestion! The main ingredients of many cold medicines, pseudephedrine and phenylephrine, are both alpha-1 agonists. When they shrink the blood vessels in your nose, you become less congested.
4. Okay, I lied a little bit. There is a use for alpha-1 agonists that has nothing to do with vasoconstriction. They do one more thing, and that is they cause the pupils to dilate. This is called mydriasis. Alpha-1 agonists are often added to the solution squirted on your eyeball at the opthamologist’s office.
Woohoo! My favorite receptors! Adrenergic receptors activate the sympathetic branch of the autonomic nervous system. So, adrenergic agonists are known as sympathomimetics, that is, they mimic a sympathetic, or “fight or flight”, response. Adrenergic antagonists are called sympatholytics.
1. There are FIVE very important subtypes of adrenergic receptor (these will be addressed in detail later). They are: alpha-1, alpha-2, beta-1, beta-2, and Dopamine.
2. The main neurotransmitter that activates adrenergic receptors is Norepinephrine (NE).
3. Adrenergic receptors are located all over the body, including the heart, blood vessels, digestive tract, and even in the uterus!
4. Agonism or antagonism of an adrenergic receptor can be accomplished by binding to the receptor directly, blocking the receptor, or messing with the release, clearance, or binding of norepinephrine.