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Epinephrine
Adrenaline, Norepinephrine, Noradrenaline
Epinephrine is the drug of choice for the emergency treatment of severe allergic reactions (Type I) to allergens, such as those present in certain insect venoms, foods, or drugs.
Norepinephrine Molecule
Image by TheVisualMD
Norepinephrine Receptor
Image by TheVisualMD
Epinephrine is a signaling molecule released from the adrenal medulla into the bloodstream as part of the sympathetic response.
Norepinephrine is a signaling molecule released as a neurotransmitter by most postganglionic sympathetic fibers as part of the sympathetic response, or as a hormone into the bloodstream from the adrenal medulla.
Source: CNX OpenStax
Catecholamine Tests
Also called: Catecholamines, Dopamine, Epinephrine, Norepinephrine
This test measures the levels of catecholamines in a blood or urine sample. Catecholamines are hormones made by the adrenal glands. The three catecholamines are epinephrine (adrenaline), norepinephrine, and dopamine. High levels can indicate certain types of rare tumors.
Adrenal Gland
Image by TheVisualMD
Figure 17.17 Adrenal Glands Both adrenal glands sit atop the kidneys and are composed of an outer cortex and an inner medulla, all surrounded by a connective tissue capsule. The cortex can be subdivided into additional zones, all of which produce different types of hormones. LM × 204. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)
The adrenal cortex releases glucocorticoids in response to long-term stress such as severe illness. In contrast, the adrenal medulla releases its hormones in response to acute, short-term stress mediated by the sympathetic nervous system (SNS).
The medullary tissue is composed of unique postganglionic SNS neurons called chromaffin cells, which are large and irregularly shaped, and produce the neurotransmitters epinephrine (also called adrenaline) and norepinephrine (or noradrenaline). Epinephrine is produced in greater quantities—approximately a 4 to 1 ratio with norepinephrine—and is the more powerful hormone. Because the chromaffin cells release epinephrine and norepinephrine into the systemic circulation, where they travel widely and exert effects on distant cells, they are considered hormones. Derived from the amino acid tyrosine, they are chemically classified as catecholamines.
The secretion of medullary epinephrine and norepinephrine is controlled by a neural pathway that originates from the hypothalamus in response to danger or stress (the SAM pathway). Both epinephrine and norepinephrine signal the liver and skeletal muscle cells to convert glycogen into glucose, resulting in increased blood glucose levels. These hormones increase the heart rate, pulse, and blood pressure to prepare the body to fight the perceived threat or flee from it. In addition, the pathway dilates the airways, raising blood oxygen levels. It also prompts vasodilation, further increasing the oxygenation of important organs such as the lungs, brain, heart, and skeletal muscle. At the same time, it triggers vasoconstriction to blood vessels serving less essential organs such as the gastrointestinal tract, kidneys, and skin, and downregulates some components of the immune system. Other effects include a dry mouth, loss of appetite, pupil dilation, and a loss of peripheral vision. The major hormones of the adrenal glands are summarized in Table
| Hormones of the Adrenal Glands | |||
|---|---|---|---|
| Adrenal gland | Associated hormones | Chemical class | Effect |
| Adrenal cortex | Aldosterone | Steroid | Increases blood Na+ levels |
| Adrenal cortex | Cortisol, corticosterone, cortisone | Steroid | Increase blood glucose levels |
| Adrenal medulla | Epinephrine, norepinephrine | Amine | Stimulate fight-or-flight response |
Source: CNX OpenStax
Fight or Flight
Image by TheVisualMD
Where an autonomic neuron connects with a target, there is a synapse. The electrical signal of the action potential causes the release of a signaling molecule, which will bind to receptor proteins on the target cell. Synapses of the autonomic system are classified as either cholinergic, meaning that acetylcholine (ACh) is released, or adrenergic, meaning that norepinephrine is released. The terms cholinergic and adrenergic refer not only to the signaling molecule that is released but also to the class of receptors that each binds.
The cholinergic system includes two classes of receptor: the nicotinic receptor and the muscarinic receptor. Both receptor types bind to ACh and cause changes in the target cell. The nicotinic receptor is a ligand-gated cation channel and the muscarinic receptor is a G protein–coupled receptor. The receptors are named for, and differentiated by, other molecules that bind to them. Whereas nicotine will bind to the nicotinic receptor, and muscarine will bind to the muscarinic receptor, there is no cross-reactivity between the receptors. The situation is similar to locks and keys. Imagine two locks—one for a classroom and the other for an office—that are opened by two separate keys. The classroom key will not open the office door and the office key will not open the classroom door. This is similar to the specificity of nicotine and muscarine for their receptors. However, a master key can open multiple locks, such as a master key for the Biology Department that opens both the classroom and the office doors. This is similar to ACh that binds to both types of receptors. The molecules that define these receptors are not crucial—they are simply tools for researchers to use in the laboratory. These molecules are exogenous, meaning that they are made outside of the human body, so a researcher can use them without any confounding endogenous results (results caused by the molecules produced in the body).
