Test 5: CV Drugs pt. 2 Flashcards
What is Ephedrine?
A synthetic non-catecholamine.
Mixed actions:
-Mild direct (A1, B1, B2). Weakly agonizes these receptors on the postsynaptic side.
-Mostly Indirect actions: Increases NE release to the post synaptic receptors. Relies on endogenous NE stores for results. Greater effect on venous side. Both Alpha and Beta.
-Increases CO and PL
-Not metabolized by MAO or COMT
-Renal elimination (mostly unchanged)
-Administered IV, IM, and PO
What is the dose of Ephedrine?
IVP: 5 - 10 mg
IM: 25 - 50 mg
What are the uses of Ephedrine?
-Can be given IM before placing a spinal to counteract hypotension
-Used in OB since it doesn’t compromise uterine blood flow
-Used post-induction to buy time to adequately fluid resuscitate
-Can use instead of Neo if pt is already bradycardic.
-Hypotension with low CO + HR
-Tx of Sympathectomy
-Temporary tx of hypovolemia
-Treat transient myocardial depression
What are the advantages of Ephedrine?
Similar to epinephrine:
-Epinephrine is 250X more potent
-Ephedrine 10X longer duration
SBP, DBP, HR and CO increase (inotrope and pressor)
What are the disadvantages of Ephedrine?
-Tachyphylaxis
-Reduced efficacy with depleted NE stores
-R/O malignant HTN with MAOIs (If pt is on MAOI anti-depressants, can lead to malignant HTN (nothing to get rid of it).
-Increased HR
Caution use in:
-Patients on NDRIs and MAOIs
-CV dz or HOCM
-Closed angle glaucoma
-Hyperthyroidism
What is Phenylephrine?
-Direct acting alpha adrenergic agonist
-Some indirect with NE release
-Mainly Alpha 1 stimulation (arterial > venous)
-Just vasoconstriction
-Metabolized by MAO (not COMT). Short DOA (<5 minutes)
What is the dose of Phenylephrine?
-40 to 80 to 160 mcg IV push
-Watch for reflex bradycardia
-Can be given as infusion: 20-200 mcg/min
What are the uses of Phenylephrine?
-Anesthesia-induced hypotension (Both GA and SAB)
-Nasal decongestant
-Hypotension with low SVR
-Temporary tx for hypovolemia
Decreased risk of fetal acidosis associated with phenylephrine when used for tx of hypotension r/t spinal
What are the effects of Phenylephrine?
CV effects:
-Reflexive DECREASE in HR
-↑ SVR, ↓ CO
-Short duration (quick on/off)
-During hypotension: will increase CBF without increase in CO
-MVO2 does not ↑↑ if hypertension is avoided
Disadvantages
-May ↓ SV and ↑ PVR
-May ↓↓ renal, peripheral, and mesenteric perfusion
-RARELY may induce vasospasm: IMA, radial, gastroepiploic artery
Metabolic effects:
-Can interfere with K+ loading
What is Vasopressin?
-Arginine vasopressin (AVP) also known as ADH
-Endogenous regulation of osmolality, cardiovascular stability, blood coagulability
-Intense peripheral vasoconstriction via V1 receptors in vascular smooth muscle (peripheral, mesenteric vasoconstriction)
-Can restore vasomotor tone in refractory arterial hypotension or relative AVP deficiency
-Refractory shock states/CPR
What are the clinical uses for Vasopressin?
Adjunct vasopressor in the perioperative setting.
-Vasoplegia (post bypass and ACE-I; septic shock)
-Sympathetic blunting by GA or high SAB
-Post-pheochromocytoma resection
-Post CPB vasodilatory shock
-Alternative to Epi in ACLS
-Concomitant use with corticosteroids in septic shock
-Adjunct to catecholamines in septic shock
What is vasoplegia?
When the post-synaptic receptors stop being receptive to Norepi/Epi.
-Occurs with patients on ACE-I therapy and post-CPB
What is the dosing for Vasopressin?
-2-4 units IVP
-10-20 unit bolus followed by infusion at 0.03- 0.1U/min
-Resuscitation dose 40 units
What are the cautions associated with Vasopressin?
-Withdrawal hypotension, DI after discontinuation
-Hyponatremia, pulmonary vasoconstriction
What is Digoxin?
-Cardiac glycoside
-Perioperative use for supraventricular tachydysrhythmias and last line in CHF
-Renal elimination
What is the MOA of Digoxin?
-Inhibition of Na/K ATPase
-Increased Ca2+ in myocardium increases inotropy without increasing HR
-Some negative chronotropic and dromotropic effects via parasympathetic enhancement
What are the cautions with the use of Digoxin?
-Narrow therapeutic index
Toxicity most common in setting of renal dysfunction and hypokalemia:
-Nausea, vomiting, arrhythmias
-Correct causes, administer antiarrhythmics, temporary pacer, digoxin antibodies
Many drug-drug interactions
-Amiodarone - MAJOR
What is Milrinone?
