ADRENERGICS - REVIEW This section combines questions and study information designed to assist you in reviewing the function and mechanism of action of adrenergic agents, and includes discussions of the following topics: 1) catecholamines (General) 2) alpha - adrenergic agents 3) beta - adrenergic agents. First, a general review of catecholamine function: Dopamine, epinephrine and levarterenol (norepi- nephrine) are three catecholamines that occur in the body. Isoproterenol is a synthetic catechol- amine. Norepinephrine is the neurotransmitter pro- duced and released at adrenergic synapses. Epinephrine is the primary catecholamine released by the adrenal medulla. Dopamine is important primarily in the CNS.
The actions of the catecholamines include: 1) peripheral excitatory action on certain types of smooth muscle 2) peripheral inhibitory action 3) cardiac excitatory action 4) metabolic actions 5) CNS excitatory actions. However, due to their different chemical structures, each of the catecholamines will produce the above sympathomimetic actions to a different degree. Each amine has a different efficacy for activating alpha and beta receptors. For alpha receptors, the efficacy in decreasing order is epinephrine, norepinephrine, dopamine, isoproterenol (no alpha activity). For beta receptors, the efficacy in decreasing order is isoproterenol, epinephrine and norepinephrine. Here are some questions to help you review catcholamines:
1. Sympathomimetic amines possessing stimulant effects on the beta receptors of the heart includeepinephrine norepinephrine isoproterenol phenylephrine Correct. Partly. Partly. Partly. No. The first three foils are correct.
ALPHA RECEPTOR AGONISTS BETA RECEPTOR AGONISTS epinephrine isoproterenol (beta-1 and beta-2) norepinephrine epinephrine (beta-1 and beta-2) phenylephrine (alpha-1) terbutaline (beta-2) methoxamine (alpha-1) albuterol (beta-2) dobutamine (beta-1) norepinephrine (beta-1) Norepinephrine has little effect on beta receptors EXCEPT in the heart. Norepinephrine is as potent as epinephrine in increasing stroke volume, coronary blood flow and causing arrhythmias. Because it dramatically increases peripheral resistance, norepinephrine induced increase in heart rate can only be observed after treatment with atropine or ganglionic blockade. In fact, when norepinephrine is injected, one actually observes a reflex slowing of the heart (bradycardia).
2. Epinephrine causes relaxation ofbronchioles cutaneous blood vessels smooth muscle of the intestinal wall radial fibers of the iris Very good. Partly. Partly. No. The first and third foils are correct. Epinephrine has both alpha and beta effects. - bronchioles are relaxed (beta effect) - cutaneous blood vessels are constricted (alpha effect) - intestinal smooth muscles are relaxed (alpha and beta effect) - radial fibers are contracted (mydriasis, which is an alpha effect)
3. Which of the following are endogenous catecholamines?epinephrine dopamine norepinephrine tyrosine Good. Partly. Partly. Partly. No. The first three foils are correct.
Tyrosine is the amino acid precursor of the endogenous catecholamines. The biosynthetic pathway of the catechol- amines is as follows: phenylalanine ---> tyrosine ---> DOPA ---> ---> DOPAMINE ---> NOREPINEPHRINE ---> ---> EPINEPHRINE The last three compounds are endogenous catecholamines.
4. Cocaine and imipramine inhibit the neuronal uptake oftyramine guanethidine norepinephrine tyrosine You are right. Partly. Partly. Partly. No. The first three foils are correct.
Tyramine, guanethidine, and norepinephrine, as well as other monoamine agents are taken up by the neuronal reuptake system. This reuptake system is blocked by many drugs such as cocaine, imipramine, chlorpromazine, etc. This phenomenon accounts for many drug interactions.
5. Precursors of norepinephrine and epinephrine in the body are3,4-dihydroxyphenylethylamine (Dopamine) phenylalanine tyrosine 3,4-dihydroxyphenylalanine (Dopa) Very good. No. All the foils are correct.