The adrenergic system also has two types of receptors, named the alpha (α)-adrenergic receptor and beta (β)-adrenergic receptor. Unlike cholinergic receptors, these receptor types are not classified by which drugs can bind to them. All of them are G protein–coupled receptors. There are three types of α-adrenergic receptors, termed α1, α2, and α3, and there are two types of β-adrenergic receptors, termed β1 and β2. An additional aspect of the adrenergic system is that there is a second signaling molecule called epinephrine. The chemical difference between norepinephrine and epinephrine is the addition of a methyl group (CH3) in epinephrine. The prefix “nor-” actually refers to this chemical difference, in which a methyl group is missing.
The term adrenergic should remind you of the word adrenaline, which is associated with the fight-or-flight response described at the beginning of the chapter. Adrenaline and epinephrine are two names for the same molecule. The adrenal gland (in Latin, ad- = “on top of”; renal = “kidney”) secretes adrenaline. The ending “-ine” refers to the chemical being derived, or extracted, from the adrenal gland. A similar construction from Greek instead of Latin results in the word epinephrine (epi- = “above”; nephr- = “kidney”). In scientific usage, epinephrine is preferred in the United States, whereas adrenaline is preferred in Great Britain, because “adrenalin” was once a registered, proprietary drug name in the United States. Though the drug is no longer sold, the convention of referring to this molecule by the two different names persists. Similarly, norepinephrine and noradrenaline are two names for the same molecule.
Having understood the cholinergic and adrenergic systems, their role in the autonomic system is relatively simple to understand. All preganglionic fibers, both sympathetic and parasympathetic, release ACh. All ganglionic neurons—the targets of these preganglionic fibers—have nicotinic receptors in their cell membranes. The nicotinic receptor is a ligand-gated cation channel that results in depolarization of the postsynaptic membrane. The postganglionic parasympathetic fibers also release ACh, but the receptors on their targets are muscarinic receptors, which are G protein–coupled receptors and do not exclusively cause depolarization of the postsynaptic membrane. Postganglionic sympathetic fibers release norepinephrine, except for fibers that project to sweat glands and to blood vessels associated with skeletal muscles, which release ACh (image).
| Autonomic System Signaling Molecules | ||
|---|---|---|
| Sympathetic | Parasympathetic | |
| Preganglionic | Acetylcholine → nicotinic receptor | Acetylcholine → nicotinic receptor |
| Postganglionic | Norepinephrine → α- or β-adrenergic receptors Acetylcholine → muscarinic receptor (associated with sweat glands and the blood vessels associated with skeletal muscles only | Acetylcholine → muscarinic receptor |
Signaling molecules can belong to two broad groups. Neurotransmitters are released at synapses, whereas hormones are released into the bloodstream. These are simplistic definitions, but they can help to clarify this point. Acetylcholine can be considered a neurotransmitter because it is released by axons at synapses. The adrenergic system, however, presents a challenge. Postganglionic sympathetic fibers release norepinephrine, which can be considered a neurotransmitter. But the adrenal medulla releases epinephrine and norepinephrine into circulation, so they should be considered hormones.
What are referred to here as synapses may not fit the strictest definition of synapse. Some sources will refer to the connection between a postganglionic fiber and a target effector as neuroeffector junctions; neurotransmitters, as defined above, would be called neuromodulators. The structure of postganglionic connections are not the typical synaptic end bulb that is found at the neuromuscular junction, but rather are chains of swellings along the length of a postganglionic fiber called a varicosity (image).
Figure 15.5 Autonomic Varicosities The connection between autonomic fibers and target effectors is not the same as the typical synapse, such as the neuromuscular junction. Instead of a synaptic end bulb, a neurotransmitter is released from swellings along the length of a fiber that makes an extended network of connections in the target effector.
Fight or Flight? What About Fright and Freeze?
The original usage of the epithet “fight or flight” comes from a scientist named Walter Cannon who worked at Harvard in 1915. The concept of homeostasis and the functioning of the sympathetic system had been introduced in France in the previous century. Cannon expanded the idea, and introduced the idea that an animal responds to a threat by preparing to stand and fight or run away. The nature of this response was thoroughly explained in a book on the physiology of pain, hunger, fear, and rage.
When students learn about the sympathetic system and the fight-or-flight response, they often stop and wonder about other responses. If you were faced with a lioness running toward you as pictured at the beginning of this chapter, would you run or would you stand your ground? Some people would say that they would freeze and not know what to do. So isn’t there really more to what the autonomic system does than fight, flight, rest, or digest. What about fear and paralysis in the face of a threat?
