Anesthesia Adjuncts (Exam IV) Flashcards
β agonism results in activation of _____ which then produces _______.
Adenylyl Cyclase (AC)
cAMP
Does Ca⁺⁺ influx or efflux during β agonism?
Influx
What types of effects does calcium influx from beta agonism produce?
- Chronotropic
- Inotropic
- Dromotropic
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
What do beta blockers do?
- They prevent catecholamines and other sympathomimetics from binding to the beta receptors on the heart, airway smooth muscle, and blood vessels through competitive antagonism.
For beta antagonists, selectivity is ____, and lost at ______ doses of antagonists.
- dose dependent
- high doses
Chronic administration of β blockers results in what effect on receptors?
Tachyphylaxis - 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
Beta blockers will ___ arterial vascular tone and ___afterload.
- decrease
- reduce
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 of Phase 4
↓ dysrhythmias during ischemia and reperfusion.
Beta blockers are great for CABG and valve patients intraop.
How will β blockers affect diastolic perfusion time?
β blockers will increase diastolic perfusion time.
The myocardium perfuses during diastole.
What type of HTN is a possible indication for β blocker therapy?
Essential Hypertension
What are the 5 indications for beta blocker therapy?
- Excessive SNS stimulation from noxious stimuli or acute cocaine ingestion.
- Thyrotoxicosis
- Cardiac dysrhythmias
- essential hypertersion
- SCIP protocol
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.
- Do not give for patients who are not already on a beta blocker.
- The protocol does not say which beta blocker or how much. It is up to you as the provider. See what kind they were on before.
What were the three β1 selective agents discussed in lecture?
What organs do these block?
- Atenolol (tenormin)
- Metoprolol (lopressor)
- Esmolol (breviblock)
- Heart/myocardium
What percentage of β receptors in the myocardium are β1 ?
75%
Do cardio-selective β-blockers cause vasodilation?
No
- What is the gold standard beta-1 blocker that we compare all others against?
- Is it specific or non specific?
- Propranolol (Enderol)
- The only Beta-1 blocker that has no cardiac selectivity. So nonspecific we don’t use this drug.
What non-selective β-blocker has active metabolites and is generally shitty for anesthesia?
Propanolol
Differentiate the clearance mechanisms of metoprolol, atenolol, and esmolol.
- Metoprolol = Hepatic
- Atenolol = renal
- Esmolol = Plasma cholinesterases
Differentiate the E½ of metoprolol, atenolol, and esmolol.
- Metoprolol E½ = 3-4 hours
- Atenolol E 1/2 = 6-7 hours
- Esmolol E½ = 9 minutes
True/False
Metorpolol. Atenolol, and esmolol all have activie metabolites
False, none of them have active metabolites. Only propranolol does
What is the protein binding of Metoprolol, atenolol, and esmolol?
All 3 have low protein binding
What type of protein binding does propranolol have?
High protein binding with a small volume of distribution.
For propranolol, the beta-1 activity is >, <, or = to Beta-2 activity?
- = to
When propanolol is given, what effect lasts longer, negative inotropy or negative 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 β1 sub-receptor types (ex. β1A, β1B, etc.)
Propanolol will decrease the clearance of which two important anesthetic drug classes?
- Opioids
- Amide LA’s
What drug is the most selective β1 antagonist?
Atenolol
What are the three benefits of Atenolol?
- Good for non-cardiac sx CAD patients (↓ complications for 2 years)
- No insulin-induced hypoglycemia
- Does not cross the BBB (no fatigue)
What is the dose for Atenolol?
5mg q10min IV
What is the dose of metoprolol?
1mg q5min (Given in 5mg “blocks”)
What two PO formulations of metoprolol are there?
- Metoprolol Tartate = multiple doses per day. E1/2 = 2-3 hours
- Metoprolol Succinate = One dose per day. E1/2 = 5-7 hours
What β blocker would be used for treat intubation stimuli?
Esmolol
Works better than lidocaine and fentanyl
What are the onset and offset of esmolol?
Onset: 5 min
Offset: 10-30min
What is the initial dose for esmolol?
- 20-30mg IV
- Second dose increase to 40-50mg
Caution should be taken when giving esmolol with which two conditions?
Why?
- Cocaine and/or epinephrine
- Can cause pulmonary edema and cardiac collapse
Beta blockers are great at reducing which 2 things?
- Heart rate
- blood pressure
Are the effects of CCBs and β-blockers additive?
No, they are synergistic. Use caution when giving at the same time.
What two scenarios were given in class for a β1 indication over a non-selective β blocker?
- DM: β2 can cause hypoglycemia by insulin potentiation
- Airway: blocking β2 potentiates bronchospasm
What volatile anesthetic will cause the greatest additive myocardial depression when combined with a β blocker?
