Pharm Semester 2 - Test 4 And Some Final Content Flashcards
(220 cards)
1
Q
Reversal of NM Blockade depends on which 5 factors?
A
- Depth of NM Block
(Must have enough spontaneous recovery -at least 2 twitches) - Dose of NMBD administered
- Rate of plasma clearance of NMBD
- AchE Inhibitor choice
- Anesthesia agent choice and depth (Volatiles potentiate NM blockade)
=> Postoperative Residual NM Blockade
2
Q
Clinical Duration of Response (min) of Pancuronium
A
60-90 (86)
3
Q
Clinical Duration of Response (min) of Rocuronium Low dose and high dose
A
Low dose: 20-35 (36)
High dose : 60-90
4
Q
Clinical Duration of Response (min) of Vecuronium
A
20-35 (44)
5
Q
Clinical Duration of Response (min) of
Atracurium
A
20-35 (46)
6
Q
Clinical Duration of Response (min) of Cisatracurium
A
20-35 (45)
7
Q
Clinical Duration of Response (min) of Mivacurium
A
12-20 (17)
8
Q
NMBD Reversal Agent: Edrophonium: Dose ?
A
0.5 to 1 mg/kg
9
Q
NMBD Reversal Agent: Edrophonium: Onset and Duration of Action
A
Onset: 1-2 min
DoA: 5-15 min
10
Q
NMBD Reversal Agent: Neostigmine: Dose?
A
.04 - .07 mg/kg
11
Q
NMBD Reversal Agent: Neostigmine:
Onset and Duration of Action ?
A
Onset: 5-10 min
DoA: 60 min
12
Q
Per Tx Wes Clinical Practice Guideline :
Succynylcholine (Anectine):
Dose?
How many mg/ml in vial?
Onset?
Duration?
A
Dose: 1-1.5 mg/kg
How many mg/ml ? 20
Onset? 30-60 sec
Duration? 5-10 min
13
Q
Per Tx Wes Clinical Practice Guideline :
Cisatracurium (Nimbex):
Dose?
How many mg/ml ?
Onset?
Duration?
A
Dose: 0.1 mg/kg
How many mg/ml: 2 mg/ml
Onset: 2-3 min (all except SCh, High Dose Roc, and Mivicurium)
Duration: 40-75 min
Reversible in 20-35
14
Q
Edrophonium Max Dose?
Neostigmine Max Dose?
A
Edrophonium: 1 mg/kg
Neostigmine: 5 mg Max (40-70 mCG/kg)
15
Q
What is the MOA of Sugammadex?
A
It’s a Selective Relaxant- Binding Agent - works by encapsulating roc or vec molecules in the plasma, removing them from the NMJ → reversal of paralysis
16
Q
Which type of molecular bonds does Suggamadex exhibit ?
A
Intermolecular/ van der Walls forces, hydrogen bonds, and hydrophobic interactions
17
Q
What are the 3 synonymous Drug classifications of NMBD Reversal Agents?
A
AcetylcholineEsterase (AchE) Inhibitors
a.k.a. Cholinergic Agents
a.k.a. COMPETITIVE ANTAGONISTS
18
Q
NMBD Reversal Agents’ MOA:
A
ACh Esterase inhibition → More ACh available to bind to alpha subunits at preganglionic sites (SNS & PNS) and NMJ
19
Q
What Antiarrhythmic Drug Class are LA’s?
A
Class I- Sodium Channel Blockers
20
Q
What is the Lidocaine Multimodal/Analgesia Intra-Op IV dose ?
And Drip dose ?
A
• 1 to 2 mg/kg IV (initial bolus) over 2 - 4 min
• 1 to 2 mg/kg/hour (drip): terminated w/in 12 - 72 hours
21
Q
S/E Lidocaine are associated with Plasma concentration doses greater than?
A
> 5 mCG/ml
22
Q
Seizures/unconsciousness can start at Plasma Concentration’s of Lidocaine at?
A
10-15 mCG/ml
23
Q
Which 3 components do LA’s have in their Molecular structure ?
A
Lipophilic portion, Hydrocarbon chain, Hydrophilic portion
24
Q
Which molecular structure portion of LA’s determine if it is an Ester or Amide?
A
The Hydrocarbon Chain
25
Local Anesthetics: How can you tell from name if Amide or Ester?
Amide’s have 2 i’s
26
What should you assess visually before administering a LA?
That it is not cloudy
27
What is the pH composition of LA’s?
**Weak Bases** w/ pKa values above physiologic pH
28
Biggest indicator of lipid solubility of LA’s?
Whether it is ionized or nonionized.
29
What is the characteristic that generally equates to a higher potency for LA’s?
**Higher Non-Ionized Fraction = Higher lipid solubility = More potent**
30
For LA’s Fraction, which is a higher determinant of potency; Non-ionized Fraction or Lipid Solubility ?
Lipid Solubility
31
Highest Potency Ester?
Tetracaine (Lipid Solubility: 80)
32
Lowest Potency Ester?
Procaine (Lipid Solubility: 0.6)
33
LA’s: Highest Potency Amide?
Tie between Bupivicaine, Levobupivicaine, Ropivicaine
(Lipid Solubility Bupivicaine: 28)
34
What is the MOA of Local Anesthetics?
Block **Voltage-gated sodium channels inside nerves**→prevent action potentials → prevent nerve signal transmission
35
What is the Minimum Effective Concentration (MEC /Cm) of LA’s?
At least 2, preferably 3 Nodes of Ranvier **(1 cm) Blocked**
36
Which nerve fibers are Fastest?
Preganglionic Type B Fibers
37
Local Anesthetics are _______ _________ with pKa values typically above physiologic pH (~7.4).
**Weak Bases**
38
LA’s with pKA’s ________ to physiologic pH => most rapid Onset of Action
pKa’s closest to physiologic pH = most rapid OOA
The closer the pKa is to 7.4, the greater the proportion of the drug is in the non-ionized (lipid-soluble) form at physiologic pH.
Ex: Lidocaine (pKa ~7.7) → rapid onset
Procaine (pKa ~8.9) → slow onset
39
In regard to LA’s , the higher the protein binding => the _______ the ____________
Local (at injection site):
• Higher protein binding → *Slower clearance* from the tissue site → Longer Duration of Action
40
What is the rate of clearance of LA’s determined by:
**Cardiac Output and Protein Binding**
41
Which 3 regional anesthesia techniques result in the highest blood concentrations of local anesthetic?
