Autonomic Pharmacology Adrenergic Drugs (*Agonist)
Prepared and Presented by: Marc Imhotep Cray, M.D. BMS/CK Teacher
*Adrenergic antagonist are covered in the Antihypertensive Agents Presentation
*Suggested Review Books & Resources Companion Notes: ANS Summary Notes Formative Assessment
ď ą Review Test for Autonomic Nervous System ď ą Review Test for Autonomic Nervous System answers and explanations
*e-Books & learning tools available to enrolled learners at thePOINT
Clinical Correlate: e-Medicine Article Epilepsy and the Autonomic Nervous System
If you are using a different review book, the chapters may be organized differently, but the material covered is approximately the same. Simply find the corresponding material in your book for each lecture. 2
Introduction
Distribution of adrenergic receptor subtypes and adrenergic receptor number are important factors in organ or cellular responses to adrenergic input Adrenergic receptor type in bronchiolar smooth muscle is principally ß2: epinephrine and isoproterenol might be expected to be effective bronchodilators because of their activity at ß2 receptors
Norepinephrine is unlikely to have this same effect due to its relative lack of activity at ß2 sites
3
Introduction cont.
Alpha receptor dominate in the cutaneous vascular beds
Norepinephrine and epinephrine cause constriction Isoproterenol with 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 4
Introduction (2) Physiological effects caused by sympathomimetics 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 baroreceptors activations 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
5
Categories 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 Effects Presynaptic effects: modulation of release of norepinephrine or acetylcholine
6
Epinephrine
Epinephrine is a potent activator of alpha and ß adrenergic receptors
Prominent Cardiovascular Effects
7
Epinephrine and Blood 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): ß1receptor effects increasing heart rate (positive chronotropic effect): ß1-receptor effects. vasoconstriction a1 receptor effects precapillary resistance vessels of the skin, kidney, and mucosa veins 8
Epinephrine and Blood Pressure (2) ď Ž
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
Epinephrine and Blood 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 10
Epinephrine and Blood Pressure (4)
As pressure rises and especially for rapid increases in pressure: baroreceptor input to the tractus solitarius of the medulla results 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) 11
Epinephrine and Blood Pressure (5) Adrenergic Sino-atrial (SA) Node Atrial muscle Atrio-ventricular (AV) node His-Purkinje System
Ventricles
Cholinergic decreased rate (vagal)
beta1; beta2
increased rate
beta1; beta 2
increased: contractility, conduction velocity
decreased: contractility, action potential duration
beta1; beta 2
increased: automaticity, conduction velocity
decreased conduction velocity; AV block
beta1; beta 2
increased: automaticity, conduction velocity
------
beta1; beta 2
increased: contractility, conduction velocity, automaticity, ectopic pacemaker
small decrease in contractility 12
Epinephrine and Blood Pressure (6) Summary Blood Pressure Blood Pressure Effects
Epinephrine
Norepinephrine
Systolic Mean Pressure Diastolic
variable
Mean Pulmonary 0.1-0.4 ug/kg/min infusion rate
At lower epinephrine doses: a lessened effect on systolic pressure occurs diastolic pressures may decrease as peripheral resistance is reduced. Peripheral resistance decreased due to Ă&#x;2-receptor effects 13
Epinephrine-Vascular Effects
Epinephrine has significant effects on smaller arteriolar and precapilliary smooth muscle
Acting through alpha1 receptors, vasoconstrictor 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 14
EpinephrineVascular Effects cont.
