IVMS-ANS Pharmacology- Adrenergic Drugs

Autonomic PharmacologyAdrenergic DrugsRecommended Reading:Adrenergic DrugsTutorial Worth Visiting:Adrenergic ANSFormative AssessmentPractice Question Set #1Prepared and Presented by:Marc Imhotep Cray, M.D.Professor Basic Medical Sciences9/30/2009IVMS 2IntroductionDistribution of adrenergic receptorsubtypes and adrenergic receptor number are important factors in organ or cellular responses to adrenergic input.Adrenergic receptor typein bronchiolar smooth muscle is principally ß2: epinephrine and isoproterenolmight be expected to be effective bronchodilators because of their activity at ß2 receptors.Norepinphrineis unlikely to have this same effect due to its relative lack of activity at ß2 sites. 9/30/2009IVMS 3IntroductionAlpha receptor dominate in the cutaneous vascular beds.Norepinephrineand epinephrine cause constriction. Isoproterenolwith limited activity at alpha receptors has little effect. Both alpha and beta adrenergic receptor are present in skeletal muscle vascular beds.Alpha receptor activation causes vasoconstriction. Beta receptor activation promotes vasodilatation. Since ß2 receptors are activated at lower, physiological concentrations, vasodilation results. 9/30/2009IVMS 4Introduction (2) Physiological effects caused by sympathomimetcs are due not only to direct effects, but also to indirect or reflex effects. Alpha receptor agonist causes an increase in blood pressure. Carotid/aortic baroreceptorsactivations initiates a compensatory reflex. Sympathetic tone is reduced (decreases heart rate) Parasympathetic tone is increased (decreases heart rate) RESULTS: Blood pressure tends to return to lower levels 9/30/2009IVMS 5Categories of Action AdrenergicsSmooth Muscle EffectsSmooth muscle activation, including activation of blood vessel vasculature (skin, kidney). Activation of glands (salivary and sweat). Smooth muscle inhibition, including inhibition of smooth muscle of the gut, bronchioles, and skeletal muscle vascular smooth muscle. Cardiac Effectsincreased heart rate (positive chronotropic effect) increased contractility (positive inotropic effect) Metabolic Effectsincrease in rate of muscle and liver glycogenolysis increase in free-fatty acid release from fat EndocrineRegulation/modulation of insulin, pituitary, and renin secretion Central Nervous System EffectsRespiratory stimulation CNS stimulation Appetite attenuation Presynaptic EffectsPresynaptic effects: modulation ofrelease of norepinephrine or acetylcholine 9/30/2009IVMS 6Epinephrine Epinephrine is a potent activator of alpha and ß adrenergic receptors Prominent Cardiovascular Effects 9/30/2009IVMS 7Epinephrine andBlood PressurePotent vasopressorSystolic pressure increases to a greater extent than diastolic (diastolic pressure may decrease)pulse pressure widens Epinephrine increases blood pressure by:enhancing cardiac contractility (positive inotropic effect): ß1-receptor effects increasing heart rate (positive chronotropic effect): ß1-receptor effects. vasoconstriction a1 receptor effectsprecapillary resistance vessels of the skin, kidney, and mucosa veins 9/30/2009IVMS 8Epinephrine andBlood Pressure (2)If epinphrine is administered relatively rapidly, the elevation of systolic pressure is likely to activate the baroreceptor system resulting in a reflex-mediated decrease in heart rate. 9/30/2009IVMS 9Epinephrine andBlood Pressure (3)A principal mechanism for arterial blood pressure control is the baroreceptor reflex.The reflex is initiated by activation of stretch receptors located in the wall of most large arteries of the chest and neck.A high density of baroreceptors is found in the wall of each internal carotid artery (just above the carotid bifurcation i.e. carotid sinus) and in the wall of the aortic