Pharm Unit 4 Flashcards
1
Q
List the intermediate acting NMBDs in order of fastest to longest time to maximum block
A
Roc (1.7 min) < Vec (2.4 min) < Atracurium (3.2 min) < Cisatracurium (5.2 min)
2
Q
Which paralytics do not have an intubating dose of 0.1 mg/kg?
A
D-tubocurarine/Rocuronium (both are 0.6 mg/kg), atracurium (0.5 mg/kg) and mivacurium (0.15 mg/kg)
3
Q
What are 3 synonymous terms for NMBD reversal agents?
A
AChE inhibitors, cholinergic agents and competitive antagonists
4
Q
How do our NMBD reversal drugs work?
A
By inhibiting AChE there is more ACh around to bind to alpha subunits
5
Q
What is the max ceiling range for Neostigmine and edrophonium?
A
Neo = 40 - 70 mcg/kg
Edro = 1 mg/kg
6
Q
What 5 factors affect NM blockade reversal?
A
Depth of the NM Block
AChE Inhibitor choice
Dose administered
Rate of plasma clearance of NMBD
Anesthesia agent choice and depth (affects residual blockade)
7
Q
Per the table from lecture one, what is the only paralytic that does not achieve 100% block?
A
d-tubocurarine
8
Q
What is the dose of neostigmine, onset and duration?
A
0.04 - 0.07 mg/kg (or 40 - 70 mcg/kg)
Onset = 5 - 10 minutes
Duration = 60 min
9
Q
What is neostigmine paired with and at what dose?
A
Glycopyrrolate at 0.2 mg per mg of Neostigmine
10
Q
What is the dose, onset and duration of sugammadex?
A
2-16 mg/kg
Onset = 1 - 4 min
Duration = 1.5 - 3 hours
11
Q
What is the dose, onset and duration of edrophonium?
A
0.5 - 1 mg/kg
Onset = 1 - 2 minutes
Duration = 5 - 15 minutes
12
Q
What is another name for TOF testing?
A
Acceleromyography
13
Q
What is the duration of clinical response of short, intermediate and long acting paralytics?
A
Short = ~15 minutes
Intermediate = 35 - 45 minutes
Long = ~80 - 85 minutes
14
Q
What is the max dose of neostigmine?
A
5 mg
15
Q
Describe the clearance of Neostigmine
A
50% renal, 30-50% is cleared by the liver if there is no renal function, making the kidneys the primary organ that gets rid of neostigmine
16
Q
What are the s/e of Neostigmine?
A
Increased Nicotinic/Muscarinic activity
CV: Bradycardia, dysrhythmias, asystole, ↓SVR
Pulmonary: Bronchoconstriction, increased airway resistance, increased salivation
GI: Hyperperistalsis, enhanced gastric fluid secretion, PONV
Eyes: Miosis
17
Q
What are our anti-cholinergic agents we pair with reversal agents?
A
Atropine and glycopyrrolate
18
Q
What is the dose of atropine and glycopyrrolate?
A
Atropine = 7 - 10 mcg/kg (watch for tachycardia)
Glycopyrrolate = 7 - 15 mcg/kg (1 mg max)
19
Q
What anti-cholinergic would you give alongside edrophonium?
A
Atropine (both drugs have a short duration)
20
Q
What anti-cholinergic would you give alongside neostigmine or pyridostigmine?
A
Glycopyrrolate (both drugs have a longer duration)
21
Q
What anti-cholinergic would you give in a patient with heart disease?
A
Glycopyrrolate slowly over 2 - 5 minutes
22
Q
What is the rule of thumb when giving glycopyrrolate and neostigmine together?
A
You need the ml’s of both to match, or have neostigmine be higher
23
Q
What reversal drugs work on Mivacurium, Gantacurium and Rocuronium?
A
Miva = Purified human plasma cholinesterase
Gan = Cystiene
Roc = Sugammadex
24
Q
What is the trade name of sugammadex?
A
Bridion
25
What are the generic names of glycopyrrolate and neostigmine?
Glyco = Robinul
Neo = Prostigmin
26
What are some chemical characteristics of sugammadex?
Y-cyclodextrin, made up of dextrose units from starch and highly water soluble
27
How does sugammadex work?
Taking advantage of intermolecular/thermodynamic bonds/forces and hydrophobic interactions, it encapsulates your paralytic drugs
28
List these drugs in increasing ability of sugammadex to nullify: Vecuronium, Pancuronium and Rocuronium
Pancuronium < Vecuronium < Rocuronium
29
What is the primary elimination method of sugammadex?
