Anesthesia Adjuncts (Exam V) Flashcards
β agonism results in activation of _____ which then produces _______.
Adenylyl Cyclase (AC)
cAMP
Does Ca⁺⁺ influx or efflux occur during β agonism?
Influx
What type of receptors are β receptors?
GPCR
What types of β receptors are there and where are they primarily located?
- β1 - Heart
- β2 - Lungs
- β3 - Fat/Muscle
Chronic administration of β blockers results in what effect on receptors?
Receptor upregulation (aka ↑ # of receptors)
After β receptor desensitization from prolonged catecholamine exposure, what drug class can restore receptor responsiveness?
β-blockers
How do β blockers protect myocytes from perioperative ischemia?
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 the slope
Prolong Phase 4 (rate of spontaneous depolarization)
↓ dysrhythmias during ischemia and reperfusion.
How will β blockers affect diastolic perfusion time?
β blockers will increase diastolic perfusion time.
What type of HTN is a possible indication for β blocker therapy?
Essential Hypertension
What are other Indications for B blocker therapy?
1.Excessive SNS stimulation (acute cocaine ingestion)
2. Thyrotoxicosis
3.Cardiac dysrhythmias
4. 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 ones already on β-blocker therapy.
What does SCIP not say?
What BB do you give? and how much?
What were the three β1 selective agents discussed in lecture?
- Atenolol (tenormin)
- Metoprolol (lopressor)
- Esmolol (breviblock)
tenormin is also known as
Atenolol
lopressor is also known as
Metoprolol
breviblock is also known as
Esmolol
Inderal is also known as
Propranolol
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 generally shitty for anesthesia?
Propranolol is known as a prototypical antagonist.
Differentiate the clearance mechanisms of metoprolol and esmolol.
- Metoprolol = Hepatic
- Esmolol = Plasma hydrolysis
What is the clearance for Propranolol and atenolol?
Propranolol = Hepatic
Atenolol = Renal
What is the E 1/2 (hrs) for Atenolol?
6-7 hrs
Which two beta-selective agents are cleared Hepatically?
Propranolol and metoprolol
What are the IV dosages for Metoprolol, Atenolol, and Esmolol?
Metoprolol = 1 to 15 mg IV
Atenolol = 5 to 10 mg IV
Esmolol = 10 to 80 mg IV
Differentiate the E½ of metoprolol and esmolol.
Metoprolol E½ = 3-4 hours
Esmolol E½ = 9 minutes
When propanolol (Inderal) is given, what effect lasts longer, negative inotropy or chronotropy?
Negative chronotropy (bradycardia) lasts longer
What is a possible reason why the heart rate slowing effects of propanolol last longer than the negative inotropic effects?
Possible Division β1 sub-receptor types (ex. β1A, β1B, etc.)
Propanolol (Inderal) will decrease the clearance of which two important anesthetic drug classes?
- Opioids
- Amide LA’s
What drug is the most selective β1 antagonist?
Atenolol (Tenormin)
What are the three benefits of Atenolol (Tenormin)?
- Good for non-cardiac sx CAD patients (↓ complications for 2 years) Only dosed 1x/day
- No insulin-induced hypoglycemia
- Does not cross the BBB (less fatigue)
What is the dose for Atenolol (Tenormin)?
5mg q10min IV
What is the dose of metoprolol (Lopressor)?
1mg q5min (Given in 5mg “blocks”)
**practical implication: Most anesthesia providers start with 1-2 mg and titrate to effect up to 5mg.(Max = 15 mg)
What two formulations of metoprolol are there?
- Metoprolol Succinate = One dose per day
- Metoprolol Tartrate = multiple doses per day
What is the elimination half time of Metoprolol Tartrate?
2-3 hours (bid-qid dosing)
What is the elimination half time of Metoprolol succinate?
5-7 hours (qd dosing)
What β blocker would be used for treat intubation stimuli?
Esmolol (Brevibloc) -RAPID
What are the onset and offset of esmolol (Brevibloc)?
Onset: 5 min
Offset: 10-30min
What is the initial dose for esmolol?
20-30mg IV
How is esmolol metabolized?
via plasma esterases (cytosol)
Caution should be taken when giving esmolol (brevibloc) with which two conditions?
Why?
- Cocaine and/or epinephrine
- Can cause pulmonary edema and collapse
Are the effects of CCBs and β-blockers additive?
No, they are synergistic
Which drug prevents tachycardia and hypertension associated with intubation?
Esmolol and Fentanyl
What two scenarios were given in class for a β1 selective indication over a non-selective β blocker?