The least?
Why does this not matter?
- Enflurane = greatest additive depression
- Isoflurane = least additive depression
- Not significant between 1-2 MAC
- What types of receptors are alpha-1 and alpha-2?
- Where are they located?
- They are both GCPRs
- Alpha-1 is in the periphery.
- Alpha-2 is in the CNS
What 2ⁿᵈ messengers are potentiated by α1 agonism?
IP₃ → Ca⁺⁺ release from SR, which affects vascular smooth muscle, and determines arteriolar resistance and venous capacity with blood pressure.
What occurs with α2 agonism?
↓ release of NE from presynaptic nerve terminals in the brainstem
What is an example of an alpha-1 agonist?
Phenylephrine
What is an example of an alpha-1 antagonist?
- Alpha-1 blockers than end in “sin” EX prazosin
What are 2 examples of an alpha-2 agonists?
- Clonidine
- Dexmetatomidine
Is phenylephrine primarily a venoconstrictor or an arterioconstrictor?
Venous constriction > arterial constriction
Phenylephrine clinically mimics norepinephrine but is….
less potent and longer lasting
What does phenylephrine indirectly release?
Small amounts of norepi
- Phenylephrine is used to treat hypotension from what 3 things?
- What are the 2 most commomn administrations?
- SNS blockade from regional anesthesia
- Inhaled/injected anesthetics
- Very useful in hypotension in CAD and AS patients because it doesn’t cause tachycardia.
- IV push and IV drip
- What is the normal dosing of phenylephrine?
- How is this drawn up/diluated?
- 100mcg/mL IV push
- The vile comes in 10mg/mL. To dilue, take the 10mg and put it into a 100mL NS bag and dilute it to give you 100mcg/mL.
What adverse effect results from phenylephrine?
How is it resolved?
- Reflex bradycardia (this happens when you have given too much phenylephrine, because peripherally you now have too much vasoconstruction that the myocardium see this and will slow down your heart rate, to maintain cardiac output)
- The reflex bradycardia will get down to a rate of 2-30pbm.
- Stopping the drug
What is an example of of a mixed alpha/beta antagonist?
Labetolol (normodyne)
What is the ratio of β to α blockade for Labetalol?
7:1
* You will have 7 times the beta effect than the alpha effect.
If you need to dilate peripherally is labetol your best choice?
No because it has much more beta effect which works on the heart than the alpha effect which works on the periphery.
- What is labetol nonspecific for?
- What is is selective for?
- non-selective antagonism for beta-1 and beta-2
- selective α1 antagonist
Which of the following receptors does Labetalol antagonize?
A. α1
B. α2
C. β1
D. β2
A, C, and D
What does labetolol do?
- Lowers systemic blood pressure by lowering SVR (dilating vessels peripherally).
- Reflex tachycardia is attenuated by beta blockade.
- What is the dose for labetalol?
- What happens if you go past the max dose?
- What is the time fo maximum effect of labetolol?
- 2.5 - 5mg IV; 10mg max
- greater than >10mg will cause tachyphylaxis
- 5-10 minutes
Mr. Spencer is in your preoperative holding room, scheduled for a CABG x 4 this am. You realize that he has not had his beta blocker this am. Which beta-blocker will you administer?
- Labetalol
- Metoprolol
- Carvedilol
- Esmolol
- Propranolol
- Metoprolol
You are in the process of extubating a patient immediately following a left carotid endarterectomy. His blood pressure is 210/64. Which of the following drugs would be most desirable?
- Labetalol
- Metoprolol
- Esmolol
- Propranolol
Esmolol (youre extubating your patient, esmolol is quick acting and quick offloading which is what you need until you get the patient extubated and calmed down)
Labetolol could drop the dBP too much.
What are the 2 most often used reasons for sympathomimetics?
- Increases systemic blood pressure
- Increase myocardial contractility.
- What are sympathomimetics lacking?
- What 2 things might this cause?
- Beta-1 specificity
- May cause intense vasoconstriction and relfex mediated bradycardia
What is the MOA of sympathomimetics?
- Activates directly or indirectly beta or alpha adrenergic GPCRs,»_space;> releases cAMP»_space;» enhances calcium influx to the cytosol»_space;»causes actin and myosin to interact more frequently
- What is the MOA of direct sympathomimetics?
- What are 4 examples
- Directly activates the adrenergic GPCRs
- EX: epi, norepi, pheynylephrine, and dopamine
- What is the MOA of an indirect acting sympathomimetic?
- What is the 1 example?
*Evokes the release of norepi from postganglionic sympathetic nerve endings.
* Ephedrine.
What is the prototypical catecholamine?
Epinephrine?
