Vasopressors Flashcards
(39 cards)
Alpha 1 receptors do more than just vasoconstrict-explain.
The positive inotropy helps explain why cardiac output only slightly decreases with the large associated increase in afterload (due to vasoconstriction) and, even more so, bradycardia (remember cardiac output is stroke volume X heart rate).
60 year-old man with coronary heart disease (CAD) is hypotensive following an induction dose of propofol with pronounced ST depressions. The CRNA administers ephedrine without resolution of the ST depressions. She states that she did not want to administer phenylephrine for fear of constricting coronary arteries. You explain:
Therefore, in this situation, the treatment would be aimed at increasing coronary perfusion pressure (AoDP – LVEDP) and decreasing heart rate. Phenylephrine accomplishes both of these goals (answer E). Phenylephrine can constrict coronary arteries, but metabolic vasodilators (nitric oxide) in the coronary arteries easily override the weak vasoconstrictive effects and the coronaries remain maximally vasodilated
Epi vs norepinephrine as far as receptors? How is dopamine affected?
Both epinephrine and norepinephrine have agonistic effects at the alpha-1, alpha-2, and beta-1 receptors, but only epinephrine has a clinically significant effect on beta-2. You can remember this easily, because you give epinephrine for bronchospasm, not norepinephrine. Neither drug agonizes the dopamine receptors.
A healthy 30 year-old test subject is given an infusion of epinephrine until his mean arterial blood pressure (MAP) increases by 20 mm Hg, and then the same is done with a norepinephrine gtt (increase the MAP by 20 mm Hg). Compared to the norepinephrine gtt, the epinephrine gtt does what?
To answer the question correctly, you need understand that norepinephrine, due to its absence of beta-2 mediated vasodilation, results in a marked increase in both systolic and diastolic blood pressures. Epinephrine, on the other hand, vasoconstricts (alpha-1) and vasodilates (beta-2), leading to more pronounced increases in systolic blood pressure (SBP) and minimal changes in diastolic blood pressure (DBP)..reread that sentence again! Because MAP is mostly dependent on DBP (MAP = 2/3 DBP + 1/3 SBP), for epinephrine to raise the MAP by 20 mm Hg, the SBP must sky rocket since the DBP begrudgingly budges up. Norepinephrine, having a pronounced effect on both DBP and SBP can produce the same MAP at a lower SBP.
Epi vs norepi on hr and cardiac output
Because of norepinephrine’s pronounced effects on SVR (answer E), baroreceptor mediated bradycardia offsets beta-1 mediated chronotropic effects, with the net effect being minimal changes to heart rate (answer C). Furthermore, the increased afterload also limits increase in stroke volume despite increased beta-1 mediated inotropy. Epinephrine, however, has a pronounced effect on heart rate (answer C) and its effects on afterload are less so than norepinephrine
Dopamine and renal flow:
Dopamine, the obvious choice, has been conclusively shown not to be renal protective in ICU patients. Its effects on splanchnic circulation at doses needed to reverse marked hypotension are also very unfavorable.
Renal arteries-are they autoregulated?
Because the renal arteries are autoregulated, perfusion is pressure dependent below a certain point (somewhere around 70-80 mm Hg).
Norepi-cardiac output and renal artery perfusion:
Norepinephrine raises blood pressure while preserving cardiac output, and thus far has been shown with the most evidence to maintain urine output and preserve kidney function (for sepsis, it will decrease renal perfusion in otherwise healthy patients through vasoconstriction).
Dobutamine works in beta receptors, but explain.
beta-1 > beta-2
Most recent guidelines for sepsis can be boiled down to the following.
If the patient is hypotensive use norepinephrine. If the cardiac performance is compromised, add an ionotrope (dobutamine). In most cases, cardiac performance is not compromised and the second line treatments are epinephrine or vasopressin, although the authors of the 2012 surviving sepsis guidelines seemed to have a “thing” for epinephrine. Under “special” circumstances, consider dopamine. Never use dopamine for renal protection. Phenylephrine is reserved for refractory cases.
The primary advantage of a norepinephrine gtt as compared to a dopamine gtt for the treatment of severe hypotension is that norepinephrine: ____. Which one causes more of an increase in cardiac output?
