Unit 4 - IV Anesthetics Flashcards
1
Q
chemical name of propofol
A
2,6-diisopropylphenol
2
Q
propofol protein binding
A
98%
3
Q
preservatives in propofol
A
- Preservative in Diprivan = disodium edetate
- Preservative in generic = sodium metabisulfite
4
Q
MOA of propofol
A
direct GABA-A agoinst
- Prolongs time channel stays open
- Increases Cl- conductance = neuronal hyperpolarization = decreased RMP
5
Q
onset & duration of propofol
A
Onset: 30-60 seconds
Duration: 5-10 minutes
6
Q
pKa of propofol
A
11
7
Q
clearance of propofol
A
Liver (P450) + extrahepatic metabolism (mostly lungs)
Clearance > liver blood flow
8
Q
when does brain concentration of propofol peak
A
~1 minute
9
Q
kinetics of propofol: what results in awakening
A
redistribution from brain
10
Q
CV effects of propofol
A
- ↓BP (↓ SNS tone, vasodilation, myocardial depression)
- ↓SVR
- ↓venous tone (↓ preload)
- ↓ contractility
11
Q
respiratory effects of propofol
A
Shifts CO2 response curve down and right (less sensitive to CO2) = resp depression, apnea
Inhibits hypoxic ventilatory drive
12
Q
CNS effects of propofol
A
- ↓ CMRO2, ↓ CBF, ↓ ICP
- No analgesia; anticonvulsant properties; myoclonus can occur
- Few reports of propofol-induced seizures
13
Q
IV anesthetic with antioxidant properties
A
propofol
14
Q
how can propofol change urine appearance
A
- Green urine = phenol excretion
- Cloudy urine = increased uric acid excretion (doesn’t indicate renal impairment or infection)
15
Q
is propofol safe with allergies to eggs, soy, and peanuts?
A
yes - Most egg allergies are allergic to albumin in egg whites
lecithin derived from yolk
16
Q
what causes propofol infusion syndrome
A
- Contains long-chain triglycerides (LCT)
- increased LCT load impairs oxidative phosphorylation and fatty acid metabolism
- Cells starved of O2 (particularly cardiac and skeletal muscle)
17
Q
risk factors for propofol infusion syndrome
A
- dose > 4 mg/kg/hr (67 mcg/kg/min)
- gtt > 48 hours
- sepsis
- continuous catecholamine infusions
- high-dose steroids
- significant cerebral injury
18
Q
clinical presentation of Propofol Infusion Syndrome
A
acute refractory bradycardia - asystole + at least one:
- Metabolic acidosis (base deficit > 10 mmol/L)
- Rhabdomyolysis
- Enlarged or fatty liver
- Renal failure
- Hyperlipidemia
- Lipemia (cloudy plasma or blood) may be early sign
19
Q
propofol infusion syndrome treatment
A
- d/c propofol
- maximize gas exchange
- cardiac pacing
- PDE inhibitors
- glucagon
- ECMO
- renal replacement therapy
20
Q
preservatives in propofol
A
- Diprivan contains EDTA as a preservative = no bronchial irritation
- Generic contains different preservatives = metabisulfite (can precipitate bronchospasm in asthmatics), benzyl alcohol (avoid in infants)
21
Q
when should opened propofol be discarded
A
syringe within 6 hours
infusion within 12 hours (tubing included)
22
Q
methods to mimimize or eliminate pain on propofol injection
A
- Injecting into larger and more proximal vein
- Give opioid before propofol injection
- Give lidocaine before injection - mixing together in syringe is controversial (theoretical risk of microemboli)
23
Q
dose of propofol to decrease itching from spinal opioids and cholestasis
A
10 mg
24
Q
chemical name of fospropofol
A
phosphono-O-methyl-2,6-diisopropylphenol
25
what class is propofol
isopropylphenol, alkylphenol
26
class of fospropofol
isopropylphenol
27
formulation of fospropofol
aqueous solution
prevents burning, doesn’t support microbial growth like lipid emulsion (no preservative)
28
MOA of fospropofol
prodrug
metabolized to propofol by alkaline phosphatase (present in vascular endothelium & liver)
29
dosing fospropofol
initial bolus 6.5 mg/kg
repeat 1.6 mg/kg not more than q4min
30
onset & duration of fospropofol
**Onset:** 5-13 min
**Duration:** 15-45 min
31
side effects of fospropofol
genital and anal burning
32
chemical name of ketamine
2-(o-Cholophenyl)-2 (methylamino) cyclohexanone hydrochloride
33
class of ketamine
arylcyclohexylamine (phencyclidine derivative)
34
IV anesthetic with the least amount of protein binding
ketamine (12%)
35
ketamine formulation
aqueous solution available as 1%, 5%, and 10% solutions
36
pKa of ketamine
7.5
37
MOA of ketamine
* NMDA receptor antagonist - antagonizes glutamate
* Secondary receptor targets: opioid, MAO, serotonin, NE, muscarinic, Na+ channels
