Lecture 1-Vasoconstrictors Flashcards
What are the three arms of the autonomic nervous system?—sympathetic innervation of ___; ___ nervous system; ___ nervous system
- Sympathetic innervation of adrenal medulla (causes the release of epinephrine into the blood)
- Sympathetic nervous system
- Parasympathetic nervous system
What neurotransmitter kicks off all of the arms of the autonomic nervous system? What receptor does it bind to?
Acetylcholine; binds to nicotinic receptors
Catecholamines bind to ___ receptors; acetylcholine binds to ___ and ___ receptors
Catecholamines bind to adrenergic receptors; acetylcholine binds to nicotinic and muscarinic receptors
The sympathetic nervous system has thoracolumbar origin from T___-L___
T1-L2
Preganglionic neurons of the sympathetic nervous system are near the ___
Spinal cord
Postganglionic neurons secrete ___-adrenergic fibers
Norepinephrine-adrenergic fibers
How is norepinephrine created?—dopamine ___ converts ___ to ___
Dopamine beta hydroxylase converts dopamine to NE
Norepinephrine signal termination—80% of norepi that is released is ___
Recycled (via reuptake)
Norepinephrine signal termination—a ___ (small/large) amount of NE dilutes away by diffusion
Small amount
Norepinephrine signal termination—20% of NE that is not recycled is metabolized by ___ and ___
MAO (monoamine oxidase) and COMT (catechol-o-methyltransferase)
What are the 4 adrenergic receptors?
- Alpha 1
- Alpha 2
- Beta 1
- Beta 2
Alpha 1 receptors are located in the ___
Periphery
Alpha 2 receptors are located in the ___ (central/peripheral) nervous system
Central
Beta 1 receptors are located in the ___
Heart
Beta 2 receptors are located in other ___ muscle
Other smooth muscle
What binds to adrenergic receptors?
Catecholamines!
When catecholamines bind to beta adrenergic receptors, the result is ___ mediated effects; stimulatory proteins activate ___, causing a change from ATP into cyclic ___; cyclic ___ pulls ___ into the cells (cardiac myocytes, peripheral vasculature, skeletal muscle) to cause contraction of skeletal muscle or dilation in the periphery
G-protein mediated effects; stimulatory proteins activate adenylyl cyclase, causing a change from ATP into cyclic AMP; cyclic AMP pulls calcium into the cells to cause contraction of skeletal muscle or dilation in the periphery
Cyclic AMP is metabolized into ___, then ___, which has no further action
Phosphodiesterase 3, then AMP
When catecholamines bind to alpha receptors, the reaction is again ___ mediated; a ____ causes increases in calcium, which leads to contraction
G-protein mediated; a second messenger causes increases in calcium, which leads to contraction
SNS—alpha 1 postsynaptic receptor—activation ___ (increases/decreases) intracellular calcium; causes smooth muscle ___ (contraction/relaxation); peripheral vaso___ (constriction/dilation); broncho___ (constriction/dilation); ___ (stimulates/inhibits) insulin secretion from beta islet cells of the pancreas; ___ (stimulates/inhibits) glycogenolysis and gluconeogenesis; my___ (driasis/osis); GI ___ (relaxation/contraction)
Activation increases intracellular calcium; causes smooth muscle contraction; peripheral vasodilation; bronchoconstriction; inhibits insulin secretion from beta islet cells of the pancreas; stimulates glycogenolysis and gluconeogenesis; mydriasis—opens up the eyes; GI relaxation
SNS—alpha 2 receptors—presynaptic in the ___; postsynaptic in the ___
Presynaptic in the PNS; postsynaptic in the CNS
Alpha 2 receptors—presynaptic in the PNS—stimulation of these receptors ___ (increases/decreases) entry of calcium into the cell; limits the release of ___
Decreases entry of calcium into the cell; limits the release of norepinephrine
Alpha 2 receptors—postsynaptic in the CNS—stimulation of these receptors causes ___ation; ___ (increased/decreased) sympathetic outflow; ___ (increased/decreased) BP; platelet ___
Sedation; decreased sympathetic outflow; decreased BP; platelet aggregation
Two medications that are alpha 2 receptor agonists = ___ and ___
Dexmedetomidine (precedex) and clonidine
The agonistic activity at the alpha 2 receptor is technically ___ (agonistic/antagonistic)
Antagonistic—through a positive action at the alpha 2 receptor, you see negative effects