Norepinephrine biosynthesis is as follows: phenylalanine --> tyrosine --> dopa --> --> dopamine --> norepinephrine
6. Agents which block the neurogenic release of catecholamines from sympathetic nerve endings includeguanethidine phentolamine bretylium hydralazine Correct. Partly. Partly. No, the first and third foils are correct. Several agents can block or decrease the amount of catecholamines released from the sympathetic nerve endings. These agents are referred to as adrenergic neuron blocking agents. This phenomenon can occur by three mechanisms. 1) inhibition of catecholamine synthesis: alpha-methyltyrosine 2) depletion of storage granules: guanethidine and reserpine 3) inhibition of release - guanethidine and bretylium
7. Indirectly acting sympathomimetic (adrenergic) amines are characterized byloss of activity after reserpine development of tachyphylaxis surmountable antagonism of their actions by cocaine potentiation of their actions by pargyline Very good. No. All foils are correct.
1) loss of "indirect" activity is observed in reserpine pretreated individuals because the stores of NE are depleted 2) tachyphylaxis develops upon repeated injections because the NE stores are depleted 3) cocaine blocks the effects of tyramine because it blocks the uptake of tyramine into the nerve terminal 4) pargyline (MAO inhibitor) potentiates the effects of tyramine because it blocks the metabolism of tyramine (a monoamine) by monoamine oxidase. In order for "indirect" acting amines such as tyramine to exert their effects, they must first be taken up by the monoamine reuptake system and then release norepinephrine from storage granules. The released norepinephrine then has a sympathomimetic effect.
8. The effect of tyramine on blood pressure is modified by pretreatment withreserpine guanethidine alpha-methyl dopa pargyline all of the above Very good. No. The answer is E.
9. The immediate precursor of epinephrine isamphetamine norepinephrine tyramine alpha-methyl dopa dopamine Correct. No. The answer is B.
10. Which of the following causes a release of norepinephrine from synaptic vesiclespropranolol terbutaline isoproterenol dobutamine tyramine Good. No. The answer is E.
11. Which of the following is an orally effective sympathomimetic which may be used in the treatment of asthma?epinpehrine phenylephrine ephedrine bretylium neostigmine Yes. No. The answer is C.
12. Which of the following drugs antagonizes the increased heart rate and force of contraction induced by cathecholamines?propranolol terbutaline dobutamine phentolamine phenoxybenzamine Correct. No, the answer is A. The positive inotropic and chronotropic effects of catecholamines are produced by beta-1 receptors and are blocked by beta blockers. propranolol is a nonselective beta blocker, terbutaline is a beta-2 agonist dobutamine is a beta-1 agonist, phenoxybenzamine is a alpha-1 blocker phentolamine is a nonselective alpha blocker
KEY WORDS AND PHRASES Direct acting sympathomimetic amines - Epi, Norepi and Isoproterenol - Direct activation of adrenergic receptors Indirect acting sympathomimetic amines - Tyramine Acts by releasing NE from neuronal cytoplasmic pool Tachyphylaxis occurs with tyramine Mixed acting sympathomimetic amines - Ephedrine - Amphetamine Monoamine Oxidase (MAO) - Responsible for intraneuronal metabolism of catecholamines Catechol-O-Methyl Transferase (COMT) - Responsible for inactivation of circulating catecholamines MAO inhibitors - Pargyline Increase NE in adrenergic neurons May cause hypertension if foods containing tyramine are ingested Reserpine - Depletes NE stores in peripherary and brain - Has been used to treat hypertension Guanethidine - Prevents nerve-induced release of NE and also depletes NE from storage granules - Used to treat severe hypertension Cocaine and Imipramine - Block reuptake of NE and other amines from extracellular fluid into presynaptic neuronal terminals
REVIEW OF ALPHA - ADRENERGIC AGENTS Alpha-1 agonists are compounds that stimulate alpha-1 adrenergic receptors. These agents produce a physiologic response that is similar to the response produced by exogenous norepinephrine ("sympathomimetic"). These agents produce; 1) constriction of blood vessels, 2) reflex bradycardia, and 3) dilation of the pupil. PHENYLEPHRINE, METHOXAMINE, AND METARAMINOL are 3 direct sympathomimetic agents that possess direct alpha-1 agonist activity.
Sympatholytic drugs block, or limit, the action of sympathomimetic amines. Alpha-1 adrenergic blocking agents block the vasoconstriction produced by epinephrine, norepinephrine, phenylephrine, methoxamine, etc. PHENTOLAMINE AND TOLAZOLINE are competitive nonselective alpha blockers. That is, the binding of these agents with alpha-1 and alpha-2 receptors is reversible. These drugs are relatively short-acting. PHENOXYBENZAMINE is an alpha-1 blocker that combines irreversibly with the alpha receptor and is therefore called a non-competitive blocker. It is seldom used clinically since its action persists for several hours. PRAZOSIN is a newer drug which has been shown to have a highly selective alpha-1 receptor antagonism. This may be the reason that it produces less reflex tachycardia than phentolamine. Let's begin with some questions designed to help you review alpha-adrenergics.