* Dissociates thalamus (sensory) from limbic system (awareness)
38
NMDA receptor is permeable to which electrolytes
sodium
calcium
potassium
39
ketamine dosing
* Induction: 1-2 mg/kg
* Maintenance: 1-3 mg/min
* Low dose infusion: 1-3 mcg/kg/min (opioid sparing effect)
* Analgesia: 0.1-0.5 mg/kg
* IM: 4-8 mg/kg
* PO: 10 mg/kg
40
ketamine onset
* IM: 30-60 sec
* IM: 2-4 min
* PO: variable
41
duration of ketamine
10-20 min (may require 60-90 min to return to full orientation)
42
clearance of ketamine
Liver (P450) - chronic use induces enzymes that metabolize it (rapid ↑ tolerance)
43
active metabolite of ketamine & its potency
norketamine (1/3 – 1/5 potency of ketamine)
44
what is the “wind up” phenomenon with NMDA receptor agonism
* wide dynamic range neurons ↑ firing rate for given stimulus
* can contribute to hyperalgesia
* ketamine **counteracts** this process
45
CV effects of ketamine
↑ SNS tone, ↑ CO, ↑ HR, ↑ SVR, ↑ PVR
**Direct** myocardial depression - unmasked in pt with **depleted catecholamine** stores (sepsis) or sympathectomy
46
resp effects of ketamine
* **Bronchodilation**; upper airway muscle tone/airway reflexes intact
* Maintains resp. drive (may have brief period of apnea)
* **No significant effect** on CO2 response curve
* ↑ salivation (glycopyrrolate helps)
47
CNS effects of ketamine
↑ CMRO2, ↑ CBF, ↑ ICP, ↑ IOP, ↑ EEG activity, nystagmus
dissociative anesthesia
48
increased risk of emergence delirium with ketamine
* age \> 15
* female
* dose \> 2 mg/kg
* personality disorder
49
prevention of emergence delirium in ketamine
benzos (versed)
50
only induction agent that provides good analgesia and opioid sparing effects
ketamine
51
analgesic effects of ketamine
* Relieves **somatic** pain \> visceral pain
* Blocks **central sensitization** and wind-up in dorsal horn
* Prevents opioid-induced **hyperalgesia** after remifentanil gtt
52
IOP with ketamine
increased only with high doses
53
when is ketamine contraindicated
acute intermittent porphyria
54
uses of esketamine
resistant depression
major depressive disorder with acute SI
55
chemical name of etomidate
R-1-methyl-1-(a-methylbenzyl) imidazole-5-carboxylate
56
what causes rapid awakening with etomidate
redistribution (NOT metabolism)
57
class of etomidate
imidazole
58
how does etomidate function in different pH
* Acidic pH = imidazole ring opens - increased water solubility
* Physiologic pH = imidazole ring closes - increased lipid solubility
59
formulations of etomidate
1. 35% propylene glycol (pain with injection)
2. lipid emulsion (less pain)
60
MOA of etomidate
GABA-A agonist
61
onset and duration of etomidate
onset 30-60 seconds
duration 5-15 minutes
62
clearance of etomidate
P450 + plasma esterases
63
CV effects of etomidate
* minimal change in HR, CO, SV
* ↓ SVR (accounts for small reduction in BP)
64
does etomidate block SNS response to DL
nope
65
resp effects of etomidate
Mild respiratory depression ( \< propofol, barbiturates)
66
neuro effects of etomidate
↓ CMRO2, CBF, ICP
* Cerebral vasoconstriction
* Cerebral perfusion remains stable
* increased risk seizures if hx seizures
67
does etomidate have analgesic effects
nope
68
why can etomidate cause myoclonus
likely d/t imbalance between inhibitory and excitatory pathways in thalamocortical tract
69
why does etomidate cause adrenocortical suppression
Cortisol & aldosterone synthesis dependent on **11-b-hydroxylase** (in adrenal medulla) - inhibited by etomidate
70
when should etomidate be avoided
sepsis, adrenal failure
71
PONV is the most common with which induction agent
etomidate
72
how long does etomidate cause adrenal suppression
Single dose suppresses adrenocortical function for 5-8 hrs
73
acute intermittent porphyria triggering agents
* ketamine
* etomidate
* barbiturates
* ketorolac
* amiodarone
* CCBs
* birth control
* lidocaine
74
examples of thiobarbiturates
thiopental, thiamylal
75
which type of barbiturate has a sulfur molecule in 2nd position
what is the effect of this
thiobarbiturates
increases lipid solubility and potency
76
barbiturate with oxygen molecule in 2nd
oxybarbiturates
77
examples of oxybarbiturates
methohexital, pentobarbital
78
barbiturate with methyl group on nitrogen
effects of methyl group
methohexital
decreased seizure threshold, increased potency
79
barbiturate with phenyl group added to carbon in 5th position
effect?
