Exam 4 - Adjuncts (pressors and dilators) Flashcards
β agonism results in activation of ____ which then produces ____
Adenylyl Cyclase (AC)
cAMP
What does increased cAMP lead to?
Influx of Ca++ leading to increased chronotopy, ionotropy, and dromotropy
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?
What is this phenomenon called?
- Receptor upregulation (aka ↑ # of receptors)
- Tachyphylaxis
The selectivty of beta antagonists is lost at ____ ?
High doses
Meaning at high doses the will block other beta receptors
After β receptor desensitization from prolonged catecholamine exposure (tachyphylaxis), how can receptor responsiveness be restored?
Change the drug or give the receptors time to downregulate
How do β blocker 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?
What does this lead to?
- Prolong Phase 4
- ↓ dysrhythmias during ischemia and reperfusion (less excitable during the refractory period)
How will β blockers affect diastolic perfusion time?
β blockers will increase diastolic perfusion time.
What 2 ways is myocardial perfusion decreased during systole?
- Aortic valve being open blocks the coronary openings
- Epicardial vessles have retrograde flow d/t increased ventricular pressures
Indications for BB therapy?
- Excessive SNS stimulation
- Thyrotoxicosis
- Essential HTN
- 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 describe?
What beta blocker to give or what dose
What were the three β1 selective agents discussed in lecture?
- Atenolol
- Metoprolol
- Esmolol
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?
Propanolol
Propanolol is the prototypical BB
Differentiate the clearance mechanisms of metoprolol, atenolol, and esmolol.
- Metoprolol = Hepatic
- Atenolol = Renal
- Esmolol = Plasma cholinesterases
Differentiate the E½ of metoprolol and esmolol.
Metoprolol E½ = 3-4 hours
Esmolol E½ = 0.15 hours (9 minutes)
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 surgery 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 until 5mg is given
What two formulation of metoprolol are there?
- Metoprolol Tartate = multiple doses per day (shorter acting)
- Metoprolol Succinate = One dose per day (longer acting)
If someone was tachycardic who is prescribed a BB, what might you deduce?
- They are not compliant
- Withdrawing from BB
Someone on a BB should not get tachycardic
What β blocker would be used for treat intubation stimuli?
Esmolol
What are the onset and offset of esmolol?
Onset: 5 min
Offset: 10-30min
What is the dose for esmolol?
20-30mg IV
Caution should be taken when giving esmolol with which two conditions?
Why?
- Cocaine and/or epinephrine
- Can cause pulmonary edema and cardiac collapse
Which drug prevents SNS stimulation from intubation the best?
Esmolol
Are the effects of CCBs and β-blockers additive?
No, synergistic
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: β2 potentiates bronchospasm
What volatile anesthetic will cause the greatest additive 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 2ⁿᵈ messengers are potentiated by α1 agonism?
IP₃ → Ca⁺⁺ release from SR
What occurs with α2 agonism?
↓ presynaptic release of NE in the brainstem
Is phenylephrine primarily a venoconstrictor or an arterioconstrictor?
Venous constriction > arterial constriction
Phenylephrine clinically mimics norepinephrine but is….
less potent and longer lasting
What drug indirectly releases small amounts of norepi?
Phenylephrine
What is the normal dosing of phenylephrine?
100mcg/mL
What adverse effect results from phenylephrine?
What diseases is this beneficial in?
- Reflex bradycardia
- CAD and AS - they cannot be tachycardic
What is the ratio of β to α blockade for Labetalol?
7:1
Is Labetalol a selective β antagonist?
No: non-selective β and selective α1 antagonist
How does Labetalol decrease BP?
Decreasing SVR
Reflexive tachycardia is attenuated by beta blockade
What is the dose for labetalol?
2.5 - 5mg IV; 10mg max
Which of the following drugs would you utilize for a post-carotid endarterectomy with a BP of 214/62 ?
Labetalol
Esmolol
Metoprolol
Esmolol
Labetolol could drop the dBP too much and has unnecessary peripheral vasodilation
Metoprolol lasts too long
A patient scheduled for a CABG x4 and has not had their BB. Which BB should you administer?