arch.9/30/2009IVMS 10Epinephrine andBlood Pressure (4)As pressure rises and especially for rapid increases in pressure:baroreceptor input to the tractus solitarius of the medullaresults in inhibition of the vasoconstrictor center and excitation of the vagal (cholinergic) centers resulting in a vasodilatation of the veins and arterioles in the peripheral vascular beds. negative chronotropic and inotropic effects on the heart. (slower heart rate with reduced force of contraction) 9/30/2009IVMS 11Epinephrine andBlood Pressure (5)AdrenergicCholinergicSino-atrial (SA) Nodebeta1; beta2increased ratedecreased rate (vagal)Atrial musclebeta1; beta2increased: contractility, conduction velocitydecreased: contractility, action potential durationAtrio-ventricular (AV) nodebeta1; beta2increased: automaticity, conduction velocitydecreased conduction velocity; AV blockHis-Purkinje Systembeta1; beta2increased: automaticity, conduction velocity------Ventriclesbeta1; beta2increased: contractility, conduction velocity, automaticity, ectopic pacemakersmall decrease in contractility9/30/2009IVMS 12Epinephrine andBlood Pressure (6) SummaryBlood PressureBlood Pressure EffectsEpinephrineNorepinephrineSystolicMean PressureDiastolicvariableMean Pulmonary0.1-0.4 ug/kg/min infusion rateAt lower epinephrine doses: a lessened effect on systolic pressure occurs diastolic pressures may decrease as peripheral resistance is reduced. Peripheral resistance decreased due to ß2-receptor effects 9/30/2009IVMS 13Epinephrine-Vascular EffectsEpinephrine has significant effects on smaller arteriolar and precapilliary smooth muscle. Acting through alpha1 receptors, vasocontrictor effects decrease blood flow through skin and kidney.Even at doses of epinephrine that do not affect mean blood pressure, substantially increases renal vascular resistance and reduces blood flow (40%). Renin release increases due to epinephrine effects mediated by ß2-receptors associated with juxtaglomerular cells. Acting through ß2-receptors, epinephrine causes significant vasodilation which increases blood flow through skeletal muscle and splanchnic vascular beds. If an a receptor blocker is administered, epinephrine ß2-receptor effects dominate and total peripheral resistance falls as does mean blood pressure--this phenomenon is termed "epinephrine reversal".9/30/2009IVMS 14Epinephrine-Cardiac EffectsEpinephrine exerts most of its effects effects on the heart through activation of ß1-adrenergic receptors.ß2-and a receptors are also present. Heart rate increases Cardiac output increases Oxygen consumption increases Direct Responses to Epinephrineincreased contractility increased rate of isometric tension development increased rate of relaxation increased slope of phase-4 depolarization increased automaticity (predisposes to ectopic foci 9/30/2009IVMS 15Epinephrine-Smooth Muscle EffectsSmooth MuscleEpinephrine has variable effects on smooth muscle depending on the adrenergic subtype present.GI smooth muscle is relaxed through activation of both alpha and ß -receptor effects. In some cases the preexisting smooth muscle tone will influence whether contraction or relaxation results following epinephrine. 9/30/2009IVMS 16Epinephrine-Smooth Muscle Effects (2)During the last month of pregnancy, epinephrine reduces uterine tone and contractions by means of ß2-receptor activation.•This effect provides the rationale for the clinical use of ß2-selective receptor agonists: ritodrine and terbutaline to delay premature labor.Uterusalpha1; beta2Pregnant: contraction (alpha1); relaxation (beta2); Non-pregnant: relaxation (beta2)variable9/30/2009IVMS 17Epinephrine-Pulmonary EffectsEpinephrine is a significant respiratory tract bronchodilator. Bronchodilationis caused by ß2-receptor activation mediated smooth muscle relaxation.