phenobarbital
increased anticonvulsant effect
80
chemical name of thiopental
5-ethyl-5-(1-methylbutyl)-2-thiobarbituric acid
81
pH of thiopental
9 (highly alkaline)
precipitates in acidic solution
82
MOA of thiopental
GABA-A agonist
* Depresses RAS in brainstem
* **Low/normal dose:** increases affinity of GABA for its binding site
* **High dose**: directly stimulates GABA-A receptor
83
thiopental dosing
Adults 2.5-5 mg/kg
Children 5-6 mg/kg
84
duration of thiopental
5-10 minutes
85
thiopental clearance
P450
86
what determines awakening with thiopental
redistribution - not metabolism
87
which causes more hypotension - propofol or thiopental
propofol
88
IV anesthetic associated with hangover effect
thiopental
89
CV effects of thiopental
* **↓ BP** r/t venodilation & ↓ preload
* -myocardial depression
* Non-immunologic **histamine release** can ↓ BP (short lived)
* Baroreceptor reflex preserved = **reflex tachy** maintains CO
90
resp effects of thiopental
Respiratory depression = shifts **CO2 response** curve to **right**
Histamine release can cause **bronchoconstriction**
91
neuro effects of thiopental
* ↓ CMRO2, CBF (cerebral vasoconstriction), ↓ ICP, ↓ EEG
* **↓ EEG** activity can cause burst suppression or isoelectric EEG
* No analgesia (low dose may ↑ pain perception)
* **Neuroprotection** against focal ischemia, not global
92
treatment of intra-arterial thiopental injection
* injection of **vasodilator** (phentolamine or phenoxybenzamine)
* Or treat with **sympathectomy**: stellate ganglion block or brachial plexus block
93
gold standard for ECT
why
methohexital
↓ seizure threshold and produces a better quality seizure
94
induction dose of methohexital
1-1.5 mg/kg
95
how is phenobarbital excreted
unchanged in urine
96
how are barbiturates metabolized
CYP450
except phenobarb- excreted unchanged in urine
97
what causes acute intermittent porphyria
**defect in heme synthesis** promotes accumulation of heme precursors
98
what 3 things is heme a key component of
Hgb
myoglobin
CYP450
99
4 situations that make acute intermittent porphyria worse
1. emotional stress
2. prolonged NPO
3. CYP450 induction
4. stimulation of ALA synthase
100
GI symptoms of acute intermittent porphyria
severe abdominal pain (most common, typically 1st)
N/V
101
CNS effects of acute intermittent porphyria
anxiety, confusion, seizures, psychosis, coma
102
PNS effects of acute intermittent porphyria
skeletal muscle weakness (risk resp failure)
bulbar weakness (risk aspiration)
103
anesthesia implications for acute intermittent porphyria
* liberal hydration
* glucose supplementation (dec. ALA synthase activity)
* heme arginate (dec. ALA synthase activity)
* prevent hypothermia
104
why might regional anesthesia be avoided in pts with acute intermittent porphyria
difficult to establish block-related complications from acute porphyria attack
105
chemical name of precedex
(S) – 4 – [1-(2,3-Dimethylphenyl)ethyl] – 1H – imidazole monohydrochloride
106
class of dexmedetomidine
imidazole
107
precedex formulation
preservative free, water soluble, pKa = 7.1
108
MOA of precedex
presynaptic alpha-2 agonism in CNS = ↓ cAMP = inhibits locus coeruleus in pons
* Produces **negative feedback** loop that reduces NE release from presynaptic nerve terminal
* ↓ SNS tone, produces sedation
109
dose of precedex
* Loading: 1 mcg/kg over 10 min
* Maintenance: 0.4-0.7 mcg/kg/hr
110
onset and duration of precedex
* onset: 10-20 min for loading dose
* duration: 10-30 min after infusion stopped
111
clearance of precedex
CYP450 enzymes
112
PO bioavailability of midazolam
50% d/t significant first-pass metabolism
113
how can rapid admin of precedex cause HTN
a2 stim. in vasculature = vasoconstriction
short lived
114
most common side effects of precedex
bradycardia
hypotension
115
neuro effects of precedex
↓ CBF; no change in CMRO2 or ICP (CMRO2-CBF uncoupling)
116
which IV anesthetic most resembles natural sleep
precedex
117
how does precedex have an antishivering effect
impairs thermoregulatory response
118
does precedex have analgesic effects?