13. The bradycardia produced by norepinephrine (levarterenol) administration is blocked byhexamethonium atropine phenoxybenzamine propranolol Correct. Partly. Partly. Partly. No. The first three foils are correct.
Injected NE is a potent vasoconstrictor. The increase in blood pressue results in a reflex slowing of the heart. The reflex slowing is mediated via the vagus nerve. - hexamethonium will block transmission of this parasympathetic nerve at the ganglia. - atropine will block the vagal effect by blocking the muscarinic receptors in the heart. - phenoxybenzamine will directly block the vasoconstrictor effects of NE at the alpha receptors in the vascular smooth muscles, therefore, blood pressure will not increase in the first place and the reflex slowing will not occur.
14. The reflex responses to the effects of a dose of tolazoline or phentolamine includeincreased activity of the sympathetic nerves to the heart increased activity of vagal fibers to the heart increased activity of sympathetic nerves to alpha receptors in arterioles decreased activity of sympathetic nerves to alpha receptors in arterioles Good. Almost. Almost. No. The first and third foils are correct. Tolazoline and phentolamine are reversible inhibitors of alpha receptors. They will block sympathetic induced vasoconstriction resulting in decreased vasculature tone. This decreased tone will be a signal for increased sympathetic outflow in an attempt to overcome the effects of alpha receptor blockade.
15. Which of the following are characteristic actions of methoxamine?marked reflex bradycardia a rise in systolic blood pressure a direct stimulant action of vascular alpha-1 receptors marked bronchodilation Correct. Partly. Partly. Partly. No. The first three foils are correct. Methoxamine is a direct alpha-1 agonist which produces - increased systolic pressure because of its potent vasoconstrictor properties - a compensatory reflex bradycardia Bronchodilation is produced by BETA agonists, NOT ALPHA agonists.
16. Phenylephrine (neosynephrine)dilates precapillary sphincters in gastric mucosa will cause miosis (pupillary constriction) as one of its pharmacological effects will promote gastric secretions and GI motility constricts the dilated arterioles in the nasal mucous membranes Right. No, only the fourth foil is correct. Phenylephrine is a direct selective alpha-1 agonist. - it constricts precapillary sphincters in gastric mucosa - it produces mydriasis - it reduces gastric secretions and GI motility - because of its ability to constrict the dilated arterioles of the nasal mucous membranes, it is often used as a nasal decongestant agent
17. Tyramineis found in foods such as wines, pickled herring, and beer is the immediate precursor for the enzmatic formation of DOPA has its affects augmented by MAO inhibitors works by inhibiting endogenous catecholamine reuptake Fine. Partly. Partly. No. The first and third foils are correct. Tyramine is an indirect sympathomimetic which works by releasing endogenous catecholamines from nerve endings. It is found naturally in fermented foods, beer, wine, etc. When ingested, it is largely metabolized by MAO in the liver. When given to patients on MAO inhibitors, an acute hypertensive crisis may occur. Tyrosine is the immediate precursor for the formation of DOPA.
18. Ephedrineacts indirectly like tyramine to release endogenous norepinephrine acts directly like methoxamine on alpha-1 adrenergic receptors is used clinically as a nasal decongestant and a pressor agent is an orally effective agent Very good. No. All the foils are correct. Ephedrine is both a direct and indirect agonist which is orally effective. It is used widely in nasal decongestants.
19. Pretreatment with phentolamine will reduce or abolish which of the following direct or indirect responses to norepinephrine?vasoconstriction bradycardia mydriasis positive inotropic response Correct. Partly. Partly. Partly. No. The first three foils are correct. Vasoconstriction and mydriasis are direct alpha-1 effects, bradycardia is reflex. The positive inotropic response is a direct beta-1 effect.
20. Effects of sympathomimetic agents which are associated with alpha-1 adrenergic receptor activation includefree fatty acid release mydriasis vasodilation vasoconstriction Correct. Partly. Partly. No. The second and forth foils are correct. Vasodilatation and free fatty acid release are mediated by beta-2 receptors.