•This action can antagonize other agents that promote bronchoconstriction. •ß2-receptor activation also decreases mast cell secretion. This decrease may be beneficial is management of asthma also.PulmonaryAdrenergicEffectsCholinergicTracheal and bronchial musclebeta 2RelaxationcontractionBronchial glandsalpha1, beta2decrease secretion; increased secretionstimulation9/30/2009IVMS 18Epinephrine-Metabolic EffectsPancreasAdrenergicEffectsCholinergicAcinialphadecreased secretionsecretionIslets (beta cells)alpha2decreased secretion---------Islets (beta cells)beta2increased secretion---------Glucagon secretion: enhanced by ßadrenergic receptor activation of pancreatic islet alpha cells. •Glycolysis-stimulated: by ßadrenergic receptor activationInsulin secretion:inhibited by a2 adrenergic receptor activation (dominant) Insulin secretion:enhanced by ß2 adrenergic receptor activation 9/30/2009IVMS 19Epinephrine-Metabolic Effects (2)LiverAdrenergicEffectsCholinergicLiveralpha1; beta2glycogenolysis and gluconeogenesis-----------Free fatty acids, increased: by ßadrenergic receptor activation on adipocytes--activation of triglyceride lipase9/30/2009IVMS 20Epinephrine-Metabolic Effects (3)Adipose TissueAdrenergicCholinergicFat Cellsalpha2; beta3lipolysis (thermogenesis)---------Calorigenic effect (20% -30% increase in O2consumption): caused by triglyceride breakdown in brown adipose tissue.9/30/2009IVMS 21Epinephrine-Metabolic Effects (4)ElectrolytesEpinephrine may activate Na+-K+ skeletal muscle pumps leading to K+ transport into cellsStress-induced epinephrine release may be responsible for relatively lower serum K+ levels preoperatively compared postoperatively.Mechanistic basis:"Preoperative hypokalemia" can be prevented by nonselective beta-adrenergic receptor antagonists {but not by cardio-selective beta1 antagonists} Possible "preoperative hypokalemia" may be associated with preoperative anxiety which promotes epinephrine release--therapeutic decisions based on preinduction serum potassium levels to take into account this possible explanation 9/30/2009IVMS 22Norepinephrine Norepinephrine is the primary neurotransmitter released by postganglionic neurons of the autonomic sympathetic systemNorepinephrine (Levophed) is a potent activator of a and ß1 adrenergicreceptors9/30/2009IVMS 23NE-Blood Pressure EffectsPotent vasopressorSystolic and diastolic pressure increasepulse pressure widens Norepinephrine (Levophed) increases blood pressure by:vasoconstriction alpha1 receptor effectsprecapillary resistance vessels of the skin, kidney, and mucosa veins Elevation of systolic pressure following norepinephrine is likely to activate the baroreceptor system resulting in a reflex-mediated decrease in heart rate. 9/30/2009IVMS 24NE-Blood Pressure EffectsBlood PressureBlood Pressure EffectsEpinephrineNorepinephrineSystolicMean PressureDiastolicvariableMean PulmonaryAdaptation of Table 10-2 from: Hoffman, B.B and Lefkowitz, R.J, Catecholamines, Sympathomimetic Drugs, and Adrenergic Receptor Antagonists, In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics,(Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) The McGraw-Hill Companies, Inc.,1996, pp.199-2429/30/2009IVMS 25NE-Arterioles EffectsArteriolesCoronary alpha1,2; beta 2 constriction;dilatation constriction Skin/Mucosaalpha1,2constrictiondilatationSkeletal Musclealpha; beta2constriction,dilatationdilatationCerebralalpha1slight constrictiondilatationPulmonaryalpha1 , beta2constriction; dilatationdilatationAbdominal visceraalpha1, beta2constriction; dilatation-------Salivary glandsalpha1,2constrictiondilatationRenalalpha1,2;beta1,2constriction;dilatation---------Based on Table 6-1: Lefkowitz, R.J, Hoffman, B.B and Taylor, P. Neurotransmission: The Autonomic and Somatic Motor