In the urine, 70% in 6 hours, 90% in 24 hours. Give with care in renal failure
30
What is the generic classification of sugammadex?
Selective relaxant-binding agent
31
What is the moderate block, deep block and extreme block dose of sugammadex?
Mod = 2 mg/kg
Deep = 4 mg/kg
Extreme = 8 - 16 mg/kg
32
S/e of sugammadex?
(all are dose related)
N/V, pruritus, Urticaria, anaphylaxis, bradycardia or just doesn't work
33
If a dose of sugammadex is given, and you have already given a dose of Roc but need to give another dose of Roc (can't use a different drug in this scenario) how long would it take for a 0.6 mg/kg dose vs a 1.2 mg/kg dose to kick in?
0.6 = 4 hours (this timeframe would still be the case if you gave 0.1mg/kg of Vec)
1.2 = 5 minutes
34
If you need to redose a paralytic after giving sugammadex, what paralytics could you give?
Sugammadex is used to reverse aminosteroids, so use benzylisoquinilones; atracurium, cisatracurium or mivacurium
35
What are some cautions to giving sugammadex?
Pt is on oral contraceptives (can bind to progesterone, contraceptive won't work for 7 days), pt is on toremifene (displaces NMBD from sugammadex), if pt is bleeding (elevates coagulation labs) and recurarization at lower than recommended doses
36
What is recurarization?
Reparalyzation, s/sx = drop in O2 sats, unresponsive patient, appears "floppy" or uncoordinated and ineffective abdominal/intercostal activity
37
If you suspect recurarization, what are you treatment goals?
Re-sedate the patient and give additional reversal agents in divided doses (such as neostigmine of 0.05 mg/kg IV)
38
What was the first local anesthetic?
Cocaine
39
1st synthetic ester and amide LA?
Synthetic ester = Procaine
Synthetic amide = Lidocaine
39
What are are some non-anesthesia related uses for LA drugs?
(think lidocaine), treat dysrhythmias (Sodium channel blocker), treat pain
40
What is the IV drip/dose of lidocaine?
Initial bolus: 1-2 mg /kg IV
Drip: 1-2 mg/kg/hour for 12 - 72 hours
41
List the plasma lidocaine concentration and their side effects (in mcg/ml)
1-5 = Analgesia
5-10 = Circum-oral numbness, tinnitus, skeletal muscle twitching, hypotension, myocardial depression
10-15 = seizures, unconsciousness
15-25 = apnea, coma
25 < cardiovascular depression
42
Describe the basic structure of an LA
A lipophilic portion connected by a hydrocarbon chain to the hydrophilic portion, bond between 1 (lipopholic) and 2 (intermediate chain) classifies it as an ester or amide
43
With the intermediate chain, what differentiates an ester vs amide?
Ester = COOR in the chain
Amide = NHCO in the chain
In general; the bond between the lipophilic portion and the intermediate chain creates the differentiation of LAs
44
What are most LAs classified as in terms of pH?
Weak bases
45
What are the ester LAs? Amide?
Ester = Procaine, chloroprocaine, tetracaine
Amides = lidocaine, prilocaine, mepivacaine, bupivacaine, levobupivacaine, ropivacaine
46
List the esters in terms of potency, onset, duration and max dose
Procaine (1), slow, 45-60 duration and max dose of 500 mg
Chloroprocaine (4), rapid, 30-45 duration and max dose of 600 mg
Tetracaine (16), slow, 60-180 duration and max dose of 100 mg
47
What is the trick to remember what is an amide vs an ester?
Amides have 2 "I's" in the name
Esters have 1 "I"
48
What is the only rapid onset amide?
Lidocaine
49
What is the potency, onset, duration and max single dose of lidocaine
1, rapid, 60-120 minutes and 300 mg
50
What is the potency, onset, duration and max single dose of Bupivacaine
4, slow, 240-480 minutes and 175 mg
51
What LA has the highest fraction non-ionized?
Mepivacaine
52
What LA has the highest lipid solubility?
Tetracaine
53
What LA has the highest VD?
Prilocaine @ 191
54
What LA has the highest clearance?
Mepivacaine, 9.78
55
What LAs are liposomes?
Lidocaine, tetracaine and buipivacaine
56
Basic MOA of LAs?
