ANS Pharmacology: Adrenergic Drugs

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

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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