SS25 Anesthesia Adjuncts (Exam 4) Flashcards
What are the subtypes of β receptors and where are they primarily located?
- β1 - Heart
- β2 - Lungs
- β3 - Fat/Muscle (disregard β3)
What type of receptors are β receptors?
GPCR
β agonism MOA
- Ligand (agonist binds)
- Activates Adenylyl Cyclase (AC)
- cAMP produced
- Enhances Ca influx
- Expected effects occurs
What effects occur with β agonism?
- Chronotropic
- Inotropic
- Dromotropic
What type of antagonism occurs at β receptors?
- Competitive antagonism
βeta-antagonist prevents ________. from binding at the heart, airway smooth muscle, and blood vessels
- catecholamines (or sympathomimetics)
Chronic administration of β blockers results in what effect on receptors?
- Tachyphylaxis
- Receptor upregulation (aka ↑ # of receptors)
- Desensitization
T/F: The selectivity of β blockers is dose-dependent but dose depenendency is lost at high doses
- True
- B blockers are dose-dependent
- At high doses, no longer selective works on all receptors (B1, B2, B3)
What effects do βeta Antangonist (β-blockers) have?
- May restore receptor responsiveness (maybe take a break from drug & switch to new one)
- Protect myocytes from perop ischemia & infarct
- May ↓ arterial vascular tone & ↓ afterload
- ↓ CO & inhibit renin release
T/F: Patient on B Blockers must be given dose within 24 hr of surgery
True
How do β blockers protect myocytes from perioperative ischemia/infarct?
- By ↓O₂ demand on the heart
T/F. β blockers will potentiate renin release.
- False. β blockers will inhibit renin release
How will β blockers affect the cardiac foci action potential?
- Decrease slope = Prolonged Phase 4
- ↓ rate of spontaneus depolarization
- ↓ dysrhythmias during ischemia and reperfusion (Ex. CABG, TVAR, Ablation)
- Myocardium perfuses during diastole
Myocardium perfuses during diastole
Bonus: Myocardium perfuses during diastole
Why?
- During systole, aortic valves leaflets are open and it blocks the opening to coronary arteries
- During systole, tiny epicardial vessels are constrictricted as well
- Diastole allows for retrograde flow so better perfusion into coronaries
How will β blockers affect diastolic perfusion time?
- Increases diastolic perfusion time = ↑ filling time
What type of HTN is a possible indication for β blocker therapy?
- Essential Hypertension
Other β- blocker indications:
- Excessive SNS stimulation (noxious stimuli, acute cocaine ingestion)
- Thyrotoxicosis (↑ thyroid)
- Cardiac dysrhythmias
- SCIP
What is SCIP?
- Describe the protocol and its goals.
- Surgical Care Improvement Protocol
- β-blockers must be given within 24 hrs of surgery for patients at risk for cardiac ischemia and pts already on β-blocker therapy.
What percentage of β receptors in the myocardium are β1 ?
75%
Do cardio-selective β-blockers cause vasodilation?
No
What non-selective β-blocker has active metabolites and is considered the prototype?
- Propanolol (Inderal)
- β1 = β2 activity
What were the (3) β1 cardio-selective drugs discussed in lecture?
- Atenolol (Tenormin)
- Metoprolol (Lopressor)
- Esmolol (Breviblock)
Differentiate the clearance mechanisms:
- Propranolol
- Metoprolol
- Atenolol
- Esmolol
- Propranolol: Hepatic
- Metoprolol: Hepatic
- Atenolol: Renal
- Esmolol: Hydrolysis (Plasma cholinesterases via cytosol)
Differentiate the E½ of the following:
- Propranolol:
- Metoprolol:
- Atenolol:
- Esmolol:
- Propranolol: 2-3 hrs
- Metoprolol: 3-4 hours
- Atenolol: 6-7 hrs
- Esmolol: 0.15 hrs = 9 minutes
When propanolol is given, what effect lasts longer, negative inotropy or negative chronotropy?
- Why?
- Negative Chronotropy (Bradycardia) lasts longer
- Possibly d/t β1 sub-receptor types (ex. β1A, β1B, etc.)
Propanolol will decrease the clearance of which two important anesthetic drug classes?
- Opioids
- AmiNe LAs (not amides)
What drug is the most selective β1 antagonist?
Atenolol (Tenormin)
What are the three benefits of Atenolol?
- Dosed only 1x daily → Good for non-cardiac sx CAD patients (↓ complications for 2 years)
- Doesn’t potentiate insulin-induced hypoglycemia
- Does not cross the BBB (less fatigue)
What is the dose for Atenolol?