SNS—beta 1 postsynaptic receptor—___ (increases/decreases) HR, conduction velocity, and myocardial contractility
Increases HR, conduction velocity, and myocardial contractility
SNS—beta 2 postsynaptic receptor—stimulation leads to smooth muscle ___ (relaxation/contraction); peripheral vaso___ (constriction/dilation); ___ (increases/decreases) BP; broncho___ (constriction/dilation); ___ (increases/decreases) insulin secretion; ___ (increases/decreases) glycogenolysis and gluconeogenesis; ___ (increases/decreases) GI mobility
Stimulation leads to smooth muscle relaxation; peripheral vasodilation (improves oxygen exchange); decreases BP; bronchodilation; increases insulin secretion; increases glycogenolysis and gluconeogenesis; decreases GI mobility
Parasympathetic nervous system has a ___ origin (CN ___, ___, ___, ___)
Craniosacral origin (CN III, V, VII, X)
Remember SNS has a thoracolumbar origin T1-L2
PNS preganglionic are near ___
Organs of innervation
Postganglia of PNS secrete ___, which stimulates ___ fibers
Acetylcholine, which stimulates cholinergic fibers
Acetylcholine activates both arms of the ___ nervous system
Autonomic nervous system (sympathetic and parasympathetic nervous systems)
___ + ___ = acetylcholine; brought together by ___ ____ase
Choline + acetyl coA = acetylcholine; brought together by choline acetyltransferase
Acetylcholine is deactivated by ___esterase; breaks acetylcholine down into ___ + ___
Acetylcholinesterase; breaks acetylcholine down into choline + acetate
Acetylcholine ___ receptors = ___ and ___ receptors
Acetylcholine cholinergic receptors = nicotinic and muscarinic receptors
Long-term activation of a receptor can cause a change in the receptor field—T/F?
True
Effector cell receptors may down or up regulate, depending on exposure to agonists/antagonists—T/F?
True
This type of regulation results from extended exposure to agonists; it reduces the number of receptors, but not their response; results in tachyphylaxis
Down regulation
When the beta 1 or alpha 1 receptors start realizing they are getting a lot of stimulation, the body will change the amount of receptors available—the body doesn’t want to become over-constricted; cannot change the amount of norepi/epi that is circulating, so the body will change the amount of receptors available; results in tachyphylaxis—can continue to give medication, but you’re not going to get anymore effect; you may also start to see the effects taper off
This type of regulation results from chronic depletion of catecholamines or use of antagonists (blockade of the receptor); increases the number of receptors, but not their sensitivity; may account for withdrawal syndrome with beta blockers
Up regulation
The body will create more receptors when it cannot increase the amount of neurotransmitter needed or if it has attempted to with no effect
Beta blocker withdrawal—when you stop a beta blocker without any kind of taper, there is potential for severe tachyarrhythmias because there are so many beta 1 receptors available. Tapering beta blockers allows the receptors to be uncoupled and prevents withdrawal symptoms
Methods of receptor desensitization/down regulation—receptor ___; ___ation; ___ regulation
Receptor uncoupling; sequestration; down regulation
This type of receptor desensitization occurs rapidly; causes inability of the receptor to bind G protein and alter the function of the receptor
Receptor uncoupling
This type of receptor desensitization occurs more slowly; causes movement of receptors from the cell surface to intracellular compartments
Sequestration
This type of receptor desensitization is a prolonged process; causes movement of receptors from the cell surface to intracellular compartments, where they are then destroyed
Down regulation
This describes residual basal activity of the autonomic system
Tone
This condition results from an uncontrolled release of catecholamines due to an adrenal gland tumor; results in constant SNS stimulation
Pheochromocytoma
Catecholamines include both ___ and ___; act on ___ receptors
Include both neurotransmitters and hormones; act on adrenergic receptors
___ are compounds that resemble catecholamines (mimic the SNS) except the hydroxyl groups are NOT present in both the 3 and 4 positions of the benzene ring
Sympathomimetics
All sympathomimetics are catecholamines—T/F?