Metoprolol - lasts longer (long case) and is cardioprotective
Which drug is an indirect acting sympathomimetic?
MOA?
Ephedrine
Causes release of NE from postganglionic SNS nerves
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?
Phenylephrine
Why is ephedrine so popular during anesthesia?
Has balanced effects on CO, HR, and SVR
Ephedrine push dosage?
1-5 mg
Which SNS agonist can be given IM?
Why would this be done?
- Ephedrine IM 50mg
- Long lasting increase in BP for OB patients who are recieving a spinal anesthetic (C section)
Why does tachyphylaxis occur with ephedrine?
Ephedrine depletes NE stores
Which BP med lasts 10x longer than epi?
Ephedrine
What is the preferred sympathomimetic for parturient patients?
Why?
Ephedrine (It doesn’t effect uterine blood flow)
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 (lower incidence of fetal acidosis)
What is the mechanism of action of vasopressin?
Stimulation of vascular V1 receptors → arterial vasoconstriction
V2 receptors → increased water reabsorption in renal collecting duct
What drug would be utilized for catecholamine-resistant hypotension?
Vasopressin
What drug would be used for ACE-Inhibitor induced resistant hypotension?
Vasopressin
Can occur with both ACEi and ARBs.
Side effects of vasopressin?
- Coronary artery vasoconstriction
- Stimulates GI smooth muscle
- Decreased PLT counts (not clinically significant)
How can you calculate MAP?
DBP + 1/3(SBP-DBP)
How does Nitric Oxide cause vasodilation?
In broad terms.
NO → GC → cGMP → Ca⁺⁺ inhibition and increased uptake by ER.
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?
Nitroprusside, due to the immediate onset and transient duration
What is the dose of Nitroprusside?
0.3 - 2 mcg/kg/min
When is nitroprusside used?
- Hypotensive necessary surgeries (aortic, spine, pheochromocytoma)
- Hypertensive emergencies (post CEA’s)
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
- Metabolic acidosis
- LOC changes
Where does nitroglycerin work?
- Large coronary arteries
- Venous capacitance vessels
Would nitroglycerin increase or decrease preload?
↓ preload
Does nitroprusside or nitroglycerin exhibit tachyphylaxis?
How is it reversed?
Nitroglycerin
Need a drug free interval of 12-15 hours (can lead to rebound ischemia)
What is the nitroglycerin dose?
5 - 10 mcg/min
What is the firstline treatment for sphincter of Oddi spasm?
What is second?
- Glucagon
- Nitroglycerin
What are the indications for nitroglycerin?
- Acute MI
- Controlled Hypotension
- Sphincter of Oddi spasm
- Retained placenta
How does hydralazine work?
↓ Ca⁺⁺ release and systemic arterial vasodilation
When does hydralazine peak?
What is it’s half-life?
- Peak: 1 hour
- ½-life: 3-7 hours (long)
What is the initial dose of hydralazine?
2.5mg
What are the three categories of CCBs?
Where do each interact?
- AV Node (Phenylalkylamines & Benzothiazepines)
- Arteriolar beds (Dihydropyridines)
How do CCBs generally work?
Bind and block L-type VG-Ca⁺⁺ channels thus ↓ Ca⁺⁺ influx and ↓ arterial vascular smooth muscle contraction
CCBs will ____ blood pressure and ____ coronary blood flow.
decrease; increase
How do CCB decrease speed of conduction?
Via blockage of Ca-channels primarily at the AV node
Which CCB has the greatest coronary artery dilation and least myocardial depression?
Nicardipine
What is the dose of nicardipine?
5mg/hr (2.5mg titration per hour) up to 15mg/hr (MAX)
Your end stage COPD patient needs emergent BP control. Which medication could worsen his PaO2?
NTG
Nitroprusside
Hydralazine
Labetalol
Nitroprusside - release of CN causes O2 dissociation from Hb