-Phosphodiesterase 3 Inhibitor
-Inodilator: Provides inotropy and vasodilation
-Non-catecholamine inotrope and relaxation of arterial and venous beds
-Increases contractility and CO
-Decreases LVEDP, CVP, and PCWP
-Adverse effects: hypotension, arrhythmias
-Uses: Heart failure (Low CO with high PVR and LVEDP), bridge to transplant
-Preferred over dobutamine in patients with high risk of arrhythmia, pulmonary hypotension, and those on chronic beta-blockade
What is the dose of Milrinone?
Titrate as IV infusion:
-0.2 to 0.75 mcg/kg/min
-Requires renal adjustment
-Can do loading dose of 50 mcg/kg TRO 10 minutes
What are the advantages to Milrinone?
Favorable myocardial profile:
-Decrease preload and afterload
-Minimal tachycardia
-Less arrhythmogenesis than Dopa or Epi
Retains efficacy when NE stores are depleted (chronic CHF)
No tachyphylaxis
What are the disadvantages to Milrinone?
Hypotension can occur with rapid IV bolus
What are the indications for the use of Milrinone?
-Low CO with high PVR and LVEDP
-Bridge to transplant
-Preferred over dobutamine in patients with high risk of arrhythmia, pulmonary hypotension, and those on chronic beta-blockade
What are Beta 2 Agonists used for?
-Relax bronchioles and uterine muscles without tachycardia
-Slowly metabolized = long duration
-Inhalation as well as IV
-Tolerance may develop
-Increase lactic acid levels
What are examples of Beta 2 Agonists?
-Albuterol: PO, inhalation – asthma
-Metaproterenol (Alupent ™) inhalation: asthma
-Terbutaline: IV, PO, SQ, inhalation - asthma or premature labor
What is Methylene Blue?
A drug used for vasoplegia.
-Reduces morbidity & mortality
-Interrupts inflammatory cascade of Nitric oxide -> Guanylyl Cyclase -> cGMP -> Vasoplegia/vasodilation
-Vasopressin and methylene blue are the 2 drugs used for vasoplegia
What are the advantages to Methylene Blue?
-Improves MAP in certain types of shock
-Patients require less pressors and have shorter ICU LOS
-Mortality benefits
-Cheap and readily available
What are the disadvantages to Methylene Blue?
-Can cause paradoxical methemoglobinemia (data from case reports and small RCTs)
-Potentially life-threatening side effects in patients on SSRIs
When would you use Methylene Blue?
If patient is on high dose Norepi/Epi AND Vasopressin and still not meeting goal MAP (vasoplegia).
-Give Methylene Blue 1-2 mg/kg IV
-If first bolus works, can repeat bolus and start drip
When is Methylene Blue contraindicated?
In patients taking SSRIs/SNRIs/MAOIs
What drugs can you give as alternatives to Methylene Blue if it’s C/I?
-Angiotensin II (consider if high risk of renal failure)
-Hydroxocobalamin (consider if high risk of thrombosis)
What is Calcium?
-Necessary for neurotransmission, coagulation, muscle contractility
-Potent inotrope: Used to treat cardiac depression. Good post CPB
-Ionized calcium responsible for physiologic effect
-Calcium sensitizers – drugs that increase myocardial contractility. Ex: Levosimendan (Increases our response to calcium)
When is Calcium used?
Reverses hypotension:
-Anesthetic induced
-CCBs
-Hypocalcemia
-CPB
-BBs
Hyperkalemic cardiotoxicity
What are the effects of Calcium administration?
-No change or decrease in HR
-Increased contractility
-Increased BP
-Increase SVR
-Variable CO
What is Glucagon?
-Peptide hormone
-Increases intracellular cAMP
-Clinical offset: redistribution and proteolysis
-Duration of action: 20-30 minutes
-Side effects: headache, severe nausea, hyperglycemia and hypokalemia
-Dose: 1-5mg IV slowly
What is Glucagon used for (CV)?
-Treatment of beta-blockade overdose due to increase cAMP in the myocardium
-Bypasses the inhibitory effect of beta-blockade
What is the MOA of Nitrates?
Indirect acting: Nitroglycerin (Has to be activated by enzymes before releases NO)
Direct acting: Nitroprusside (releases NO spontaneously)
Work on the NO pathway.
-NO is released by blood vessel capillary endothelial cells, cause relaxation by entering cell. Guanylyl Cyclase converts GTP to GMP, cGMP causes relaxation.
-Nitric oxide activates smooth muscle soluble guanylyl cyclase (GC) to form cGMP.
-Increased intracellular cGMP inhibits calcium entry into the cell, thereby decreasing intracellular calcium concentrations and causing smooth muscle relaxation
-NO also activates K+ channels, which leads to hyperpolarization and relaxation.
-NO acting through cGMP can stimulate a cGMP-dependent protein kinase that activates myosin light chain phosphatase, the enzyme that dephosphorylates myosin light chains, which leads to relaxation.
How are Nitrates removed?
Nitrates are removed (De-nitrated) by:
-Smooth muscle: glutathione S-transferase
-Mitochondrial enzyme: aldehyde dehydrogenase
What are the effects of Nitrates?
