Receptores Adrenergicos

ADRENERGIC PHARMACOLOGY
This study guide is designed to facilitate the understanding of sympathomimetics and sympatholytics and the adrenergic receptors at which these drugs interact to produce their therapeutic effects. The first lecture and handout will cover basic information regarding adrenergic receptors and how these receptors function in mediating the activity of the sympathetic nervoussystem. Hyperlinks are also available to enhance your understanding of the material. To facilitate your learning this material is covered in Chapter 10 in Goodman and Gilman's Pharmacologic Basis of Therapeutics, Tenth Edition.
A link to the top 200 prescription drugs (by number of US prescriptions) for 2001 can be found at this link http://www.rxlist.com/top200.htm. Of this number, 20 products(10 % of the total) contain drugs to be discussed in these 3 lectures. Therefore, a clear understanding of these drugs and the receptors that they act upon is of obvious importance and relevance.
Learning Objectives, Lecture I
1. Integrate pharmacodynamic principles to aid in the understanding of adrenergic receptors and the actions of drugs on these receptors.
2. Understand the criteriaupon which alpha and beta receptors are defined.
3. Understand the second messenger systems utilized by alpha and beta receptors and how activation of these receptors leads to a change in physiologic function.
4. Understand the effects of alpha and beta receptor activation on the heart and blood vessels.
5. Understand the effects of isoproterenol, epinephrine and norepinephrine on thecardiovascular system.

Key drugs
Isoproterenol - Isuprel

Epinephrine - Adrenalin

Norepinephrine- Levophed
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The adrenergic receptors which subserve the responses of the sympathetic nervous system have been divided into two discrete subtypes: alpha adrenergic receptors (alpha receptors) and beta adrenergic receptors (beta receptors). The classification of these receptors, and indeedreceptors in general, is based on the interaction of agonists and antagonists with the receptors.
| PUTATIVESTRUCTUREOFADRENERGICRECEPTORS |
PROPOSED BINDING OF NE TO THE BETA RECEPTOR | |
Beta Receptors
Beta receptors have been further subdivided into beta1 and beta2 receptors. It should be pointed out that beta3 and beta4 receptors have recently been isolated, cloned and characterized. Thebeta3 receptor may be involved in regulating the metabolism of fatty acids. This receptor could be the site of antiobesity drugs in the future. The functions of the beta4 receptor remains to be discovered. For the purposes of this material we will focus on the beta1 and beta2 receptors only. The classification of beta receptors is based on the interaction of a series of drugs with thesereceptors. The ability of epinephrine, norepinephrine and isoproterenol to increase the force of myocardial contraction was examined and the dose-response curves shown below were obtained. Equilibrium dissociation constants for these ligands were ISO, 80 nm, E, 800 nM, and NE, 1000 nM. Thus, the rank order of affinities for the beta receptor in the heart is ISO>E>NE. A beta receptor with thesecharacteristics is referred to as a beta1 receptor. The equilibrium dissociation constant is often used as a "finger print" to identify a receptor. Regardless of its location, the receptor will interact in the same manner with ligands and have the same dissociation constants for agonists and antagonists. The logic above is a standard approach to differentiate receptors. The interaction of agonists andantagonists with receptor systems often indicates heterogeneity within the main receptor population. These different receptors are referred to as receptor subtypes. Receptor subtypes are routinely exploited in drug development to make ligands that interact selectively with one subtype in preference to another. Specific examples of this principle are presented in these lectures and throughout the...