IV, Tracheal, Caudal
*Mnemonic:
“I Think Careful Providers Ensure Best Safety Standards.” Sub means below so subcutaneous is lowest*
42
Which 3 RA techniques result in the lowest blood concentrations?
Subcutaneous, Sciatic, Brachial
43
Esters metabolized through _________ by ___________ in ________ > liver
Amides Metabolized through ____________ ___________ in the ___________
**Esters** metabolized through *Hydrolysis* by *cholinesterase*(enzyme) in *plasma* > liver
**Amides** metabolized through *Microsomal enzymes* in the *liver*
44
What is the main Metabolite that causes allergies in Esters?
**Para-AminoBenzoic Acid (PABA)**
45
Which LA property is most important when it comes to the duration of the drug?
**Protein binding** is more important than Clearance (from site of action)
*Higher protein binding = longer duration*
46
What is the Max Dose of Lidocaine for Local Anesthesia (Infiltration/Regional) without and with Epi?
Maximum Infiltration/RA dose: 300 mgs without
& 500 mgs w/EPI
47
Prilocaine’s metabolite converts hemoglobin to methemoglobin with doses >600 mg. What is the dose of the treatment, Methylene Blue?
TX: Methylene Blue
**1- to 2 mgs/kg IV over 5 mins.
Total dose not to exceed 7 to 8 mg/kg**
48
Bupivicaine and Ropivicaine’s main protein binding site?
**α1-Acid glycoprotein**
49
Among Ester LA’s, what is the order of hydrolysis (fastest to slowest), and how are they metabolized?
Order:**Chloroprocaine > Procaine > Tetracaine**
Metabolism: Hydrolyzed by plasma cholinesterases
50
Benzocaine main S/E?
**Methemoglobinemia**
51
Cocaine has Decreased Metabolism in which pt populations?
**Decreased in: Parturients (about to give birth), Neonates, Elderly, Severe Liver Dz**
52
To figure out Ionization vs non-ionization of Acid:
pk written ________ pH?
And which major class of IV anesthetic drugs are weak acids?
Acid: Weak Acid (*Barbiturates*): pK **After** pH:
pH- pK:
+= ionized (water soluble: undesired)
- = non-ionized (active: desired)
53
To figure out Ionization vs non-ionization of Base:
pk written ________ pH
Basic Drug (LA or Opioids): pK **Before** pH:
pK- pH:
+= ionized (water soluble: undesired)
- = non-ionized (active: desired)
54
These LA adjuvants do what to the pharmacokinetics of LA’s?
Dexmedetomidine IV, Magnesium w/ SAB, Clonidine & Ketamine with Peds RA, and Dexamethasone w/ either IV or mixed w/LA
Increased Duration
55
Why are LA’s used with vasoconstrictors?
**LA’s duration of action is proportional to amount of time the drug is in contact with nerve fibers.**
*They Prolong duration of action – Vasoconstriction slows blood flow at injection site, reducing systemic absorption and allowing the anesthetic to stay near nerve longer.*
56
What is the dose of
1:1,000 Epi?
1:10,000?
1:1,000 Epi = 1,000 mCG/mL
1:10,000 Epi = 100 mCG/ml
*1:1,000 → means 1g in 1,000 mL
And 1:10,000 → means 1g in 10,000 mL*
57
What are the 7 uses of LA ?
1) Local
2) Peripheral N. Block
3) Intravenous
4) Epidural
5) Spinal
6) Topical
7) Tumescent Liposuction
58
What is the Lidocaine Max Single Dose (mg) for:
IVRA, Topical?
PNB, Infiltration, Epidural?
Spinal?
IVRA,Topical: 300 mg
PNB, Infiltration, Epidural: 300 mg, 500mg w/epinephrine
Spinal:100 mg
59
What is the Bupivicaine Max Single Dose (mg) for:
PNB, Infiltration, Epidural without and with Epinephrine?
Spinal?
PNB, Infiltration, Epidural: 175mg, 225 w/ Epinephrine.
Spinal: 20 mg
60
Which local anesthetics have the greatest to least topical anesthetic effect?
**Cocaine (4% to 10%) > Tetracaine (1% to 2%), Lidocaine (2% to 4%)**
61
Eutectic Mixture of LA (EMLA cream)- Lidocaine and **Prilocaine**:
Onset of Action:
OOA for Skin grafting:
OOA for Cautery, Venipuncture, lumbar puncture, arterial cannulation, myringotomy:
Onset of Action: **45 min** (thicker epidermis)
OOA for Skin grafting: **2 hrs**
OOA for everything else: Cautery, Venipuncture, lumbar puncture, arterial cannulation, myringotomy: **10 min**
62
*Where* is Epi contraindicated with LAs?
• Epi should NOT be injected intracutaneously (i.e., directly into skin anywhere),
AND
• Epi should NOT be injected into tissues supplied by end arteries (like fingers, toes, penis, nose, ears)- no collateral blood flow
Both contraindications => vasoconstriction=> ischemia, necrosis
63
In a peripheral nerve block, which areas are affected and recover first?
• Onset: **Proximal areas are blocked first,** then distal.
• Recovery: **Proximal areas recover first,** then distal.
64
What is Peripheral Nerve Blocks’ Onset of Action dependent on ?
Onset of Action for Lidocaine?
Onset of Action for Bupivicaine?
• OOA: Dependent on LA’s pKa
*Lower pKa (closer to 7.4) → more non-ionized form → faster onset - ‘pKa Predicts Pace’*
• Lidocaine: 3 minutes
• Bupivacaine: 15 minute
65
In neuraxial anesthesia, which fiber types are blocked fastest among B fibers, A-gamma and A-beta fibers (medium-sized), and C fibers?
• Myelinated Preganglionic B fibers (SNS): **fastest** > Myelinated A (medium) and B fibers: **faster** > *Unmyelinated* C fibers (small)
66
With regard to segmental block in Neuraxial Anesthesia, what is the Sequence of Blockade?
1. SNS
2. Sensory
3. Motor
67
In spinal anesthesia, how do sensory, sympathetic (SNS), and motor effects align segmentally?
