Adrenergic receptors:Anatomy, physiology, andpharmacological interactionsSANDRA M. MAREE, BS, CRNAWinston-Salem, North Carolina

The author presents a review of theperipheral autonomic nervous system and itssympathetic component with specialemphasis given to the neurotransmitter andthe adrenergic receptor site. Also discussedare pharmacological interactions andclinical considerations.

The success of anesthesia and the surgical experi-ence is dependent on many factors including anintact autonomic nervous system and the ability ofthe patient to respond reflexly to stress. Cardiacrate and rhythm, as well as airway resistance, islargely controlled by the antagonistic effects of thesympathetic and parasympathetic nervous systems.Alterations in cardiovascular or pulmonary func-tions are beacons which warn the anesthetist ofimbalances in the involuntary nervous system. In-hibiting or exciting either segment may result incardiac dysrhythmias, dysfunction or bronchospas-tic disorders.

Dysrhythmias of vagal predominance havebeen treated for years with drugs such as the anti-cholinergics, resulting in competitive antagonismof acetylcholine at the cholinergic muscarinic re-ceptors. The majority of problems that developduring the administration of anesthesia, however,is of sympathetic origin. Appropriate managementof these potentially hazardous problems is depen-dent upon an understanding of the adrenergic sys-tem and its effector site, the alpha and beta re-ceptor.

The adrenergic systemThe autonomic nervous system plays a major

role in maintaining homeostasis. Two major divi-sions of this system, the sympathetic and parasym-pathetic, consist of neurons and ganglia which in-nervate glands, the heart, blood vessels, and vis-ceral smooth muscle. In general, the two divisionshave antagonistic effects. The parasympathetic seg-ment functions to conserve or restore the organismwhile the sympathetic segment prepares the orga-nism for "fight or flight."

Pharmacologically, these systems are classifiedas cholinergic and adrenergic systems. Cholinergicis a term describing those fibers which releaseacetylcholine as their neurotransmitter. Acetylcho-line is effective on both nicotinic and muscarinicreceptors. Adrenergic is a term describing thosefibers which release norepinephrine as their neuro-transmitter. Norepinephrine is effective on alphaand beta receptors. The systems, their receptors,and the effects of receptor stimulation are sum-marized in Table 1.1.2

Sympathetic division of the autonomic ner-vous system originates from cells located in thelateral horns of the spinal cord from T 1 to L2-3. 3

These preganglionic fibers leave the cord andsynapse with postganglionic nerve cells, located inthe ganglia on each side of the vertebral column orin the abdominal cavity. Once a synapse has oc-curred, the impulse is carried by postganglionicfibers to the adrenergic neuroeffector junction.

Anatomically, the postganglionic sympatheticnerve consists of a cell body, long axon, and ex-

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Table 1.Autonomic Nervous System

Parasympathetic

AChNicotinic

III

AACh

Alpha1) Vasoconstriction

Beta 11) Increased heart rate2) Increased contractility3) Increased conduction

velocity

Beta21) Dilatation of bronchioles2) Dilatation of arterioles

Muscarinic1) Stimulation or inhibition

of smooth muscle2) Stimulation of exocrine

glands3) Slowing of cardiac con-

duction4) Decreased myocardial

contractility

Nico tinic1) Stimulation of autonomic

ganglia2) Stimulation of adrenal

medulla to releasecatecholamines

3) Stimulation of skeletalmuscle at motor end plate

( Preganglionic fibers

- - - - - - < Postganglionic fibers

Table 2.Synthesis of Norepinephrine

Tyrosine

Tyrosine Hydroxylase

Dopa

Decarboxylase

Dopamine

Dopamine BOxidase

Norepinephrine

PhenylethanolamineN-methyl-transferase

Epinephrine

tensively branched terminals. The distal end ofthis nerve and the adjacent effector cells (whichare innervated by this neuron) is known as theneuroeffector junction. The nerve terminal con-tains the machinery for the synthesis, storage, re-lease, and metabolism of the adrenergic neuro-transmitter. The effector cell contains the machin-ery which receives the transmitter and initiates thealteration of cellular function.