21. Which of the following is ("irreversible") true with respect to phenoxybenzamine?produces a nonequilibrium type of blockade antagonize the increase in heart rate produced by sympathetic nerve stimulation produces blockade of long duration "reverses" the blood pressure response to isoproterenol Correct. Partly. Partly. No. The first and third foils are correct. Phenoxybenzamine is an irreversible alpha-1 antagonist with a long duration of action. It will not reverse the effects of isoproterenol because isoproterenol is a beta agonist; similarly, it will not block the beta-1 receptor mediated tachycardia induced by sympathetic nerve stimulation.
22. Norepinephrine slows the human pulse rate bacauseperipheral resistance is decreased norepinephrine has a direct negative chronotropic action the blood pressure is decreased a baroreceptor reflex is activated Good. No. Only the fourth foil is correct. Remember that increased blood pressure due to NE induced vasoconstriction is followed by a compensatory reflex bradycardia.
23. Cocaine is thought to produce supersensitivity to injected norepinephrine byblocking norepinephrine metabolism blocking uptake of norepinephrine into sympathetic nerve terminals acting as a secondary neurotransmitter substance decreasing neuronal thresholds to stimulation none of the above Good. No. The answer is B.
In addition to being a local anesthetic, cocaine also blocks re-uptake of norepinephrine into nerve terminals causing vasoconstriction when applied locally to mucus membranes.
24. Which of the following drugs exaggerates both the pressor response to norepinephrine and the depressor response to acetylcholine?atropine succinylcholine phenoxybenzamine hexamethonium propranolol Yes. No. The answer is D.
Pressor response = Increased blood pressure Depressor response = decreased blood pressure. Injection of NE results in marked vasoconstriction followed by a reflex bradycardia which opposes the pressor response. This reflex is mediated through the parasympathetic system and can be blocked by hexamethonium at the ganglia. Injection of ACh results in marked vasodilation followed by a reflex tachy- cardia which opposes the depressor response. This depressor response is mediated by the sympathetic system and can be blocked by hexamethonium at the ganglia. In each case the "exaggeration" is caused by blockade of the compensatory reflex.
25. When applied topically to the eye, which of the following agents produces dilation of the pupil without affecting accommodation?atropine pilocarpine phenylephrine neostigmine phentolamine Very good. No. The answer is C.
atropine - parasympatholytic pilocarpine - parasympathomimetic phenylephrine - sympathomimetic neostigmine - parasympathomimetic phentolamine - sympatholytic PUPIL ACCOMODATION sympathomimetics ---- contracts radial muscle --- dilates no effect sympatholytics ---- relaxes radial muscle --- constricts no effect parasympathomimetics- contracts sphincter muscle- constricts parasympathomimetics- contracts ciliary muscle---------------accommodate parasympatholytics -- relaxes sphincter muscle -- dilates parasympatholytics -- relaxes ciliary muscle -------------- unaccommodate ACCOMMODATED EYE UNACCOMMODATED EYE near vision sharp near vision blurred far vision sharp
26. Which of the following agents reduces the pressor responses to norepinephrine?propranolol phenoxybenzamine both neither Yes. No. The answer is B. propranolol - nonselective beta blocker phenoxybenzamine - irreversible alpha-1 blocker
27. Prazosinis more effective for treatment of hypertension than phentolamine since it produces little reflex tachycardia is a direct vasoconstrictor is a highly selective alpha-1 antagonist its effects are blocked by propranolol Correct. Partly. Partly. No. The first and third foils are correct.