Acting through ß2-receptors, epinephrine causes significant vasodilatation 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" 15
Epinephrine- Cardiac Effects
Epinephrine exerts most of its effects on the heart through activation of ß1adrenergic receptors. ß2- and α-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
16
Epinephrine- Smooth Muscle Effects Smooth 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 17
Epinephrine- 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 ß2selective receptor agonists: ritodrine and terbutaline to delay premature labor Pregnant: contraction (alpha1); relaxation Uterus alpha1; beta2 variable (beta2); Nonpregnant: relaxation (beta2) 18
Epinephrine- Pulmonary Effects Epinephrine is a significant respiratory tract bronchodilator Bronchodilation is 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 and this decrease may be beneficial is management of asthma also
Pulmonary Adrenergic Tracheal and bronchial muscle Bronchial glands
Effects
Cholinergic
beta 2
Relaxation
contraction
alpha1, beta2
decrease secretion; increased secretion
stimulation 19
Epinephrine- Metabolic Effects Insulin secretion: inhibited by α2 adrenergic receptor activation (dominant) Insulin secretion: enhanced by ß2 adrenergic receptor activation
Pancreas Adrenergic Effects
Cholinergic
Acini
alpha
decreased secretion
secretion
Islets (beta cells)
alpha2
decreased secretion
---------
Islets (beta cells)
beta2
increased secretion
---------
Glucagon secretion: enhanced by ß adrenergic receptor activation of pancreatic islet alpha cells Glycolysis- stimulated: by ß adrenergic receptor activation 20
Epinephrine- Metabolic Effects (2) Liver Adrenergic Liver
alpha1; beta2
Effects
Cholinergic
glycogenolysis and ----------gluconeogenesis
Free fatty acids, increased: by Ă&#x; adrenergic receptor activation on adipocytes--activation of triglyceride lipase
21
Epinephrine- Metabolic Effects (3) Adipose Tissue Adrenergic Fat Cells
alpha2; beta3
lipolysis (thermogenesis)
Cholinergic ---------
Calorigenic effect (20% - 30% increase in O2 consumption): caused by triglyceride breakdown in brown adipose tissue
22
Epinephrine- 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 cardioselective β1 antagonists) Possible "preoperative hypokalemia" may be associated with preoperative anxiety that promotes epinephrine release-therapeutic decisions based on pre-induction serum potassium levels to take into account this possible explanation
23
Norepinephrine
Norepinephrine is the primary neurotransmitter released by postganglionic neurons of the autonomic sympathetic system Norepinephrine (Levophed) is a potent activator of α and ß1 adrenergic receptors 24
NE- 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
N.B. Elevation of systolic pressure following norepinephrine is likely to activate the baroreceptor system resulting in a reflex-mediated decrease in heart rate 25
NE- Blood Pressure Effects Blood Pressure Blood Pressure Effects
Epinephrine
Norepinephrine
Systolic Mean Pressure Diastolic
variable
Mean Pulmonary
Adaptation 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 Pharmacological Basis of Therapeutics,(Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) The McGrawHill Companies, Inc.,1996, pp.199-242
26
NE-Arterioles Effects Arterioles
Adrenergic
Cholinergic
Coronary
alpha1,2; beta 2
constriction; dilatation
constriction
Skin/Mucosa
alpha1,2
constriction
dilatation
Skeletal Muscle
alpha; beta2
constriction,dilatation
dilatation
Cerebral
alpha1
slight constriction
dilatation
Pulmonary
alpha1 , beta2
constriction; dilatation
dilatation
Abdominal viscera
alpha1, beta2
constriction; dilatation
-------
Salivary glands
alpha1,2
constriction
dilatation
Renal
alpha1,2;beta1,2
constriction;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 Pharmacological 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.
27
NE-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
N.B. Pressor effects of NE (Levophed) are blocked by alpha-receptor blockers ECG changes following NE (Levophed) are variable, depending on extent of reflex vagal effects 28
NE- Peripheral Circulation Effects Peripheral Circulation Peripheral Circulation
Epinephrine
Norepinephrine
Total Peripheral Resistance Cerebral Blood Flow
no effect or decrease
Muscle Blood Flow
no effect or decrease
Cutaneous Blood Flow
Renal Blood Flow Splanchnic Blood Flow
no effect or increase
increase, decrease 0.1-0.4 ug/kg/min IV infusion
Therapeutic use: Norepinephrine may be used in treatment of shock
29
Dopamine Cardiovascular Effects (Dopamine) 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 pressure with little effect on diastolic pressures.
