Adrenergic Agonists & Antagonists Flashcards
From where is norepinephrine released?
post-ganglionic sympathetic fibers at end organ tissues (except in eccrine sweat glands and some blood vessels)
From where is acetylcholine released?
Preganglionic sympathetic fibers and all parasympathetic fibers
How is the action of NorEpi terminated
Primarily reuptakeinto postganglionic nerve ending; also diffusion from receptor sites or via metabolism by monoamine oxidase
Where are alpha1-receptors located
smooth muscle throughout the body
What is occurs with activation of alpha1-receptors
contraction of smooth muscle
- midriasis, bronchoconstriction, vasoconstriction, uterine contraction, constriction of sphincters
- myocardium has alpha1-receptors –> positive inotropic effect
- most important clinical effect is vasoconstriction
What occurs with activation of peripheral alpha2-receptors
Inhibits NorEpi release
Vasoconstriction
What occurs with activation of CNS alpha2-receptors
Sedation and reduced sympathetic outflow –peripheral vasodilation and lower BP
Where are most B1 receptors located and what occurs with activation of these receptors?
Heart
+ Chronotropy
+ Dromotropy (conduction)
+ inotropiy
What occurs with activation of B2 receptors?
Smooth muscle relaxation: bronchodilation, vasodilation, uterus relaxation, bladder and gut
What occurs with activation of dopamine receptors - D1 and D2?
D1: mediates vasodilation in kidney, intestine and heart
D2: antiemetic properties (e.g., as in droperidol)
What are the naturally occurring cathecolamines and what is unique about their structure
Epinephrine, Norepi, Dopamine
All have a 3,4-dihydroxybenzene structure
What receptors does phenylephrine act on and what is its primary effect?
Selective alpha1-agonist
Peripheral vasoconstriction
Why does phenylephrine cause bradycardia?
Reflex bradycardia is mediated by the vagus nerve and can reduce cardiac output
Can tachyphylaxis occur with phenylephrine infusions? what is a typical infusion rate (mcg/kg/min)?
YES
0.25-1mcg/kg/min
What receptors does dexmedetomidine act on?
alpha-2 (200:1 alpha2:alpha1)
What is the half life of dexmedetomidine?
2-3 hours
What is the recommended dose of dexmed?
loading dose 1mcg/kg over 10 minutes, followed by infusion 0.2-0.7mcg/kg/hour
What can occur with abrupt cessation of dexmed after >48h of adminstration?
Withdrawal: hypertensive crisis
Where is epinephrine synthesized
Adrenal medulla
What is a typical range for an epinephrine infusion?
2-20mcg/min
On which receptors does NorEpi act?
Alpha-1 and 2; Beta-1
What receptors does dopamine act on at low doses (0.5-3mcg/kg/min)? What effect does this have?
Dopamine receptors (DA1) Vasodilates renal vasculature and promotes diuresis and natruiresis No beneficial effect on renal function
What receptors does dopamine act on at moderate doses (3-10mcg/kg/min)? What effect does this have?
Beta-1
Increased myocardial contractility, rate, SBP, CO
Myocardial oxygen demand increases disproportionately to supply
What receipts does dopamine act on at high doses (10-20 mcg/kg/min):? what effect does this have?
Alpha-1
increase in peripheral vascular resistance (fall in renal blood flow)
What is isoproterenol’s mechanism of action?
Beta agonist (Beta 1 and 2)
What receptors does dobutamine act on? What are its clinical effects?
B1 and B2 (more selective for B1)
Rise in CO secondary to increased myocardial contractility
Decrease in peripheral vascular resistance (B2 activation)
LV filling pressure decreases
Coronary blood flow increases
What is a typical range for dobutamine infusion?
2.5-20 mcg/kg/min
How does phentolamine work? What physiological effects are seen?
Alpha-1 and alpha-2 blockade. Causes smooth muscle relaxation and thus lowers BP
This drop in BP leads to a reflex tachycardia
What clinical conditions is phentolamine used for?
HTN caused by excessive alpha-stimulation: pheochromocytoma, clonidine withdrawal
Prevention of tissue necrosis following extravasation of IV fluids with alpha agonist (e.g., norepi)
What receptors does labetalol act on?
alpha1, beta1, beta2. Alpha to Beta ratio is 1:7
How long does it take for Labetalol’s peak effect?
5 minutes (IV)
Which beta blockers are selective for Beta1 receptors?
Atenolol, esmolol, metoprolol
What is the distribution half life and elimination half life of esmolol? How is esmolol eliminated?
Distribution: 2 minutes
Elimination: 9 minutes
Eliminated by hydrolysis by RBC esterase
What is propranolol’s mechanism of action
Non-selective B1 and B2 blocker
Decreases BP by decreasing myocardial contractility, lowering HT, decreasing renin release
Decreases myocardial oxygen demand
What is carvedilol’s mechanism of action?
Mixed beta and alpha-blocker
Why should alpha-1 receptors be blocked with an alpha antagonist (e.g., phentolamine, phenoxybenzamine) before administration of a beta-antagonist?
Unopposed alpha can lead to extreme HTN