• **Sensory block:** at the level of denervation
• **SNS block:** 2 segments *above (cephalad to)* sensory block
• **Motor block:** 2 segments *below* sensory block
*Even though drug spreads in a continuous column (CSF), the effect appears "staggered" because different fibers drop out at different concentrations*
68
Most Notable Dermatome Landmarks
C2: Occiput
C6: Thumb
C7: Middle Finger
C8: Pinky
T4: Nipples
T10: Umbilicus
L1: Inguinal Region (Groin)
L4: Knee (anterior)
L5: Foot Dorsum (top), big toe
S1: Lateral foot, little toe
S2-S4: Saddle region
69
Spinal Anesthesia Block (SAB) is produced by direct injection of LA into the _____________ _________.
The principle site of action is the _____________ ___________
Subarachnoid “space” - where CSF resides
Principle site of action: Preganglionic Fibers
70
With SAB’s the ________ is more important than the concentration of drug (%) or volume (mLs) of solution injected.
The ___________ ____________ of LA is important in determining the spread of the drug
**dose**
**specific gravity**
71
• Adding _________ makes the LA hyperbaric (heavier → sinks)
• Adding ________ ________ makes it hypobaric (lighter → floats), and this determines how the drug spreads in the spinal canal.
• Adding _glucose_ makes the LA hyperbaric (heavier → sinks)
• Adding _distilled water_ makes it hypobaric (lighter → floats), and this determines how the drug spreads in the spinal canal.
72
In spinal blocks, there is no ________ ________ of SNS, sensory and motor blockade.
**No Differential Zone**
*Meaning SNS, sensory, and motor fibers are all blocked together (not in a graded fashion like in epidurals)*
73
What are the Recommended Doses of :
Regional Anesthesia Lidocaine with Epi?
and Highly Diluted Lidocaine with Epi for Tumescent Liposcution?
Regional Anesthesia Lidocaine with Epi: **7 mg/kg**
Highly diluted Lidocaine with Epi for Tumescent Liposuction: **35 to 55 mg/kg**
(Higher dose is safe with Tumescent d/t Tissue Buffering System; Subcutaneous fat & connective tissues soak up lidocaine like a sponge- less systemic absorption)
74
Which types of molecular bonds does Sugammadex exhibit?
1)Intermolecular forces (van
der Walls)
2) Thermodynamic bonds (hydrogen)
3) Hydro*phobic* interactions
75
Allergies are more common with which type of LA’s?
Esters **(PABA)** > Amides
76
What is the preservative in LA’s most responsible for allergic reaction ?
**Methylparaben:** found in both amides and esters
77
With Regard to LA’s, what is Local Anesthesia Systemic Toxicity (LAST) due to?
Due to **Excess Plasma Concentration** of the drug
Entry into systemic circulation from inactive tissue redistribution, accidental IV injection, or other factors
78
With LA’s , what CNS symptoms will you see with LAST (Local Anesthesia Systemic Toxicity)?
Early agitation, Drowsiness, Facial twitch > Seizure
*Hyperkalemia decreases Vrm → promotes seizures*
79
Which LA’s have the highest risk of causing LAST (Local Anesthesia Systemic Toxicity) CV Symptoms?
**Bupivacaine > Ropivacaine > Lidocaine**
(amides and liver both have an i; higher chance of toxicity w/ liver metabolism)
80
What 2 major factors predispose Pregnant patients to local anesthetic toxicity?
-Decreased Plasma Protein-Binding (↓ albumin & alpha-1 acid glycoprotein) → ↑ free drug
-Increased Nerve Sensitivity to LA’s- hormonal effect (achieve nerve block faster & at lower doses)
*Pregnancy decreases plasma cholinesterase, but toxicity rare w/ esters. Amide toxicity is the danger w/ Pregnancy*
81
What plasma concentration of Lidocaine can you begin seeing LAST symptoms ?
5 mCG/mL: Early signs like circumoral numbness (no major CV effects yet)
82
With accidental IV administration of ______ you will have cardiac dysrhythmias up to asystole
**Bupivicaine**
83
What measures would you take for Treatment of LAST in pt receiving LA’s (7)?
1. Stop LA immediately
2. Call for help
3. 100% O2..inhibit hypoxemia and metabolic acidosis (acidosis enhances LA binding to sodium channels =worsens toxicity)
4. Hyperventilation
5. Initiate lipid emulsion therapy ASAP (Intralipid 20%)
6. Sedation: Barbiturates or Propofol (if stable)
7. Use low-dose epinephrine if circulatory support is needed (10–100 mCG IVP)
84
The treatment of Local Anesthetic Systemic Toxicity (LAST) standard of care is lipid emulsion therapy (Intralipid).
What is the MOA?
**Creates a lipid compartment to absorb LA and provides fat for myocardial metabolism**
85
Treatment of LA Systemic Toxicity
Standard of Care: Intralipid Therapy- Lipid Emulsion.
What is the bolus dose?
What is the Infusion?
Max dose within first 30 minutes?
-**Bolus: 1.5 *mL*/kg of 20% lipid emulsion
-Infusion: 0.25 *mL*/kg/MIN for at least 10 minutes
-Max of 10 *mL*/kg within first 30 minutes**
86
For the Treatment of Systemic Toxicity, the
Standard of Care is Intralipid Therapy- Lipid Emulsion.
What is the Epinephrine dose?
Epinephrine dose: 10 to 100 mCG
87
Neural Tissue Toxicity with LA caused by high concentrations and/ or prolonged exposure can cause _________ or _____________ neurological injury
Transient or permanent
88
One LA complication of Neural Tissue Toxicity is Cauda Equina Syndrome. What is this?
• Diffuse injury at the lumbosacral plexus which causes varying degrees of:
• *Sensory anesthesia*
• Bowel + bladder sphincter dysfunction
• Weakness or paraplegia
89
What are the 2 major causes of Anterior Spinal Artery Syndrome (a LA complication of Neural Tissue Toxicity)?
1. Decreased Perfusion:
Effects of: **HypoTN or vasoconstrictor** drugs, PVD, Spinal Cord Compression (d/t epidural abscess or hematoma)
2. Vessel Injury: **Thrombosis or vasospasm** of the
bilateral anterior spinal artery
90
Which drugs can cause Methemoglobinemia (a LA complication)?
And what is the Treatment? How long for treatment to reverse the complication?