- DM: interferes with glycogenolysis and potentiates insulin
- Airway: potentiates bronchospasm and ventilatory depression
What volatile anesthetic will cause the most significant additive myocardial depression when combined with a β blocker?
The least with what gas?
Why does this not matter?
- Enflurane = most significant additive depression
- Isoflurane = least additive depression
- Not significant between 1-2 MAC
What 2ⁿᵈ messengers are potentiated by α1 agonism?
IP₃ → Ca⁺⁺ release from SR
What occurs with α2 agonism?
↓ release of NorEpi from presynaptic nerve terminals (brainstem)
Is phenylephrine primarily a venous constrictor or an arterial constrictor?
Venous constriction > arterial constriction
Phenylephrine clinically mimics norepinephrine but is….
less potent and longer lasting. (indirectly releases a small amount of NorEpi)
What is the normal dosing of phenylephrine?
100mcg/mL IV push
Phenylephrine is used to treat hypotension from?
SNS blockade by regional anesthesia
inhaled/ injected anesthetics
very useful in CAD and Aortic stenosis… no tachycardia
What adverse effect results from phenylephrine?
How is it resolved?
- Reflex bradycardia
- Stopping the drug
What is the ratio of β to α blockade for Labetalol?
7:1 for IV form.
Is Labetalol a selective β antagonist?
No! Labetalol is non-selective β and selective α1 antagonist
Which of the following receptors does Labetalol antagonize?
A. α1
B. α2
C. β1
D. β2
A, C, and D
What is the dose for labetalol?
2.5 - 5mg IV; 10mg max (d/t tachyphylaxis)
max effect of IV dose 5-10 min
Which of the following drugs would you utilize for a post-carotid endarterectomy with a BP of 214/62 ?
Labetalol
Esmolol
Esmolol
Labetolol could drop the DBP too much.
You have a patient scheduled for a CABG x4 and you realize he has not had his BB. Which BB will you administer? why?
Metoprolol
It is longer acting and protects the myocardium
What are the effects of labetalol?
Lowers systemic BP by decreasing SVR (reflex tachycardia attenuated by beta-blockade)
Which drug is an indirect acting sympathomimetic?
Ephedrine - evoke the release of NorEpi from postganglionic sympathetic nerve endings.
Releases NorEpi
What are sympathomimetics most often used for?
Increase myocardial contractility
but mainly to increase systemic blood pressure
What could you see as a side effect with sympathomimetic agents lacking B1 specificity?
They can cause intense vasoconstriction and reflex-mediated bradycardia.
Explain the MOA of sympathomimetics?
They activate directly or indirectly beta or alpha-adrenergic GPCRs.
cAMP enhance calcium influx into the cytosol
actin and myosin interact more forcefully cross bridging
What is the prototype catecholamine?
Epinephrine
Ephedrine is used in sympathetic depression from?
- inhaled/injected anesthetics
- BP response much less intense; last 10x longer than epi.
What is the IV push dose of epinephrine?
How long does it last?
- 2-8 mcg IV bolus
- 1-5 min
What is the infusion dose of epinephrine for β2 effects?
1-2 mcg/min
What is the infusion dose of epinephrine for β1 effects?
4 mcg/min
What is the infusion dose of epinephrine for predominantly α effects?
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 PVR?
Phenylephrine
Which SNS agonist can be given IM?
- Ephedrine IM 50mg
- local vasoconstriction insufficient to delay uptake.
Why does tachyphylaxis occur with ephedrine?
Ephedrine depletes NorEpi stores
Is the BP response when giving ephedrine more or less intense than epinephrine?
Bp response much less intense; ephedrine lasts 10x longer than epi
What is the preferred sympathomimetic for parturient patients?
Why?
Ephedrine (It doesn’t effect uterine blood flow and used in hypotension s/p Spontaneous abortion)
How does phenylephrine compare to ephedrine in parturient patients?
Phenylephrine has similar effects but has the additional benefit of a higher umbilical pH in neonates.
What is the mechanism of action of vasopressin?
Stimulation of vascular V1 receptors → arterial vasoconstriction
What drug would be utilized for catecholamine-resistant hypotension?
Vasopressin
What drug would be used for ACE-Inhibitor induced resistant hypotension?
Vasopressin
Resistant hypotension can occur with both ACEi and ARBs.
Name a few side effects to look for when administering Vasopressin:
Coronary artery vasoconstriction
simulates GI smooth muscle (abd pain, N/V)
decreased platelet counts and antibody formation
How does Nitric Oxide cause vasodilation?
In broad terms.