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Adrenergic nerve terminalThe principal adrenergic neurotransmitter is

norepinephrine. 4 The adrenergic neuron synthe-sizes the catecholamine, stores it in small granules,and finally releases it in response to an appropriatestimulus. The synthesis of norepinephrine isthrough a series of enzyme-controlled steps, sum-marized in Table 2.5

Phenylethanolamine-N-methyl-transferase isfound in the adrenal medulla and is responsiblefor converting 80% of the medullary norepineph-rine to epinephrine. Although the medullaryhormones are released and interact with the adren-ergic sites during stress, norepinephrine acts as themediator in homeostasis.

The arrival of an action potential at the post-ganglionic nerve terminal causes norepinephrineto be released into the synaptic cleft. It then dif-fuses across the cleft to participate in the neuro-transmitter-receptor interaction. Following this in-teraction, the response is terminated almost entirelyby the uptake and return of norepinephrine fromthe receptor and synaptic cleft back into the nerveterminal. Small amounts may be inactivated in thecytoplasma by monoamineoxidase but most will bereturned to the storage vesicle for reuse."

Journal of the American Association of Nurse Anesthetists

Sympathetic

iACh

Nicotinic

NE

Adrenergic receptor

Since Erhlick proposed that drugs react withspecific cellular sites and Langley suggested thatthe chemical substances which mediate autonomicactivity from nerve to effector cells react with spe-cific receptor sites, the concept of receptors hasbecome firmly rooted in pharmacological thought.7

In 1930, Cannon and Rosenbleuth proposed twohypothetical adrenergic neurotransmitters, an ex-citatory one (sympathin E) and an inhibitory one(sympathin I), to explain the varied effects.

This concept, however, did not unveil themysteries of the adrenergic neuroeffector junction.In 1948, Ahlquist published a paper concerningadrenotropic receptors. He suggested that thevaried effects of sympathetic activity are due todifferent receptor types in the effector cell and notto different neurotransmitters. The presence ofdifferent adrenergic receptors could be demon-strated by differing orders of potency within a sin-gle series of closely related compounds on differentphysiological systems.

He found that the order of potency of sixsympathomimetic amines in animals was the samefor excitatory systems, but differed for several in-hibitory systems. Epinephrine and norepinephrinewere most active and isoproterenol the least activein terms of vasoconstriction and pupil dilation.Isoproterenol was the most active and norepineph-rine the least active as a vasodilator and cardiacstimulant.

Allquist therefore proposed the classificationof alpha and beta adrenotropic receptors: alphafor the least responsive to isoproterenol and betafor the most responsive to isoproterenol. 8 Approx-imately 10 years later it was discovered that di-chloroisoproterenol selectively antagonized thoseeffects of catecholamines, classified by Ahlquist asbeta effects, thus strengthening the argument fortwo types of adenoceptors. . 10

The classification of receptors is based onseveral types of evidence which are all related tothe actions of drugs upon tissues or cells. Thechemical structure of the transmitter or drug pro-vides a measure of specificity. Although both epi-nephrine and digitoxin increase the force of myo-cardial contraction, they are different chemicallyand tlheir mechanism of action is also different.

Effects whicli are opposite in character, pro-duced by two different agents, can be presumedto act through different receptor mechanisms. Forexample, the negative chronotropic effect of acetyl-choline on the sinoatrial node is due to an inter-action at the cholinergic muscarinic receptor; the

positive chronotropic effect of epinephrine is dueto an interaction at the adrenergic beta receptor.

In addition, differing orders of potency for asingle series of closely related compounds on sev-eral biological systems are evidence for differentreceptor types in the various systems. The degreeof vasoconstrictor activities of norepinephrine(NE), epinephrine (E) and isoproterenol (I) from

ascending to decending order is:NE -- E - I.The order of potency for cardiac stimulation

is:I -- E -NE.Finally, selective antagonism of the effects of

neurotransmitter provides the strongest basis forreceptor classification. The cardiac positive inotro-pic effect of epinephrine can be blocked by a betaadrenergic receptor blocking drug but the effectsof digitalis cannot be blocked by the same drug.The vasoconstrictor effects of norepinephrine canbe blocked by an alpha adrenergic receptor block-ing drug but not by a beta blocking drug.

