Wk 10: Sympathomimetic agents Flashcards
Naturally occurring catecholamines (3)
Epinephrine
Norepinephrine
Dopamine
Synthetic catecholamines (2)
Isoproterenol
Dobutamine
Epinephrine is a hormone synthesized, stored, and released from the _______ _______
adrenal medulla
Epinephrine’s natural functions upon release into circulation include (5)
-Regulation myocardial _______
- _________ _________
-_____ and ____ smooth muscle tone
-________ secretions
-Metabolic processes (______ and ______)
-Regulation myocardial contractility
-Heart rate
-Vascular and bronchial smooth
muscle tone
-Glandular secretions
-Metabolic processes
(glycogenolysis and lipolysis)
Epinephrine receptors
Alpha 1
Alpha 2
Beta 1
Beta 2
Why isn’t oral administration of epinephrine effective?
Rapid metabolism in GI mucosa and liver
What routes can epinephrine be administered?
Subcutaneous
IM
IV
Epinephrine is poorly _______ soluble, preventing its ready entrance into the _____ ______ _____ and accounting for the lack of _______ _______
lipid
central nervous system
cerebral effects
Epinephrine clinical uses:
-___________
-Severe ________ and _______
-Cardiopulmonary __________
-Promotion of myocardial ________ and increase __________ ________
-Can be added to LA as a “marker” or to decrease _______ absorption and prolong DOA
-Anaphylaxis
-asthma and brochoconstriction
-Cardiopulmonary resuscitation
-promotion of myocardial contractility and increase vascular resistance
-systemic
____________ has the most significant metabolic effect on metabolism of all the catecholamines
Epinephrine
Release of endogenous epinephrine and the resulting __________ and inhibition of _______ secretion is the most likely explanation for perioperative hyperglycemia
glycogenolysis
insulin
Coagulation is accelerated by _________
epinephrine
A hypercoagulable state present during the intraoperative and postoperative period may reflect stress-associated release of _________
epinephrine
Norepinephrine is the endogenous neurotransmitter synthesized and stored in __________ sympathetic nerve endings and released with sympathetic nerve stimulation
postganglionic
Norepinephrine receptors
Alpha 1 > B1
B2 (weak)
The primary utility of norepinephrine is as a potent ________ to increase total peripheral vascular resistance and mean arterial pressure
vascoconstrictor
What is first-line agent in the treatment of refractory hypotension during severe sepsis?
Norepinephrine
Norepinephrine-induced vasoconstriction and redistribution of flow may increase ________ blood flow and _______ _______ in severely hypotensive septic patients
splanchnic
urine output
Norepinephrine side effects
Use as an inotropic agents limited by its action as a ___________ _________
potent vasoconstrictor
Norepinephrine side effects
Excessive vasoconstriction and decreased perfusion of renal, splanchnic, and peripheral vascular beds may lead to end-organ _______ and ________
hypoperfusion
ischemia
__________ is an endogenous catecholamine that regulates cardiac, vascular, and endocrine function.
Is an important neurotransmitter in the central and peripheral nervous systems
Dopamine
Despite identical IV infusion rates, there may be a ___ to ____ -fold variability in plasma concentrations produced by this drug, even in healthy individuals with normal drug metabolism
Dopamine
10-75
Dopamine receptors
B1 > B2
Alpha 1
D1 D2
Dopamine increases cardiac output by stimulation of ____ receptors, increasing ______ ______
Beta 1
stroke volume
Rapid metabolism of dopamine with an elimination half life of ___ to ___ minutes mandates its use as a continuous infusion
1 to 2 minutes
______________ is used clinically to increase cardiac output in patients with decreased contractility, low systemic BP, and low urine output as may be present after cardiopulmonary bypass or with chronic heart failure
Dopamine
Dopamine is unique among the catecholamines in being able to simultaneously:
-Increase myocardial _________
-Increase ________ blood flow
-Increase ________ _________ rate
-Excretion of _________
-Increase __________ output
contractility
renal
glomerular filtration
sodium
urine
Which catecholamine is associated most with dose-related sinus tachycardia and the potential to cause ventricular arrhythmias?
Dopamine
(vs. dobutamine or epinephrine)
Dopamine may presdispose to mycardial ischemia by:
precipitating ________, increasing ________, increasing _______, and precipitating coronary artery _________
tachycardia
contractility
afterload
vasospasm
__________ is the most potent activator of all sympathomimetics with beta 1 and beta 2 activity ____ to ____ times more potent than epinephrine and at least _____ times more active than NE
Isopreterenol
2 to 3
100
Isoproterenol receptors
Beta 1
Beta 2
The cardiovascular effects of isoproterenol reflect activation of beta 1 receptors in the ______ and beta 2 receptors in the _______ _______
heart
skeletal muscle
Isoproterenol
Although cardiac output may increase, the ___________ may decrease
Mean arterial pressure (MAP)
Does baroreceptor-mediated reflex bradycardia occur with isoproterenol?