When is the only other time you will push epinephrine outside of ACLS?
Heart cases
What is the IV push dose of epinephrine?
How long does it last?
- 2-8mcg IVpush
- 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 SVR?
- What 2 things does it not have an effect on?
- Phenylephrine due to alpha-1 agonism.
- Does have an effect on cardiac output and heart rate.
Which vasopressor has a middle of the road effect for all factors (alpha, beta, CO, HR, and PVR)?
- Ephedrine
- Because it is so middle of the road for its effects it is the most often used vasopressor in the OR.
- What is ephedrine commonly used for?
- The BP ressponse is much less intense and last 10x longer than what other vasopressor?
- Sympathetic depression from inhaled/injected anesthetics
- epinephrine
Which SNS agonist can be given IM?
Why would this be done?
- Ephedrine IM 50mg
- Long lasting increase in BP for OB patients.
Why does tachyphylaxis occur with ephedrine?
Ephedrine depletes NE stores and you will start to see a declining result if you have to give multiple doses of ephedrine.
What is the preferred sympathomimetic for OB patients?
Why?
Ephedrine IM 50mg (It doesn’t effect uterine blood flow)
How does phenylephrine compare to ephedrine in parturient/OB patients?
Phenylephrine has similar effects on blood pressure but has the additional benefit of a higher umbilical pH in neonates. The higher umbilical pH is a reason why many providers are now switching from epherdrine to phenylephrine on delivering moms.
What is vasopressin?
a synethic preparation of ADH that we normally have stored in the posterior pituitary gland.
What is the mechanism of action of vasopressin?
- Stimulation of vascular V1 receptors → arterial vasoconstriction.
- It also increases renal-collecting duct permeability and water is reabsorbed.
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.
What are the side effects of vasopressin?
- CV = coronary artery vasoconstriction
- GI= stimulates GI smooth muscle and causes abd pain, and nausea/vomitting
- Other = decreased platelet counts and antibody formation
You have just completed the induction for a patient undergoing a TKA with a history of DM, Osteoarthritis, and CAD. For induction, she received Fentanyl 150 mcg, Propofol 140 mg, and Vecuronium 10 mg. She is intubated and on Sevoflurane ET 3% in 1L oxygen/1L air. Her BP is 70/30 and HR 54.
- What is the MAP?
- Do we need to intervene?
- Why or why not?
- If so, what do we do first?
- If the patients remains hypotensive after interventions, what vasopresssor would you try first?
- MAP = (2xD +S/3) = 43
- Yes we need to interve
- Because the MAP is too low, we aren’t perfusing anything with a MAP that low.
- Reduce the Sevo (3% is too high, needs to be about 2%), the sevo they need is . Give ephedrine. Give IV fluid because they have been NPO for maybe 12 hours or longer.
- Ephedrine (either your first or second dose). (no epi because they have CAD and might cause the myocardium to be ischemic due to too much vasoconstriction), (no phenylephrine necause the HR is already low), (You could use phenylephrine if the patient was previously on beta blockers and they are really blocked out and that is why their heart rate and BP is so low, then a beta agonist such as ephedrine wont work. In this case use phenylephrine which is a beta agonist) (no vasoconstriction because it will cause worsening vasoconstriction withj the CAD)
During the maintenance phase of the anesthetic you notice: BP 80/42, HR 92. In addition to a fluid bolus, you decide to administer?
- Ephedrine
- Phenylephrine
- Fentanyl
- Vasopressin
- Glycopyrolate
- Phenylephrine
Mrs. Jones is undergoing a radical hysterectomy for uterine cancer. Her home meds include: calcium, multivitamins, enalapril and levothyroxine. She has required 3 doses of Ephedrine with poor results. Which of the following might be good idea?
- IV fluid bolus
- Albumin bolus
- PRBC’s
- Vasopressin
- Vasopressin
- Could also give small fluid boluses.
- If the fluid doesn’t work, give her some albumin
- Can transfuse RBCs if she has a hemoglobin less than 10.
What are 4 examples of vasodilators?
- Nitrates
- Nitroprusside
- Minoxadil
- Hydralazine
How does Nitric Oxide cause vasodilation?
In broad terms.
NO → GC → cGMP → Ca⁺⁺ inhibition into the smooth muscle and increased uptake by the endoplasmic reticulum.
What are the 6 things nitric oxide is involved in?
- Cardiovascular tone relaxation
- Platelet regulation
- CNS neurotransmitter
- GI smooth muscle relaxation
- Immune modulation
- Pulmonary artery vasodilation
How can vasodilators alleviate pulmonary congestion?
By decreasing venous return via venodilation
- What are 2 nitro-vasodilators?
- How do they work?