**Prilocaine, benzocaine** > lidocaine, nitroglycerine, sulfonamides & phenytoin (‘Pretty blue lips need some perfusion’)
Treatment: Methylene blue 1 mg/kg over 5 mins (max: 7 to 8 mg/kg)
-Reversal from metHgb (Fe 3+) to Hgb (Fe2+) is within **20 to 60 minutes**
91
What is the MOA of Cocaine Toxicity (a LA complication)?
MOA: SNS stimulation by blocking presynaptic uptake of **NE and dopamine => increased NE & dopamine postsynaptic levels**
92
What are the CV (5), Paturient, and CNS adverse effects of Cocaine Toxicity (a LA complication) which last up to 6 weeks?
• CV: **HTN, tachycardia, coronary vasospasm, MI (infarction & ischemia), ventricular dysrhythmias (including Vfib)**
• Parturient: decreased UBF => **fetal hypoxemia**
• CNS: Hyperpyrexia => **seizures**
• Treatment: benzodiazepines, nitroglycerin, avoid beta-blockers
93
Which NMBA’s are metabolized via Hoffman elimination?
What is clinical significance?
Atracurium and Cisatracurium
(Dustin *Hoffman* loves his *AC*)
Hoffman elimination is temp dependent: Low Temp => Longer Duration of Action
94
Which NMBA’s have increased duration of action with low temp?
Vecuronium & Pancuronium doubles duration,
Atracurium and Cisatracurium
(The VP loves AC)
95
Which NMBA’s are the Benzylisoquinolones?
Cisatracurium , Atracurium, Mivacurium
(CAM Newton drives a Benzy)
96
How are the 3 Aminosteroid NMBA’s metabolized?
• Vecuronium and Rocuronium = Hepatic metabolism
• *P*ancuronium= Renal (*P*ee it out)
97
Neostigmine is 50% cleared by Kidneys
Pyridostigmine and Edrophonium are 75% cleared by Kidneys
CRF will cause ________ ________ ___ _________
CRF will cause longer duration of action
98
NMBD Reversal Agents increase __________/_________ Activity as a side effect
Increase Nicotinic / Muscarinic Activity
*Think PNS*
99
NMBD Reversal Agents’ Increased Nicotinic/ Muscarinic Activity causes which CV Side effects (4)?
Bradycardia, dysrhythmias, asystole, ↓SVR
*Think PNS*
100
NMBD Reversal Agents’ Increased Nicotinic/ Muscarinic Activity causes which Pulmonary Side effects?
Bronchoconstriction, increased airway resistance & increased salivation
*Think PNS*
101
NMBD Reversal Agents’ Increased Nicotinic/ Muscarinic Activity causes which GI and Ocular Side effects?
GI: Hyperperistalsis, enhanced gastric fluid secretion, PONV
Ocular: Miosis
*Think PNS*
102
What is the Sugammadex dose with an extreme block?
8 to 16 mg/kg
_Recurarization: not
observed at appropriate doses_
103
What are the side effects of Sugammadex (6)?
• Dose related: N/V, Pruritus, Urticaria (hives).
• Anaphylaxis
• Marked Bradycardia
• Doesn’t work
104
If need to re-administer NMBA after Sugammadex (Bridion) has been given, what is the Faster option:
Minimum waiting time? NMBA and dose to be administered?
Faster option: Re-dose Rocuronium early:
-Wait at least 5 minutes, then give high dose of Rocuronium = 1.2 mg/kg
(This works because it’s a large enough dose to overcome residual sugammadex in circulation)
105
If need to re-administer NMBA after Suggamadex (Bridion) has been given, what is the Slower Option:
Minimum waiting time? NMBA and dose to be administered?
Option 2: Standard dosing after enough time has passed:
• Wait at least 4 hours, then you can give usual doses:
→ Rocuronium: 0.6 mg/kg
→ *Or* Vecuronium: 0.1 mg/kg
106
If need to re-administer NMBA after Suggamadex (Bridion) has been given, and can’t wait the 5 minutes needed to administer high dose Rocuronium, what do you administer?
If you can’t wait, and need to reparalyze before 5 minutes is up, use a nonsteroidal NMBA (like cisatracurium or atracurium), which sugammadex doesn’t bind/affect.
107
Which patients/ scenarios would you exercise caution with when using Sugammadex?
• Oral Contraceptives: advise to use backup contraceptive for 7 days
• Toremifene: Reverses NMBD displacement- delayed/incomplete reversal
• Coagulopathy/Bleeding; Transient increased PTT, PT, INR
• Risk of Recurarization: especially w/ Deep neuromuscular blockade, Obese patients, Renal Fx (delayed drug clearance)
108
What is Recurarization?
The *return of muscle weakness or reparalysis* after initial recovery from a neuromuscular blocker, usually due to *inadequate reversal or drug redistribution*
109
What is the Dose, OOA, and DOA of Edrophonium?
Dose: 1 mg/kg
OOA: 1-2 min
DOA: 5-15 minutes
*Rapid
110
What is the Dose, OOA, and DoA of Neostigmine?
Dose: 0.04 - 0.07 mg/kg
OOA: 5-10 min
DOA: 60 min
“Neo needs 5 to 10, lasts ’til 60, dose is ~0.05 mg per kg”
111
What are the s/s of recurarization?
• **Can sometimes verbalize suffocating feeling
• Unable to sustain head lift or hand grasp
• Worst case: Pharyngeal collapse & Respiratory obstruction**
112
What are the Treatment Goals w/ recurarization?
**Treat urgently and aggressively
- Re-sedate patient (Light sedation for anxiolysis/comfort while reversal kicks in)
- Give additional reversal agents in divided doses
(Neostigmine - longer duration of action: 0.05 mg/kg IV)**
113
Esmolol (Brevibloc)
Onset?
Offset?
Initial Dose?
Onset: 5 min - Rapid!
Offset: 10-30 min - Rapid!
Initial Dose: 20-30 mg IV
114
Esmolol is especially helpful in which 2 situations?
-Treating intraoperative noxious stimulation (intubation)
-Treating Cocaine/epinephrine absorption (from procedure, not Cocaine Toxicity = Beta Blockers contraindicated)
*SNS surge control*
115
Beta 1 Selective Beta Blockers are indicated in which 2 patient populations?
Diabetics and Obstructive Lung Diseases
*Non-selective BB’s interfere with glycogenolysis, potentiate insulin, bronchospasm, and ventilatory depression*
116
Giving Beta blockers with CCB’s (especially non-dihydropyridines like verapamil or diltiazem) can cause cause ___________ ___________.