No because MAP is not increased
Metabolism of isoproterenol in the _______ by catechol-O-methyltransferase is ________, necessitating a continuous infusion to maintain therapeutic plasma concentrations
liver
rapid
_________ is used to increase heart rate in adults in presence of heart block
Isoproterenol
_________ is used to provide sustained increases in heart rate before insertion of a temporary or permanent cardiac pacemaker
Isoproterenol
___________ is a synthetic catecholamine derived from isoproterenol consisting of a 50:50 racemic mixture of two sterioisomers
Dobutamine
Dobutamine receptors
Beta 1 > Beta 2
Alpha (high doses)
Dobutamines effects on ____ receptors increases at higher doses
alpha
_________ stimulates SA node automaticity as well as AV node and ventricular conduction
Dobutamine
(tachyarrhythmias)
Rapid metabolism of dobutamine (half life ___ mins) necessitates continuous infusion
2 mins
Dobutamine increases myocardial contractility (____ and ______ receptors) and causes a modest degree of peripheral vasodilation ( _____ receptors)
Beta 1 and alpha 1
Beta 2
Dobutamine is used to : (2)
-improve cardiac output in patients with CHF
-Weaning from CPB
Vasodilators may be combined with ________ or _________ to decrease afterload, optimizing cardiac output in the presence of increased _______
dobutamine
dopamine
SVR
The use of dobutamine may be limited by the occurrence of ________
tachyarrhythmias
Tachyarryhthmias in dobutamine occur more frequently at ______ _____ or in patients with underlying _______ or _______ _________
higher doses
arrhythmias
heart failure
Synthetic noncatecholamines
Ephedrine
Phenylephrine
_________ is an indirect and direct acting synthetic sympathomimetic
Indirect: stimulates release of endogenous ____
Direct: stimulates ___ and ___ -adrenergic receptors
Ephedrine
NE
alpha and beta
The slow inactivation and excretion of ________ are responsible for the prolonged duration of action of this sympathomimetic
ephedrine
Ephedrine uses:
-Increase BP in presence of SNS blockade produced by _____ _____
-Hypotension due to _______-or _________ anesthetics
regional anesthesia
inhaled or injected anesthetics
__________ was considered the preferred sympathomimetic for administration to parturients experiencing decreased systemic blood pressure owing to spinal or epidural anesthesia
alpha agonists such as __________ may be preferable for treatment of maternal hypotension
Ephedrine
Phenylephrine
Cardiovascular effects of ephedrine resemble those of __________, its systemic BP-elevating response is ________ ________ and lasts approximately ____ times longer
epinephrine
less intense
1o
IV ephedrine results in increases in: (3)
-Sys. and dys. BP
-HR
-CO
Ephedrine receptors
Alpha 1
Beta 1 > Beta 2
Phenylephrine receptor
Alpha 1
The principle mechanism for cardiovascular effects produced by ephedrine is increased myocardial _________ due to activation of ___ receptors
contractility
B1
In the presence of ______________, the cardiovascular effects of ephedrine may resemble responses more typical of alpha-adrenergic receptor stimulation
preexisting beta-adrenergic blockade
A second dose of ephedrine produces a less intense systemic blood pressure response than the first dose (_______________, occurs with many sympathomimetics
tachyphylaxis
___________ mimics the effects of NE but is less potent and longer lasting
Phenylephrine
Phenylephrine stimulates ____ receptors by a direct effect, with only a small part of the pharmacologic response being indirect-acting d/t its ability to evoke the release of ________
alpha 1
NE
Phenylephrine primarily causes ________ rather than ________ constriction
venoconstriction
Phenylephrine uses:
-Increase BP in presence of SNS blockade produced by _____ _____
-Peripheral vasodilation due to _______-or _________ anesthetics
-As a _________ infusion in adults to maintain normal BP during surgery
regional anesthesia
inhaled or injected anesthetics
continuous
Selective Beta 2- adrenergic agonists (3)
Albuterol
Metaproterenol
Terbutaline
Selective phophodiasterase inhibitors
Milrinone
Amrinone
Selective beta 2 agonists relax ________ and _______ smooth muscle, but in contrast to isopreterenol generally lack stimulating ____ effects on the heart
bronchiole and uterine
B1
Which of the beta 2 agonists can be administered MDI, PO, and subcutaneously?