Nervous Systems, In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics,( Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-Hill Companies, Inc.,1996, pp.110-111.AdrenergicCholinergic9/30/2009IVMS 26NE-Vascular EffectsNorepinephrine significantly increases total peripheral resistance, often inducing reflex cardiac slowing.Norepinephrine (Levophed) causes vasoconstriction in most vascular beds. Blood flow is reduced to the kidney, liver and skeletal muscle. Glomerular filtration rates are usually maintained. Norepinephrine may increase coronary blood flow (secondary to increased blood pressure and reflex activity)Norepinephrine (Levophed) may induce variant (Prinzmetal's) angina Pressor effects of norepinephrine (Levophed) are blocked by alpha-receptor blockers. ECG changes following norepinephrine (Levophed) are variable, depending on the extent of reflex vagal effects.9/30/2009IVMS 27NE-Peripheral CirculationEffectsPeripheral CirculationPeripheral CirculationEpinephrineNorepinephrineTotal Peripheral ResistanceCerebral Blood Flowno effect or decreaseMuscle Blood Flowno effect or decreaseCutaneous Blood FlowRenal Blood FlowSplanchnic Blood Flowno effect or increaseincrease, decrease0.1-0.4 ug/kg/min IV infusionTherapeutic use: Norepinephrinemay be used in treatment of shock9/30/2009IVMS 28Dopamine Vasodilator:At low doses, dopamine(Intropin) interactions with D1 receptor subtype results in renal, mesenteric and coronary vasodilation.This effect is mediated by an increase in intracellular cyclic AMP Low doses result in enhancing glomerular filtration rates (GFR), renal blood flow, and sodium excretion. Positive inotropism:At higher doses, dopamine increase myocardial contractility through activation of ß1 adrenergic receptors Dopamine (Intropin) also promotes release of myocardial norepinephrine. Dopamine (Intropin) at these higher dosages causes an increase in systolic blood and arterial pulse pressurewith little effect on diastolic pressures. Cardiovascular Effects (Dopamine)Vasopressor:At high doses dopamine(Intropin) causes vasoconstriction by activating a1 adrenergic receptors 9/30/2009IVMS 29Therapeutic use (Dopamine)Cardiogenic and hypovolemic shockby enhancing renal perfusion despite low cardiac outputOligouria may be an indication of inadequate renal perfusionExample: dopamine may be used, in postoperative cardiopulmonary bypass patients who exhibit:low systemic blood-pressure increased atrial filling pressures low urinary output Unique among catecholamines in that Dopamine can simultaneously increasemyocardial contractility glomerular filtration rate sodium excretion urine output renal blood flow 9/30/2009IVMS 30Therapeutic use (Dopamine) (2)Increased sodium excretion following dopamine may be due to inhibition of aldosterone secretion. Dopamine may inhibit renal tubular solute reabsorption(suggesting that natriuresis & diuresis may occur by different mechanisms.) Fenoldopamand dopexamine: newer drugsmay be useful in treating heart failure by improving myocardial contractility 9/30/2009IVMS 31Therapeutic use (Dopamine) (3)Dopamine (Intropin) at higher dosesincreases myocardial contractility by ß1 -adrenergic receptor activation. Ventilation effects:--dopamine IV infusion interferes with ventilatory responses to arterial hypoxemiaDopamine (Intropin)acts as inhibitory neurotransmitter at carotid bodies) Consequence:Unexpected ventilation depression in patients treated with IV dopamine (Intropin) to enhance myocardial contractility 9/30/2009IVMS 32DopexamineDopexamine--synthetic catecholamine Activation of dopaminergic and beta 2 receptors Slight positive inotropic effect (beta2-adrenergic agonists activity; potentiation those endogenous norepinephrinesecondary to reuptake blockade) Dopexamine enhances creatinine clearance 9/30/2009IVMS 33Isoproterenol (Isuprel)Activates ß adrenergic receptors (both ß1 -and ß2 -receptor subtypes) Has limited action at a adrenergic receptors i.v. influsion of isoproterenol results in a slight decrease in mean blood pressure with a marked drop in diastolic pressure. ß2 -adrenergic receptor-mediated reduction in peripheral resistance (reflected in the diastolic pressure effects) is primarily due to vasodilation of skeletal muscle vasculature. Renal and mesenteric vascular beds are also dilated. 