This study guide will facilitate the understanding of sympathomimetics and sympatholytics and the adrenergic receptors at which these drugs interact. The educational goal is to understand the uses in dental practice of drugs that interact at the adrenergic receptors as well as toxicities that could occur as a result of these interactions.
In addition, dental patients are likely to be taking drugs that act at these receptors. The presence of these drugs could modify the actions of drugs prescribed in dental practice as well as produce interactions that could have serious consequences.
Learning Objectives, Lecture I 1. Integrate pharmacodynamic principles to understand the actions of drugs that interact with the adrenergic receptors and how these interactions are relevant to dental practice. Understand the effects of epinephrine and norepinephrine on the cardiovascular system.
Understand the rationale and potential toxicities for the use of epinephrine in dental practice. Understand the mechanisms for drug interactions involving drugs used in cardiovascular therapeutics as they relate to dental practice. Key drugs Epinephrine - Adrenalin Norepinephrine- Levophed. The classification of these receptors, and indeed receptors in general, is based on the interaction of agonists and antagonists with the receptors.
The actions of epinephrine, widely used in combination with local anesthetic drugs, are produced as a result of interactions with these receptors. Beta Receptor Systems Most tissues express multiple receptors. However, the dominant beta receptor in the normal heart is the beta 1 receptor while the beta 2 receptor is the dominant regulatory receptor in vascular and non vascular smooth muscle.
Epinephrine activates both the beta 1 and beta 2 -receptors. Norepinephrine activates only the beta 1 -receptor. Effect of Beta 1 Receptor Activation on the Heart : Activation of the beta 1 receptor leads to increases in contractile force and heart rate. 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. 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.
Or the excessive use or overdose of sympathomimetic medication like pseudoephedrine or those used to treat attention deficit disorders. Severe alcohol withdrawal may also induce sympathetic overdrive. Excessive stimulation of the sympathetic receptors can result in dangerously high blood pressure, tachycardia, dysrhythmias and hyperthermia, any one of which may cause organ damage with the real potential for organism death.
Now let's switch to the parasympathetic or cholinergic receptors. 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.
Any adrenergic effects on cells are generally mediated by G protein-coupled receptors. Other areas of smooth muscle contraction are: Ureter. Vas deferens. Hair arrector pili muscles. Uterus when pregnant. Urethral sphincter. Blood vessels of ciliary body stimulation causes mydriasis. Induction of glucagon release from the pancreas.
0コメント