False—sympathomimetics resemble catecholamines but because they do not have hydroxyl groups present in the 3 and 4 positions of the benzene ring, they are not catecholamines
Catecholamines = ___ + ___ group with ___, ___ OH- groups attached to the benzene ring
Catechol + amine group with 3, 4 OH- groups attached to the benzene ring
3 types of sympathomimetics—naturally occurring ___ (i.e.: epi, norepi, dopamine); synthetic ___ (not in our bodies naturally but have the catecholamine structure); synthetic ___ (not in our bodies naturally and don’t have the catecholamine structure)
Naturally occurring catecholamines; synthetic catecholamines; synthetic non-catecholamines
All sympathomimetics are derived from ___
Beta phenylethylamine
Presence of hydroxyl groups on the ___ and ___ position of the benzene ring of the beta phenylethylamine creates a ___; drugs with this composition are ___
Hydroxyl groups on the 3 and 4 position of the benzene ring of the beta phenylethylamine creates a catechol; drugs with this composition are catecholamines
Epinephrine, norepinephrine, dopamine, isoproterenol, and dobutamine are all ___ because they have hydroxyl groups on the 3 and 4 positions of the benzene ring
Are all catecholamines
Ephedrine and phenylephrine are synthetic ___
Non-catecholamines (because they don’t have hydroxyl groups on the 3 and 4 positions of the benzene ring)
Clinical use of sympathomimetics—most often used as positive inotropes to improve cardiac ___; vasopressor to elevate ___ from unacceptable low levels
Most often used as positive inotropes to improve cardiac contractility; vasopressor to elevate blood pressure from unacceptable low levels
Sympathomimetics can also be used clinically for treatment of ___ in the asthmatic patient; management of ___; ___ management; and addition to local anesthetic to ___ (slow/speed up) systemic absorption
Treatment of bronchospasm in the asthmatic patient; management of anaphylaxis; arrhythmia management; and addition to local anesthetic to slow systemic absorption (and thus prolong the duration of action of the local)
Metabolism of catecholamines—all drugs containing the 3,4 dihydroxybenzene structure (catecholamines) are rapidly inactivated by what two enzymes?
- MAO—monoamine oxidase
- COMT—catechol-o-transferase
___ (what enzyme?) is present in the liver, kidneys, and GI tract; catalyzes oxidative deamination
MAO
___ (what enzyme?) methylates the hydroxyl group of catecholamines
COMT
Catecholamines are inactivated by ___ and ___
MAO and COMT
Non-catecholamines do not have the catecholamine structure, so they can be broken down by ___ but NOT by ___
Can be broken down by MAO but NOT by COMT (because they don’t have the hydroxyl group of catecholamines)
Reuptake of catecholamines—inhibition of this uptake mechanism produces a greater potentiation of effects of epinephrine than does inhibition of either enzyme—T/F?
True
Because 80% of catecholamines undergo reuptake; the other 20% are metabolized by MAO/COMT
Metabolism of synthetic non-catecholamines—they lack a ___-hydroxyl group; not metabolized by ___; dependent on ___ for metabolism
Non-catecholamines lack a 3-hydroxyl group; not metabolized by COMT; dependent on MAO for metabolism
Metabolism of synthetic non-catecholamines is often ___ (slower/faster) than that of catecholamines
Slower
Because they are not being taken up/stored away and they only have one enzyme responsible for their metabolism
Metabolism of synthetic non-catecholamines—inhibition of MAO may ___ (shorten/prolong) their duration of action
Prolong their duration of action (because they are only metabolized by MAO)
Metabolism of synthetic non-catecholamines—patients on MAO inhibitors may manifest exaggerated responses when treated with synthetic non-catecholamines—T/F?
True
Sulfoconjugation reactions—genetic polymorphism of single nucleotides (SNPs) may affect the metabolism of catecholamines and phenylephrine—T/F?
True
Sulfoconjugation reactions—SULT1A___ and SULT1A___ polymorphisms primarily affect ___ metabolism by making its metabolism even slower
SULT1A3 and SULT1A4 polymorphisms primarily affect phenylephrine metabolism by making its metabolism even slower
What class of vasoconstrictors undergo reuptake?
Catecholamines—epi, norepi, dopamine
Sympathomimetics like ephedrine and phenylephrine undergo reuptake—T/F?
False—sympathomimetics like ephedrine and phenylephrine do NOT undergo reuptake—they are metabolized by MAO
Ephedrine and phenylephrine are metabolized by COMT—T/F?
False—they are only metabolized by MAO because they do not have the hydroxyl groups in the 3,4 positions of the benzene ring
The structure of catecholamines is unique because they have a hydroxyl group on the 3,4 position of the benzene ring—T/F?
True
Catecholamines are metabolized by COMT only—T/F?
