Adjuncts (4) Flashcards
1
Q
What are the 3 subtypes of beta receptors?
A
- GPCRs
- Occupancy by agonists
- Occupancy by antagonists
2
Q
What is the response when beta receptor is occupied by an agonist?
A
- Activates adenylyl cyclase to produce cAMP
- Enhance Ca influx
- Chronotropic, inotropic, dromotropic effects
3
Q
What type of antagonists bind to beta receptor?
A
Competitive antagonists
4
Q
Beta 1 effects vs Beta 2 effects:
A
Beta 1: heart
Beta 2: lungs
5
Q
Beta-antagonists have selective affinity for __ ________ receptors
A
Beta adrenergic
6
Q
What is the MOA of beta antagonists?
A
Prevent catecholamine/sympathomimetics binding on:
- Heart
- Airway smooth muscle
- Blood vessel
7
Q
What does chronic administration of beta antagonists cause?
A
Increase number of receptors
8
Q
What are the effects of beta antagonists?
A
- Restore receptor responsiveness
- Protect myocytes from periop ischemia/infarction
- Decrease arterial vascular tone/ reduce afterload
- Decrease CO and inhibit renin release
9
Q
How do beta antagonists function to restore receptor responsiveness?
A
After desensitization from catecholamines (tachyphylaxis)
10
Q
What are the cardiac effects of beta blockers?
A
- Decrease slope of phase 4
- Decrease rate of spont. depolarization
- Decrease dysrhythmias during ischemia and reperfusion
- Increase diastolic perfusion time
11
Q
What are indications for beta blocker use?
A
- Excessive SNS stimulation
- Thyrotoxicosis
- Cardiac dysrhthmias
- Essential HTN
- SCIP (surgical care improvement protocol)
12
Q
What are some examples of SNS stimulation requiring beta blockers?
A
- Noxious stimuli
- Acute cocaine ingestion?
13
Q
What does SCIP say about beta blockers?
A
Beta blocker within 24hrs for patient at risk for MI or on rx beta blockers
14
Q
What does SCIP leave up to provider to decide?
A
- Which BB
- How much BB
15
Q
List 3 beta 1 selective beta blockers discussed in lecture:
A
- Atenolol (Tenormin)
- Metoprolol (Lopressor)
- Esmolol (Breviblock)
16
Q
75% of beta receptors in the myocardium are ______ selective
A
Beta1
17
Q
If an agent is beta 1 selective what does it not cause?
A
Does not cause vasodilation
18
Q
Which beta blocker is the drug we compare others to (prototype) but isnt widely used?
A
- Propranolol (inderall)→ Super non-specific beta blocker/ no cardiac selectivity
- B1=B2
- Bradycardia last longer than negative ionotropic effects
19
Q
How do we decide which beta blocker to use?
A
Based of clearance and half-life and factoring patient comorbidities
20
Q
Which B1 selective antagonist is cleared by plasma esterases?
A
Esmolol
21
Q
Which B1 selective antagonist is cleared by the kidneys?
A
Atenolol
22
Q
Which B1 selective antagonist is cleared by the liver?
A
Metoprolol and Propranolol
23
Q
Which B1 antagonist has active metabolites?
A
Propranolol (another reason we dont use)
24
Q
What are the E1/2 times for B1 blockers?
A
Propranolol: 2-3 hrs
Metoprolol: 3-4 hrs
Atenolol: 6-7 hrs
Esmolol: 9 minutes
25
Which B1 blocker has high protein binding?
Propranolol
*All other B1 blockers have low protein binding*
26
What is the adult IV dose for propranolol?
1-10mg
27
What is the IV dose for metoprolol?
1-15mg
1mg every 5 minutes IV (in blocks of 5mg)
28
What is the IV dose for atenolol?
5-10mg
5mg increments every 10 min IV
29
Whats the IV dose for Esmolol?
10-80mg
Inital dose 20-30mgIV (can increase 2nd dose 40-50mg since half life is so short)
30
Propranolol decreases the clearance of _______ and ___________ due to decrease in cardiac output associated with bradycardia
Opioids, LAs
31
Which beta blocker is the most B1 selective?
Atenolol (Tenormin)
32
Which beta blocker is useful in pre/post non-cardiac surgery in CAD patients? How?
Atenolol→ decreases complications such as MI for 2 years (dosed 1x/day)
33
Does atenolol potentiate hypoglycemia? Does it make pts drowsy?
- Does not potentiate insulin-induced hypoglycemia
- Does not enter CNS (less fatigue compared to nonspecific BB)
34
Metoprolol is beta ____ selective, but _____________, _____________, and ____________ effects of B2 receptors are intact
B1
Bronchodilator, vasodilator, metabolic
35
What are the 2 PO formulations of metoprolol?
- Tartrate: E1/2 time 2-3hrs
- Succinate: E1/2 time 5-7hrs
36
Does metoprolol tartrate or succinate have better control?
Probably Tartrate because the 1/2 life is shorter so the regime is to take up to 4x a day compared to succinate which is once a day
37
When do we see therapeutic effect of Esmolol? What is the offset?