9/30/2009IVMS 34Isoproterenol (Isuprel) (2)Activation of cardiac ß1 -adrenergic receptors: increased contractility and heart rate. Activation of ß2 -adrenergic receptors: Bronchial and GI smooth muscle relaxation. Isoproterenol and ß2 -selective adrenergic agonists inhibit antigen-mediated histamine release.Isoproterenol: Limited therapeutic uses:emergency settings to treat heart block or severe bradycardia management of torsades de pointes(a ventricular arrhythmia)9/30/2009IVMS 35Isoproterenol (Isuprel) (3)management of torsades de pointes (a ventricular arrhythmia) Isoproterenol (Isuprel) adverse effects:palpitations tachycardia arrhythmias coronary insufficiency 9/30/2009IVMS 36Dobutamine (Dobutrex)Structurally similar to dopamine (Intropin). Pharmacological effects exerted through interaction with a and ß adrenergic receptor interactionsno effect on release no action through dopamine receptorsPharmacological effects are due to complex interactions of (-) and (+) enantiometic forms present in the clinically used racemate with aand ß adrenergic receptors. Dobutamine (Dobutrex)is a positive inotropicagent usually causing limited increase in heart rate.Positive inotropismis mediated through ß adrenergic receptor activation. Some peripheral a1 activity causes modest vasoconstriction, an effect opposed by dobutamines ß2 effects.9/30/2009IVMS 37Dobutamine (Dobutrex) (2)Dobutamine (Dobutrex): Adverse Effects Significant blood pressure and heart rate increases may occur. Ventricular ectopy Increased ventricular following rate in patient with atrial fibrillation. Increased myocardial oxygen demand that may worsen post-infarct myocardial damage Dobutamine (Dobutrex): Therapeutic Use Short-term management of pump failure following surgery, during acute congestive heart failure, or post-myocardial infarction. Uncertain long-term efficacy. 9/30/2009IVMS 38ß2 Selective Adrenergic AgonistsMetaproterenol (Alupent) Terbutaline (Brethine) Albuterol (Ventolin,Proventil) Ritodrine (Yutopar) 9/30/2009IVMS 39Metaproterenol (Alupent)ß2 adrenergic receptor-selective: resistant to COMT (catechol-O-methyl transferase) metabolism Less ß2 selective compared toterbutaline (Brethine) and albuterol (Ventolin,Proventil). May be used for long-term and acute treatment of bronchospasm9/30/2009IVMS 40Terbutaline [Brethine]ß2 adrenergic receptor-selective: resistant to COMT Active after oral, subcutaneous, or administration by inhalation Rapid onset of action. Used for management of chronic obstructive lung disease and for treatment of acute bronchospasm (smooth muscle bronchoconstriction), including status asthmaticus 9/30/2009IVMS 41Albuterol [Ventolin]ß2 adrenergic receptor-selective Effective following inhalation or oral administration. Commonly used in chronic and acute asthma management. 9/30/2009IVMS 42Ritodrine (Yutopar)ß2 adrenergic receptor-selective: developed as a uterine relaxant May be administered by i.v. in certain patients for arresting premature labor; if successful, oral therapy may be started ß2 adrenergic receptor-selective agonists may not improve perinatal mortality and may increase maternal morbidity In women being treated for premature labor, ritodrine (Yutopar) or terbutaline (Brethine) may cause pulmonary edema . 