Anatomically, adrenergic receptors have notbeen clearly defined. The concept of receptors ispharmacological; adrenergic receptors can bethought of as hypothetical parts of effector cellsthat selectively receive molecules with the generalstructure of norepinephrine. Although alpha andbeta receptors recognize and bind the basic catecho-lamine structure, subtle differences in molecularstructure determine distinct pharmacologic spe-cificity. The ability to bind a beta receptor is gen-erally increased by a bulky substitution on theamino N (as seen with isoproterenol).

Affinity for alpha receptors is decreased bysuch substitutes. A hydroxyl group on the B carbonenhances binding of both alpha and beta receptors.Only molecules tlat can bind to receptors byvirtue of a complementary structure between re-ceptor and drug will be active. Once such bindinghas occurred, a biologic process may or may not bestimulated, depending on whether a stimulationor blocker has occupied the receptor."

The "second messenger"Although the exact nature of drug receptor

interaction is not known, the link between receptorbinding and biologic response seems to be a socalled second messenger such as 3'5' adenosine-monophosphate (AMP). AMP is a cyclic nucleotideformed from adenosinetriphosphate (ATP). Theenzyme responsible for synthesizing adenyl cyclase(CAMP) is activated by catecholamines, especially

epinephrine and others with strong beta actions.Adenyl cyclase is situated in the cell membrane

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and the pharmacological effects of the catechola-mines on the heart and smooth muscle may be dueto stimulation of the enzyme through an action onbeta receptors. The mechanism of alpha adrenergicstimulation is less clear; it may be associated withincreased levels of 3'5' guanosine monophosphate.12

Regardless of either the exact nature of thereceptor or the mechanism of transmitter-receptorinteraction, receptor binding of endogenouscatecholamines or exogenous sympathomimeticamines activates a biologic response. Alpha recep-tors are associated with most of the usual adrener-gic excitatory functions, such as vasoconstrictionor stimulation of uterine or ureteral muscles. Betareceptors are usually associated with inhibitoryadrenergic functions such as vasodilation and in-hibition of uterine and bronchial muscles.

In tissues that possess both types of receptorssuch as blood vessels of the skeletal muscles, alphareceptor stimulation is usually excitatory; beta re-ceptor stimulation is usually inhibitory. Heartmuscle and lung tissue contain only beta receptors.However, stimulation of beta receptors in the heart

is excitatory and results in a positive chronotropicand inotropic effect. Stimulation of beta receptorsof the lung is only inhibitory and results in re-laxation of bronchial muscle.1 8

Recently, beta receptors have been separatedinto beta1 (cardiac) and beta 2 (bronchial andperipheral vascular receptors). Stimulation of beta1receptors increases heart rate and contractility.Stimulation of beta2 receptors results in dilatationof the bronchioles and arterioles. By knowing theusual response to alpha and beta stimulation andthe anatomic distribution of these receptors, it ispossible to predict pharmacologic responses toeither natural neurotransmitters or syntheticadrenergic drugs. Table 3 represents a partial list-ing of the organ, its adrenergic receptor, and thephysiological response of stimulation.14

Although the anesthetist is concerned with alladrenergic responses, adrenergic receptors in thecirculatory system are of great significance in theanesthetized patient. Stimulation of beta receptorsin the heart results in an increased rate of pace-maker discharge, increased contractility, increased

Table 3.Responses to Adrenergic Stimulation

Tissue Receptor Responses

Heartsino-atrial nodeatriaatrioventricular nodeventriclecoronary blood vessels

cardiac metabolism

Blood veselsskinskeletal muscleveinsrenal

arterioles

Lungbronchial smooth muscle

Gastrointestinal tractstomach

intestine

Liverglycogen stores

Other smooth musclespleenuterus (pregnant)uterus (nonpregnant)

beta1beta 1beta 1beta 1alphabetabeta

alphabeta 2alpha, betaalpha, betadopaminergicalpha, beta

beta 2

betaalphaalpha, beta

alpha, beta 2

alphaalphabeta2

increased rateincreased contractilityincreased conductionincreased contractilityvasoconstrictionvasodilatationglyogenolysis; increase in cyclic 3'5'-AMP;

increase in adenyl cyclase activity

vasoconstrictionvasodilatationvasoconstrictionvasoconstriction or vasodilatation

vasoconstriction or vasodilatation

relaxation

decreased motility; tonecontraction of sphincterdecreased motility; tone

glycogenolysis

contractioncontractionrelaxation

Journal of the American Association of Nurse Anesthetists142

metabolic activity, and increased oxygen consump-tion. These effects can be antagonized with betaadrenergic blocking drugs but not with alphablocking drugs.

