ANS Pharmacology & Pathophysiology 2 Flashcards
Which is NOT an endogenous sympathomimetic?
a. ephedrine
b. dopamine
c. norepinephrine
d. epinephrine
a. ephedrine
Endogenous catecholamines include
epinephrine, norepinephrine, and dopamine
Synthetic catecholamines include
dobutamine
isoproterenol
Endogenous and synthetic catecholamines may produce
hypertension
arrhythmias
myocardial ischemia
The effects of endogenous and synthetic agonists are dependent on their
specificity for alpha and beta adrenoreceptors and dopaminergic subtypes
What is the classification of ephedinre?
synthetic noncatecholamine
sympathomimetic
Administration of beta 2 adrenoreceptors agonists in aerosolized form minimizes
side effects such as anxiety, tremor, and restlessness
Isoproterenol and dobutamine have _________ activity
beta 1 and some beta 2
Epinephrine and norepinephrine undergo metabolism by
catechol-O-methyl transferase and monoamine oxidase to yield vanillymandelic acid
_________ is assayed as part of the diagnostic work-up of pheochromocytoma
VMA or vanillymandelic acid
Adrenergic agonists mimic ___________ effects via
SNS; direct receptor activation or by encouraging endogenous catecholamine release
What is the receptor and dosing of epinephrine?
B1>B2, alpha 1
0.01-0.2 mcg/kg/min.
What is the receptor and dosing of norepinephrine?
alpha 1, beta 1>beta 2
0.01-0.2 mcg/kg/min.
What is the receptor and dosing of dopamine?
beta 1>beta 2, alpha 1
2-20 mcg/kg/min.
What is the receptor and dosing of isoproterenol?
B1>B2
0.015-0.15 mcg/kg/min.
What is the receptor and dosing of dobutamine?
B1>B2>A1
2-20 mcg/kg/min
What is the receptor and dosing of ephedrine?
a, beta indirect
bolus 5-25 mg IV
up to 50 mg IM
What are the systemic effects of catecholamines?
decreased digestive system activity
dilation of bronchioles
increased heart rate
liver converts glycogen to glucose
high blood pressure
Epinephrine has more potency at beta receptors than
norepinephrine
The net effect of epi depends on the balance of the receptor types in the individual tissues and organs. Organs with a higher incidence of B2 receptors such as skeletal muscle will see
vasodilation
With epinephrine, organs with a higher incidence of alpha 2 receptors such as the mesentery and kidneys will experience
vasoconstriction
The net effect of epinephrine depends on the
dose
Low doses of epinephrine favor
beta stimulation (increased HR, CO, inotropy, and pulse pressure, and a decrease in SVR)
High doses of epinephrine favor
alpha effects (increased SVR and decreased CO)
Significant metabolic changes related to epinephrine administration include
increase in blood glucose
hypokalemia occurs due to a transcellular potassium shift
Norepinephrine has mostly_________ effects and minimal _______ effects
alpha 1 and beta 1; beta 2
Describe the differences in receptor affinity with high doses of norepinephrine versus low.
low doses favor B1 stimulation
high doses favor beta 1 and alpha effects
The systemic vasoconstriction effect of norepinephrine is _________ epinephrine
greater
Describe how the does of dopamine stimulates different receptors.
low dose dopamine (<3 mcg/kg/min) stimulates D1 receptors
moderate doses of dopamine (3-8 mcg/kg/min) stimulate alpha1 and beta 1 adrenergic receptors in the heart and periphery
high dose dopamine (>10 mcg/kg/min) acts a a pure alpha 1 agonist
Postsynaptic D1 receptors cause
vasodilation of renal, GI, coronary, and cerebral vessels
Presynaptic D2 receptors
inhibit norepinephrine release and thus cause vasodilation
Dopamine ___________ prevent or reverse AKI or failure
Does NOT
Dopamine undergoes what kind of metabolism?
metabolic degradation by catechol-O-methyl transferase and MAO (same as norepi & epi!)
The end product of dopamine metabolism is
homovanillic acid
Isoproterenol is derived from
dopamine
IV infusion dose of isoproterenol is
0.015-0.15 mcg/kg/min.
What is the MOA of isoproterenol?
potent sympathomimetic with B1 and B2 activity (2-3x potency of epinephrine)
What can isoproterenol precipitate?
supraventricular and ventricular arrhythmias
What does dobutamine do?
enhances myocardial contractility and reduces vascular tone
What is the IV infusion dose of dobutamine?
2-20 mcg/kg/min.
Uses of dobutamine include:
inotropic agent in those with pulmonary hypertension (beta 2 stimulation reduces pulmonary vascular resistance)
potent inotrope that may be used in select cases of heart disease, MI, and depressed myocardial states
dobutamine stress echo to assess heart function during exertion
What is the MOA of dobutamine?
selective b1 agonist with mild B2 effects
Adverse effects of dobutamine include
extending cardiac muscle infarction
increasing AV conduction which can trigger rapid ventricular rate in those with A-fib
What is the drug class of ephedrine?
synthetic, noncatecholamine sympathomimetic
What receptors does ephedrine stimulate?
both alpha and beta receptors (indirect agent as well)
_______________ is seen with repeat administrations of ephedrine due to ____________
tachyphylaxis; due to depletion of presynaptic norepinephrine
Ephedrine has mild stimulating effects because
it crosses the BBB
Short-acting beta 2 agonist drugs include
albuterol
terbutaline
levalbuterol
Long-acting B2 agonist drugs include
salmetrol
formoterol
An FDA “black box” warning is attached to the
longer-acting B2-selective agents (salmeterol & formoterol) d/t risk of asthma-related death
-possibly d/t development of airway hyperresponsiveness
What effect does beta 2 agonists have on the uterus?
increased cAMP leading to decreased Ca2+ levels–> uterine smooth muscle relaxation and a tocolytic effect
With escalated doses of B2 agonists over time, the B2
selectivity wanes, and B2 effects such as tachycardia and arrhythmias may become apparent
Chronic B2 agonist therapy can lead to
down-regulation of the target receptors resulting in tachyphylaxis
also evidence of airway hyperresponsiveness
What potent alpha agonist is the chemical precursor of epinephrine?
norepinephrine
Which adrenoreceptor agonist is metabolized by the liver?
ephedrine
Which synthetic catecholamine is derived from dopamine?
isoproterenol
Which drug has the greatest increase in MAP?
norepinephrine
Which drug is the precursor of norepinephrine?
dopamine
Which drug results in a large increase of renal blood flow?
dopamine