5mg q10min IV
What 3 effects does Metoprolol (Lopressor) have?
- Bronchodilator, Vasodilator, & Metabolic effects of β2 receptors intact
What is the dose of metoprolol?
- 1mg q5min x 5 (for a total of 5 mg)
- repeat set if needed
What two PO formulations of Metoprolol are there?
- Metoprolol Tartate
- Metoprolol Succinate
Compare Metoprolol Tartate & Metoprolol Succinate:
- E1/2 times
- dosing
- which one is more commonly prescribed?
- Metoprolol Tartate:
-E1/2 = 2 - 3 hrs
-dosing 2-4x day - Metoprolol Succinate
-E1/2 = 2 - 3 hrs
-dosing 1x day - More likely to Rx Metoprolol Succinate d/t increased compliance but less HR cntrl
(typically see Tartate more in hospital setting
What β blocker would be used for treat intraop noxious stimuli (ie: intubation)?
- dose:
- onset:
- duration:
Esmolol
- dose: 20 - 30 mg IV
- onset: (5 mins)
- duration: 10 - 30 mins
- rapid on & offset
Caution should be taken when giving Esmolol with which two conditions present?
Why?
- Cocaine and/or Epinephrine absorption
- Can cause pulmonary edema/collapse
Based off graph:
- Which drug prevents Tachycardia & HTN associated with intubation?
- Which drug would you give if increased Tachycardia & HTN was rlt to pain?
- Esmolol
- Fentanyl
Are the effects of CCBs and β-blockers additive?
No, synergistic
What two conditions should a β1 cardio-selective be used over a non-selective?
- DM: β2 can cause hypoglycemia by insulin potentiation
- Airway: β2 potentiates bronchospasm
What volatile anesthetic will cause the greatest additive cardiac depression when combined with a β blocker?
- The least additive cardiac depression?
- Why does this not matter?
- Enflurane = greatest additive depression
- Isoflurane = least additive depression (best for myocardium)
- Not significant between 1-2 MAC
αlpha receptors:
- subtypes:
- receptor type:
- α1 & α2
- GPCR
What occurs with α1 agonism?
- 2nd messenger synthesis = IP₃
- Ca⁺⁺ release from SR
- Affect vascular smooth muscle
- Determines arterial resistance, venous capacity, & BP
What occurs with α2 agonism?
- ↓ release of NE from presynaptic terminal (brainstem)
Is phenylephrine primarily a venoconstrictor or an arterioconstrictor?
More Venous constriction effects
T/F: Phenylephrine is less potent and short-lasting compared to NE.
False
- less potent & longer-lasting
Phenylephrine clinically mimics NE and ______ releases small amounts of NE.
- Indirectly
Indications for Phenylephrine:
- SNS blockade by regional
- Inhaled/Injectable anesthetics
- CAD/A. stenosis (b/c it doesn’t call tachycardia)
What is the normal dose of phenylephrine?
- 100mcg/mL IV push
- Can also do continuous infusion if requiring frequent IV pushes
What adverse effect results from phenylephrine?
- How is it resolved?
- Reflex bradycardia d/t very high SVR
- Stop drug
What is Labetalol effects?
- Non-selective β1&2 and Selective α1 antagonist
- has peripheral effects
- ↓ SVR = ↓ systemic BP and ↑ reflex tachycardia
What is the ratio of β to α blockade for Labetalol?
- 7:1 in IV form
- 7x non-selective β1&2 v. selective α1 antagonist
Which of the following receptors does Labetalol antagonize?
A. α1
B. α2
C. β1
D. β2
α1, β1, β2
What is the dose for labetalol?
- peak effect:
- 2.5 - 5mg IV; 10mg max
- 5 - 10 mins
- Tachyphylaxis (+)
Which βeta blocker would you administer to patient sceduled for CABG x4 and forgot to take β blocker at home?
- Metoprolol (Lopressor) IV
During extubation from L CEA, BP spikes 214/62. Which β blocker would you give?
- Labetalol
- Esmolol
- Esmolol
- Rationale: Labetolol could drop the DBP too much
Sympathomimetics (Vasopressors) uses:
- Increase systemic BP
- Increase myocardial contractility
What are 2 AE that can happen if sympathomimetics lack β1 specificity?
- Intense vasoconstriction
- Reflex bradycardia
Sympathomimetics: MOA
- Activate directly or indirectly α or β adrenergic GPCRs
- cAMP enhance Ca release SRminto cytosol
- Actin & Mysin interact forcefully (↑ crossbridging)
Which drug(s) is an direct-acting sympathomimetic?
