Access your subscriptions. Free access to newly published articles. Purchase access. Rent article Rent this article from DeepDyve. Access to free article PDF downloads. Save your search. Customize your interests. Create a personal account or sign in to:. Privacy Policy. So-called selective agents will activate additional adrenergic receptors if the dosage is abnormally high.
In this section we discuss the responses—both therapeutic and adverse—that can be elicited with sympathomimetic drugs. Because many adrenergic agonists activate more than one type of receptor see Table Consequently, rather than attempting to structure this presentation around representative drugs, we discuss the actions of the adrenergic agonists one receptor at a time.
Our discussion begins with alpha 1 receptors, and then moves to alpha 2 receptors, beta 1 receptors, beta 2 receptors, and finally dopamine receptors. For each receptor type, we discuss both the therapeutic and adverse responses that can result from receptor activation.
To understand the effects of any specific adrenergic agonist, all you need are two types of information: 1 the identity of the receptors at which the drug acts and 2 the effects produced by activating those receptors. Combining these two types of information will reveal a profile of drug action. This is the same approach to understanding neuropharmacologic agents that we discussed in Chapter Before you continue, I encourage you to review Table We are about to discuss the clinical consequences of adrenergic receptor activation, and Table If you choose not to memorize Table In this section we discuss the therapeutic and adverse effects that can result from activation of alpha 1 -adrenergic receptors.
As shown in Table Activation of alpha 1 receptors elicits two responses that can be of therapeutic use: 1 vasoconstriction in blood vessels of the skin, viscera, and mucous membranes ; and 2 mydriasis.
Of the two, vasoconstriction is the one for which alpha 1 agonists are used most often. Using these drugs for mydriasis is rare. Hemostasis is defined as the arrest of bleeding, which alpha 1 agonists support through vasoconstriction. Alpha 1 agonists are given to stop bleeding primarily in the skin and mucous membranes. Epinephrine, applied topically, is the alpha 1 agonist used most for this purpose.
Nasal congestion results from dilation and engorgement of blood vessels in the nasal mucosa. Drugs can relieve congestion by causing alpha 1 -mediated vasoconstriction. Specific alpha 1 -activating agents employed as nasal decongestants include phenylephrine administered topically and pseudoephedrine administered orally. Alpha 1 agonists are frequently combined with local anesthetics to delay systemic absorption.
The mechanism is alpha 1 -mediated vasoconstriction, which reduces blood flow to the site of anesthetic administration. Why delay anesthetic absorption? Because keeping the drug at the local site of action prolongs anesthesia, allows a reduction in anesthetic dosage, and reduces the systemic effects that a local anesthetic might produce. The drug used most frequently to delay anesthetic absorption is epinephrine.
Because of their ability to cause vasoconstriction, alpha 1 agonists can elevate blood pressure in hypotensive patients. Please note, however, that alpha 1 agonists are not the primary therapy for hypotension.
Rather, they are reserved for situations in which fluid replacement and other measures either are contraindicated or have failed to restore blood pressure to a satisfactory level.
Activation of alpha 1 receptors on the radial muscle of the iris causes mydriasis dilation of the pupil , which can facilitate eye examinations and ocular surgery. Note that producing mydriasis is the only clinical use of alpha 1 activation that is not based on vasoconstriction. All of the adverse effects caused by alpha 1 activation result directly or indirectly from vasoconstriction.
Alpha 1 agonists can produce hypertension by causing widespread vasoconstriction. Severe hypertension is most likely with parenteral dosing. If the IV line used to administer an alpha 1 agonist becomes extravasated, seepage of the drug into the surrounding tissues may result in necrosis tissue death.
The cause is lack of blood flow to the affected area secondary to intense local vasoconstriction. If extravasation occurs, the area should be infiltrated with an alpha 1 -blocking agent e.
Alpha 1 agonists can cause reflex slowing of the heart. The mechanism is this: alpha 1 -mediated vasoconstriction elevates blood pressure, which triggers the baroreceptor reflex, causing heart rate to decline. In patients with marginal cardiac reserve, the decrease in cardiac output may compromise tissue perfusion. Alpha 2 receptors in the periphery are located presynaptically, and their activation inhibits NE release. Several adrenergic agonists e.