NO → GC → cGMP → Ca⁺⁺ inhibition entry into smooth muscle and increased uptake by endoplasmic reticulum.
What is Nitric Oxide involved in? in terms of in the body?
CV tone relaxation
platelet regulation
CNS neurotransmitter
GI smooth muscle relaxation
Immune modulation
Pulmonary artery vasodilation
Name two nitro-vasodilators discussed in lecture
Sodium nitroprusside
nitroglycerin
What does Nitroprusside dissociate on contact with?
What is the result?
Dissociates on contact with oxyhemoglobin → methemoglobin, NO, and cyanide released.
What does nitroprusside vasodilate?
Causes relaxation of arterial and venous vascular smooth muscle.
What vasodilator absolutely requires arterial line monitoring and requires continuous administration?
Nitroprusside.
What is the dose of Nitroprusside?
0.3mcg/kg/min titrated to 2 mcg/kg/min
When is cyanide toxicity seen?
With higher IV doses of sodium nitroprusside (SNP)
Cyanide radical accumulates due to sulfur donor/methemoglobin exhaustion.
When would you suspect cyanide toxicity?
- Increasing dose of sodium nitroprusside (SNP) needed
-metabolic acidosis
- increased mixed-venous sats (tissues are not using O2)
- CNS dysfunction/change in LOC occurs.
When is nitroprusside used?
- production of controlled hypotensive surgeries (aortic, spine, pheochromocytoma)
- Hypertensive emergencies (carotid surgery)
How do Nitro-vasodilators work?
2 medications mentioned?
Decreasing SBP by: decreasing SVR….art vasodilators: treat effects of vasoconstriction.
Decrease venous return: venous dilator: alleviate pulmonary/systemic congestion.
Meds: sodium nitroprusside & Nitroglycerin
Where does nitroglycerin work?
- large coronary arteries (relaxation of arterial vascular smooth muscle (high doses))
- Venous capacitance vessels (venous pooling)
Does nitroprusside or nitroglycerin exhibit tachyphylaxis?
Nitroglycerin
What is the nitroglycerin dose?
5 - 10 mcg/min infusion and titrate
What are the indications for nitroglycerin?
-S Sphincter of Oddi spasm (during cholecystectomy/opioid induced)
-CControlled Hypotension (less potent than SNP)
-A Acute MI (relieves Pulm congestion, decreases O2 requirements, limits MI size)
-R Retained placenta
How does hydralazine work?
- ↓ Ca⁺⁺ release and systemic arterial vasodilation
- can cause extreme hypotension and rebound tachycardia
When does hydralazine onset/peak?
What is it’s half-life?
- Peak/onset: peak plasma concentration 1 hr.
- ½-life: 3-7 hours (not a great choice for us in the OR)
What is the initial dose of hydralazine?
2.5mg IV
What are the three categories of CCBs?
Where do each interact?
- AV Node (Phenylalkylamines & Benzothiazepines)
- Vasculature (Dihydropyrimidines)
How does tachyphylaxis happen with nitroglycerin?
- dose dependent and duration dependent (24 hrs)
- limits vasodilation
- drug-free intervals of 12- 15 hours reverse tolerance
Rebound ischemia? d/t tachyphylaxis and the abrupt cessation.
Do CCB increase the speed of conduction?
No! they decrease the speed of conduction, mostly through the AV node
How do CCBs generally work?
Bind and block VG-Ca⁺⁺ channels, thus ↓ Ca⁺⁺ influx. (L-type) = inhibits excitation-contraction coupling.
L-type Ca++ channels = found in cardiac myocytes, cardiac nodal tissue, and vascular smooth muscle.
What is used for short-term control of HTN?
Nicardipine (Cardene)
CCBs will ______ systemic blood pressure via peripheral vasodilation and ________ coronary blood flow.
decrease; increase
Which CCB has the greatest coronary artery dilation and least myocardial depression?
Nicardipine (Cardene)
What is the dose of nicardipine?
5mg/hr (2.5mg titration x 4 to max of 15mg/hr)
50% drug decrease 30 min after D/C
What antihypertensive works primarily through altering venous capacitance?
Nitroglycerin
Your end-stage COPD patient needs emergent blood pressure control in the ICU. Which of the following medications might worsen his PaO2 the most?
Sodium nitroprusside
Your physician is closing the neck incision following an uneventful right CEA. you have reversed the muscle relaxant and the patient is spontaneously breathing at 20/min; BP 140/90 and climbing. Your 1st intervention is?
Give a narcotic (25 mcg fent then a longer-acting narcotic, maybe dilaudid or morphine)