Additive effects (additive bradycardia, AV block, hypotension, etc.)
117
Which volatile anesthetic has the greatest potential for additive myocardial depression when combined with beta blockers?
Which has the least?
Greatest with Enflurane and least with Isoflurane
118
Alpha-1 receptors are primarily ___________, found on ________ _______ muscle , and mediate ____________.
Alpha-1 receptors are primarily *peripheral*, found on *vascular smooth muscle*, and mediate *vasoconstriction*.
119
Alpha-2 receptors are primarily found in the ______, (especially in the __________).
Alpha-2 receptors are primarily found in the CNS, (especially in the brainstem).
120
Alpha-1 receptor activation: location, pathway, and effect?
Location: Peripheral (vascular smooth muscle)
Pathway: GPCR activation → ↑2nd messengers: IP3 → ↑ Ca²⁺ release from SR
Effect: Causes vasoconstriction, ↑SVR, ↑BP
121
Alpha-2 receptor activation: location, function, and effect?
Location :CNS (brainstem), Presynaptic terminals
Function: GPCR activation → ↓ cAMP
Effect: Inhibits Norepinephrine release, ↓ BP, ↓ Sympathetic outflow
122
What agent causes venous constriction > arterial constriction and mimics norepinephrine?
Phenylephrine
*Less potent but longer-lasting than norepinephrine*
123
What is the major S/E to be aware of with Phenylephrine (Neosynephrine)?
Reflex bradycardia
*Peripheral vasoconstriction so intense that the heart slows as low as 20’s to enhance cardiac filling and contraction*
124
Phenylephrine is very useful in treating hypotension in __________ and ________ __________ pt’s because it does not cause tachycardia.
CAD and Aortic stenosis patients
*Pure alpha-1 agonist, causing vasoconstriction without stimulating beta receptors (which affect heart rate and contractility)*
125
Which receptors does IV labetalol (Normodyne, Trandate) block?
And what are its hemodynamic effects?
Selective alpha-1, Non-selective beta blocker
Alpha 1 blockade → ↓ SVR → ↓ BP
Beta blockade prevents Reflex Tachycardia
126
What is Labetolol’s IV beta:alpha blocking ratio?
Onset?
and dosing?
-Ratio 7:1 (beta:alpha)
-Max effect in 5–10 min
-Usual dose 2.5–5 mg IV, max 10 mg (due to tachyphylaxis)
127
Scenario Practice: 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 and why?
Metoprolol because IV, longer acting, and B1 specific so best at preserving coronary perfusion
128
Scenario Practice: 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 and why?
Esmolol because fast and B1 Specific so will decrease Systolic BP (by decreasing CO: BP= CO x SVR)
129
Sympathomimetics are most often used for which 2 effects?
-Increase myocardial contractility
-Increase systemic blood pressure
130
Sympathomimetic agents without β₁ specificity cause which two effects?
Intense vasoconstriction & reflex-mediated Bradycardia
131
What receptors do sympathomimetics act on and what is their MOA?
Activate alpha or beta GPCRs (directly or indirectly):
→ Beta 1 receptors ↑ cAMP → ↑ Ca²⁺ influx → stronger actin-myosin interaction → stronger heart contraction
→ Alpha-1 receptors use IP₃/Ca²⁺ → vascular smooth muscle contraction → Arterial vasoconstriction.
132
Which is the only Indirect acting Vasopressor/ Sympathomimetic?
Activate alpha or beta GPCRs (directly or indirectly) → Beta receptors ↑ cAMP → ↑ calcium influx → stronger heart contraction; Alpha-1 receptors use IP₃/Ca²⁺ to cause vascular contraction.”
133
How long does a bolus dose of 2-8 mCG of Epinephrine last?
1-5 minutes
134
What are the Epinephrine infusion doses and which receptors do they predominantly work on at each dose?
• 1-2 mCG/min = beta 2 (half the beta 1 dose)
• 4 mCG/min = beta 1
• 10-20 mCG/min = Predominately alpha
135
Which Vasopressor/ Sympathomimetic does everything “about average” so used a lot in OR?
Ephedrine
136
Which Vasopressor/ Sympathomimetic has the greatest effect on CO & HR?
What is its single IV dose?
Epinephrine
1-2 mCG
137
What are Phenylephrine’s effects on Cardiac Output and HR?
Decreases CO and HR
*A pure alpha-1 agonist without any beta effects, it’s Increases in SVR can lead to Reflex Bradycardia which contributes to Decreased CO, especially if preload isn’t increased*
138
What are the Single IV doses of
Epinephrine?
Ephedrine ?
Phenylephrine?
And Vasopressin?
Epinephrine: 1-2 mCG
Ephedrine: 5-10 mg
Phenylephrine: 50 -100 mCG
And Vasopressin: 1-2 units
139
Ephedrine has a _________ and ___________ rise in BP and lasts 10x longer than _____________
Slower and steadier
Epinephrine
140
Which Sympathomimetic/ vasopressor is usually given to offset hypotension caused by inhaled/injected anesthetics?
Ephedrine
141
Why does ephedrine exhibit tachyphylaxis with repeated use?
Ephedrine relies on endogenous Norepinephrine release, so repeated use depletes NE stores, reducing effectiveness (tachyphylaxis).
142
Which Sympathomimetic/ Vasopressor is preferred for parturient and which one has recently become more favored?
Ephedrine
Recently, Phenylephrine has become more favored due to higher umbilical pH in neonates
143
What are the S/E of following systems with Vasopressin:
CV?
GI?
Other?
CV: Coronary artery vasoconstriction
GI: Abd pain, N&V
Other: Decreased platelets and antibodies
144
What is the MOA of Nitri*c* Oxide?
It’s a chemical messenger that activates **c**GMP → *↓ Ca²⁺ influx* & ↑ ER Ca²⁺ uptake → smooth muscle relaxation/ vasodilation
*“More Cyclics, Less Calcium = Loose vessels”*
145
What are Nitric Oxide’s Roles/ Functions? (6)
• Neurotransmitter = Brain signaling
• Opens vessels = ↓ SVR,↓ BP
• Clots ↓ = Prevents platelet aggregation
• Activates Immune Modulation = Modulates immune response
• Moves Bowels = GI Smooth muscle relaxation
• Pulmonary Artery Vasodilation = Relieves pulmonary hypertension
146
What are the mechanism, onset, and monitoring needs of Sodium Nitroprusside?