The vascular system has both alpha and betareceptors. Systemic arterial and arteriolar vasocon-striction is clearly an alpha receptor function.Alpha adrenergic blocking drugs antagonize theeffect but beta blocking drugs do not. Vasodilatorresponses are considered to be a function of betareceptors since this response is blocked by betablocking drugs and not by alpha.

The coronary circulation is poorly understood.There is evidence that the epicardial coronarieshave an abundance of alpha receptors, whereas,the intramuscular arteries have an abundance ofbeta receptors. The overall effect of sympatheticstimulation, however, is moderate dilatation of thecoronary vasculature and increase in blood flow.Sympathetic activity increases cardiac rate, rhythm,and myocardial oxygen consumption. Metabolicfactors are probably the major controllers of myo-cardial blood flow.15

The renal vascular bed is primarily an alphareceptor system that responds to most catechola-mines by constriction. Recent work has shown thatdopamine increases renal blood flow by acting ondopaminergic receptors in the renal and mesentericbeds. This response is not altered by either alphaor beta blockade.

Pharmacological considerations ofadrenergic receptors

There are a number of pharmacological ma-neuvers that alter sympathetic function by pre-venting norepinephrine from interacting withadrenergic receptors. In addition, a number ofdrugs are available today which augment or sup-press sympathetic function by stimulating or block-ing alpha and beta receptors.

Drugs which interact with a receptor and elicita response are termed agonists; compounds whichinteract with receptors and prevent the action ofagonists, are referred to as antagonists.8 Endogenouscatecholamines and exogenous sympathomimeticamines are adrenergic agonists. These drugsare classified as catecholamines (epinephrine,norepinephrine, dopamine, isoproterenol and do-butamine) and noncatecholamines (methoxamine,phenylephrine, ephedrine and metaraminol).

They produce their effect either through a di-rect action on adrenergic receptors, through therelease of catecholamines from adrenergic nerveterminals (indirect effect), or a combination ofboth. These drugs may stimulate only alpha re-ceptors, beta receptors, or both. Isoproterenol isthe prototype for beta adrenergic stimulators;methoxamine is the prototype for alpha stimula-tors. The site and mechanism of action of com-monly used sympathomimetic amines are sum-marized in Table 4.

The selection of the proper sympathomimeticfor patients with cardiovascular dysfunction is de-

April/1980

Table 4.Classification of Adrenergic Receptor Stimulants

Drug Site of Action MechanismAlpha Beta

1. Epinephrine +++ +++ Direct(Adrenalin®)

2. Norepinephrine ++++ +++ Direct(Levarterenol )

3. Isoproterenol ++++ Direct(Isuprel®)

4. Dopamine ++ +++ Direct(Intropin®)

5. Dobutamine + ++++?(Inotrex ®)

6. Methoxamine ++++ Direct(Vasoxyl®)

7. Phenylephrine ++++ Direct(Neosynephrine®)

8. Ephedrine + ++ Direct andIndirect

9. Metaraminol ++++ + Direct and(Aramine®) Indirect

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pendent upon identification of the pathophysio-logical process, and the understanding of the re-ceptor and the site of action of the drug.

Alpha adrenergic agonists are useful in mod-ifying circulatory function primarily by their vaso-constrictor action. They elicit reflex vagal brady-cardia and may be useful in the treatment ofparoxysmal atrial tachycardia. Pure alpha agonists,such as vasoxyl, lack direct cardiac effects but mayinduce cardiac dilatation and decompensation byincreasing afterload or the resistance against whichthe heart must work. The selection of this type ofdrug for a patient in cardiogenic shock is inappro-priate and hazardous.

Pure beta agonists, such as isoproterenol, havebeen used effectively in the acute management ofcomplete heart block. Due to its positive inotropicand chronotropic effects as well as vascular dilita-tion, it also has been used for cardiogenic shock.More recently, dopamine (which has less potentialfor tachyarrhythmias and good potential for im-proved renal blood flow) and dobutamine (whichdemonstrates beta1 selectively with mild chrono-tropic and arrhythmogenic effects) have replacedisoproterenol.17

The response of adrenergic receptor agoniststhat stimulate both alpha and beta receptors isdose dependent. Infusions of epinephrine at a rateof 1-2 xg/min primarily affect beta receptors; 2-10

g/min affect alpha and beta receptors; 10-16g/min primarily affect alpha receptors.'1 In large

doses (greater than 20 g/kg/min), dopamine'saffect on alpha receptors overshadows its action ondopaminergic receptors and results in renal vaso-constriction similar to that produced by norepi-nephrine.