Here is a brief overview of some useful alpha adrenergic agents: Alpha - Adrenoceptor Agonists: Metaraminol - mixed adrenoceptor agonist - absorbed after oral administration, but usually used parenterally - used almost exclusively for treatment of hypotension Phenylephrine - powerful alpha-1 receptor stimulant; vasoconstrictor in nasal mucosa - little effect on beta-receptors in heart Methoxamine - exclusive alpha-1 stimulating agent - produces reflex bradycardia - used as a pressor agent in hypotensive states
Alpha - Adreoceptor Antagonists Alpha blockers - Phentolamine (alpha-1 and alpha-2) - Phenoxybenzamine (alpha-1) - Prazosin (alpha-1) - Doxasosin (alpha-1) - Terasosin (alpha-1) Alpha blockers can 1) Eliminate the pressor response to epinephrine and convert it to a depressor response 2) Produce postural hypotension 3) Increase gut motility due to alpha block 4) Cause miosis and inhibition of ejaculation Phentolamine uses - Diagnosis and treatment of pheochromocytoma - Prevent local necrosis following accidental infiltration of NE Phenoxybenzamine uses - Under investigation in treatment for shock Prazosin, Doxasosin and Terasosin uses - highly selective alpha-1 blocker for hypertension (produces little reflex tachycardia) - treatment of obstructive prostatic hyperplasia
A BRIEF OVERVIEW OF BETA - ADRENERGIC AGENTS Stimulation of beta receptors produces vasodilation of blood vessels found in skeletal muscle, increases the force and rate of contraction of cardiac muscle, and relaxes nonvascular smooth muscle. Agents that activate beta receptors (agonists) include the following: Isoproterenol has agonist activity on both beta-1 and beta-2 receptors, with NO alpha activity. Epinephrine and norepinephrine act on both alpha and beta receptors. Norepinephine exerts its primary influence on cardiac tissue through its beta-1 agonist activity. Metaproterenol, albuterol, and terbutaline are beta-2 selective agonists which are effective orally or inhaled. Their selectivity gives maximal broncho- dilatation with decreased cardiac effects, tachycardia or arrhythmias. Terbutaline is also used for its bronchodilatory effects. Terbutaline and ritodrine are similar and have been used to suppress premature labor. Their beta-2 selective actions relax uterine muscle.
Typical agents which block beta receptors (antagonists) include PROPRANOLOL, METOPROLOL, LABETALOL, TIMOLOL, and PINDOLOL. PROPRANOLOL blocks almost all the effects of injected catecholamines except vasoconstriction. METOPROLOL is a cardioselective blocking agents that blocks beta-1 receptors in the heart. Beta-adrenergic receptors in the heart are primarily beta-1 receptors, while the beta-adrenergic receptors in most smooth muscle are beta-2 receptors (vasodilatory). LABETALOL is a reversible beta-adrenoreceptor antagonist with affinity for both alpha and beta receptors. Its affinity for alpha receptors is less than phentolamine but it is alpha-1 selective. Labetalol also has non- selective beta blocking ability with an affinity less than propranolol. TIMOLOL like propranolol is a general non-selective beta-blocker. It is comparable to propranolol in its efficacy in treatment of hypertension or angina. It is especially useful in lowering intraocular pressure in glaucoma. PINDOLOL is also a beta-blocker but it also has some beta agonist activity. Nevertheless, it is useful in angina, hypertension and glaucoma. Here are some questions designed to help you review beta-adrenergic agents:
28. Propranololprevents the vasodilator action of epinephrine interferes with sympathetic control of the heart interferes with the bronchodilator action of epinephrine interferes with the elevation of blood pressure produced by epinephrine Good. Partly. Partly. Partly. No. The first three foils are correct. Propranolol is a beta blocker. The responses described in the first three foils are all mediated by beta receptors and hence would be blocked by propranolol. The pressor response induced by epinephrine is mediated by alpha receptors and would NOT be blocked by propranolol.
29. Which of the following effects of epinephrine would be blocked by propranolol but not by phentolamine?stimulation of muscle glycogenolysis increased rate of contraction in the heart relaxation of vascular smooth muscle contraction of vascular smooth muscle Correct. Partly. Partly. Partly. No. The first three foils are correct. Again, constriction of vascular smooth muscle is alpha-receptor mediated.
30. Stimulation of beta-1 adrenergic receptors in the heart result inan increase in heart rate (positive chronotropy) increased myocardial contraction (positive inotropy) an increase in metabolic activity of the myocardium coronary vasoconstriction Correct. Partly. Partly. Partly. No. The first three foils are correct. Stimulation of beta receptors results in dilation of the coronary vasculature.
31. A beta receptor agonist would be expected to produce which of the following?cardiac arrhythmias spasm of accommodation of the eye for near vision intestinal relaxation rise in blood pressure Correct. Partly. Partly. No. The first, second and third foils are correct. Remember beta agonists stimulate the heart (beta-1 effect) and relax most smooth muscle (beta-2 effect), including the ciliary muscle that accommodates the eye.