• Mechanism: Relaxes both arterial and venous smooth muscle
• Onset: Immediate but transient duration
Monitoring needs:
• Requires continuous infusion
• Requires arterial BP monitoring
147
What happens when Sodium Nitroprusside (Nipride) contacts oxyhemoglobin?
Rapidly reacts with oxyhemoglobin, forming methemoglobin and releasing:
• Nitric Oxide (causes vasodilation) & Cyanide
148
What is Sodium Nitroprusside’s (SNP) Initial Dose and what can it be titrated up to ?
• Initial dose: 0.3 mCG/kg/min
• Titrate up to: 2 mCG/kg/min
“Never start above 0.3 mCG/kg/min”
149
What are the clinical uses of Sodium Nitroprusside (SNP)?
Used to induce Controlled Hypotension in:
• Aortic, carotid, & spine Sx’s
• Pheochromocytoma
& in Hypertensive Emergencies
150
Cyanide Toxicity is seen with higher doses of Sodium Nitroprusside due to accumulation of _________ ___________ when _________ _________/_____________ are depleted
Cyanide Toxicity is seen with higher doses of Sodium Nitroprusside due to accumulation of *cyanide radicals* when *sulfur donors/methemoglobin* are depleted.
151
When should you suspect cyanide toxicity from Sodium Nitroprusside (4)?
• Increasing SNP doses required to maintain BP
• **Increased mixed venous O₂ sats** (tissues not extracting O₂)
• Metabolic acidosis
• **CNS changes: altered LOC**
152
What are the vascular targets and hemodynamic effects of Nitrogly*c*erin?
• Primarily dilates **Venous *_C_*apacitance Vessels** → causes venous pooling → less blood reaches the right heart → decreased preload
• Dilates large coronary arteries
• At higher doses, causes arterial vasodilation
153
What is the initial dose for Nitroglycerin
• Initial dose: 5–10 mCG/min IV infusion, titrate as needed
154
What is tachyphylaxis dependent on with Nitroglycerin?
How long is the drug free interval to reverse tolerance? And what may this cause?
• Tachyphylaxis is dose and duration-dependent (often within 24 hrs)
• Drug-free interval of 12–15 hrs can reverse tolerance, but may cause Rebound Ischemia
155
What are the clinical uses of Nitroglycerin?
• Cardiac: Acute MI, Controlled Hypotension (< potent than SNP)
• **GI: Sphincter of Oddi Spasm (cholecystectomy or opioid induced)**
• OB: Retained placenta
156
What class is Hydralazine in?
What’s its MOA?
and is its key effect?
Class: Direct *systemic arterial* vasodilator
Mechanism: ↓ intracellular Ca²⁺ → smooth muscle relaxation
Effects:↓ SVR
*Risk of rebound tachycardia and extreme hypotension
157
What is Hydralazine’s
Onset?
Half Life?
Initial Dose?
• Onset: Peak plasma level ~1 hour
• Half-life: 3–7 hours
• Initial dose: 2.5 mg IV
*Too Slow and Lasts Too Long*
158
Which Types of Calcium Channel blockers are Selective for AV Node (Decrease HR)?
and which are selective for arteriolar beds (Vasodilation)?
AV Node (Decrease HR) : Phenylalkylamines & Benzothiazepines (Nondihydropyrimidines)
*“**N**on-**D**HP’s = **N**egative **D**romotropy”*
Arteriolar bed (Vaso**d**ilation): **D**ihydropyrimidines
159
What is the MOA of CCB’s?
• Bind to *L-type voltage-gated* calcium channels
• Decrease calcium influx into cells
• Inhibit excitation-contraction coupling in vascular smooth muscle and myocardium
160
What are the major effects of calcium channel blockers (CCBs), and which ones have specific actions?
All CCBs:
• ↓ vascular smooth muscle contractility → *peripheral vasodilation*
• ↓ SVR and BP
• **↑ coronary blood flow**
Non-dihydropyridines (verapamil, diltiazem):
• ↓ speed of conduction, especially through AV node
*“Non-D’s = Negative Dromotropy”*
161
Which CCB has the greatest coronary artery dilation and peripheral artery dilation without any SA or AV Node depression?
Nicardipine
*Fairly fast but not drastic drop in BP*
162
What is the dose for Nicardipine (Cardene) drip and its max?
What situations is it ideal for?
Dose: 5 mg/hr
• Increase 2.5 mg/hr x 4 to max of 15 mg/hr
Ideal for short term HTN control and when expecting very strong SNS stimulus like cutting neck or pheochromocytoma
163
Which antihypertensive works primarily through altering venous capacitance?
Nitroglycerin
164
Your end-stage COPD patient needs emergent blood pressure control in the ICU. Which vasodilator medication might worsen his PaO2 the most?
Sodium nitroprusside causes both arterial and venous dilation, including pulmonary vessel dilation → blunts hypoxic pulmonary vasoconstriction (HPV) → blood is shunted to poorly ventilated alveoli → worsens hypoxemia
165
LA’s typically have an average pKa of ~8. What is the purpose and benefit of alkalinizing local anesthetic (LA) solutions?
Alkalinization increases the non-ionized (lipid-soluble) fraction.
Benefits = *Onset, Depth, Spread*:
• Epidurals usually take ~20 min, *alkalization speeds up onset* by 3–5 mins in peripheral & epidural blocks
• Enhances block depth
• Increases spread- better anesthesia (especially in epidurals)
166
Which classification of LA’s has the higher average Protein Binding Percentage?
Amides
(Lidocaine: 70% up to Ropivicaine: 94%)
167
Which classification of LA’s has the lower average Protein Binding Percentage?
Esters
(Procaine: 6% up to Tetracaine: 76%)
168
What are the cardiovascular system effects of local anesthetic systemic toxicity (LAST)?
High plasma concentrations Block cardiac Na⁺ channels:
• Conduction delays → Negative inotropy
• ECG changes: Prolonged PR interval, QRS widening
169
What are the CV effects of local anesthetic systemic toxicity (LAST) with **accidental Bupivicaine administration**?
• Severe Hypotension, AV block
• Dysrhythmias: SVTs, ST-T wave changes, PVCs, QRS widening, V-tach
• Can progress rapidly to Cardiac Arrest
170
What are the Treatment goals with local anesthetic systemic toxicity (LAST)?