Excessive activity of the sympathetic nervoussystem can have a deleterious effect on cardio-vascular function. At times it is necessary to blockthe effector organ response to sympathetic impulsesin order to control hemodynamics. The adminis-tration of chloropromazine, droperidol and methyl-prenisolone results in mild alpha adrenergic block-ade on vascular smooth muscle. Hypotension mayoccur in the volume depleted patient.

Phenoxybenzamine (Dibenzyline®) is a longacting alpha antagonist used for peripheral vascu-lar diseases such as Raynaud's disease and in thepreoperative preparation of a patient for the re-moval of a pheochromocytoma. It is administeredin doses of 20-100 mg. Adverse effects include or-thostatic hypotension and tachycardia.

Phentolamine (Regitine®) is an alpha adrener-gic blocker with a rapid onset of action. It can begiven as a single bolus injection of 1-3 mg or as a

continuous infusion of 0.1-0.5 mg/min, titratedto the desired response. Reflex tachycardia andarrhythmias may be associated with its use.

Propranolol (Inderal®) is a beta receptor an-tagonist which competitively reduces the effect ofa beta agonist at the adrenergic beta receptor. 19

Because of its ability to decrease heart rate, con-tractility, and cardiac output, it leads to a reduc-tion in myocardial oxygen consumption and there-fore is widely used in the medical management ofangina pectoris. It is also useful in the preoperativemanagement of hypertension, thyrotoxicosis, andmigraine headache. Its value in the managementof preoperative or perioperative dysrhythmias, es-pecially those that are catecholamine induced, isunquestioned. Perioperatively, an intravenous doseof 0.25 to 0.5 mg is given initially, followed byadditional doses up to a cumulative total dose of3 to 5 mg given over a five to ten minute period. 20

In the early 1970's, it was popular practice todiscontinue propranolol two weeks preoperatively.In 1975, Miller reported the development of un-toward myocardial ischemic events in a significantnumber of patients who were abruptly withdrawnfrom this antagonist. 21

Since then, the pharmacokinetics of proprano-lol have been studied extensively. The half-life ofthis drug is 3.4 to 6 hours after discontinuation ofchronic oral administration. It disappears from theplasma and atria within 24 to 48 hours and thechronotropic and inotropic responses return tonormal within 24 to 48 hours after discontinuingdoses of 30 to 240 mg/day. 22 Other authors havedemonstrated no unusual hemodynamic functionduring surgery in patients with coronary arterydisease receiving moderate doses of oral proprano-101ol.28

The decision to either continue, taper or dis-continue the drug is dependent upon the reasonthe patient is receiving the drug. For the patientwith coronary artery disease, abrupt withdrawal ofpropranolol in the preoperative period may bedangerous. If deemed advisable, it is recommendedthat it be slowly tapered in a monitored environ-ment.

Beta adrenergic blockersThe major side effects encountered with the

intraoperative administration of propranolol in-clude bronchoconstriction and excessive cardiacdepression. If severe hypotension develops, theanesthetist muist understand the pharmacology ofbeta receptor blockade. Beta blocking drugs arecompetitive antagonists and there is always a dose

Journal of the American Association of Nurse Anesthetists144

of the agonist (isoproterenol) that will overcomethe antagonist.

In the face of beta blockade however, theusual dose of isoproterenol (1-6 ,g/min) may haveto be increased to 20 nug/min. Sympathomimeticswith both alpha and beta effects should be used withcaution. With significant beta blockade, the alphaeffects of the drug will be pronounced. With car-diac depression, this vasoconstriction and increasein afterload may be hazardous.

If the treatment of myocardial depression withisoproterenol is not effective, the anesthetist canconsider the use of glucagon, calcium chloride ordigitalis. Glucagon has a separate receptor site onthe cell wall and releases adenyl cyclase to convertATP to CAMP. This results in a positive inotropiceffect which is independent of the beta receptors.Calcium chloride and digitalis work intracellularlyat the level of the contractile proteins to improvemyocardial contractility.