False—catecholamines are metabolized by MAO and COMT
Vasoconstrictors—hemodynamic effects—___ (increase/decrease) arterial resistance and afterload; ___ (increase/decrease) SVR and MAP; ___ (increase/decrease) venous return; ___ (increase/decrease) preload and CO
Increase arterial resistance and afterload; increase SVR and MAP; increase venous return; increase preload and CO
Vasoconstrictors—reflex changes—___ (increased/decreased) heart rate; ___ (increased/decreased) conduction; occasionally, ___ (increased/decreased) contractility
Decreased heart rate; decreased conduction; occasionally, decreased contractility
May see these reflexive changes in response to the vasoconstriction (alpha 1 effect) that occurs with vasoconstrictors
Vasoconstrictors—non-cardiac effects—broncho___ (dilation/constriction); glyco__ (genolysis or genesis); ___ (release/inhibition) of insulin, renin, pituitary hormone; CNS ___ (stimulation/inhibition)
Bronchodilation; glycogenolysis; release of insulin, renin, pituitary hormone; CNS stimulation
Risk of end organ damage and mortality from hypotension increases with time—T/F?
True
MAP < 65 mm Hg for 13-28 minutes; MAP < 50 mm Hg for 1 minute
Contraindications/complications of vasoconstrictors—can worsen ___ failure; can exacerbate ___ failure; can ___ (increase/decrease) renal blood flow; can mask ___volemia
Can worsen LV failure; can exacerbate RV failure; can decrease renal blood flow; can mask hypovolemia
What are (3) natural catecholamines?
- Epi
- Norepi
- Dopamine
Dopamine is broken down to NE; NE is broken down to epi; all are structurally related and can be recycled
Epinephrine is a ___ (natural/synthetic) catecholamine; stimulates ___, ___, and ___ receptors
Natural catecholamine; stimulates alpha 1, beta 1, and beta 2 receptors
Epinephrine is the most potent activator of ___ receptors; ___-___x more potent than NE
Alpha 1 receptors
2-10x more potent than NE
Epinephrine uses—___ma; ___laxis; cardiac ___; ___ing; to prolong ___ anesthesia; decrease ___ absorption of local anesthetics
Asthma; anaphylaxis; cardiac arrest; bleeding; to prolong regional anesthesia; decrease systemic absorption of local anesthetics
Epinephrine is first line for ___ and ___
Cardiac arrest and anaphylaxis
Epi ___ (increases/decreases) lipolysis, glycogenolysis; ___ (stimulates/inhibits) secretion of insulin; ___ (increases/decreases) blood sugar
Increases lipolysis, glycogenolysis; inhibits secretion of insulin; increases blood sugar
Epi ___ (increases/decreases) renal blood flow, even in the absence of changes in systemic BP; it is a potent renal vaso___ d/t its ___ effects; stimulates ___ release (indirect effect)
Decreases renal blood flow, even in the absence of changes in systemic BP; it is a potent renal vasoconstrictor d/t its alpha 1 effects; stimulates renin release (indirect effect)
Epinephrine has dose-specific effects—T/F?
True
Low doses of epi (1-2 mcg/min) = ___ effects in peripheral vasculature predominate; the net effect is ___ (increased/decreased) SVR and distribution of blood to ___; MAP essentially remains ___
Beta 2 effects in peripheral vasculature predominate; the net effect is decreased SVR and distribution of blood to skeletal muscle (which improves oxygen exchange in the peripheral vasculature); MAP essentially remains the same
Intermediate doses of epi (4 mcg/min) = ___ effects; ___ (increased/decreased) heart rate, contractility, and CO; ___ (increased/decreased) automaticity may lead to dysrhythmias
Beta 1 effects; increased heart rate, contractility, and CO; increased automaticity may lead to dysrhythmias
High doses of epi (> 10 mcg/min) = ___ effects; potent vaso___ including cutaneous, splanchnic, and renal vascular beds; no significant effect on ___ arterioles; used to maintain myocardial and cerebral ___; reflex ___cardia can occur
Alpha 1 effects; potent vasoconstrictor including cutaneous, splanchnic, and renal vascular beds; no significant effect on cerebral arterioles; used to maintain myocardial and cerebral perfusion; reflex bradycardia can occur
You can lose the effects of lower dose epi when higher doses are given—T/F?
True
Reflex bradycardia can occur at higher doses of epi in response to the massive increase in SVR that you get from alpha-1 effects of high dose epi—T/F?