The common epithet of “fight or flight” is being enlarged to be “fight, flight, or fright” or even “fight, flight, fright, or freeze.” Cannon’s original contribution was a catchy phrase to express some of what the nervous system does in response to a threat, but it is incomplete. The sympathetic system is responsible for the physiological responses to emotional states. The name “sympathetic” can be said to mean that (sym- = “together”; -pathos = “pain,” “suffering,” or “emotion”).
Source: CNX OpenStax
Epi-Pen Jr. (1)
Image by Intropin/Wikimedia
Epinephrine is the drug of choice for the emergency treatment of severe allergic reactions (Type I) to allergens, such as those present in certain insect venoms, foods, or drugs. It can also be used in the treatment of anaphylaxis of unknown cause (idiopathic anaphylaxis) or exercise-induced anaphylaxis. Epinephrine, when given intramuscularly or subcutaneously, has a rapid onset and short duration of action.
Epinephrine acts on both alpha and beta adrenergic receptors. Through its action on alpha adrenergic receptors, epinephrine lessens the vasodilation and increased vascular permeability that occurs during an anaphylactic reaction and can lead to loss of intravascular fluid volume and hypotension. Through its action on beta adrenergic receptors, epinephrine causes bronchial smooth muscle relaxation that helps alleviate bronchospasm, wheezing, and dyspnea that may occur during anaphylaxis.
Epinephrine also helps alleviate pruritus, urticaria, and angioedema, and may be effective in relieving gastrointestinal and genitourinary symptoms of anaphylaxis because of its relaxer effects on the smooth muscle of the stomach, intestine, uterus and urinary bladder.
Source: DailyMed/Epinephrine Injection, USP
Epipen design
Image by Chemistryroxpharmacysux/Wikimedia
Epinephrine auto-injector is indicated in the emergency treatment of severe allergic reactions (Type I) including anaphylaxis to stinging insects (e.g. order Hymenoptera, which includes bees, wasps, hornets, yellow jackets and fire ants), and biting insects (e.g. triatoma, mosquitos), allergen immunotherapy, foods, drugs, diagnostic testing substances (e.g. radiocontrast media), and other allergens, as well as anaphylaxis to unknown substances (idiopathic anaphylaxis) or exercise-induced anaphylaxis. Epinephrine auto-injector is intended for immediate administration in patients with a history of anaphylactic reactions. Selection of the appropriate dosage strength is determined according to patient body weight.
Such reactions may occur within minutes after exposure and consist of flushing, apprehension, syncope, tachycardia, thready or unobtainable pulse associated with a fall in blood pressure, convulsions, vomiting, diarrhea and abdominal cramps, involuntary voiding, wheezing, dyspnea due to laryngeal spasm, pruritus, rashes, urticaria, or angioedema. Epinephrine auto-injector is designed as emergency supportive therapy only and is not a replacement or substitute for immediate medical care.
Source: DailyMed/Epinephrine Injection, USP
Epinephrine Injection
Also called: Adrenaclick®, Adrenalin®, Auvi-Q®, EpiPen®, Symjepi™, Twinject®, Epinephrine Auto-Injector
Epinephrine injection is a prescription medicine used to treat allergic emergencies (anaphylaxis). Anaphylaxis can be life threatening, can happen within minutes, and can be caused by stinging and biting insects, allergy injections, foods, medicines, exercise, or unknown causes.
Epinephrine-ampule
Image by Jfoldmei/Wikimedia
As children return to school, they should be prepared for the classroom. That includes having emergency treatments on hand if they have known allergic reactions to bee stings, food allergies and other allergens. These allergic reactions, called anaphylaxis, can be fatal, but can be managed with emergency treatments called epinephrine, along with emergency medical care.
Some parents may have a hard time obtaining these treatments because of the surge of demand at the beginning of school year.
It is important to know there are several options out there. This is how parents can make sure their kids have emergency epinephrine treatments tucked safely into their backpack:
Adverse reactions to epinephrine include anxiety, apprehensiveness, restlessness, tremor, weakness, dizziness, sweating, palpitations (heart racing sensation), pallor (paleness), nausea and vomiting, headache, and respiratory (breathing) difficulties. Rare cases of serious skin and soft tissue infections have been reported after epinephrine injection.
Source: Food and Drug Administration (FDA)
Epinephrine Oral Inhalation
Also called: Primatene® MIST
Epinephrine oral inhalation is an over-the-counter bronchodilator used for temporary relief of mild symptoms of intermittent asthma, including wheezing, tightness of chest and shortness of breath.
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