If propranolol is to be continued until thetime of surgery, other potential problems must beanticipated. A number of studies of anestheticdrug interactions with propranolol have beendone. Methoxyflurane and enflurane have a syner-gistic effect with the drug; halothane and morphinehave additive hemodynamic effects with the beta-blocker. Since parasympathetic effects may pre-dominate with the combination of anesthesia andbeta blockade, these patients should receive amplepreanesthetic anticholinergic medication. Thequaternary ammonium compound glycopyrrolateis a good choice since it produces an effect threeto five times the duration of atropine. 24

Since the patient may not be able to respondto hypovolemia by increasing the heart rate, vol-ume replacement must be adequate. Finally, be-cause of the theoretical possibility of hypoglycemia,these patients should receive parenteral glucose.

Until recently, propranolol was the only betaadrenergic blocker approved for use in this coun-try. In the United Kingdom and other countries,there are at least seven more beta blockers in cur-rent use. Ahlquist recently stated that he found itdifficult to understand the attitude of the U.S.Federal Drug Administration (FDA) concerningthis class of drugs; and he hoped science and com-mon sense would prevail over bureaucratic inde-cision.2 5

However, metoprolol tartrate (Lopressor®), asynthetic selective beta1 blocking agent, has re-cently been approved by the FDA for use as anantihypertensive. The usual initial dose is 50 mgtwice daily. Maintenance dosage is approximately100 mg twice a day with a range of 100 to 450 mg

per day. Although it has a preferential effect onbeta1 receptors in cardiac muscle, this effect is notabsolute. In higher doses, the beta2 receptors ofbronchial and vascular musculature are alsoblocked and the anesthetic considerations are sim-ilar to those of propranolol.

Finally, one should remember that someadrenergic antagonists produce their effect withblockade sympathetic nervous system activity (re-ducing the amount of norepinephrine releasedfrom the nerve terminal). They do not block re-ceptors; therefore, the circulatory system is re-sponsive to sympathomimetic amines which actdirectly on adrenergic receptors, but not neces-sarily to those which act indirectly. The mechanicalactions of these drugs include either depletion ofthe nerve endings of norepinephrine, inhibition ofnorepinephrine synthesis, or block of release with-out depletion.

Reserpine (Serpasil®) depletes the nerve end-ings of norepinephrine. Guanethidine (Ismelin®)initially prevents the release of norepinephrinefrom the storage area but it later displaces thetransmitter and prevents its re-uptake.2 6

Tlhe antiarrhythmic bretylium tosylate (Brety-lol®) alters adrenergic stimulation of the heart bythree mechanisms. High concentrations releasenorepinephrine from adrenergic neurons. Lowerconcentrations inhibit the release. Finally, it mayblock the uptake of norepinephrine into adrener-gic nerves and potentiate the action of this agoniston adrenergic receptors. In doses of 5-10 mg/kg,bretylium can be useful in the treatment of life-threatening ventricular arrhythmias that are unre-sponsive to lidocaine. 27 Serious side effects such ashypotension preclude its routine use.

ConclusionThe patient scheduled for anesthesia is de-

pendent upon an intact autonomic nervous systemfor stability. Imbalances can threaten the patient'ssurvival and, therefore, must be promptly recog-nized and treated. Proper preoperative and intra-operative management of the surgical patient isdependent upon an understanding of the periph-eral adrenergic system, its effector site and drugsthat augment or suppress sympathetic function.

ACKNOWLEDGEMENT'he author wishes to express her gratitude to Shirley

Crump, CRNA, DI)irector, Nurse Anesthesia Program, NorthCarolina Baptist Hospital; Gaynell Hayes, English teacher,Winston-Salem Forsyth County School System; and ConnieHayes. senior secretary, North Carolina Baptist Hospital, NurseAnesthesia Program for their assistance in the preparation of thisarticle.