Bind to voltage gated Na channels and block/inhibit Na passage in nerve membranes -> slows depolarization and APs can't reach threshold
57
What are 3 factors affecting blockade with an LA?
Lipid solubility or non/ionized form, repetitively simulated nerve, diameter of the nerve
58
What is MEC?
Minimum effective concentration of an LA, 1 MEC = 2-3 nodes of Ranvier blocked (about 1 cm blocked)
59
What fibers block fastest? Slowest?
Fast = Preganglionic B fibers
Slow = C fibers
60
Which pKa's have the most rapid onset?
Those closest to physiologic pH
61
What factors influence absorption of an LA?
Site of injection, dosage, use of epinephrine and pharmacologic characteristics of the drug
62
List the routes of LA administration from least amount uptaken in the blood to most
SubQ < Sciatic < Brachial < Epidural < Paracervical < Caudal < Tracheal < IV
63
What is the primary determinant of LA potency?
Solubility
64
What are the 2 primary factors that affect clearance of LAs?
CO and protein binding
65
List these LAs from least to most protein bound (Bupivacaine, mepivacaine and lidocaine)
Lidocaine < mepivacaine < bupivacaine (this is the MOST protein bound)
66
What metabolizes Amides?
Microsomal enzymes in the liver
67
What amide metabolizes fastest? Slowest?
Fast = prilocaine
Slow = Bupivacaine, ropivacaine and etidocaine
68
What metabolizes esters? General concern?
Hydrolysis by plasma cholinesterase, they have an a metabolite with an allergy concern: PABA
69
In general, what metabolize faster, amides or esters?
Esters
70
What LAs are subject to a first pass pulmonary effect?
Lidocaine, Bupivacaine and prilocaine
71
What LA class has pregnancy concerns?
Amides (they cross the placental barrier more than esters). Another concern is ion trapping of the fetus
72
List the amides from least to most protein bound
Prilocaine (55%) Lidocaine (70%) and Bupivacaine (95%)
73
Lidocaine metabolite?
Xylidide
74
What is the max dose of lidocaine with and without epi
Without = 300mg
With = 500 mg
75
What is the primary concern with Prilocaine?
Can convert Hgb into MetHgb
76
Tx for MetHgb related to prilocaine?
Methylene blue 1-2 mg/kg IV over 5 min, max dose of 7-8 mg/kg
77
What LAs prefer to bind to a1-Acid glycoprotein?
Bupivicaine, Ropivacine
78
What esters are primarily broken down by hydrolysis? list them from least to most broken down by hydrolysis
Tetracaine < procaine < chloroprocaine
79
What LA is a weak acid?
Benzocaine
80
How does alkalization affect LAs?
Faster onset, enhances depth and increase the spread
81
With a pH of 7.4, random drug is a weak acid with a pKa of 8.5, is it more ionized or non-ionized?
Non-ionized
82
With a pH of 7.4 random drug is a weak base with a pKa of 9.1, is it more ionized or non-ionized?
More ionized
83
What adjuvants mixed with LAs can increase their duration?
Dexmedetomidine IV, magnesium, chlonidine/ketamine and dexamethasone
84
Why do we use constrictors with LAs?
The duration of action of a LA is proportional to the time the drug is in contact with nerve fibers. So by using a constrictor, we can increase the length of the LA
85
What is the concentration of 1:200,000? 1:500,000?
(divide 1 mil/x) 5 mcg/ml and 2 mcg/ml
86
What is the concentration of 1:10,000 and 1:1,000
10k = 100 mcg/ml or 0.1 mg/ml
1k = 1000 mcg/ml or 1 mg/ml
87
What is 1% concentration? 2? 4?
1 = 10 mg/ml
2 = 20 mg/ml
4 = 40 mg/ml
88
What is the 0.25% concentration? 0.5?
0.25 = 2.5 mg/ml
0.5 = 5 mg/ml
89
Clinical Scenario: Your surgeon injected 20 mLs of Bupivacaine 0.25% with 1:200,000 of Epi.
What are the total mgs for Bupivacaine and the total mcgs for Epinephrine?
B: 0.25% = 2.5 mg/ml, 2.5 mg x 20 ml = 50 mg total
E: 1:200,000 = 5 mcg/ml x 20 = 100 mcg total
90
What is the normal and epi dose of lidocaine and bupivacaine?
L: 300 mg alone, 500 w/epi
B: 175 mg alone, 225 w/epi
91
Primary use for cocaine?