Vasopressor: At high doses dopamine (Intropin) causes vasoconstriction by activating α1 adrenergic receptors
30
Therapeutic use (Dopamine) Cardiogenic and hypovolemic Unique among catecholamines in that Dopamine can shock simultaneously increase by enhancing renal perfusion myocardial contractility despite low cardiac output glomerular filtration rate Oligouria may be an indication of sodium excretion inadequate renal perfusion Example: dopamine may be used, in urine output renal blood flow postoperative cardiopulmonary bypass patients who exhibit: low systemic blood-pressure increased atrial filling pressures low urinary output
31
Therapeutic 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.) Fenoldopam and dopexamine: newer drugs
may be useful in treating heart failure by improving myocardial contractility
32
Therapeutic use (Dopamine) (3)
Dopamine (Intropin) at higher doses increases 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
33
Dopexamine
Dopexamine-A synthetic analogue of dopamine a β1 and β2-adrenergic receptor agonist Slight positive inotropic effect (beta 1adrenergic agonists activity; potentiation those endogenous norepinephrine secondary to reuptake blockade) Dopexamine enhances creatinine clearance
Action dopamine receptor: D1 mediates relaxation of vascular smooth muscle in renal, mesenteric, cerebral and coronary arteries Mild action at D2 receptors decreases NE release
34
Isoproterenol (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 35
Isoproterenol (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)
36
Isoproterenol (Isuprel) (3)
management of torsades de pointes (a ventricular arrhythmia)
Isoproterenol (Isuprel) adverse effects:
palpitations tachycardia arrhythmias coronary insufficiency 37
Dobutamine (Dobutrex)
Structurally similar to dopamine (Intropin). Pharmacological effects exerted through interaction with α 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 α and ß adrenergic receptors Dobutamine (Dobutrex) is a positive inotropic agent usually causing limited increase in heart rate Positive inotropism is mediated through ß adrenergic receptor activation. Some peripheral a1 activity causes modest vasoconstriction, an effect opposed by dobutamines ß2 effects
38
Dobutamine (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.
39
ß2 Selective Adrenergic Agonists
Metaproterenol (Alupent)
Terbutaline (Brethine)
Albuterol (Ventolin,Proventil)
Ritodrine (Yutopar) 40
Metaproterenol (Alupent)
ß2 adrenergic receptor-selective: resistant to COMT (catechol-O-methyl transferase) metabolism Less ß2 selective compared to terbutaline (Brethine) and albuterol (Ventolin,Proventil). May be used for long-term and acute treatment of bronchospasm 41
Terbutaline [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 42
Albuterol [Ventolin]
ß2 adrenergic receptor-selective Effective following inhalation or oral administration Commonly used in chronic and acute asthma management
43
Ritodrine (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 44
Adverse Effects-B2 Agonists
Excessive cardiovascular stimulation Skeletal muscle tremor (tolerance develops, unknown mechanism) due to ß2 adrenergic receptor activation Over usage may be a factor in morbidity and mortality in asthmatics
45
Alpha1 Selective Adrenergic Agonists
Alpha1 selective adrenergic agonists activate 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 agonists are used clinically in management of hypotension and shock 46
Alpha1 Selective Adrenergic Agonists Direct Acting ď Ž Phenylephrine (Neo-Synephrine) and methoxamine (Vasoxyl) are directacting vasoconstrictors Mixed Acting ď Ž Mephentermine (Wyamine) and metaraminol (Aramine) act both by direct receptor activation and by promoting epinephrine release 47
Methoxamine (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) 48
Phenylephrine (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 49
Alpha 2 Selective Adrenergic 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.