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REFERENCES(1) Stoelting, R. 1978. The Autonomic Nervous System: Physi-ology. ASA Annual Refresher Course Lectures. 202A:1.(2) Drain, C. 1976. Current Concepts on the Pharmacodynamicsof Adrenergic and Cholinergic Receptors. The AANA Journal.44: 275-277.(3) Best and Taylor. 1973. Physiological Basis of MedicalPractice. 9th Ed. The Williams and Wilkins Company, Baltimore.p. 9-55.(4) Carrier, 0. 1972. Pharmacology of the Peripheral AutonomicNervous System. Year Book Medical Publishers, Chicago. p. 17.(5) Goth, A. 1976. Medical Pharmacology. 8th Ed. C. V. MosbyCompany, St. Louis. p. 65.(6) Stoelting, R. 1978. op cit, p. 4.(7) Moran, N. 1966. Adrenergic Receptors, Drugs and theCardiovascular System (1) Modern Concepts of CardiovascularDisease. 35: 94.(8) Ahlquist, R. 1948. A Study of the Adrenotropic Receptors.Am. J. of Phy. 153: 586-600.(9) Powell, C. and Slater, I. 1958. Blocking of Inhibitory Adren-ergic Receptors by a Dichloro Analog of Isoproterenol. J.Pharmacol. Exp. Ther. 122: 480.(10) Moran, N. and Perkins, M. 1958. Adrenergic Blockade ofthe Mammalian Heart by a Dichloro Analog of Isoproterenol.J. Pharmacol. Exp. Ther. 124: 223.

(11) Lefhowitz, 1976. B-Adrenergic Receptors: Recognition andRegulation. N. Eng. Jr. Med. 295: 323-328.(12) Ibid., p. 323-328.(13) Goldberger, E. 1977. Treatment of Cardiac Emergencies.

C. V. Mosby Company, St. Louis, p. 297-298.(14) Antonaccio, M. 1977. Cardiovascular Pharmacology. RavenPress, New York. p. 339.(15) Guyton, A. 1976. Textbook of Medical Physiology. 5th Ed.W. B. Saunders Company, Philadelphia. p. 324.(16) Goth, A. op. cit, p. 7.(17) Sonnenblick, E.; Frishman, W.; and LeJemtel, T. 1979.Dobutamine: A New Synthetic Cardioactive Sympathetic Amine.N. Eng. J. Med. 300: 19.(18) Kaplan, J. 1978. The Autonomic Nervous System: Pharma-

cology. ASA Annual Refresher Course Lectures. 202B: p. 2.(19) Conolly, M.; Friedrick, K; and Dollery, C. 1976. Progressin Cardiovascular Diseases. 14: 207.(20) Kaplan, J. op cit, p. 4.(21) Miller, R.; Olson H.; and Amsterdam, E. 1975. PropranololWithdrawal Rebound Phenomenon. N. Eng. J. Med. 239: 416.

(22) Kaplan, J. 1977. The Pharmacological Treatment of theCardiovascular System. ASA Annual Refresher Course Lectures.212: 2-3.(23) Kopriva, J.; Brown, A.; and Pappas, G. 1978. Hemo-

dynamics During General Anesthesia in Patients ReceivingPropranolol. Anesthesiology. 48: 28-33.(24) Winnie, A. 1978. Beta Blockers in Anesthesia. First Annual

Nurse Anesthetist Review Course. Society of Air Force Anesthe-siologist, San Antonio. 102-B: 7.(25) Ahlquist, R. 1977. Present State of Alpha and Beta Adren-

ergic Drugs: Beta Blocking Drugs. American Heart Journal.93: 119.(26) Brown, B. 1978. Anesthetic Considerations for the Hyper-tensive Patient. ASA Annual Refresher Course Lectures. 203: 3.(27) Weser, J. 1979. Bretylium Drug Therapy. N. Eng. J. Med.

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AUTHORSandra M. Maree, CRNA, BS, received her Bachelor's

degree from Guilford College, and graduated from Watts Hos-pital School of Nursing and North Carolina Baptist HospitalSchool of Anesthesia for Nurses in North Carolina. She iscurrently Assistant Director of the Anesthesia Program forNurses at North Carolina Baptist Hospital and instructor ofnurse anesthesia at Bowman Gray School of Medicine inWinston-Salem. She lectures extensively, and presently serves onthe Council of Recertification.

This paper was presented as part of the Session on thePharmacology of Anesthesia at the 46th Annual Meeting andProfessional Sessions of the American Association of NurseAnesthetists, held in St. Louis, Missouri in August, 1979.

Journal of the American Association of Nurse Anesthetists