Nasal surgery
92
What is EMLA?
Eutectic mixture of LAs
93
What is the dose and onset of EMLA cream?
2.5% lido and 2.5% prilocaine, 1-2 gms per 10 cm sq of area, 45 minute onset
94
Cautions to use of EMLA cream?
MetHgb, skin wounds or amide allergies
95
When is subQ LA w/epi contraindicated?
Tissues with end arteries (digits, ears, nose, penis)
96
What is the general trend of numbing with an LA?
Proximal body parts numb first followed by distal, proximal recovers first followed by distal (core numbs first and recovers first)
97
What LAs is generally used in a Bier block?
Lidocaine is most commonly used (mepivacaine is the "better" choice per slide 66)
98
Describe the steps of a Bier block
Iv start -> exsanguination -> double cuff -> LA injection -> IV DC
99
With neuraxial anesthesia, list the systems of sensory, motor and SNS in correct sequence of blockade (first to blockade to last)
SNS then sensory then motor
100
With spinal anesthesia (direct injection) describe the level of sensory effect, SNS and motor effects via level of the spinal cord
Sensory = same level of denervation
SNS = 2 spinal segments cephalad (above) of sensory
Motor = 2 spinal segments below
101
What do we base the dosage of subarachnoid block on?
Height of patient (volume of subarachnoid space)
Segmental level of anesthesia desired
Duration of anesthesia desired
102
What is most important when giving a drug via the subarachnoid space: dose, concentration or volume of drug?
dose
103
Most common drug used in an epidural?
Lidocaine
104
Describe the differential zone of SNS, sensory and motor blockade with an epidural
No difference
105
Describe tumescent liposuction
SubQ infiltration of large volumes (5L) of dilute lidocaine (0.05% to 0.1%) with 1:100,000 (10 mcg/ml) of epi
106
How would you dose neuraxial anesthesia in terms of volume?
1 ml starting at 5 foot tall, then 0.1 ml per inch above 5 feet
107
PABA is a common source of allergic reactions with LAs, what is the other mentioned in lecture?
Methylparaben
108
Are allergies more common in esters or amides? Why?
Esters because they have PABA
109
LAST = LA systemic toxicity, what are 2 common reasons this can occur?
Entrance into the systemic circulation from inactive tissue redistribution and clearance metabolism or accidental direct IV injection
110
What does the magnitude of systemic absorption depend on with LAs?
Dose, Vascularity of site, epinephrine use and physiochemical properties
111
What lab value in conjunction with suspected toxic levels of lidocaine can promote seizures?
Hyperkalemia
112
What changes EKG changes are consistent with high plasma concentrations of lidocaine?
Slowed conduction: prolonged PR, QRS widening
113
IV bupivacaine is far more cardiotoxic than lidocaine, with toxic plasma levels, what EKG changes would you expect to see?
Precipitous hypotension, AV block, Cardiac dysrhythmias: SVTs, ST changes, PVCs, widening of QRS, V-tach
114
What can predispose you to LA CV toxicity?
Pregnant, hypoxic/acidotic/hyercarbic, on BBS/Dig/CCBs, epi or neo may prevent systemic toxicity
115
What is the most cardiotoxic amide?
Bupivacaine
116
What are the 3 goals with suspected systemic LA toxicity?
1) Prompt airway management
2) Circulatory support
3) Removal of LA from receptor sites
(in this order per the slide, from lecture, Castillo says he would do 3, 1, 2)
117
Basic interventions in CNS systemic toxicity?
100% O2, hyperventilate, barbiturates/benzos/propofol for seizures, epinephrine
118
What is the best pharmacologic treatment LA systemic toxicity?
Lipid rescue
119
What is the dose for lipid emulsion in lipid rescue? Adjunct medication? Last ditch effort if it doesn't work?
Bolus: 1.5 ml/kg of 20% lipid emulsion
Infusion: 0.25 ml/kg/minute for 10 minutes
Adjunct: 10 - 100mcg of epi
Last ditch resort: CPB (cardiopulmonary bypass)
120
Max dose of lipid rescue?
8 ml/kg
121
What are the 3 categories of neural tissue toxicity (make sure to say toxicity in your best Serj Tankian voice)?