-Vascular Smooth Muscle dilation (gradient of response). Arteries vs veins
-Increased venous capacitance/decreased PL = risk of orthostatic hypotension
-Baroreceptor and hormonal responses to 🡻 arterial pressure
-Redistribution of blood flow
-Slight positive inotropic effect via nitric oxide (due to PDE)
-Can work on Erectile tissue and Pulmonary HTN (Sildenafil)
-Inc cGMP = decreased platelet aggregation
-Nitrates react to form Methemoglobin (not a huge issue in adults unless long-term therapy)
What are the toxicity S/Sx of Nitrates?
Directly related to the extent of vasodilation that occurs.
-Headache, flushing, tachycardia, orthostatic hypotension
-Contraindicated with increased ICP
How does Tolerance to Nitrates form?
Mechanisms not completely understood:
-Reduced bioactivation +/- loss of soluble guanylate cyclase
-Systemic compensation
Variable tolerance depending on which nitrate is used
-Nitroprusside (SNP) not as affected
-NTG > SNP
What is Nitroglycerin?
An indirect acting vasodilator.
-Activation of cGMP causes vasodilation
-Affects venous > arterial
-Clinical offset: redistribution, metabolism in smooth muscle and liver
-Duration 5-10 minutes
-Onset 2-3 minutes
What is the dosing of Nitroglycerin?
Bolus dosing (profound HOTN):
-40-80 mcg IVP
IV infusion:
-0.1-7 mcg/kg/min or 5 mcg/min and up
What are the effects of Nitroglycerin?
Marked vasodilation causing:
-Reflex increased HR and Contractility
-Decreased BP, PL, SVR/PVR
-Variable CO
What are advantages to Nitroglycerin?
-Preload reduction
-No metabolic toxicity (compared to SNP)
-Effective for myocardial ischemia (vasodilates coronaries)
-Effective for CHF
-Increases vascular capacity (useful post CPB)
-Dilates pulmonary vascular bed
What are disadvantages to Nitroglycerin?
-↓ BP = ↓Coronary Perfusion Pressure (CPP)
-Reflex tachycardia (Dose related)
-Inhibits HPV (less than NTP)
-May increase ICP
-May be absorbed by PVC tubing (titrate to effect)
-Tolerance
-Dependence
-Methemoglobinemia
What are clinical uses for Nitroglycerin?
-Relief of Coronary Artery vasospasm
-Redistribution of blood flow to ischemic coronary areas (MI)
-Reduced ischemia = improved inotropy and increased VF threshold
-At high doses (up to 10 mcg/kg/min) has Arterial effects (Decreased SVR = reduced wall stress and MVO2)
What is Nitroprusside?
Direct acting vasodilator.
-Dilates both venous and arterial but slightly more arterial at usual doses
-Clinical onset <1min.
-Duration 3-5 mins.
-Longer half-life than NTG
What is the dosing for Nitroprusside?
Bolus dosing: (careful!) 20 mcg
Infusion:
-0.1-2 mcg/kg/min
What are the effects of Nitroprusside?
-Reflex increase in HR and Contractility
-Dose-dependent decrease in BP and SVR/PVR
-Decreases PL
-Variable effect on CO
What are the advantages to Nitroprusside?
-Duration of action: Quick on & off
-Systemic and pulmonary vasodilation
-Highly effective for all types of HTN
-More arterial vasodilation than NTG
-Good for AL reduction
What are disadvantages to Nitroprusside?
-Cyanide toxicity
-Unstable in light
-Reflex tachycardia (responds to BB)
-Blunts HPV (More than NTG)
-Vascular steal
-Caution with managing chronic hypertension
-Rebound hypertension
-Increased ICP
-Inhibited platelet function
Why is there a risk of Cyanide toxicity with Nitroprusside?
-NTP rapidly metabolized to cyanide
-Adults normally able to “detoxify” NTP
-Issue in peds
-Biggest issues with large, prolonged dosing and with hepatic and renal disease
How do you diagnose Cyanide toxicity?
-Challenging in anesthetized patients
-Hypertension and metabolic acidosis (lactate >8)
-Late signs: CV collapse with hypotension
-Seizures/coma; mydriasis
-Onset often preceded by tachyphylaxis
-Elevated SVO2
What is the treatment for Cyanide toxicity?
-Stop the NTP
-100% O2
-Sodium thiosulfate (150 mg/kg over 15 minutes)
What causes vasopressin to be released by the Posterior Pituitary?
-Hyperosmolarity
-Decreased atrial receptor firing
-Angiotensin 2
-SNS Stimulation
What are the actions of V1 receptor stimulation?
-Constriction of blood vessels (inc SVR)
-Increases intracellular calcium
-Tx of esophageal varices
What are the actions of the V2 receptor stimulation?
-Increased fluid reabsorption by the kidneys (increased blood volume)
-Antidiuresis.
What are advantages/disadvantages of Vasopressin?
Advantages:
-Independent of adrenoreceptors
-Effective with vasoplegia unresponsive to usual means
-ACLS: restore coronary perfusion without ↑HR
Disadvantages:
-Symptoms of ↓BF to mesentery, bronchoconstriction, etc
-Decrease hepatic BF (esp. if used with α1 agonists)
-Decreased platelet count
-Lactic acidosis (?)
