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Thursday, March 30, 2017

How do respiratory and cardiac medicines work?

I thought it would be neat to do a pithy review of how respiratory and cardiac medicines work. We will begin here with a basic anatomy lesson, beginning with the nervous system. As we proceed through our discussion I will introduce some of the medicine we commonly use. So, let us begin.

There are two nervous systems.
  1. Autonomic Nervous System:  It controls the many body functions that you do not have control over, such as your heart, vessels, stomach, and intestines.  
  2. Somatic Nervous System:  It allows you to control various parts of your body, such as your arms, legs, and breathing.  
For the case of this post, we are only concerned with the sympathetic nervous system. I will delve into the somatic nervous system in a future post.

Sympathetic Nervous System:  It has two divisions that both effect heart, smooth muscles, iris of the eye, salivary glands, and urinary bladder.
  1. Sympathetic Nervous System (SNS): Also called flight or fright.  It prepares the body to handle stress, either real or perceived. The stress could be trauma, or it could be someone holding a gun to your head.  It could be that you just heard about a family member dying, or your boss is screaming at you.  When any sort of stress occurs, your sympathetic response causes vasoconstriction to increase your blood pressure and heart rate. At the same time, this response relaxes your involuntary smooth muscles to dilate air passages to make breathing clear and easy. It also relaxes the involuntary smooth muscles of your bladder and gastrointestinal tract (might make you have an accident). The purpose of all this is to prepare you to do battle, or to run from it. Various medicines can mimic all or any of the sympathetic responses, and are called sympathomimetic medicine, or adrenergic agonist medicines.  
  2. Parasympathetic Nervous System (PNS): It generally does the opposite of the sympathetic. It causes vasodilation to lower blood pressure and lower heart rate. It also causes involuntary smooth muscles to constriction to normalize the flow of air through air passages, and to help you gain control of your bladder and gastrointestinal tract. Medicines that mimic this response are called parasympathomimetic or cholineric agonists. Medicines that block this are called anticholinergic medicines. 
Receptors:  Along all the muscles and vessels inside your body are receptor sites.  Many of these are attached along nerves, and are at the receiving end of an impulse.  When certain hormones are sent along the nerve and received by that receptor, a series of chemical reactions occur that causes a response by the muscle or vessel (either dilation or contraction). 

The main organ that makes the hormone that we are concerned with is the adrenal gland, which sits on either side of the kidney.  When you become excited or stressed, this gland secretes adrenaline that is sent down neurons to the various receptor sites.  Adrenalin extracts were discovered and named just prior to the turn of the 20th century, and isolated in 1901. It was learned that these extracts (later learned to be the hormone adrenaline) mimic the sympathetic response, and worked great for asthma and hay fever.  It is for this reason that receptor sites for this system are called adrenergic receptors.  In Britain the term adrenaline continues to be used, although in the United States the name epinephrine is used.  So this should explain some of the wording used here.  

Alpha Receptor sites:  Hormones released by the SNS system become attached to the following receptors to cause the following responses:
  1. Beta 1 (B1):  Located on heart muscle. When stimulated, it causes vasoconstriction. This makes blood vessels narrow, so the heart will have to generate a stronger force to pump blood through them. Your heart rate will also increase. Cardiac output is directly correlated with blood pressure, so a rising cardiac output can be measured by taking a blood pressure. It can also be felt when you palpate a full and bounding pulse. It is for this effect that epinephrine is used during cardiac arrest. It is a strong vasopressor (increases blood pressure). It's easy to remember because you have 1 heart. 
  2. Beta 2 (B2):  Located in lungs.  Causes smooth muscles that wrap around the airways to relax and this causes bronchodilation.  This is easy to remember because you have 2 lungs (right and left).
  3. Alpha 1 (A1):  Located in peripheral blood vessels.  Causes vasoconstriction to increase heart rate and force of contraction (increased blood pressure). It's easy to remember because you have 1 heart. 
  4. Alpha 2 (A2): Located by the nerve synapse.  Causes vasodilation to lower blood pressure. These act like a thermostat, and once the heart rate and force are too high, it shuts turns them down.  
Adrenaline (epinephrine):  This hormone regulates the SNS response and readies the body for flight or fight.  Adrenaline is released and attaches to B2, A1, or A2 receptors. It's a strong bronchodilator and vasopressor. 
Noradrenaline (norepinephrine):  Attach to B2 and A1 to act as vasopressors. 