- MOA
- Epi, NE, Phnylephrine, Dopamine
- Directly activates adrenergic-Rs
Which drug(s) is an indirect-acting sympathomimetic?
- MOA
- Ephedrine
- Aids in release of NE from postganglionic sympatheric nerve endings
Image skipped during lecture:
Prototype catecholamine
Epinephrine
- cardiac cases & ACLS use only
What is the single bolus IV push dose for Epinephrine?
- Duration of action
- 2 - 8 mcg IVpush
- 1 - 5 min
Epinephrine:
- infusion dose for β2 effects:
- infusion dose for β1 effects:
- infusion dose for α1 effects:
- 1-2 mcg/min
- 4 mcg/min
- 10-20 mcg/min
What catecholamine will have the greatest effect on heart rate and cardiac output?
- Epinephrine
What catecholamine will have the greatest effect on SVR?
- Phenylephrine
- pure αlpha
Ephedrine single IV dose:
- 5 - 10 mg IV
Ephedrine is commonly used in sympathetic depression from what?
- Inhaled/ injectable anesthetics
- BP response less intense & last up to 10x longer than Epinephrine
- Tachyphylaxis (+++)
Why does tachyphylaxis occur with Ephedrine?
- Ephedrine depletes NE stores
What is the preferred sympathomimetic for parturient (woman in labor) patients?
Why?
- Ephedrine can be given d/t hypotension that occurs from spinal SAB
- It doesn’t effect uterine blood flow
- Typically given immediatly after spinal placed for c-section to prevent hypotension
Compared to Phenylephrine, Ephedrine has an equal BP response, but _________ (higher/lower) umbilical pH in neonates.
- higher
What drug would be utilized for catecholamine-resistant hypotension?
- Derivative:
- Single IV dose:
- Vasopressin
-Derivative of Arginine Vasopressin (ADH) - Single dose dose: 1-2 units
Vasopressin MOA:
- Stimulates V1 receptors to cause arterial vasoconstriction
- Increases renal-collecting duct permeability (more water is reabosorped)
Vasopressin side effects:
(Cardiac, GI, Other)
- Cardiac: Coronary artery vasoconstriction
_ GI: Stimluates GI smooth muscle: abd. pain, cramps, N/V. - Other: ↓PLT count & antibody formation
T/F: Vasopressin can be used for ACE-Inhibitor resistant hypotension?
- True
Review image.
You just completed induction on a TKA patient w/ hx of DM, OA, & CAD using Propofol, Vecuronium, & Fentanyl. Pt is intubated on Sevo ET 3%. BP 70/30 HR 54. What is your first intervention?
- ↓ vaporizer: it’s closest & quickest
- Give Ephedrine and/or IVF
Per lecture, what are the 2 pressor(s) of choice for hypotension in CAD patients (place in order)?
- Ephedrine
- Phenylephrine
β-agonist won’t work if fully βeta blocked. You have to give an _____________ agonist.
𝜶lpha agonist
During maintanence phase: BP 80/42 HR 92. In addition to an IVF bolus, what is the drug of choice?
- Phenylephrine
- ↑ SVR = ↑ BP without causing tachycardia
Pt with hx of uterine cancer and takes ACEIs at home becomes hypotensive and does not respond to Ephedrine pushes x3. What are the next 2 steps?
- IVFs, Vasopressin
- Vasopressin is a good option for patients already on ACEIs
Formula to find MAP:
SBP + (2 * DBP) / 3
Per lecture, which drugs are considered vasodilators?
- Nitrates (ie: Nitroglycerin)
- Sodium Nitroprusside
- Minoxidil
- Hydralazine
How does Nitric Oxide cause vasodilation?
- NO → GC → cGMP → Ca⁺⁺ entry inhibited into smooth muscle → increased uptake in SR
Which processes are NO involved in? (6)
- Cardiovascular tone relaxation
- Plt regulation
- CNS neurotransmitter
- GI smooth muscle relaxation
- Immune moduation
- Pulmomary Artery Vasodilation
Nitro- vasodilators MOA:
- ↓ Systemic BP by:
- ↓ SVR: arterial vasodilators treat effects of vasoconstriction
- ↓ Venous Return: venous vasodilators alleviate pulmonary/systemic congestion
How can nitro-vasodilators alleviate pulmonary congestion?
- By decreasing venous return via venodilation
What vasodilator absolutely requires continuous monitoring and an invasive arterial line monitoring?
