Understand the potential sites of action for sympathomimetics and the difference between a direct and indirect acting agonist. Understand the pharmacologic actions and therapeutic actions of drugs that act at the beta 1 and beta 2 -adrenergic receptors as well as the alpha 1 -adrenergic receptor. Know the mechanism of action and effects of amphetamine and cocaine. Understand how the pressure of sympathomimetics alters the dental management of patients. Sympathomimetics: synthetic analogs of naturally occurring catecholamines that mimic the actions of the endogenous neurotransmitters.
These agents can be divided into direct and indirect acting sympathomimetics. Direct acting agonists or antagonists can act at postsynaptic receptors. Indirect acting agonists release neurotransmitters from presynaptic nerve terminals to produce a sympathomimetic effect.
Inhibition of the membrane uptake of catecholamines by drugs such as cocaine and tricyclic antidepressants produce a sympathomimetic effect. Inhibition of monoamine oxidase by drugs such as Tranylcypromine. In congestive heart failure, the failing heart is not able to eject blood as efficiently as the normal heart. As a result there is a decrease in cardiac output which triggers a host of compensatory actions. These include fluid retention, vasoconstriction, an increase in peripheral vascular resistance, an increase in the levels of circulating catecholamines and tissue hypoxia.
Dopamine and dobutamine activate the myocardial beta 1 receptor and thus increase the force of contraction of the failing heart. This will result in an increase in cardiac output. These drugs are reserved for use in the acute management of heart failure.
These agents have a higher affinity lower equilibrium dissociation constant for beta 2 receptors when compared to beta 1. Therefore, they selectively activate beta 2 receptors when compared to beta 1. Uses 1.
Airways dysfunction; bronchial asthma, chronic bronchitis, emphysema In airways dysfunction, beta 2 selective agonists relax airways thus decreasing airways resistance. Premature labor In premature labor, the beta 2 selective agonists relax uterine smooth muscle.
Drugs that relax uterine smooth muscle are referred to as tocolytic agents. Side effects related to dental practice 1. Xerostomia, with inhaler usage. These structural modifications of the parent catecholamine nucleus result in drugs that are orally active and have longer plasma half-lives. However, these same modifications result in lower affinity for the receptor than do the endogenous agonists epinephrine or norepinephrine.
There are two structural classes of alpha 1 agonists phenethylamines which are closely aligned in structure to epinephrine and the imidazolines, compounds structurally unrelated to epinephrine. Levonordeferin is a phenyethylamine that has been used in dental practice in combination with local anesthetics. Hypotension-to increase blood pressure during a surgical procedure where a general anesthetic has induced hypotension 2.
Ophthalmic preparations-to induce mydrasis also in topical preparations for symptomatic release of eye irritation. Cough and cold preparations-Induces constriction of nasal mucosa decreases resistance to air flow.
Indirect Acting Sympathomimetics These agents require the presence of endogenous catecholamines to produce their effects. They have little activity if catecholamines are depleted. Cocaine: Blocks reuptake of monoamines into nerve endings. Cocaine also has local anesthetic activity. Amphetamine: Promotes the release of NE from nerve endings. Amphetamine can also block the reuptake of norepinephrine. Amphetamine-like compounds 1.
Methylphenidate A major site action of cocaine, amphetamine and amphetamine-like agents is in the CNS. These drugs produce a feeling of well being and euphoria. As a result the drugs carry a significant abuse liability.
Both cocaine and amphetamine are on the FDA schedule 2. Uses of Cocaine 1 below , Amphetamine and Amphetamine-like agents below 1. Cocaine has limited use as a local anesthesic and vasoconstrictor in surgical procedures involving oral, laryngeal or nasal cavities. Appetite suppression 3. Hyperactivity in children 4. Recall that epinephrine can be absorbed systemically after intraoral administration.
This epinephrine can be taken up by nerve terminals and this uptake contributes to the the termination of the actions of epinephrine.