9/30/2009IVMS 43Adverse Effects-B2 AgonistsExcessive cardiovascular stimulation Skeletal muscle tremor (tolerance develops, unknown mechanism) due to ß2 adrenergic receptor activation Overusage may be a factor in morbidity and mortality in asthmatics. 9/30/2009IVMS 44Alpha1 Selective Adrenergic AgonistsAlpha1 selective adrenergic agonistsactivate a adrenergic receptors in vascular smooth muscle producing vasoconstriction.Peripheral vascular resistance is increased. Blood pressure may be increased, causing a reflex reduction heart rate a1 adrenergic agonistsare used clinically in management of hypotension and shock. 9/30/2009IVMS 45Alpha1 Selective Adrenergic AgonistsDirect ActingPhenylephrine (Neo-Synephrine) and methoxamine (Vasoxyl)are direct-acting vasoconstrictors. Mixed ActingMephentermine (Wyamine) and metaraminol (Aramine)act both by direct receptor activation and by promoting epinephrine release.9/30/2009IVMS 46Methoxamine (Vasoxyl)specific alpha1 receptor agonistincreases peripheral resistance causes an increase in blood pressure that precipitates sinus bradycardia (decreased heart rate) due to vagal reflex. Reflex bradycardia may be block by atropine (muscarinic antagonist) Clinical use:hypotensive states termination (by vagal reflex) of paroxysmal atrial tachycardia (adenosine may be preferable) 9/30/2009IVMS 47Phenylephrine (Neo-Synephrine)Specific alpha1 receptor agonistIncreases peripheral resistance Causes an increase in blood pressure that precipitates sinus bradycardia (decreased heart rate) due to vagal reflex. Reflex bradycardia may be block by atropine (muscarinic antagonist) Clinical use:hypotensive states mydriatic nasal decongestant 9/30/2009IVMS 48Alpha 2 SelectiveAdrenergic Agonists and Miscellaneous Adrenergic Agonistsalpha2 selective adrenergic agonists are used to treat essential hypertension. Mechanism of action:activation of central a2 adrenergic receptors at cardiovascular control centers activation decreases sympathetic outflow, reducing sympathetic vascular tone. 9/30/2009IVMS 49alpha2 Selective Adrenergic AgonistsClonidine (Catapres)is primarily used in treating essential hypertension. A prolonged hypotensive response results from a decrease in CNS sympathetic outflow. This response is due to a2 selective adrenergic receptor activation9/30/2009IVMS 50alpha2 Selective Adrenergic AgonistsClonidine (Catapres)(2)Adverse Effects:dry mouth sedation sexual dysfuction Clonidine's a2 selective adrenergic receptor activation of vascular smooth muscle may increase blood pressure in patients with severe autonomic dysfunctionwith profound orthostatic hypotension (in these patients the reduction of central sympathetic outflow in not clinically important)9/30/2009IVMS 51alpha2 Selective Adrenergic Agonists and Miscellaneous Adrenergic AgonistsAlpha-methyl DOPA (methyldopa (Aldomet)),metabolically converted to alpha-methyl norepinephrine, is used for treating essential hypertensionA prolonged hypotensive response results from a decrease in CNS sympathetic outflow. This response is due to a2 selective adrenergic receptor activation. Adverse Effects:dry mouth sedation 9/30/2009IVMS 52alpha2 Selective Adrenergic Agonists and Miscellaneous Adrenergic AgonistsAmphetamine CNS stimulant (releasing biogenic nerve terminal amines):respiratory center mood elevation decreased perception of fatigue Other effects: headache, palpitations, dysphoriaAppetite suppression Weight loss due to decrease food intake psychological tolerance/dependence 9/30/2009IVMS 53Amphetamine (2) Indirect acting sympathomimeticToxicity:CNS:restlessness, tremor, irritablity, insomnia, aggressiveness, anxiety, panic, suicidal ideation, etc. Cardiovascular:arrhythmias, hypertension or hypotension, angina GI:dry mouth, anorexia, vomiting, diarrhea, cramping