Sodium Nitroprusside
Sodium Nitroprusside: MOA
- Relaxation of arterial and venous vascular smooth muscle
What does Nitroprusside dissociate on contact with?
- What is the result?
- Dissociates immediately on contact with oxyhemoglobin → methemoglobin, NO, and cyanide released.
- cyanide toxicity risk
What is the dose of Nitroprusside?
- onset?
- duration?
- Initial 0.3 mcg/kg/min
- Max: 2 mcg/kg/min
Duration: INSTANT transient onset
When is Sodium Nitroprusside (SNP) used?
- Controlled Hypotension: Aortic, Spine, Pheochromocytoma
- Hypertensive emergencies & Carotid sx (CEA)
What drug is used to treat cyanide toxicity?
Methylene blue
What signs would tip you off to possible cyanide toxicity secondary to nitroprusside administration?
- ↑ dosing need for sodium nitroprusside
- ↑ SvO₂ (mixed venous) & ↑ Metabolic acidosis ↑ b/c tissues are not using O2
- CNS dysfunction/LOC changes
Where does nitroglycerin work?
- Large coronary arteries
- Venous capacitance vessels
- Lead to venous pooling & relaxation of vascular smooth muscle @ high doses
Would nitroglycerin increase or decrease preload?
↓ preload
Does nitroprusside or nitroglycerin exhibit tachyphylaxis?
Nitroglycerin
What tachyphylactic effects that can occur with NTG?
- Dose & Duration dependent
- Limits vasodilation
- Drug free interval 12-15 hrs reverses tolerance; may have possibe rebound ischemia .
What is the nitroglycerin dose?
- Initial dose = 5 - 10 mcg/min infusion and titrateable
- No max but ↑ dose not equal ↑resoonse
What is the first line treatment for sphincter of Oddi spasm?
What is second?
- Glucagon
- Nitroglycerin
What are the indications for nitroglycerin?
-
Acute MI
-relieves pulm congestion, ↓ O2 requirements, limits MI size -
Controlled Hypotension
-Less potent than SNP -
Sphincter of Oddi spasm
-Occurs during cholecystectomy/opioid induce -
Retained placenta
-Continued bleeding
Hydralazine: MOA:
- Direct systemic arterial vasadilator
- ↓ ITP =↓ Ca⁺⁺ release
Hydralazine:
Onset:
1/2 Life:
- Peak: 1 hour
- ½-life: 3-7 hours
too slow on & off; not good for sx.
What is the initial dose of Hydralazine?
2.5 mg IV
Hydralazine: Adverse effects
- Extreme hypotension
- Rebound tachcardia
What are the three types of CaCBs?
- Include their selectivity (where they act)
- Phenylalkylamines - AV Node
- Benzothiazepines - AV Node
- Dihydropyridines - Arteriolar Bed
- If a CaCB is selective for AV node, the HR will __________ (decrease/increase) more.
- If a CaCB is selective for the arteriolar bed, there will be more ______________ (vasoconstrictive/vasodilatory) effects.
- decrease
- vasodilatory
CaCBs: MOA
- Bind to L-type V-G Ca channels
- ↓ Ca⁺⁺ influx
- Excitation-contraction coupling inhibited
CaCBs will ______ blood pressure and ________ coronary blood flow.
decrease; increase
Effects of CaCBs:
- ↓ vascular smooth muscle contractility
-Peripheral vasodilation = ↓ SVR & systemic BP
-↑ coronary BF
-Dihydropyridines - ↓ Speed of conduction mainly via AV node
-Phenylalkylamines
-Benzothiazepines
Which CCB has the greatest coronary artery dilation and least myocardial depression?
Nicardipine (Cardene)
Nicardipine:
- Clinical use:
- Dose:
- E 1/2:
- Clinical use: short-term severe HTN (ie: expecting strong stimuli like SBP 220s but wont’t need for prolonged time)
- Dose: 5 mg/hr
-Titrate:(↑ 2.5 mg/hr x4 )
-Max 15 mg/hr - E 1/2: 50% decrease 30 mins after d/c
Which antihypertensive works primarily through altering venous capacitance?
NTG
Which antihypertensive will worsen the PaO2 (the most) of an end-stage COPDr who needs emergent BP?
Sodium Nitroprusside
Surgeon is closing on R CEA. CRNA has reverse muscle relaxant and pt is breathing spontaneously. BP and HR are elevated. What is youre first intervention?
- Give narcotic
- Based off how high BP is, may need to start Nicardipine (Cardene)