Terbitaline
_______ are the preferred treatment for acute episodes of asthmas and the prevention of exercise-induced asthma
Beta 2 adrenergic agonists
Beta 2 agonists are divided into those with an intermediate DOA ( ___ to ___ hours) and those that are long acting (>___ h)
3-6
12
Beta-2 adrenergic agonists may be administered as continuous infusions to stop _______ _______ ______ (_______ )
premature uterine contractions (tocolytics)
Beta-2 adrenergic bronchodilators can be administered (4)
Orally
Inhalation
Subcutaneously
IV injection
The _________ route for beta 2 agonist bronchodilators is the preferred route because the side effects are fewer for any degree of bronchodilation
inhaled
With optimal inhalation technique approximately ___% of alpha 2 agonists is delivered from the MDI to the lungs, the remainder is deposited in the mouth, pharynx, and larynx
12%
Technique for administering beta 2 agonist with MDI
Discharge inhaler while taking a slow deep breath over ___ to___ seconds, and then hold the breath at full inspiration for ___ seconds
5 to 6
10
Beta 2 agonist
The presence of an ETT decreases by approximately ___% to ____% the amount of drug delivered by a MDI that reaches the trachea
50-70
Beta 2 agonist
Actuation of the MDI during a mechanically delivered __________ increases the amount of drug that passes beyond the distal end of the tracheal tube
inspiration
Side effects of Beta 2 agonists
The widespread distribution of beta 2 adrenergic receptors makes it likely that undesired responses result when beta 2 adrenergic agonists undergo ___________ absorption
systemic
The principle side effect in awake subjects of beta 2 adrenergic agonists treatments is ________
tremor
Increased _________ _______ is less common with the selective beta 2 adrenergic agonists
heart rate
In patients with acute, severe ________, beta 2 agonists may cause transient decrease in ________ ______ presumed to reflect relaxation of compensatory _________ in areas of deceased ventilation
asthma
arterial oxygenation
vasoconstriction
(supplemental oxygen indicated)
Acute metabolic responses to beta 2 adrenergic agonists include: (3)
Hyperglycemia
Hypokalemia
Hypomagnesemia
_________ is the preferred selective beta 2 adrenergic agonist for the treatment of acute bronchospasm due to asthma
Albuterol
Administration of albuterol is most often by a MDI, producing about ______ mcg per puff
100
The duration of action of inhaled dose of Albuterol is about ___ hours, but significant relief of symptoms may persist up to ___ hours
4
8
The effects of Albuterol and volatile anesthetics on bronchomotor tone are ________
additive
___________ is a predominantly beta 2 adrenergic agonist that may be administered ______, _______, or by _______ to treat asthma
Terbutaline
orally
subcutaneously
inhalation
The subcutaneous administration of terbutaline ( _____mg) produces responses that resemble those of _______, but the duration of action is _________
0.25
epinephrine
longer
Phosphodiesterase inhibitors are a heterogenous group of ____________ ____________ compounds that exert a competitive inhibitory action on phosphodiesterase enzymes
noncatecholamine
nonglycoside
The PDE III inhibitors have their greatest clinical usefulness in patients who would benefit from combined ______ and _______ therapy
inotropic
vasodilatory
___________ is a derivative of amrinone with almost ____ times the inotropic potency of amrinone but less adverse effects
milrinone
30
Because of its reduced incidence of side effects, ________ has replaced amrinone in clinical use
milrinone
PDE III inhibitors
Cardiac output improves both as a result of increased ________ as well as vascular smooth muscle relaxation of _________ and ________ vessels
inotropy
peripheral and pulmonary
Milrinone may be useful in management of acute _______ _______ dysfunction
left ventricular
Milrinone can be useful when weaning high-risk patients from ____________ ____________
cardiopulmonary bypass
Milrinone may potentiate the effects of ________ agents as well as help increase inotropy in chronic heart failure patients who have downregulation of _____ adrenergic receptors
adrenergic
beta 1
Milrinone is useful in the setting of _______ __________
decreases _______ _______ pressures more effectively than other positive inotropic drugs
pulmonary hypertension
pulmonary artery
Milrinone is associated with more ________ and greater decrease in _______ and ______ than dobutamine
vasodilation
SVR
BP
Unlike dobutamine, milrinone rarely causes __________
tachycardia
Milrinone may be preferred in situation with high _______ _______, elevated _______ _______ pressure, need for continued _____ blockade, decreased responsiveness to ________ therapy, and increased risk for _________________
filling pressures
pulmonary artery
beta
catecholamine
tachyarrhythmias
Rapid administration of milrinone may decrease ________, decrease ________, and result in hypotension
May also be associated with arrhythmias due to enhanced ____ node conduction
SVR
venous return
AV
______ is present in the body in greater amounts than any other mineral
calcium
Calcium is important for
-__________ transmission
-________ _______ contraction
-________ _______ contractility
-Blood ___________
_ ___________ necessary for release of neurotransmitters
neuromuscular
skeletal muscle
cardiac muscle
coagulation
exocytosis
Calcium is the principal component of ________
bone
Calcium is a potent _________-
inotrope
Increasing the plasma concentrations of ionized calcium with exogenous administration of calcium chloride or calcium gluconate is commonly used to treat cardiac depression as may accompany:
-delivery of ________ ________
-transfusion of ________ blood
-following termination of _______ _____
volatile anesthetics
citrated
cardiopulmonary bypass
Ionized calcium typically represents approximately ___ % of the total plasma concentration
45%
Acidosis ______ ionized calcium
Alkalosis _____ ionized calcium
increases
decreases
Normal plasma ionized calcium (3)
1-1.26 mmol/L
2-2.5 mEq/L
4-5mg/dL
