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Volume 1, Number 16
Weekly EMS Drill
Pharmacology Discussion - Epinephrine
OBJECTIVE: This week’s drill will start a series of discussions regarding the drugs that we carry in the
CCFD and a review of some of the actions and indications for these drugs.
The first drug of discussion is Epinephrine. Epinephrine is our first line drug of choice for all cardiac arrested
patients, and is useful in mediating the effects of asthma and anaphylaxis.
Epinephrine is both a neurotransmitter and a hormone. The name is derived from Greek words epi- and nephros
literally meaning “on the kidney”, a reference to the adrenal gland from which epinephrine is produced. In the
normally functioning body, it boosts the supply of oxygen and glucose to the brain and skeletal muscle, while
concurrently suppressing other non-emergent body processes. It affects both alpha and beta adrenergic receptor
sites in a dose related manner, which is the primary impetus for using it in an arrested patient.
Alpha receptor site stimulation exerts multiple actions on the body. A person who experiences a sympathetic
response will have alpha1 receptors activated in the liver, which stimulates glycogenolysis, with the end result
of increasing blood glucose levels. The cells would need this extra energy when their output demand goes up as
a result of the “fight or flight” response. Most of us are more familiar with the other locations of alpha receptor
sites, in most smooth muscle and the splanchnic vessels, as well as the skin. Stimulation of these sites would
trigger vasoconstriction.
Beta receptor sites have three subtypes, beta1, beta2, and beta3. Beta1 receptor sites (for our purposes) are
primarily located in the heart. Stimulation of these receptor sites would cause an increase of the intracellular
concentration of a second messenger referred to as cyclic adenosine monophosphate (cAMP). This messenger
in the cardiac cells is the primary driver behind the familiar effect of beta1 stimulation, namely increased
cardiac output. This is accomplished through three genres, raised heart rate (referred to as positive chronotropic
effect), increased initiation and conduction of cardiac electrical impulses, (positive dromotropic effect), and
increased muscular contraction force, thus increasing blood volume expelled with each beat (ejection fraction).
This is referred to as a positive inotropic effect.
Beta2 receptor sites are also widespread, and exert multiple actions. For purposes of this discussion, the effects
include smooth muscle relaxation in the bronchi, dilation of arteries in skeletal and cardiac muscle,
glycogenolysis and gluconeogenesis, inhibition of histamine release from MAST cells, and promotion of insulin
release from pancreatic beta cells.
Beta3 receptor sites have a role in enhancing lipolysis in adipose tissue, for energy production in times of stress.
While beta1 and -2 receptor sites are more pertinent to our discussion of an arrested patient, the third Beta effect
has a role in explaining why long term stress can increase a person’s cholesterol levels, because lipolysis will
have a tendency to release triglycerides free into the bloodstream, leading to cardiac and vascular disease.
In an arrested patient, studies have shown that increased hydrostatic pressure in the area of the heart helps with
perfusion to the affected cells, and possibly increases the effectiveness of delivered energy to terminate
ventricular fibrillation. To that end, a relatively large dose of epinephrine (1 mg) administered IV will have a
tendency to interact with the alpha1 receptor sites in the periphery, causing vasoconstriction and a shift of blood
to the central core of the body. Due to the drug being quickly sequestered following administration, subsequent
doses can be administered every three to five minutes without concern of toxicity, as long as the patient remains
pulseless.
The increased heart rate and contractility (beta1) effect can also be of benefit in an arrested patient, particularly
a patient presenting in asystole or a patient being treated following the PEA algorithm. There is the possibility
of increased irritability of the cardiac tissue following ROSC (return of spontaneous circulation), but that effect
can usually be mitigated after the fact, assuming a successful outcome of resuscitative efforts.
Epinephrine is also the drug of choice for treating anaphylaxis due to the receptor site agonist effects discussed
earlier. Large scale histamine release from MAST cell degranulation will cause a two-fold life threatening
effect, that of bronchoconstriction and pulmonary compromise due to airway narrowing, and increased venule
and capillary permeability. The latter will lead to an interstitial shift of fluid and loss of vascular volume,
inducing a lack of perfusion to the tissues (shock). Epinephrine is ideally suited to counteract these histamine
effects, as alpha1 receptor stimulation would have a tendency to restore capillary integrity through
vasoconstriction, while the beta effects would counteract the further release of histamine itself, stimulating
bronchodilation in the pulmonary smooth muscle, and increasing output from the heart.
Great care must be taken with administration of epinephrine in this situation, because overabundant
administration could precipitate extreme tachycardic states, (including V-TACH) and severe hypertension.
Limiting the overall dose to no more than 0.5 mg by subcutaneous administration would generally be effective
in controlling the anaphylactic symptoms, without adversely affecting the patient’s hemodynamic status. CCFD
protocol gives approval for IV epinephrine in the case of severe reactions. In that case, one would utilize the
1:10,000 strength pre-filled syringe (NEVER push epinephrine 1:1,000 IV) and push SLOWLY no more than
0.5 mg to avoid adverse effects.
We will continue our discussion of drugs next week.