yes via a2 stimulation in dorsal horn (↓substance P & glutamate release)
119
precedex dose for preop sedation in peds
3-4 mcg/kg 1 hour preop for preop sedation in peds
120
relative potency of benzos
lorazepam \> midazolam \> diazepam
121
additive in diazepam and lorazepam that causes venous irritation
propylene glycol
122
chemical name of midazolam
8-chloro-6-(2-fluorophentl)-1-methyl-4 H-imidazol[1,5-a][1,4]benzodiazepine
123
formulation of midazolam
imidazole ring = hydrophilic & lipophilic properties
124
how does midazolam function in different pH
* Acidic pH = imidazole ring opens = increased water solubility
* Physiologic pH = imidazole ring closes = increased lipid solubility = crosses BBB freely
125
preservatives in midazolam
0.01% disodium edetate, 1% benzyl alcohol
126
MOA of midazolam
GABA-A agonist = increased **frequency of channel opening** = neuronal hyperpolarization
127
dosing of midazolam
- IV sedation: 0.01-0.1 mg/kg
- Induction: 0.1-0.4 mg/kg
- PO in children: 0.5-1 mg/kg
128
metabolite of midazolam
1-hydrozymidazolam (active)
* 0.5x potency of midazolam
* Rapidly conjugated to inactive compound
* Renal failure prolongs effects
129
midazolam clearance
CYP450 (liver and intestine)
130
onset and duration of midazolam
onset 30-60 sec IV
duration 20-60 min IV
131
CV effects of midazolam
Minimal with sedation dose
Induction dose: ↓ BP and SVR
132
patients more sensitive to resp depressant effects of midazolam
COPD
133
neuro effects of midazolam
sedation dose: minimal
induction dose: decreased CMRO2, CBF
134
can midazolam produce isoelectric EEG
nope
135
IV anesthetics with skeletal muscle antispasmodic effects
benzos
136
why does diazepam remain in the body for such a long time?
whats its elimination half time?
Undergoes **enterohepatic recirculation**
43 hours
137
how long do amnestic effects of lorazepam last
up to 6 hours
138
indications of remimazolam
induction & maintenance for adults undergoing procedural sedation lasting 30 min or less
139
dosing of remimazolam
* procedural sedation induction = 5 mg IV per 1 min (2.5 mg for sicker pts)
* Maintenance of procedural sedation = 2.5 mg IV over 15 seconds, **min q2min**
140
when does peak sedation occur with remimazolam
3-3.5 minutes after admin
141
**T½** of remimazolam
0.5-2 minutes
142
when does remimazolam have to be discarded
discard single-use vial after 8 hours
143
key benefits of remimazolam over midazolam
faster onset, deeper sedation, faster recovery
144
when is remimazolam contraindicated
pts with hx severe hypersensitivity reaction to Dextran 40
145
metabolism of remimazolam
Rapidly metabolized by non-specific **plasma esterases**
146
remimazolam dosing in liver dysfunction
pts with severe liver dysfunction should still receive decreased dose
147
MOA of flumazani
Competitive GABA-A receptor antagonist
148
dosing of flumazanil
Initial dose 0.2 mg IV, titrated in 0.1 mg increments q1min
149
IV anesthetic that is a carboxylated imidazole structure
etomidate