Effect: 5 minutes
Offset: 10-30 min
38
What is esmolol useful to treat during a case?
Intraoperative noxious stimuli (ex: intubation or emergence)
*weight BP vs pain (esmolol vs fent)*
39
Why is it not a good idea to treat a patient with excess SNS activity (ex: cocaine/epi absorption sq or topical) with beta blockers?
Causes pulmonary edema and CV collapse
*BB remove ability of the heart to increase HR and contractility to compensate for catecholamine induced increased LV afterload*
40
- Good change from baseline HR and BP with Fentanyl and Esmolol
- Better decrease in SBP with Fentanyl but have to consider respiratory impact
41
Which medication is synergistic with beta blockers?
Calcium channel blockers
42
What are indications for the use of beta selective (B2) drugs?
- Diabetes
- Airway
43
Are there interactions between beta blockers and volatiles?
Potential additive myocardial depression
*Not significant between 1-2 MAC*
44
Which volatile has the greatest potential for myocardial depression with used with beta blockers? Which has the least?
Enflurane greatest risk
Isoflurane least risk
45
Your patient is on beta blockers with a history of MI. Which volatile anesthetic would be the best for this patient?
Isoflurane (less risk of myocardial depression)
46
What are the subtypes of alpha receptors?
- GPCRs
- Alpha-1 (periphery)
- Alpha-2 (CNS)
47
What happens when an agonist binds to an alpha-1 receptor?
- ↑ synthesis of 2nd messengers IP3
- ↑ Ca2+ release from SR
- Constrict vascular smooth muscle
48
Occupancy by an agonist on alpha-1 determines arteriole resistance, venous capacity, and ____________ __________.
Blood pressure
49
What happens when an agonist binds to alpha-2 receptor?
- ↓ release of NE from presynaptic nerve terminals (brainstem)
50
Give an example of an alpha-1 agonist:
Phenylephrine
51
Give an example of alpha-1 antagonist:
Phenoxybenzamine
52
Give an example of alpha-2 agonist:
Clonidine, Precedex
53
What med is useful in aortic stenosis hypotension d/t minimal tachcardia?
Phenylephrine
54
What is the MOA of phenylephrine?
- Venous constriction > Arterial constriction
- Mimics Ne but less potent and longer lasting
- Indirectly releases small amounts of NE
55
What is phenylephrine used to treat?
- SNS blockade by regional anesthesia
- Inhaled or injected anesthetics
- CAD/Aortic stenosis (no tachycardia)
- Common to give IVP or gtt
56
What is the MOA of phenylephrine causing reflex bradycardia?
Strong vasoconstriction in the periphery (when giving too much) the heart slows down→ can get to 20-30bpm
57
What receptors does labetalol antagonize?
Selective alpha-1, non selective beta-1 and beta-2
58
What is the ratio of beta to alpha blockade from Labetalol?
7:1 (for IV)
*meaning 7x non selective beta effect compared to alpha effect*
59
What is the MOA of labetalol?
Lower systemic BP by decreasing SVR (reflex tachycardia attenuated by beta blockade
60
What is the dose and expected max effect of labetalol?
Dose: 2.5-5mg IV (increase to 10mg IV d/t tachyphylaxis)
Max effect: 5-10 min post IV dose
61
Not propranolol—non specific and will mess with airway (bronchoconstriction)
Not Esmolol- too quick (doesn’t protect myocardium from repolarization injuries)
Not Carvedilol- PO
Not Labetalol: shorter acting and has peripheral effects
Answer: Metoprolol
62
Esmolol: fast acting beta 1 to focus on SBP decrease
63
What effects can occur with sympathomimetic agents lacking beta-1 specificity?
- Intense vasoconstriction
- Reflex bradycardia
64
What is the MOA of sympathomimetics (vasopressors)?
- Activate (directly or indirectly) beta or alpha adrenergic GPCRs
- cAMP enhances calcium in cytosol
- Actin and myosin interact more forcefully
65
What is the action of a direct acting sympathomimetic? Examples?
Directly activate adrenergic receptors
- Epi
- NE
- Phenylephrine
- Dopamine
66
What is the action of indirect acting sympathomimetic? Examples?
Evoke release of NE from postganglionic sympathetic nerve endings
- Ephedrine
67
What is the prototype catecholamine?
Epi
68
How long does a single bolus of 2-8mcg of epi last?
1-5 min
69
What surgical cases is it common to have epi infusions? Which doses of epi gtt have beta vs alpha effects?
Heart cases common to have pt on epi
- 1-2 mcg/min = Beta-2
- 4mcg/min = Beta-1
- 10-20 mcg/min = Alpha
70
Good to know this chart:
71
What is a common usage for ephedrine?
Sympathetic depression from anesthetics (inhaled or injected)
72
How does ephedrine BP response compare to epi?
Less intense BP response than Epi→ ephedrine lasts 10x longer
73
Why does tachyphylaxis occur with ephedrine?