32. Isoproterenol produces which of the following effects?causes bradycardia tends to increase peripheral resistance causes gut hyperactivity increases blood glucose Correct. No. Only the forth foil is correct.
33. Isoproterenol is therapeutically useful as a bronchodilator because ithas no significant effects on the heart decreases pulmonary blood flow and pulmonary congestion is a potent stimulant of alpha-adrenergic receptors is a potent stimulant of beta-adrenergic receptors Right. No, only the forth foil is correct. Isoproterenol is a non-selective beta agonist and its use in the treatment of respiratory disorders is accompanied by many cardiac side effects such as - tachycardia - palpitations - arrythmias The selective beta-2 agonists such as terbutaline and metaproterenol have minimal cardiac side effects.
34. Propranolol is used in the treatment of which of the following?diabetes mellitus hypovolemic shock severe bronchial asthma certain cardiac arrhythmias Correct. No. Only the forth foil is correct.
Propranolol is used in the treatment of a) cardiac arrhythmias b) angina pectoris c) hypertension d) pheochromocytoma Propranolol is contraindicated in the following situations a) congestive heart failure b) hypotension c) complete heart failure d) asthma or other obstructive pulmonary disorders Propranolol should be used with caution in patients receiving a) insulin or other oral hypoglycemics b) other sympatholytic drugs c) MAO inhibitors
35. Drug X given in therapeutic doses is found to produce an increase in heart rate, a fall in diastolic blood pressure, an increase in systolic blood pressure, and bronchodilatation. Drug X may benorepinephrine (Levarterenol) epinephrine phenylephrine (Neosynephrine) isoproterenol Correct. Partly. Partly. No. The second and forth foils are correct.
DRUG HEART RATE DIASTOLIC PRESSURE SYSTOLIC PRESSURE BRONCHI NE slowed (reflex) increased increased little effect phenylephrine slowed (reflex) increased increased no effect EPI increased(direct) decreased increased relaxed ISO increased(direct) decreased increased relaxed
36. Propranololdilates the arterioles in voluntary muscle antagonizes sympathetic "drive" to the heart antagonizes all of the peripheral actions of ephedrine may cause bronchiolar constriction Correct. Partly. Partly. No. The second and forth foils are correct. Propranolol is a beta blocker. Since sympathetic outflow results in relaxation of many nonvascular smooth muscles its blockade may lead to constriction of these muscles such as the bronchial muscles. Ephedrine produces affects of both alpha and beta receptors and propranolol will only block the beta receptor - mediated effects.
37. Isoproterenolincreases the rate of firing of the sinoatrial node effectively increases the ventricular rate in the presence of complete atrioventricular heart block relaxes bronchiolar smooth muscle reduces peripheral resistance all of the above Correct. No. The answer is E.
38. Which of the following drugs is a selective beta-2 stimulant?butoxamine isoproterenol terbutaline all of the above Yes. No. The answer is C. Terbutaline is a beta-2 selective agonist; butoxamine is a beta-2 selective antagonist. Isoproterenol is nonselective!
39. Selective beta-2 receptor agonists such as terbutaline and ritodrineare useful in treatment of premature labor are useful in treatment of glaucoma are useful in treatment of asthma are useful in treatment of angina Very good. Partly. Partly. No. The first and third foils are correct.
40. Timolol and pindololare nonselective beta-blockers with partial agonist activity are used in treatment of angina, hypertension and glaucoma both neither Yes. No. The answer is B. Both are used for treatment of angina, hypertension and glaucoma but only pindolol has partial agonist activity.
Here are some important concepts regarding beta - adrenergic agents KEY WORDS AND PHRASES Isoproterenol is a pure beta-1/beta-2 agonist - Inotropic and chronotropic effects on heart - Dilates blood vessels and bronchial muscles - Can be used in treatment of asthma Epinephrine has both alpha and beta activity - Dilates vessels in skeletal muscle - Constricts blood vessels to skin, mucosa, kidney - Increases blood pressure due to increased cardiac output and vasoconstriction - Can also be used in treatment of asthma Beta stimulation (effects different from CV effects) - Bronchial relaxation - Intestinal relaxation - Increased blood glucose - Increased fatty acids in blood - Increased metabolic activity (calorigenesis) Beta-1 receptors -- primarily heart and kidney Beta-2 receptors -- primarily smooth muscle