Treatment:urinary acidification by ammonium chloride hypertension: nitroprusside or alpha adrenergic receptor antagonist CNS: sedative-hypnotic drugs 9/30/2009IVMS 54Amphetamine (3)Therapeutic Use:Narcolepsy Obesity Attention-deficit hyperactivity disorder 9/30/2009IVMS 55Methylphenidate (Ritalin) Mild CNS stimulant, chemically related to amphetamine Effects more prevalent on mental than motor activities General pharmacological profile similar to amphetamine Major Therapeutic Use:Narcolepsy Attention-deficit hyperactivity disorder9/30/2009IVMS 56Ephedrine alpha and ß adrenergic receptor agonist Indirect sympathomimetic also, promoting norepinephrine releasenon-catechol structure, orally active Pharmacological effects:increases heart rate, cardiac output usually increases blood pressure may cause uriniary hesitancy due to stimulation of a smooth muscle receptors in bladder base. bronchodilation: ß adrenergic receptor response 9/30/2009IVMS 57Ephedrine(2)Limited Clinical Use due to better pharmacological alternatives (asthma, heart block, CNS stimulation) Vasoconstrictors for Nasal Mucosal Membranes and for the Eye9/30/2009IVMS 58Adrenergic Drug Lists SummaryDrugReceptorsEpinephrinealpha1, alpha2ß1, ß2Norepinephrine (Levophed)alpha1, alpha2, ß1Isoproterenol (Isuprel)ß1, ß2Dobutamine (Dobutrex)ß1(alpha1)Dopamine (Intropin) D-1 (alpha1and ß1at high doses)Catecholamines9/30/2009IVMS 59Adrenergic Drug Lists SummaryDirect adrenoceptor agonistsDrugReceptor SelectivityPhenylephrine (Neo-Synephrine)alpha1Methoxamine (Vasoxyl)alpha1Oxymetazoline (Afrin)alpha1, alpha2Clonidine (Catapres)alpha2Ritodrine (Yutopar)ß2Terbutaline (Brethine)ß2Albuterol (Ventolin,Proventil)ß2Salmeterol (Serevent) ß29/30/2009IVMS 60Adrenergic Drug Lists SummaryIndirect sympathomimetics•Ephedrine, Pseudoephedrine •Cocaine •Tyramine •Amphetamine•Release & direct receptor activation •Uptake Inhibitor •Release •see ephedrine, but greater CNS actions 9/30/2009IVMS 61Adrenergic Drug Lists SummaryAlpha-Adrenoceptor antagonistsDrugReceptor Selectivity (a1vs. a2)Prazosin (Minipress)alpha1Terazosin (Hytrin)alpha1Trimazosinalpha1Doxazosin (Cardura)alpha1Phentolamine (Regitine)non-selectivePhenoxybenzamine (Dibenzyline)only slightly selective for alpha1(non-competitive)Tolazoline (Priscoline)non-selectiveLabetalol (Trandate, Normodyne)alpha1(also non-selective beta-antagonist)Yohimbine (Yocon) alpha29/30/2009IVMS 62Adrenergic Drug Lists Summaryß-Adrenoceptor antagonistsDrugReceptor Selectivity (ß1vs. ß2)Propranolol (Inderal)non-selectiveMetoprolol (Lopressor)ß1Esmolol (Brevibloc)ß1Atenolol (Tenormin)ß1Nadolol (Corgard)non-selectiveTimolol (Blocadren)non-selectivePindolol (Visken)non-selective (partial agonist)Labetalol (Trandate, Normodyne)non-selective (selective a1-antagonist)9/30/2009IVMS 63EffectorAction of Sympathetic (Thoracolumbar) DivisionAction of Parasympathetic (Craniosacral) DivisionEye (pupil)Dilation (ex)Constriction (ex)HeartRateAcceleration (ex)Slowing (in)ContractilityIncreased (ex)Decreased (in)ArteriolesSkin and most othersConstriction (ex)—Skeletal muscleDilation (ex)—GlandsSalivaryViscid secretion (ex)Watery secretion (ex)Lacrimal—Secretion (ex)SweatSecretion (ex)—Bronchial muscleRelaxation (in)Contraction (ex)GI tractMuscle wallRelaxation (in)Contraction (ex)SphinctersContraction (ex)Relaxation (in)Urinary bladderFundusRelaxation (in)Contraction (ex)Trigone; sphincterContraction (ex)Relaxation (in)PenisEjaculation (ex)Erection (in)UterusRelaxation (in)—MetabolismLiverGluconeogenesis (ex)—Glycogenolysis (ex)—9/30/2009IVMS 64Adrenergics High Yield Synopsis (1)9/30/2009IVMS 65Adrenergics High Yield Synopsis(2)9/30/2009IVMS 66Adrenergics High Yield Synopsis(3)9/30/2009IVMS 67Adrenergics High Yield Synopsis(4)9/30/2009IVMS 68Adrenergics High Yield Synopsis(5)