1.Prompt Airway management
2.Circulatory support
3.Removal of LA from receptor sites (w/ Intralipid tx)
171
What is the Treatment for local anesthetic systemic toxicity (LAST)?
1. Stop LA immediately
2. Call for help
3. 100% O2 (inhibit hypoxemia and metabolic acidosis)
4. Hyperventilation
5. Initiate lipid emulsion therapy ASAP
6. Sedation: Barbiturates or Propofol (if stable)
7. Epinephrine if needed (10 -100 mCG)
172
What is the standard of care for treating local anesthetic systemic toxicity (LAST) and what is its MOA?
• Treatment: 20% lipid emulsion (Intralipid)
Mechanism:
• **Creates a lipid sink (“compartment”) that absorbs local anesthetic from tissues
• Provides fatty acids for myocardial metabolism**
173
What is the Dosing protocol for Lipid Emulsion Therapy in LAST?
• Bolus: 1.5 mL/kg of 20% lipid emulsion
• Infusion: 0.25 mL/kg/min for >10 minutes (at least 10 min)
• If needed in first 30 minutes: Up to 10 mL/kg total
174
What additional treatments are used if lipid therapy is insufficient in LAST?
• Epinephrine: 10–100 mCG doses
• No response: Initiate Cardiopulmonary Bypass (CPB)
175
What are causes of Anterior Spinal Artery Syndrome related to local anesthetics (4)?
• *Hypotension or vasoconstrictor drug effects*
• Peripheral vascular disease (PVD)
• Spinal cord compression (epidural abscess or hematoma)
• *Thrombosis or vasospasm* of bilateral anterior spinal arteries
176
In relation to local anesthetics, what is the issue that methemoglobinemia causes, and which drugs causes it?
Problem: Decreased oxygen-carrying capacity when metHgb > 15%
Causes:
• **Prilocaine, benzocaine** > lidocaine, nitroglycerin, phenytoin, sulfonamides
177
How is the LA complication methemoglobinemia (especially w/ Prilocaine & Benzocaine) treated?
How long does it take for recovery?
• Treatment:
• Methylene blue 1 mg/kg IV over 5 minutes (max 7–8 mg/kg)
• Mechanism: Reversal from Fe³⁺ (methemoglobin) back to Fe²⁺ (normal hemoglobin) is *within 20–60 minutes*
178
What is the mechanism of cocaine toxicity (local anesthetic)?
Blocks *presynaptic reuptake* of Norepinephrine and Dopamine → increased postsynaptic NE & Dopamine levels (SNS stimulation)
179
What are the major adverse effects of cocaine toxicity?
Adverse Effects (can last up to 6 weeks):
• Cardiac: **HTN, tachycardia, coronary vasospasm, MI, ventricular dysrhythmias (incl. V-fib)**
• Parturient: ↓ uterine blood flow → **fetal hypoxemia**
• CNS: Hyperpyrexia → **seizures**
180
What is the Treatment for cocaine toxicity?
Nitroglycerin, Benzodiazepines,
Avoid beta-blockers
(Beta 2 Blockade => Vasocontriction = BAD)
181
What measures would you take to control seizures with Local Anesthetic Systemic Toxicity (LAST)?
-Supplemental oxygen
-Lipid emulsion therapy: Intralipid 20% infusion to bind circulating LA
-**Muscle relaxant (Succinylcholine or NMBA)**
-Propofol (only if hemodynamically stable)
-Benzodiazepines (midazolam or diazepam)
182
Why do pregnant patients generally require lower doses of local anesthetics (3)?
• They have Decreased Plasma Cholinesterase levels (→ ↑ Ester LA’s)
• Decreased Protein Binding → ↑ free/ unbound Amide LA’s→ ↑ Transplacental transfer
• Risk of Fetal Ion Trapping and Toxicity
183
Describe ion trapping in the context of local anesthetics and pregnancy?
• LA crosses from maternal blood to more acidic fetal blood → becomes ionized → gets “trapped” and accumulates in fetus
184
What does the fetal-maternal arterial lidocaine concentration graph show?
Fetal lidocaine levels are higher during fetal acidemia than with a normal pH because more ion trapping occurs
*A higher FA/MA ratio (closer to 1) = more drug crossed the placenta to the fetus*
185
How does pregnancy affect local anesthetic (LA) dosing and why?
Lower LA doses needed during pregnancy because there is Decreased Plasma Protein Binding (= more free drug)
186
How does recurarization typically present in the PACU, and what are the signs and symptoms (4)?
Presentation:
• Immediately apparent by declining SaO₂ and worsening respiratory effort
Signs and Symptoms:
• ↓ O₂ saturations
• Unresponsive or altered mental status
• Floppy, uncoordinated movements
• Ineffective abdominal and intercostal muscle activity (poor breathing effort)
187
How does Dose affect the beta-1 selectivity of beta antagonists?
Selectivity is Dose Dependent. At *high doses, selectivity is lost* with ANTagonists - both beta-1 and beta-2 receptors are blocked = cardiac + pulmonary + vascular effects
188
What happens to beta receptors with chronic beta blocker use, and why does a rebound effect occur if the drug is stopped abruptly?
• Chronic beta blocker use causes *upregulation of of beta receptors* -body tries to compensate for blocked sympathetic input
• If beta blocker is suddenly stopped → more receptors & suddenly they’re unblocked = exaggerated SNS response: rebound HTN, Tachy, arrhythmias
189
How can beta blockers restore beta receptor responsiveness after catecholamine desensitization?
• Chronic catecholamine stimulation (NE, Epi) causes beta receptor desensitization (tachyphylaxis).
• Beta blockers temporarily block receptor overstimulation, allowing receptors to recover & regain normal sensitivity over time (improves CHF survival)
190
What are the cardiovascular effects of beta blockers, especially perioperatively?
• Protect myocytes from ischemia and infarction (↓ myocardial O2 demand)
• “Mixed” beta blockers (Labetalol,Carvedilol) reduce arterial vascular tone → ↓ SVR
• ↓ CO
• Block Renin release (↓BP)
191
With Spinal/Subarachnoid Blocks, what role does the specific gravity of the local anesthetic (LA) play?
The **specific gravity** of the LA determines the **spread of the drug** in the CSF
192
With Epidural LA’s, _________ crosses the placenta more than ___________.