Transient Neurologic Symptoms (TNS)
Cauda Equina Syndrome
Anterior Spinal Artery Syndrome
122
Describe the pathophysiology of transient neurologic symptoms (TNS)
Moderate to severe pain (lower back, buttocks & posterior thighs) within 6 to 36 hours after uneventful single-shot SAB
Cause = unknown, seen more often with lidocaine
Tx = Trigger point injection and NSAIDs
Generally recover in 1-7 days
123
Describe the pathophysiology of cauda equina syndrome
Diffuse injury @ lumbosacral plexus varying degrees of sensory anesthesia, bowel & bladder sphincter dysfunction, & paraplegia
Associated: large lumbar disc herniation, prolapse or sequestration with urinary retention.
Cause = unknown
124
Describe the pathophysiology of anterior spinal artery syndrome
Lower extremity paresis with a variable sensory deficit.
Cause: uncertain if its thrombosis or spasm of the bilateral anterior spinal artery
Other etiologies = effects of hypotension or vasoconstrictors drugs; PVD, spinal cord compression d/t epidural abscess or hematoma
125
Prilocaine and benzocaine are the 2 LAs most likely to have MetHgb issues, what 4 other drugs may also create MetHgb?
Lidocaine, nitroglycerine, phenytoin and sulfonamides
126
Lidocaine toxicity effect on respirations?
Lidocaine depresses the ventilatory response to arterial hypoxemia, making this condition particularly dangerous in COPD patients
127
What is the common cause of hepatotoxicity related to LA use?
Treatment of post-herpetic neuralgia using bupivacaine
128
What parturient effects does cocaine have?
Decreased uterine blood flow = fetal hypoxemia
129
What intermediate-acting NMBD has the longest time to maximal block?
Cisatracurium
130
What are the anti-cholinergics paired with our AChE inhibitors?
Atropine and glycopyrrolate
131
What organ primarily clears pyridostigmine and edrophonium?
The kidneys, around 75%
132
What twitches constitute a moderate block? Deep block?
Mod = the 2nd twitch appears during a TOF
Deep = if twitch recovery requires 1-2 post-tetanic counts
133
What amide must be avoided if pregnant?
Mepivacaine (prolonged elimination in the fetus/newborn)
134
What is the extended release name of bupivacaine?
Exparel
135
What ester LA is the most protein bound?
Tetracaine
136
What is the dose of lidocaine in tumescent LA?
35 - 55 mg/kg
137
How much lidocaine can each gram of subQ tissue absorb?
1 mg
138
What preservative is found in both esters and amides?
Methylparaben
139
What is the max dose of glycopyrrolate?
1 mg
140
In order for sugammadex to exert it's effect, what state must the drug be in?
Unbound or free drug in plasma
141
When does recurarization occur with sugammadex?
With too low of a dose
142
What amide is the most protein bound? least?
Most = levobupivacaine
Least = prilocaine
143
What amide is closest to physiologic pH?
Mepivacaine
144
What LA has the highest lipid solubility?
Tetracaine
145
What fast ester and slow amide may be combined?
Chloroprocaine and bupivacaine
146
Generic name of Sux?
Anectine
147
Generic name of Cisatracurium?
Nimbex
148
Generic name of Vecuronium?
Norcuron
149
Generic name of Rocuronium?
Zemuron
150
Generic name of Pancuronium?
Pavulon
151
What ester has the shortest duration? Longest?
Short = Chloroprocaine
Long = Tetracaine
152
What amides have the shortest duration (2 of them)?
Lidocaine and prilocaine
153
What amides have the longest duration (3 of them)?
Bupivacaine, levobupivacaine and ropivacaine
154
What amide is broken down by CYP450?
Ropivacaine
155
What amide LA administration is not improved with concomitant administration of epi?
Bupivacaine
156
Do motor or sensory fibers need a higher concentration of LA? Why?
Motor; because they have 2x the diameter they need more LA to anesthetize
157
If the pKa of a weak base is 9.1 is it more ionized or non-ionized?
Ionized
158
If the pKa of a weak base is 4.5 is it more ionized or non-ionized?
Non-ionized
159
Describe the concentration of tumescent liposuction solution
Lidocaine 0.05 - 0.1%
Epi at 1:100,000 or 10 mcg/ml
160
What esters are not effective as topical agents?
Procaine and chloroprocaine
161
What esters may be used topically?
Cocaine and tetracaine
162
What amide has the highest possible dose you can give?
Prilocaine
163
What ester has the highest possible dose you can give?
Chloroprocaine
164
What amide has the highest lipid solubility?
Bupivacaine
165
What amide is metabolized the fastest?
Prilocaine