50
Alpha2 Selective Adrenergic Agonists Clonidine (Catapres) is primarily used in treating essential hypertension. ď Ž A prolonged hypotensive response results from a decrease in CNS sympathetic outflow. ď Ž This response is due to a2 selective adrenergic receptor activation 51
alpha2 Selective Adrenergic Agonists
Clonidine (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 dysfunction with profound orthostatic hypotension (in these patients the reduction of central sympathetic outflow in not clinically important) 52
alpha2 Selective Adrenergic Agonists and Miscellaneous Adrenergic Agonists Alpha-methyl DOPA (methyldopa (Aldomet), metabolically converted to alphamethyl 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
53
Alpha 2 Selective Adrenergic Agonists and Miscellaneous Adrenergic Agonists Amphetamine 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
54
Amphetamine (2) Indirect acting sympathomimetic Toxicity: 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 55
Amphetamine (3) Therapeutic Use: Narcolepsy Obesity Attention-deficit hyperactivity disorder
56
Methylphenidate (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 disorder 57
Ephedrine α 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 urinary hesitancy due to stimulation of a smooth muscle receptors in bladder base. bronchodilation: ß adrenergic receptor response
58
Ephedrine(2) ď Ž
ď Ž
Limited Clinical Use due to better pharmacological alternatives (asthma, heart block, CNS stimulation) Vasoconstrictors for Nasal Mucosal Membranes and for the Eye
59
Adrenergic Drug Lists Summary Catecholamines Drug
Receptors
Epinephrine
alpha1, alpha2 ß1, ß2
Norepinephrine (Levophed)
alpha1, alpha2, ß1
Isoproterenol (Isuprel)
ß1, ß2
Dobutamine (Dobutrex)
ß1 (alpha1)
Dopamine (Intropin)
D-1 (alpha1 and ß1 at high doses)
60
Adrenergic Drug Lists Summary Direct adrenoceptor agonists Drug
Receptor Selectivity
Phenylephrine (Neo-Synephrine)
alpha1
Methoxamine (Vasoxyl)
alpha1
Oxymetazoline (Afrin)
alpha1, alpha2
Clonidine (Catapres)
alpha2
Ritodrine (Yutopar)
ß2
Terbutaline (Brethine)
ß2
Albuterol (Ventolin,Proventil)
ß2
Salmeterol (Serevent)
ß2 61
Adrenergic Drug Lists Summary Indirect sympathomimetics
•Ephedrine, Pseudoephedrine •Cocaine •Tyramine •Amphetamine
•Release & direct receptor activation •Uptake Inhibitor •Release •see ephedrine, but greater CNS actions 62
Adrenergic Drug Lists Summary Alpha-Adrenoceptor antagonists Drug
Receptor Selectivity (Îą1 vs. Îą2)
Prazosin (Minipress)
alpha1
Terazosin (Hytrin)
alpha1
Trimazosin
alpha1
Doxazosin (Cardura)
alpha1
Phentolamine (Regitine)
non-selective
Phenoxybenzamine (Dibenzyline)
only slightly selective for alpha1 (noncompetitive)
Tolazoline (Priscoline)
non-selective
Labetalol (Trandate, Normodyne)
alpha1 (also non-selective betaantagonist)
Yohimbine (Yocon)
alpha2 63
Adrenergic Drug Lists Summary ß-Adrenoceptor antagonists Drug
Receptor Selectivity (ß1 vs. ß2)
Propranolol (Inderal)
non-selective
Metoprolol (Lopressor)
ß1
Esmolol (Brevibloc)
ß1
Atenolol (Tenormin)
ß1
Nadolol (Corgard)
non-selective
Timolol (Blocadren)
non-selective
Pindolol (Visken)
non-selective (partial agonist)
Labetalol (Trandate, Normodyne)
non-selective (selective a1antagonist) 64
Heart Rate
Acceleration (ex)
Slowing (in)
Contractility
Increased (ex)
Decreased (in)
Skin and most others
Constriction (ex)
—
Skeletal muscle
Dilation (ex)
—
Salivary
Viscid secretion (ex)
Watery secretion (ex)
Lacrimal
—
Secretion (ex)
Sweat
Secretion (ex)
—
Relaxation (in)
Contraction (ex)
Relaxation (in)
Contraction (ex)
Contraction (ex)
Relaxation (in)
Fundus
Relaxation (in)
Contraction (ex)
Trigone; sphincter
Contraction (ex)
Relaxation (in)
Penis
Ejaculation (ex)
Erection (in)
Uterus
Relaxation (in)
—
Gluconeogenesis (ex)
—
Glycogenolysis (ex)
—
Kidney
Renin secretion(ex)
—
Fat Cells
Lipolysis (ex)
Arterioles
Glands
Bronchial muscle GI tract Muscle wall Sphincters Urinary bladder
Metabolism Liver
65