With Epidural LA’s, *Lidocaine* crosses the placenta more than *Bupivacaine*
193
In the graph showing protein binding of local anesthetics, how does increasing total drug concentration affect protein binding, and what is the order most to least bound shown?
The % of Protein Bound LA is Inversely related to the Plasma Concentration (as Total Drug Concentration ↑, Protein Binding ↓)
• Order of protein binding: Bupivacaine > Mepivacaine > Lidocaine
194
What are the 3 Important LA Properties and what do they dictate?
195
As demonstrated on graph, the addition of Epinephrine to Lidocaine or Prilocaine ____________ systemic anesthetic by _______- _________
Decreases
By One- third
196
What are the signs and symptoms of Anterior Spinal Artery Syndrome?
• Lower extremity flaccid paresis (weakness)
• Variable sensory loss:
• Loss of Pain and Temperature sensation
• Preserved proprioception
197
What type of Receptors are Beta agonists?
What is the sequence that leads to their effects (7)?
All are G-protein coupled receptors . Occupancy by agonists → adenylyl cyclase → cAMP → Ca²⁺ influx → Chronotropic, inotropic, and dromotropic effects
198
Beta ANTagonists have selective affinity for Beta adrenergic receptors that prevent catecholamines / sympathomimetics from binding on which 3 sites?
Heart, airway smooth muscle, blood vessels
199
Chronic administration of Beta Antagonists causes ___________ of Beta receptors
Upregulation (>#)
200
Beta Antagonists may restore __________ after desensitization from catecholamines (tachyphylaxis)
Responsiveness
201
What are Mixed Beta ANTagonists’ ( Carvedilol, Labetolol) affects on :
Arterial vascular tone?
Afterload?
COP?
Renin Release?
Decrease Arterial vascular tone (Arterial Vasodilation and Decreased SVR), Afterload, & COP.
Inhibit Renin Release
202
What are Beta ANTagonists’ affects on Slope of Cardiac Phase 4?
What are the effects of this?
Decreased Slope of Phase 4
Effects:
-Decreased rate of spontaneous depolarization & dysrhythmias during ischemia and reperfusion.
-Increased diastolic perfusion time.
203
Indications for Beta Blockers (5)?
• Thyrotoxicosis
• Essential hypertension
• Excessive SNS stimulation (Noxious stimuli)
• Cardiac dysrhythmias
• Surgical Care Improvement Protocol (SCIP)
204
Survival Care Improvement Protocol dictates that _______ _______ be given within _____ _______ of surgery to patients already receiving them to reduce cardiac risk. Does not dictate which one or how much.
Beta Blockers be given within 24 hours of surgery
205
Selective B1 Blocker Comparison:
What is the E 1/2 Time (hrs) of:
Metoprolol?
Atenolol?
Esmolol?
Metoprolol: 3-4 hrs
Atenolol: 6-7 hrs
Esmolol: 0.15 hrs: (9 min)
206
Propranolol (Inderal) descreases clearance of which 2 drug classes?
Opioids and Amine LA’s
*Since decreases COP, means it will decreance clearance of meds cleared by liver*
207
Which Beta Blocker is the most Beta 1 Selective and when is this important ?
Atenolol (Tenormin)
Important when B2 receptor agonist activity is necessary
(ex: Asthma, COPD, PVD where B2 helps maintain vasodilation)
208
How is Atenolol (Tenormin) helpful for pre/post non cardiac surgery in CAD patients?
Decreases complications (myocardial ischemia) for 2 years
209
Metoprolol (Lopressor) is a selective B1 ANTagonist with 2 oral formulations:
What are the drug names and the E 1/2 time of each?
• Tartrate: E½ time 2-3 hours..bid-qid dosing
• Succinate: E½ time 5-7 hours…qd dosing ?
210
What is the Metoprolol (Lopressor) IV dose?
Usually dosed IV 1 mg, q 5, max 5 mg
Common for rate control w/ AFib or SVT.
211
What is the best Opioid Agonist/ Antagonist choice for Cardiac Catheterization?
Nalbuphine
*CV: no increase in BP, PA BP, HR, or atrial filling pressures => √√√ cardiac catheterization patients*
212
Gas Laws: What is Dalton’s Law?
“**D**alton = Partial pressures A**D**d up”
*P_total = P₁ + P₂ + P₃…
The total pressure in the circuit equals the sum of each gas's partial pressures, including volatile agent*
213
Gas Laws: What does FICK’s Law describe in relation to volatiles?
Once the molecules get to the alveoli, they move around randomly and begin to Diffuse (Fick’D) into the pulmonary capillary
*Diffusion dependent on 1) Partial Pressure 2) Gas’ Solubility (Diffusion) and 3) Membrane Thickness.
CO₂ diffusion 20x > O₂ despite weight — thanks to solubility (FICK)*
214
Gas Laws: What is Graham’s Law?
Molecules diffuse through pores and channels without colliding
*Smaller* molecules effuse faster (*Graham*’s) but dependent on solubility (diffusion = FICK’s law)
215
Gas Laws: What is Henry’s Law?
“**H**enry **s**ays: **H**igher Pressure = **H**igher **S**olubility”
*Solubility ∝ Partial Pressure”; [Gas] = k × P
This is how Overpressurization and Uptake work: Increasing alveolar driving pressure → Increases uptake*
216
Gas Laws: What is Boyle’s Law?
**Boyle’s** Law : Pressure ↑, Volume ↓ (inverse) when temp and gas quantity are constant.
*Application:
As PPV begins, _**bellows** contract_ (Volume ↓), Pressure ↑ within ventilator & circuit
=> Anesthetic gases flow from high pressure to low pressure (lungs)*
Reminder: Volume ≠ gas quantity. Volume is a physical space. Gas quantity is number of moles (stays constant unless gas enters or exits).
217
If FI is higher, what phase are we in ?
F**I**> FE (ET, FA) during **I**nduction
*You’re delivering more than what’s in alveoli because the agent is being taken up by blood/tissues*
218
If FI ≈ FE (ET, FA) what phase are you in ?
Maintenance
*Uptake and delivery are balanced; no more net uptake of volatile into blood*
219
If FE (ET, FA) > FI, what phase are we in ?
Emergence
*No more agent delivered; the agent is now washing out of the blood/tissues into alveoli.*
220
Phenylephrine is _______ potent but __________-lasting than norepinephrine
Phenylephrine is *less* potent but *longer-lasting* than norepinephrine