Fewer arrhythmia.
While it is true that norepinephrine does not require further metabolism for its receptor-ligand effects (answer C) and that it does not stimulate DA receptors (answer D), this is not the reason for its preference for treating severe hypotension. Endogenous dopamine is converted into norepinephrine (within storage vesicles of some tissues), but exogenously administered dopamine is converted to a lesser extent. Both dopamine and norepinephrine can result in significant alpha-1 receptor stimulation, and the degree to which these drugs do that is dose dependent (answer E). Dopamine, more than norepinephrine, at various doses, increases cardiac output to a greater extent than norepinephrine (see question 4), which typically has mild effects (at best) on cardiac output.
Metabolism of catechilamones in liver vs neurons: ____. Final result of the metabolism: _______. Dosing for people on MAOIs: ______
In the liver, catecholamines are first metabolized by COMT, then MAO. In nerve endings, catecholamines are first metabolized by MAO and then COMT. In either tissue, both enzymes are used
Patients on MAO inhibitors (MAOIs) theoretically will require lower doses because of inhibition of the metabolic pathways, but response in an individual to catecholamines is very variable among individuals for numerous reasons that no broad generalizations can be made (answer D), but if you had to guess, the ABA would be looking for lower doses, not higher doses.
Dopamine at low, moderate, and high doses. Also-low dose dopamine and renal stuff?
At low doses of dopamine (<3 mcg/kg/min), dopamine has significant agonistic effects on DA1 receptors (renal artery vasodilatation) and relatively weak effects at other adrenergic receptors. The overall effect of this is a minimal increase in heart rate & contractility (both major determinants of myocardial oxygen consumption) and significant diuresis. In the past, low dose dopamine infusions were considered to be renal protective, but that has since been strongly disputed (essentially disproven in ICU patients as a whole). Although urine output increases, kidneys continue to fail at the same rate, with or without low dose dopamine. Moderate doses of dopamine (answer B) tend to have beta > alpha receptor effects (increased heart rate, contractility, vasodilatation) leading to increased cardiac output. Unfortunately, myocardial oxygen demand often outpaces myocardial oxygen delivery (set up for non-STEMIs). At even higher doses of dopamine (answer C & D), alpha-1 effects start to predominate with increased systemic vascular resistance and renal blood flow starts to decrease. Answer E is an unusually high dose of dopamine.
What drug is inverted dobutamine? When should you use it, when should you not?
Dooexamine. Think of dopexamine as an inverted dobutamine: in that instead of dobutamine’s B1»>B2 effects, dopexamine has B2»>B1 effects as well as potent DA effects as well. Dopexamine is used to increase cardiac output in the setting of CHF. The strong beta 2 effects reduces afterload and with combined weak beta-1 mediated increases in contractility, stroke volume increases (answer B). However, since beta-2 (vasodilatory) effects are pronounced, it should not be used in the setting of already low systemic vascular resistance states such as sepsis, as blood pressure will significantly decrease
Dobutamine-all of the receptors it hits, and what happens with SVR
Dobutamine is a racemic mixture, with one enantiomer having beta-1»>beta-2 agonism and the other enantiomer having alpha-1 agonism. The overall effect is strong beta-1 effects, and nearly equal vasodilatation (beta-2) and vasoconstriction (alpha-1) effects (minimal reduction of systemic vascular resistance*).
*Its a minor point, but the “minimal” reduction of SVR can be (over)emphasized by some texts. In practice, dobutamine will often lower the BP a bit in some situations, but less so than milrinone. What that means is that the increase in CO is not so great to overcome the decrease in SVR (remembering that BP = CO X Resistance
How does ephedrine work? How does its tachyphylaxis work? How do pts on MAOIs respond?
Ephedrine is an indirect adrenergic agonist and its mechanism of action likely involves increased post-synaptic norepinephrine release and/or decreased norepinephrine reuptake. As these stores of norepinephrine are depleted, the efficacy with each subsequent dose tends to decrease. Patients on norepinephrine reuptake inhibitors or MAOIs can have unpredictable responses to ephedrine.
What is dromotrophy?
Dromotropic effects relate to the conduction speed of electrical impulses within the heart
The pressors that work on Beta receptors work through which second messenger system?? What about milrinone?