True
Racemic epinephrine = mixture of levo- and dextrorotatory isomers that ___ (constrict/dilate) edematous mucosa; used to treat severe ___ and post-extubation or traumatic airway ___
Mixture of levo- and dextrorotatory isomers that constrict edematous mucosa; used to treat severe croup and post-extubation or traumatic airway edema
Racemic epi treatment lasts ___-___ minutes
30-60 minutes
Racemic epi—observe for ___ hours after treatment to monitor for ___arrhythmias
Observe for 2 hours after treatment to monitor for tachyarrhythmias—great risk of this because you can get systemic absorption, even though it is being administered via inhalation
Side effects of epinephrine—no ___ effects (see more of this with norepinephrine)
No CNS effects
Side effects of epinephrine—___glycemia; my___ (driasis/osis); platelet ___; ___ing; ___ache; ___or; ___ea; ___arrhythmias
Hyperglycemia; mydriasis; platelet aggregation; sweating; headache; tremor; nausea; tachyarrhythmias
Monitor BG, RR, O2 sat, HR, BP
Norepinephrine is an ___ (endogenous/exogenous) catecholamine; responsible for maintaining BP by adjusting ___; ___ (increases/decreases) systolic, diastolic, and mean arterial pressure
Endogenous catecholamine; responsible for maintaining BP by adjusting SVR; increases systolic, diastolic, and mean arterial pressure
Norepinephrine is the first line choice for ___ because it does not significantly increase ___
First line choice for sepsis because it does not significantly increase the heart rate (like epi does)
If someone is tachycardic and hypotensive, you don’t want to give a medication that has strong ___ effects, because the heart rate will increase even more; want to pick a drug that is more ___ based
You don’t want to give a medication that has strong beta 1 effects, because the heart rate will increase even more; want to pick a drug that is more alpha based
Norepinephrine is a potent vasoconstrictor of ___, ___, and ___ vascular beds; may ___ (increase/decrease) renal blood flow and cause ___uria; may lead to ___ infarct; peripheral ___perfusion can lead to ___ of digits
Renal, mesenteric, and cutaneous vascular beds; may decrease renal blood flow and cause oliguria; may lead to mesenteric infarct; peripheral hypoperfusion can lead to gangrene of digits
Norepinephrine is primarily a/an ___ agonist
Alpha 1 agonist
___ effects of norepinephrine are overshadowed by alpha 1 effects
Beta 1 effects
Norepinephrine has beta 2 effects—T/F?
False—no beta 2 effects
Norepinephrine—cardiac output may ___ (increase/decrease) at low doses; higher doses may cause cardiac output to ___ (increase/decrease) because of ___ (increased/decreased) afterload and baroreceptor-mediated reflex ___cardia
Cardiac output may increase at low doses; higher doses may cause cardiac output to decrease because of increased afterload and baroreceptor-mediated reflex bradycardia
Norepinephrine may cause refractory ___tension
Refractory hypotension
Norepinephrine has ___ (more/less) metabolic effects than epinephrine because it has no ___ effects
Less metabolic effects than epinephrine because it has no beta 2 effects (only at larger doses)
Norepinephrine is used during ___ and ___ pathways after volume corrections are made
Sepsis and shock pathways
Epi vs. norepi cardiac effects—___ increases HR; ___ keeps HR neutral, may cause reflex bradycardia at higher doses
Epi increases HR; norepi keeps HR neutral, may cause reflex bradycardia at higher doses
Epi vs. norepi cardiac effects—___ significantly increases CO; ___ keeps CO neutral or may decrease it at higher doses
Epi significantly increases CO; norepi keeps CO neutral or may decrease it at higher doses (d/t increased afterload and baroreceptor-mediated reflex bradycardia)
Epi vs. norepi cardiac effects—___ can cause tachyarrhythmias; ___ can cause bradyarrhythmias
Epi can cause tachyarrhythmias; norepi can cause bradyarrhythmias
Epi vs. norepi BP effects—___ has a greater effect on mean arterial and diastolic pressures
Norepi
Epi vs. norepi circulation—epi ___ (increases/decreases) total peripheral resistance; norepi ___ (increases/decreases) total peripheral resistance
Epi decreases total peripheral resistance; norepi increases total peripheral resistance
Epi vs. norepi circulation—epi ___ (increases/decreases) cerebral blood flow; norepi ___ (increases/decreases) cerebral blood flow
Epi increases cerebral blood flow; norepi decreases cerebral blood flow
Epi vs. norepi circulation—epi ___ (increases/decreases) muscle blood flow; norepi ___ (increases/decreases) muscle blood flow
Epi increases muscle blood flow; norepi decreases muscle blood flow (because no beta 2 effects)
Epi vs. norepi circulation—epi ___ (increases/decreases) splanchnic blood flow; norepi ___ (increases/decreases/has little to no effect) splanchnic blood flow
Epi increases splanchnic blood flow; norepi has little to no effect on splanchnic blood flow (may slightly increase it)
Epi metabolic effects—___ (increases/decreases) O2 consumption; ___ (increases/decreases) blood glucose; ___ (increases/decreases) blood lactic acid; ___ (increases/decreases) eosinophilic response
Increases O2 consumption; increases blood glucose; increases blood lactic acid; increases eosinophilic response
Epi causes ___ (more/less) O2 consumption than norepi because it increases HR and CO
More O2 consumption than norepi
Norepi and epi both increase the amount of blood pumped per beat, but epi increases CO more than norepi d/t increases in HR—T/F?