However, their ability to activate alpha 2 receptors in the periphery has little clinical significance because there are no therapeutic applications related to activation of peripheral alpha 2 receptors.
Furthermore, activation of these receptors rarely causes significant adverse effects. In contrast to alpha 2 receptors in the periphery, alpha 2 receptors in the CNS are of great clinical significance. By activating central alpha 2 receptors, we can produce two useful effects: 1 reduction of sympathetic outflow to the heart and blood vessels and 2 relief of severe pain.
The central alpha 2 agonists used for effects on the heart and blood vessels, and the agents used to relieve pain, are discussed in Chapters 15 and 22 , respectively.
All of the clinically relevant responses to activation of beta 1 receptors result from activating beta 1 receptors in the heart; activation of renal beta 1 receptors is not associated with either beneficial or adverse effects. As indicated in Table Heart failure is characterized by a reduction in the force of myocardial contraction, resulting in insufficient cardiac output. Because activation of beta 1 receptors in the heart has a positive inotropic effect i.
This condition is characterized by profound hypotension and greatly reduced tissue perfusion. Drugs that activate the beta 1 receptor can be used in heart failure to improve the contractile state of the failing heart. Drugs that activate the beta 1 receptor also increase heart rate. Indeed, excess stimulation the beta 1 receptor can induce significant increases in heart rate and arrhythmias.
Arrhythmias are a major concern with drugs such as epinephrine that can be absorbed systemically after intra-oral injection. Effect of Beta 2 Receptor Activation on Smooth Muscle: Activation of the beta 2 receptor leads to vascular and nonvascular smooth muscle relaxation.
Drugs that activate the beta 2 receptor can be used to treat as asthma by relaxing airway smooth muscle and premature labor by relaxing uterine smooth muscle. Alpha receptors have been further subdivided into alpha 1 and alpha 2 receptors. Both epinephrine and norepinephrine activates both the alpha 1 and alpha 2 receptors.
Presynaptic Alpha 2 Receptors Alpha 2 receptors also exist presynaptically associated with nerve terminals. Activation of these receptors inhibits the release of norepinephrine. Norepinephrine acts at presynaptic alpha 2 receptors to inhibit its own release. Postsynaptic Alpha 1 Receptors on Vascular Smooth Muscle: Associated with vascular smooth muscle are a large number of alpha 1 receptors relative to beta 2 receptors. Activation of these receptors by sympathetic nervous system transmission or drugs will result in vasoconstriction and an increase in peripheral resistance and systemic arterial blood pressure.
Applications to Therapeutics Oral dosing of norepinephrine or epinephrine is not possible due to the rapid metabolism of catechol nucleus in gastrointestinal mucosa and liver. Therefore, these agents are given I. Epinephrine is often used in combination local anesthetic agents to prolong the duration of anesthetic action.
This would include articaine, bupivacaine or lidocaine. This combination is used because epinephrine can induce vasoconstriction thus limiting the diffusion of the local anesthetic from the site of injection. This not only prolongs the actions of the local anesthetic but also to reduce the toxicity of the local anesthetic by limiting its systemic absorption.
Lidocaine in toxic doses can produce cardiac arrthythmias and convulsions. Epinephrine can also be topically applied in surgical procedures to induce vasoconstriction and thus reduce blood loss. Epinephrine is used in the treatment of shock and in emergency situations related to bronchial asthma.
Clinical studies have shown that epinephrine blood levels increase following its intraoral administration. The risk of this increase is dependent on characteristics of the patient. For example, hypertensive patients or those with other cardiovascular disease or patients taking other drugs that affect sympathetic nervous system function are at higher risk than patients without these conditions.
Systemically absorbed epinephrine could also increase heart rate and exacerbate cardiac rhythm disturbances or myocardial ischemia. Learning Objectives Lecture II 1. 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.
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