- Sodium nitroprusside and nitroglycerin
- They decreases systemic blood pressure by decreasing SVR, arterial vasodilation and treating effects of vasoconstriction.
- They also decrease venous return, venous dilation, alleviates pulmonary and systemic congestion
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?
Arterial and venous vasculature
What vasodilator absolutely requires arterial line monitoring?
Why?
- Nitroprusside.
- Because it has immediate onset and transiet duration of action that requires continuous administration.
What is the dose of Nitroprusside?
0.3 - 2 mcg/kg/min
When is nitroprusside used?
- For the production of controlled hypotension in the OR (aortic, spine, and pheochromocytoma.)
- Hypertensive emergencies (post CEA’s)
When is cyanide toxicity seen with nitro-vasodilators?
- With higher IV doses of the vasodilator
- With cyanide radical accumulate due to sulfur donors and methemoglobin exhaustion.
What drug is used to treat cyanide toxicity?
Methylene blue
What signs would tip you off to possible cyanide toxicity secondary to nitroprusside administration?
- ↑ need for nitroprusside
- ↑ SvO₂, because tissues arent oxygenating
- Metabolic acidosis
- CNS dysfunction/ LOC changes
Where does nitroglycerin work?
- Venous capacitance vessels
- Large coronary arteries to a lesser extent. Will not dilate completely blocked coronary arteries.
Would nitroglycerin increase or decrease preload?
↓ preload
- Does nitroprusside or nitroglycerin exhibit tachyphylaxis?
- What does this cause?
- Nitroglycerin
- Limits vasodilation, Dose dependent and duration dependent within 24 hours, and a drug free interval of 12-15 hours will reverse the tachyphylaxis.
What is the nitroglycerin dose?
5 - 10 mcg/min infusion
What are the 4 main uses of nitrogylcerin?
- Acute MI (relives pulmonary congestion, decreases O2 requirements, and limits MI size)
- Controlled hypotension (less potent than SNP)
- Sphincter of Oddi spasms (during cholecystectomy/ opioid unded)
- For retained placenta
What is the firstline treatment for sphincter of Oddi spasm?
What is second?
- Glucagon
- Nitroglycerin
- How does hydralazine work?
- Does it have any venous dilator effects?
- What 2 things can it cause?
- A direct strong systemic arterial vasodilator that ↓ Ca⁺⁺ release, and decreases ITP
- Has hardly any venous dilator effect
- Causes hypotension and rebound tachycardia
When does hydralazine peak?
What is it’s half-life?
What are the issues with this?
- Peak: 1 hour
- ½-life: 3-7 hours
- In the OR it starts to slow and lasts too long. Not a great choice
What is the initial dose of hydralazine?
2.5mg
What are the three categories of CCBs?
Where do each interact and what does it cause?
- AV Node (Phenylalkylamines & Benzothiazepines) cardiac output and heart rate decrease
- Vasculature (Dihydropyridines) vasodilation in the arteriolar beds.
How do CCBs generally work?
Bind and block VG-Ca⁺⁺ channels (L-type) thus ↓ Ca⁺⁺ influx, which inhibits excitation-contraction coupling in he heart.
What are the 2 main effects of calcium channel blockers?
- Decrease vascular smooth muscle contractility which causes peripheral vasodilation (decreases SVR and systemic blood pressure) and increases coronary blood flow.
- Decreases speed of conduction particularly through the AV node (slowing of heart rate)
CCBs will ____ blood pressure and ____ coronary blood flow.
decrease; increase
Which CCB has the greatest coronary artery dilation and least myocardial depression?
Nicardipine (cardene)
Nicardipine is most often used in the OR because…
It is the best calcium channel blocker used for short term control of extreme hyptertension in the OR specifically when doing CEA, pheochromocytoma, or during hyptersive crisis where SBP is up in the 240s.
What is the dose of nicardipine?
5mg/hr (Increase 2.5 mg/hr x 4 to max of 15mg/hr)
How much of nicardipine decreases 30 minutes after it is D/Ced?
50%
Which antihypertensive works primarily through altering venous capacitance?
- Hydralazine
- Sodium nitroprusside
- Nitroglycerin
- Nicardipine
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?
- Nitroglycerin
- Sodium nitroprusside
- Hydralazine
- Labetalol
Sodium nitroprusside
Your physician is closing the neck incision following an uneventful right carotid endarterectomy. You have reversed the muscle relaxant and the patient is spontaneously breathing at 20/min; BP 140/90 and climbing, HR 84 and climbing. Your 1st intervention is:
- Increase the MAC of gas?
- Give narcotic?
- Begin cardene drip?
- Redose the NMBD?
- Something else?
- 1st intervention is to begin a cardene drip
- Can also give 25mcg of fentanyl and then dilaudid as a suppliment.