True
___ is a parent catecholamine
Dopamine
Dopamine has a tiered response to dosing just like epinephrine—T/F?
True
Ephedrine is a synthetic ___
Noncatecholamine
Ephedrine has direct and indirect actions; principle effect is ___
Indirect
Ephedrine works at ___ and ___ receptors
Alpha 1 and beta receptors
Beta stimulation from ephedrine may evoke ___, particularly in sensitized myocardium
Arrhythmias
Ephedrine causes ___ (increased/decreased) myocardial contractility; venoconstriction is ___ (greater/less than) arteriolar constriction, which ___ (increases/decreases) preload; with ___ (increased/decreased) heart rate and myocardial contractility, it ___ (increases/decreases) cardiac output; ___ (increases/decreases) systolic and diastolic BP as a result
Increased myocardial contractility; venoconstriction is greater than arteriolar constriction, which increases preload; with increased heart rate and myocardial contractility, it increases cardiac output (beta 1 receptor action); increases systolic and diastolic BP as a result
With ephedrine, ___ can occur; for this reason, ephedrine is typically given as ___, not as a ___
Tachyphylaxis—can lose total effect after a few days; for this reason, ephedrine is typically given as intermittent blouses, not as a continuous infusion
Ephedrine preserves or increases ___ blood flow; causes bronchial smooth muscle ___ (relaxation/contraction)
Preserves or increases uterine blood flow; causes bronchial smooth muscle relaxation
Ephedrine and phenylephrine have a rapid onset with a ___ (shorter/longer) duration of action than epi/norepi; may get peak effect within ___-___ minutes and can last for ___-___ minutes; can give in bolus doses and get more of a sustained effect than you will get with epi/norepi
Rapid onset with a longer duration of action than epi/norepi; may get peak effect within 10-15 minutes and can last for 20-25 minutes; can give in bolus doses and get more of a sustained effect than you will get with epi/norepi
Ephedrine is like epi—alpha 1 effects ___ (are/are not) as strong as epi; ___ (more/less) intense; lasts ___ (shorter/longer) than epi
Alpha 1 effects are not as strong as epi; less intense; lasts longer than epi
Side effects of ephedrine—___tension; ___omnia; urinary ___; ___ache; ___ness; ___or; ___tations; ___osis
Hypertension; insomnia; urinary retention; headache; weakness; tremor; palpitations; psychosis
Ephedrine can have drug interactions with ___ d/t reuptake blockade and ___ may exaggerate HTN or cause significant arrhythmias
Drug interactions with cocaine d/t reuptake blockade and amphetamines may exaggerate HTN or cause significant arrhythmias
Phenylephrine is a synthetic ___
Non-catecholamine
Phenylephrine is a direct ___ agonist; increases ___load > ___load; small ___ effect
Direct alpha 1 agonist; increases preload > afterload; small beta 1 effect
Phenylephrine ___ (increases/decreases) peripheral vascular resistance when CO is adequate; will see reflex ___cardia in response to ___ (increase/decrease) in SVR
Increases peripheral vascular resistance when CO is adequate; will see reflex bradycardia in response to increase in SVR
Phenylephrine may be used to improve coronary perfusion pressure without chronotropic side effects—T/F?
True
Phenylephrine is not safe to use in pregnant patients—T/F?
False—OK to use in pregnant patients
Net effect of phenylephrine is increased pressure and flow without changing CO in normal individuals—T/F?
True
Phenylephrine may decrease cardiac output in patients with ischemic heart disease; for this reason, may need to use NTG or IABP to decrease ischemic injury—T/F?
True
Ephedrine is often used in OB because it preserves uterine blood flow—T/F?