Depleted NE stores
74
Typical IM dose of ephedrine?
50mg IM (common with c-section spinal to avoid hypotension)
75
Why is ephedrine preferred over phenylephrine in OB patients?
- No affect on uterine blood flow
- Equal BP response between ephedrine and phenylephrine→ but higher umbilical pH in neonates with ephedrine (higher pH= better for baby)
76
What is the MOA of vasopressin? What is the preparation of vasopressin?
- Stimulates vascular V1 receptors to cause arterial vasoconstriction
- Increases collecting duct permeability→ water reabsorbed
- Preparation of arginine vasopressin (ADH)
77
When is vasopressin indicated over other pressors?
- Catecholamine resistant hypotension
- ACE inhibitor resistance hypotension
78
What are some side effects of vasopressin?
- Coronary artery vasoconstriction
- Stimulate GI smooth muscle (abd pain, N/V)
- Decreased platelet and antibody formation
79
Calculation for MAP:
Diastolic + 1/3 (systolic- diastolic)
80
If a pt heart rate is in the 50s with BP 70/30, when would it be ok to use phenylephrine?
If the patient is beta blocked can give alpa agonist with out worry for reflex bradycardia
*giving beta agonist to pt who is on beta blockers will not work*
81
IV fluid bolus (.5-1L)
Vasopressin→ she is on ace inhib
82
What is the MOA of Nitric Oxide?
cGMP inhibits calcium entry in smooth muscle and increases uptake by endoplasmic reticulum
83
What processes is nitric oxide involved in?
- Cardiovascular tone relaxation
- Platelet regulation
- CNS neurotransmitter
- GI smooth muscle relaxation
- Immune modulation
- Pulmonary artery vasodilation
84
What is MOA of sodium nitroprusside?
Immediate relaxation of arterial and venous vascular smooth muscle→ requires continuous admin and art line monitoring
85
What are metabolites of sodium nitroprusside?
Dissociates when contacting oxyhemoglobin→ methemoglobin and releases cyanide and NO
86
What is the initial dose and titration of Nipride?
Initial: 0.3mcg/kg/min
Titrate to 2mcg/kg/min
87
What is Nipride commonly used for?
- Controlled hypotension (aortic surgery, pheochromocytoma, spine surgery)
- Hypertensive emergencies (carotid surgery)
88
When is cyanide toxicity seen with sodium nitroprusside?
Higher IV doses→ CN radical accumulate d/t sulfur donors and methemoglobin exhaustion
89
What issues might clue you in on potential CN toxicity when a pt is receiving sodium nitroprusside?
- Higher doses of nipride needed
- Mixed venous sat increases (tissues arent using O2)
- Metabolic acidosis
- CNS dysfunction/ change in LOC
90
What is MOA of nitroglycerin?
Acts on venous capacitance vessels and large coronary arteries
- Venous pooling
- Relaxes arterial vascular smooth muscle at high doses
91
What is the purpose of off intervals associated with nitro?
12-15hr drug free intervals reverses tolerance/tachyphylaxis
92
What is the initial dose of nitro?
5-10 mcg/min infusion and titrate
93
What are common uses for nitroglycerin?
- Acute MI (decreases pulm congestion and O2 requirements→ limits size of MI)
- Controlled hypotension (less potent than nipride)
- Sphincter of Oddi spasm
- Retained placenta
94
What is the class and MOA of Hydralazine?
- Direct systemic arterial vasodilator
- Decreases calcium release
- Extreme hypotension and rebound tachycardia
95
What is the onset, half time, and initial dose or hydralazine?
Onset: Peak plasma conc. 1 hr
Half time: 3-7 hours
Initial dose: 2.5mg IV
96
Why is hydralazine not great for use in the OR?
Too slow and lasts too long
97
What is the MOA of calcium channel blockers?
- Bind to receptors on VG calcium channels (L-type)
- Decrease calcium influx (inhibit excitation-contraction coupling)
- Decrease vascular smooth muscle contractility
- Decreases speed of conduction (AV node)
98
What are the different types of CCBs?
- Phenylalkylamines: selective for AV node
- Benzothiazepines: selective for AV node
- Dihydropyrimidines: selective for arteriolar beds
99
How do CCBs decrease vascular smooth muscle contractility?
- Peripheral vasodilation
- Decrease SVR and systemic blood pressure
- Increase coronary blood flow
100
What is the only CCB used in the OR?
Cardene (Nicardipine)→ replaced sodium nitroprusside
101
What makes cardene different from other CCBs?
Coronary artery perfusion and peripheral artery dilation without changing HR or conduction (no myocardial depression)
102
What is the starting dose and titrate rate of cardene?
Starting dose: 5mg/hr
Titrate: 2.5mg/hr to max of 15mg/hr
103
How long does it take for cardene to clear 50% after stopping?
30 minutes
104
Nitroglycerin
105
106
Give narcotic→short acting opioid now (25mcg of fent) then longer acting (dilaudid or morphine)
OR could just need to extubate