Thus, the risk of hypertension and other problems associated with systemic absorption of epinephrine will be greater in patients taking cocaine or amphetamine-like drugs. Methamphetamine can be produced from over the counter cough and cold medications such as pseudoephedrine. Isoprenaline is a nonselective agonist. Adrenergic signal transduction : This schematic shows the mechanism of adrenergic receptors. The result is that high levels of circulating epinephrine cause vasoconstriction.
Smooth muscle behavior is variable depending on anatomical location. One important note is the differential effects of increased cAMP in smooth muscle compared to cardiac muscle. Increased cAMP will promote relaxation in smooth muscle, while promoting increased contractility and pulse rate in cardiac muscle.
Common or still unspecified effects include: vasoconstriction of cardiac arteries coronary artery , vasoconstriction of veins, and decreased motility of smooth muscle in the gastrointestinal tract. The former interacts with calcium channels of the endoplasmic and sarcoplasmic reticulum, thus changing the calcium content in a cell. This triggers all other effects. It causes vasoconstriction in many blood vessels, including those of the skin, gastrointestinal system, kidney renal artery , and brain.
Other areas of smooth muscle contraction are:. Antagonists may be used in hypertension. Learning Objectives Describe adrenergic neurons and receptors in the autonomic nervous system. Key Terms adrenoreceptor : These are a class of G protein-coupled receptors that are targets of the catecholamines, especially norepinephrine noradrenaline and epinephrine adrenaline.
Many cells possess these receptors, and the binding of a catecholamine to the receptor will generally stimulate the sympathetic nervous system. G protein-coupled receptors : These comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal transduction pathways and, ultimately, cellular responses. The EMS1 Academy hosts "Module 8: PathophysiologyPathophysiology," a 3-hour course to prepare providers to handle the patient with a pathophysiological emergency.
Visit the EMS1 Academy to learn more. When these buttons are turned on or off, things happen in your body. If you learn about these receptors and their actions described below, you will be able to understand what a beta-blocker drug does or what to expect from an alpha-agonist medication or how cocaine can be bad for you.
All of the receptors that we will discuss have additional actions that are not listed below, but these extra actions are not essential to your understanding of these receptors as they apply to the prehospital practice of medicine. The types of sympathetic or adrenergic receptors are alpha, beta-1 and beta Alpha-receptors are located on the arteries. When the alpha receptor is stimulated by epinephrine or norepinephrine, the arteries constrict.
This increases the blood pressure and the blood flow returning to the heart. The blood vessels in skeletal muscles lack alpha-receptors because they need to stay open to utilize the increased blood pumped by the heart. Remember the fight or flight response? It would not make sense to take blood from other parts of the body and pump it to the muscles so we can run away or defend ourselves if the blood vessels in the skeletal muscles are also constricted and cannot benefit from the increased blood circulation providing extra oxygen and nutrients.
So what do you think happens if we block these alpha-receptors? Right, the arteries dilate. Thus an alpha-blocker medication causes vasodilation and can be used to treat hypertension. Next are the beta receptors. Beta-1 receptors are located in the heart. When beta-1 receptors are stimulated they increase the heart rate and increase the heart's strength of contraction or contractility. The beta-2 receptors are located in the bronchioles of the lungs and the arteries of the skeletal muscles.
When these receptors are stimulated, they increase the diameter of the bronchioles to let more air in and out during breathing and they dilate the vessels of the skeletal muscles so they can receive the increased blood flow produced by stimulating the alpha and beta 1 receptors. So reflect for a moment: If norepinephrine or epinephrine is the neurotransmitter of the sympathetic nervous system and it interacts with all the receptors we just described, then we know that norepinephrine or epinephrine stimulates the alpha, beta-1 and beta-2 receptors and thus it is an alpha agonist, a beta-1 agonist and a beta-2 agonist.
When we administer epinephrine or adrenaline to a patient, we expect alpha, beta-1 and beta-2 agonist effects; we expect an:. We can also stimulate a single receptor site such as a beta-2 agonist medication like an albuterol inhaler that stimulates beta-2 receptors in the lungs then we can dilate the bronchioles in the patient with bronchospasm without causing excessive stimulation of the heart. The sympathetic receptors can be over-stimulated by the non-therapeutic use of substances like cocaine and methamphetamines.
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