True
Phenylephrine may be used in pregnant patients and is associated with better fetal acid-base status; however, there is a higher risk of maternal bradycardia with phenylephrine than with ephedrine that is responsive to atropine—T/F?
True
Other uses of phenylephrine—drug induced ___; ___ agent; nasal ___
Drug induced priapism; mydriatic agent; nasal decongestant
Phenylephrine causes reflex ___cardia; ___ (increases/decreases) renal and splanchnic blood flow; ___ (increases/decreases) pulmonary artery resistance and pressure
Reflex bradycardia; decreases renal and splanchnic blood flow; increases pulmonary artery resistance and pressure
Phenylephrine has no risk of tachyarrhythmias but can still cause bradyarrhythmias—T/F?
True
Phenylephrine is like norepinephrine because it has significant ___ effects without any significant ___ effects; it is ___ (more/less) potent than norepinephrine and has a ___ (shorter/longer) duration of action
It has significant alpha 1 effects without any significant beta effects; it is less potent than norepinephrine and has a longer duration of action
Epi and norepi are ___; they have a ___ (slower/faster) onset with a ___ (longer/shorter) duration of action than synthetic non-catecholamines
Natural catecholamines; they have a faster onset with a shorter duration of action than synthetic non-catecholamines
Ephedrine and phenylephrine are ___; they have a slightly ___ (slower/faster) onset with a ___ (shorter/longer) duration of action than natural catecholamines
Ephedrine and phenylephrine are synthetic non-catecholamines; they have a slightly slower onset with a longer duration of action than natural catecholamines
(3) posterior pituitary hormones
- Vasopressin (ADH)
- DDAVP—synthetic ADH
- Oxytocin
Vasopressin has potent ___/___ effects to increase BP
Antidiuretic/vasopressor effects to increase BP
100:100
Oxytocin ___ (does/does not) have any antidiuretic/vasopressor effects
Does not
1:1
DDAVP has more ___ effect than ___ effect
More antidiuretic effect than vasopressor effect
1200:0.39
Vasopressin is used to preserve cardiocirculatory homeostasis in patients with advanced vasodilatory shock—T/F?
True
Vasopressin can be used in patients who have failed or are resistant to conventional vasopressor therapy; patients who experience adverse effects of conventional vasopressor therapy—T/F?
True
Unlike catecholamines, effects of vasopressin are preserved during ___ia and severe ___osis
Preserved during hypoxia and severe acidosis
Vasopressin has ___ effects, as well as ___ effects
Vasopressor effects, as well as antidiuretic effects
Binding of vasopressin to ___ receptors causes intense arterial vasoconstriction
V1 receptors
Binding of vasopressin to ___ receptors in the renal collecting ducts increases the permeability of the cell membranes, resulting in the passive reabsorption of water
V2 receptors
Advantages of vasopressin over epi—epi ___ (increases/decreases) myocardial oxygen consumption, which can contribute to risk of developing post-resuscitation MI and arrhythmias; vasopressin has no direct effect on ___, thus reducing myocardial ___ use
Epi increases myocardial oxygen consumption, which can contribute to risk of developing post-resuscitation MI and arrhythmias; vasopressin has no direct effect on heart rate, thus reducing myocardial oxygen use
Advantages of vasopressin over epi—catecholamines may not work well in an ___ environment associated with CPR
Acidic
Vasopressin is at least as effective as epi, may have fewer adverse effects than epi, and therefore is a reasonable alternative to epi in the treatment of cardiac arrest—T/F?
True
Adverse effects of vasoconstrictors—cardiac ___; pure alpha agonists can activate ___ reflex-mediated ___cardia and possibly ___ (increase/decrease) CO
Cardiac dysrhythmias; pure alpha agonists can activate baroreceptor reflex-mediated bradycardia and possibly decrease CO
Vasoconstrictors drug interactions—antihypertensives may ___ (increase/decrease) the pressor response to indirect acting drugs or ___ (inhibit/enhance) the response to direct acting drugs
Decrease the pressor response to indirect acting drugs or enhance the response to direct acting drugs
I.e.: if patient is on a beta blocker, patient may be hypersensitive to vasoconstrictors d/t up regulation of the beta receptors on the cardiomyocytes—could result in a very severe tachyarrhythmia d/t beta 1 stimulation of an up regulated field
Vasoconstrictors and drug interactions—tricyclic antidepressants and MAO inhibitors increase the availability of endogenous ___; results in an exaggerated response with ___ (direct/indirect) acting agents; worse in the first ___-___ days of therapy, then a ___ (up/down) regulation of receptors occurs
Increase the availability of endogenous norepinephrine; results in an exaggerated response with indirect acting agents (i.e.: ephedrine, phenylephrine); worse in the first 14-21 days of therapy, then a down regulation of receptors occurs
It is okay to continue TCAs and MAOIs in the perioperative period—T/F?