The beta receptors (which answers A, B, & D activate) lead to a G-protein (Gs to be specific) mediated stimulation of adenylate cyclase which converts adenosine triphosphate (ATP) to cAMP, which has downstream effects, ultimately leading to increased intracellular calcium concentrations. cAMP is metabolized by phosphodiesterases, which milrinone (answer E) inhibits the action of this enzyme. Therefore, beta-1 or -2 receptor activation increases cAMP production and phosphodiesterase inhibitors decrease the degradation of cAMP. In either case, cAMP levels rise.
Give me the phenylephrine receptor breakdown situation:
Alpha-1 receptor agonism also leads to increased intracellular calcium levels, but not through cAMP. The alpha receptor, also a member of the g-protein receptor family, stimulates phospholipase C, splitting phosphatidyl inositol (into inositol triphosphate and 1,2-diacylglycerol), leading to release of calcium from the sarcoplasmic reticulum.
cAMP works how? Like what does it activate to increase I tracellukar calcium?
cAMP activates protein kinase A, which acts at multiple sites of the sarcoplasmic reticulum (responsible for the majority of calcium release used for contraction). The released calcium binds to troponin (answer D), allowing actin/ myosin (answer E) mediated contraction
Tell me about milrinone and its effects. What does it do with chronotropy? Lusitropy? Preload and afterload?
Milrinone is selective for phosphodiesterase 3, resulting in increased intracellular cAMP. In the heart this leads to increases in contractility (answer C) and probably lusitropy (answer D, see question 14). At very high levels, heart rate can increase, not decrease (answer E). Milrinone leads to significant arterial and venous vasodilation, decreasing afterload and preload
On transesophageal echocardiogram (TEE), a hypotensive patient is seen with a failing right heart and increasing tricuspid regurgitant jet, despite the absence of overt left heart failure. Which of the following medications is the next BEST step: Milrinone Nitric Oxide Nitrous oxide Dobutamine Fenoldopam
Inhaled nitric oxide is a direct vasodilator. By delivering it through the respiratory tract, in primarily effects the vasculature near the site of the alveoli, thereby lowering pulmonary artery pressures (which are leading to the right ventricular failure in this patient). Because nitric oxide is metabolized almost immediately (in seconds) systemic decreases in blood pressure are minimal. Milrinone (answer A), and far less so dobutamine (answer D), can also have vasodilatory properties leading to decreased pulmonary artery pressures, but both (especially milrinone) can lead to systemic hypotension. Fenoldopam (answer E) is a pure DA1 agonist, leading to systemic vasodilation and increased renal blood flow. Nitrous oxide (answer C) increases pulmonary artery pressures.
Tell me about Nitric oxide-how does it work, why are pts with pulm HTN on viagra pills? What other type of hemoglobin can they make?
Nitric oxide (NO) stimulates guanylate cyclase (answer D), increasing cGMP levels (answer A). cGMP leads to the relaxation of smooth muscle (by several mechanisms) leading to vasodilation. cGMP is broken down by the 5th isoform of phosphodiesterase (PDA5, answer B), which sildenafil is an inhibitor of (and is why pulmonary hypertension patients are on “Viagra” pills). Because the NO is inspired, it is only active at vasculature near the alveoli, increasing perfusion to well ventilated alveoli, decreasing V/Q mismatch (answer C). NO can bind to the haeme moiety in haemoglobin, leading to methaemoglobin,
Tell me about Nesitride. What does it do? How does it compare to a spinal? How does it affect contractility?
Nesiritide is a recombinant BNP, leading to stimulation of guanylate cyclase (and increased cyclic guanosine monophosphate (cGMP)) with resultant vasodilation (answer C). It is indicated for part of the treatment for severe decompensated heart failure (answer D) by decreasing afterload and encouraging forward flow. Both spinal anesthesia and nesiritide will decrease afterload, although spinal anesthesia is difficult to titrate and may have profound preload effects as well. Nesiritide has no effect on contractility (answer B). Although nesiritide is essentially BNP, a BNP level does not need to be obtained prior to its use. Notice that this question did not say that spinal anesthesia and nesiritide have the same effects overall, just that they both decrease afterload.
