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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

Review Test for


Autonomic Nervous
System
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 2: epinephrine and
isoproterenol might be expected to be
effective bronchodilators because of their activity
at 2 receptors

Norepinephrine is unlikely to have this same effect


due to its relative lack of activity at 2 sites

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 2 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

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

Epinephrine

Epinephrine is a potent activator of alpha and


adrenergic receptors

Prominent Cardiovascular Effects

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): 1receptor effects


increasing heart rate (positive chronotropic effect): 1-receptor
effects.
vasoconstriction a1 receptor effects
precapillary resistance vessels of the skin, kidney, and
mucosa
veins
8

Epinephrine and
Blood 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.

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 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 2-receptors associated with juxtaglomerular
cells
14

EpinephrineVascular Effects cont.

Acting through 2-receptors, epinephrine causes


significant vasodilatation which increases blood
flow through skeletal muscle and splanchnic
vascular beds
If an a receptor blocker is administered,
epinephrine 2-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 1adrenergic receptors.
2- and -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 -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 2-receptor activation
This effect provides the rationale for the clinical use of 2selective 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 2-receptor activation mediated smooth
muscle relaxation
This action can antagonize other agents that promote
bronchoconstriction
2-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 2 adrenergic receptor activation (dominant)
Insulin secretion: enhanced by 2 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 adrenergic receptor activation of pancreatic


islet alpha cells
Glycolysis- stimulated: by adrenergic receptor activation
20

Epinephrine- Metabolic
Effects (2)
Liver
Adrenergic
Liver

alpha1; beta2

Effects

Cholinergic

glycogenolysis
and
----------gluconeogenesis

Free fatty acids, increased: by 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 1 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 and 1 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 1
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 1 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 1 - 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 1 and 2-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 adrenergic receptors (both 1 - and


2 -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

2 - 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 1 - adrenergic receptors:


increased contractility and heart rate.
Activation of 2 - adrenergic receptors: Bronchial and GI
smooth muscle relaxation.
Isoproterenol and 2 -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 and
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 and
adrenergic receptors
Dobutamine (Dobutrex) is a positive
inotropic agent usually causing
limited increase in heart rate
Positive inotropism is mediated
through adrenergic receptor
activation.
Some peripheral a1 activity causes
modest vasoconstriction, an effect
opposed by dobutamines 2 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

2 Selective Adrenergic
Agonists

Metaproterenol (Alupent)

Terbutaline (Brethine)

Albuterol (Ventolin,Proventil)

Ritodrine (Yutopar)
40

Metaproterenol (Alupent)

2 adrenergic receptor-selective: resistant to


COMT (catechol-O-methyl transferase)
metabolism
Less 2 selective compared to terbutaline
(Brethine) and albuterol (Ventolin,Proventil).
May be used for long-term and acute
treatment of bronchospasm
41

Terbutaline [Brethine]

2 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]

2 adrenergic receptor-selective
Effective following inhalation or oral
administration
Commonly used in chronic and acute
asthma management

43

Ritodrine (Yutopar)
2 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
2 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
2 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
Phenylephrine (Neo-Synephrine) and
methoxamine (Vasoxyl) are directacting vasoconstrictors
Mixed Acting
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.
A prolonged hypotensive response
results from a decrease in CNS
sympathetic outflow.
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
and 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: adrenergic receptor response

58

Ephedrine(2)

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 1, 2

Norepinephrine (Levophed)

alpha1, alpha2, 1

Isoproterenol (Isuprel)

1, 2

Dobutamine (Dobutrex)

1 (alpha1)

Dopamine (Intropin)

D-1 (alpha1 and 1 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)

Terbutaline (Brethine)

Albuterol (Ventolin,Proventil)

Salmeterol (Serevent)

2
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 (1 vs. 2)

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


-Adrenoceptor antagonists
Drug

Receptor Selectivity (1 vs. 2)

Propranolol (Inderal)

non-selective

Metoprolol (Lopressor)

Esmolol (Brevibloc)

Atenolol (Tenormin)

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