True
If a patient is on a TCA or MAOI, you should use a/an ___ (increased/decreased) dose of direct acting drugs
A decreased dose
Vasoconstrictor drug interaction with cocaine—cocaine interferes with ___ of catecholamines; both exogenous and endogenous catecholamines exhibit enhanced effects
Interferes with reuptake of catecholamines
Cocaine + vasoconstrictors produces central and peripheral sympathetic stimulation, resulting in vaso___, ___cardia, and potentially, ___
Vasoconstriction, tachycardia, and potentially, arrhythmias
Vasoconstrictors will have a ___ (shorter/longer) duration of action in cocaine users because cocaine blocks the reuptake of catecholamines
Longer duration of action in cocaine users
Acute cocaine toxicity may best be managed with ___ blockade
Adrenergic blockade—alpha AND beta blockade
Acute cocaine toxicity—never want to use just a ___ blocker
Just a beta blocker—i.e.: propranolol, metoprolol, atenolol
Acute cocaine toxicity—if you only pick an alpha or beta blocker, you will see unopposed stimulation of the other side that is not being blocked which can cause ischemia—T/F?
True
___ and ___ are better choices for acute cocaine toxicity because they provide both alpha and beta blockade
Labetalol and carvedilol
Vasoconstrictors and drug interactions—natural weight loss products that contain ephedra (ephedrine, pseudoephedrine)—long-term use results in ___ from depletion of endogenous catecholamine stores and may contribute to perioperative hemodynamic ___ and cardiovascular ___; stop product at least ___ hours before surgery to prevent
Long-term use results in tachyphylaxis from depletion of endogenous catecholamine stores and may contribute to perioperative hemodynamic instability and cardiovascular collapse; stop product at least 24 hours before surgery to prevent
Treat extravasation of vasoconstrictors with ___
Phentolamine
Phentolamine is an ___; peripheral vaso___; treats skin ___ secondary to norepinephrine, dopamine, and epinephrine; 5-10 mg injected around the site of extravasation
Phentolamine is an alpha 1 and 2 antagonist; peripheral vasodilator; treats skin necrosis secondary to norepi, dopamine, and epi; 5-10 mg injected around the site of extravasation
Goal of treatment of extravasation is peripheral vaso___; want to combat vaso___/alpha ___ effects
Peripheral vasodilation; want to combat vasoconstriction/alpha 1 effects
Can also use ___, ___ as alternatives to phentolamine for treatment of extravasation
Nitroglycerin, terbutaline (cause beta 2 dilation to combat alpha 1 constriction)
If < 2 years old, apply NTG ointment to extravasated area; if persists, administer diluted terbutaline
If > 2 years old, administer terbutaline subcutaneously and apply NTG ointment; can re-administer terbutaline 15 mins later if no improvement is seen and continue with NTG ointment
Ephedrine can be given as a continuous infusion—T/F?
False—not recommended for continuous infusion d/t risk of tachyphylaxis—body recognizes that there is too much NE and negative feedback mechanisms kick in
Giapreza is AKA ___
Angiotensin II
In studies, giapreza effectively increased blood pressure when added to conventional treatments used to raise blood pressure—T/F?
True
Giapreza is dosed in nanograms/kg/min—T/F?
True
Giapreza/angiotensin II causes vaso___ and increases ___ release
Vasoconstriction and increases aldosterone release
Giapreza peak effect = ___ minutes
5 minutes
Half-life of giapreza = ___
< 1 minute
Giapreza is metabolized by ___ and ___
ACE and aminopeptidases
Giapreza has drug interactions with ___ and ___
ACEIs and ARBs
ARBs—angiotensin II cannot bind to its receptor
ACEIs—prevent conversion of angiotensin I to angiotensin II
Giapreza possible concerning side effect = ___ and ___; prophylactic treatment for ___ should be used; package insert states risk > ___%
Deep venous and arterial thrombosis; prophylactic treatment for blood clots should be used; package insert states risk > 10%
Other side effects of giapreza include ___cardia, ___ium, thrombo___
Tachycardia, delirium, thrombocytopenia
