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Table
of Contents
-
ß2 selective adrenergic
agonists
-
a-Selective
Adrenergic Agonists
-
a2
Selective
Adrenergic Agonists
-
Introduction
-
Clonidine
(Catapres)
-
Guanfacine
(Tenex)
-
Guanabenz
(Wytensin)
-
a-methyl DOPA
(Aldomet)
-
Miscellaneous
Amphetamine
-
Clinical Use of Sympathomimetic
Agents
|
-
Amphetamines
-
Adrenergic
Neuronal Blocking Drugs
-
Classification of
adrenoceptors (
a1, a2,ß1,
ß2
and D1), molecular consequences of their
activation, and their important locations.
-
Catecholamine
Metabolic Transformations
-
Pulmonary
Uptake
-
Adrenergic
and Cholinergic Effects on End Organs
-
Clinical
Uses: Sympathomimetic Drugs: a/b Adrenergic Agonists
-
Therapeutic
Uses of Indirect-Acting Adrenergic Agonists
-
Adverse
Effects: b Adrenergic Antagonists
-
a-Adrenergic
Antagonists
-
Introduction
-
a1-adrenergic
receptor antagonists
-
a2-adrenergic receptor antagonists
-
Phenoxybenzamine
(Dibenzyline)
-
Phentolamine(Regitine)
and tolazoline (Priscoline)
-
Prazosin
(Minipress) and Terazosin (Hytrin)
-
Others
-
b Adrenergic
Antagonists
-
Introduction
-
ß receptor blockers: Effects
on the heart
-
ß receptor blockers:
Antihypertensive
Effects
-
Pulmonary
Effects
-
Metabolic
Actions
-
Nonselective-ß adrenergic
receptor antagonists
-
propranolol
-
nadolol
-
timolol
-
labetalol
-
Cardioselective ß1 adrenergic
receptor antagonists
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metoprolol
-
esmolol
-
atenolol
-
Adverse Effects of ß
adrenergic
receptor antagonists
-
Therapeutic
Uses
|
Epinephrine
Blood Pressure
-
Potent vasopressor
-
Systolic pressure
increases to a greater extent
than diastolic (diastolic
pressure may decrease)
-
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
-
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.
As pressure rises and especially for
rapid increases in pressure:
-
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)
|
|
Sino-atrial (SA) Node
|
beta1; beta2
|
increased rate
|
decreased rate
(vagal)
|
Atrial muscle
|
beta1; beta 2
|
increased:
contractility, conduction velocity
|
decreased: contractility, action potential duration
|
Atrio-ventricular (AV)
node
|
beta1; beta 2
|
increased:
automaticity, conduction velocity
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decreased conduction velocity; AV block
|
His-Purkinje System
|
beta1; beta 2
|
increased:
automaticity, conduction velocity
|
------
|
Ventricles
|
beta1; beta 2
|
increased:
contractility, conduction velocity, automaticity, ectopic
pacemaker
|
small decrease
in contractility
|
Blood Pressure
Blood
Pressure Effects
|
Epinephrine
|
Norepinephrine
|
Systolic
|
|
|
Mean Pressure
|
|
|
Diastolic
|
variable
|
|
Mean Pulmonary
|
|
|
0.1-0.4 ug/kg/min
infusion rate
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 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.199-242
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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 ß1-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".
Cardiac Effects
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Smooth Muscle
Uterus
|
alpha1;
beta2
|
Pregnant: contraction
(alpha1); relaxation (beta2); Non-pregnant: relaxation
(beta2)
|
variable
|
Pulmonary
|
Adrenergic |
Effects |
Cholinergic |
Tracheal
and bronchial muscle |
beta 2 |
Relaxation |
contraction |
Bronchial
glands |
alpha1,
beta2 |
decrease
secretion;increased secretion |
stimulation |
Metabolic Effects
Pancreas
|
Adrenergic |
Effects |
Cholinergic |
Acini |
alpha |
decreased
secretion |
secretion |
Islets
(beta cells) |
alpha2 |
decreased
secretion |
--------- |
Islets
(beta cells) |
beta2 |
increased
secretion |
--------- |
Liver
|
Adrenergic |
Effects |
Cholinergic |
Liver |
alpha1;
beta2 |
glycogenolysis
and gluconeogenesis |
----------- |
Adipose Tissue
|
|
Adrenergic
|
|
Cholinergic
|
Fat Cells
|
alpha2;
beta3
|
lipolysis
(thermogenesis)
|
---------
|
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
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