Dopamine:  It is also created by the adrenal gland, and drugs that mimic it attach to A1 and A2 receptors to cause vasoconstriction and increased rate and force of heart and increased blood pressure. When attached to receptor sites, it stimulates the release of norepinephrine to generate a better blood pressure (vasopressor)

Dobutamine:  Effects B1 receptor sites and causes increased heart rate and strength of cardiac contraction (increased blood pressure).  It is generally used for heart failure (CHF) to make the heart a stronger muscle.  It increases cardiac output and blood pressure without much increase in heart rate. 

Beta blockers:  These are drugs that block the beta receptors.  The effect is mainly to try to control blood pressure, although a major side effect may be to cause narrowed air passages.  It is for this reason Beta blockers should be used with caution on patients with asthma or similar lung diseases. 

Albuterol:  It is a refined version of epinephrine without the side effects.  It has a strong affinity to B2 receptors and only slight affinity to B1 and A1.  Studies in the early 1990's showed that epinephrine was no better than albuterol for treating asthma. Side effects are also considered to be generally negligible. It has gone on to become the best selling asthma medicine of all time.

Levalbuterol:  It is a refined version of Albuterol, having the same strong B2 effect with minimal B1 and A1 affect. Some early studies showed that it was stronger and with fewer side effects than albuterol, although this has not been confirmed in the clinical setting. It is still under patent, and so most clinicians prefer to use the lesser expensive albuterol. 

Adrenal Gland:  It makes the hormones that effect upon the adrenergic receptor sites.  It makes the neurotransmitter dopamine, which goes through a series of chemical changes to become the neurotransmitter norepinephrine and then the neurotransmitter epinephrine. It also makes the neurotransmitter acetylcholinen which acts upon the PNS receptor sites, which are referred to as Cholinergic Receptor Sites. 

Cholinergic Receptor Sites:  Receptor sites used for the PNS are called cholinergic receptors.  The main neurotransmitter here is acetylcholine, hence the name cholinergic. It is used to cause bronchoconstriction and vasodilation, or to return things back to normal.  It basically has the opposite effect as the SNS.  The two types of receptors are:
  1. Nicotonic:   Found in central nervous system, autonomic ganglia, and striated muscle. 
  2. Muscarine:  Found in cardiac and smooth muscle, exocrine glands and brain
Atropine:  It competes with aceylcholine for muscarine receptors, and therefore blocks the effects of the PNS.  This results in an increase heart rate and bronchodilation.  It is used for bradycardia and asystole (flatline, non beating heart).   Herbs that contained this chemical were used for asthma-like symptoms going all the way back to ancient Egypt.  So when you read the history of asthma, you will probably hear about asthma cigarettes, incense, and other inhaled methods.  The active ingredient was always atropine, and the herbs it was contained in were strammonium and belladonna. 

Atrovent:  This is a refined version of atropine without the side effects.  It is recommended as a preventative medicine for COPD and severe asthma.  It needs to be taken four times a day to obtain the full effect, as it only lasts 4-6 hours. 

Spiriva:  This is a refined version of Atrovent that lasts 12 hours and only needs to be taken twice a day.

(Originally published in 3/9/13; edited and updated for accuracy.)

  1. Guy, Jeffrey, "Pharmacology for the prehospital setting," 2007, U.S., Jones and Bartlett Learning, 

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