PHARMACOLOGY-IV anesthetics Flashcards
(138 cards)
1
Q
Propofol MOA= Onset= Duration= pKa=
A
MOA= GABA-A agonist increasing Cl- conductance and neuron hyperpolarization. Prevents AP
Onset= 30-60 seconds
Duration= 5-10 minutes
pKa=11
2
Q
Propofol Clearance= Active metabolite= Induction dose= Maintenance dose=
A
Clearance= liver + extra hepatic metabolism (lungs)
Active metabolite= none
Induction dose= 1.5-2.5 mg/kg IV
Maintenance dose= 25-200 ,cg/kg/min
3
Q
Propofol
Respiratory effects=
CV effects=
CNS effects=
A
Respiratory effects= decreased respiratory drive
CV effects= decreased BP, SVR, preload, and contractility
CNS effects= Decreased ICP and IOP, NO analgesia +/- SZ activity
4
Q
What is the chemical name and class for propofol
A
Name = 2,6- diisopropylphenol Class = Isopropylphenol
5
Q
How do GABA-A receptors react when stimulated
A
Cl- conductance is increased, hyperpolarizing the neuron. This reduces the resting membrane potential making an action potential less likely
6
Q
What causes the respiratory depressant effect when propofol is administered
A
A shift in the CO2 response curve down and to the right means there is less sensitivity for CO2 to drive respirations
7
Q
What specific respiratory drive does propofol inhibit
A
hypoxic ventilatory drive
8
Q
How are cerebral blood flow and oxygen consumption affected by propofol
A
Both are decreased
9
Q
What miscellaneous properties does propofol have
A
Antioxidant properties = free radical scavenger
Altered urine color d/t phenol excretion (green) or increased uric acid excretion (cloudy)
10
Q
What are 2 preservatives that may be added to propofol
A
- Disodium edetate (Diprivan)
2. sodium metabisulfate (generic)
11
Q
Can patients with allergies to soy, peanuts, and egg receive propofol
A
Yes
12
Q
What part of an egg is used in propofol production.
How does this relate to people with egg allergies
A
Egg lecithin found in propofol is derived from the yolk
People are usually allergic to the albumin in the egg white
13
Q
What are clinical presentations of propofol infusion syndrome
A
Metabolic acidosis (base deficit > 10 mmol) Rhabdomyolysis Renal failure Hyperlipidemia Enlarge fatty liver Lipemia
14
Q
What is the treatment for propofol infusion syndrome
A
D/C propofol Initiate cardiac pacing Start PDE inhibitors ECMO Glucagon CRRT
15
Q
What is the discard time for infusion and syringes of propofol
A
Infusion = 12 hours Syringes = 6 hours
16
Q
How do the additives in propofol cause possible complications
A
Metabisulfite = bronchospasm in asthmatic patients
Benzyl alcohol = should be avoided in infants
17
Q
Other than sedative properties, what properties does propofol contain
A
Antipruritic
Antiemetic
Antioxidant
18
Q
D/t the long-chain triglycerides in propofol what can be impaired?
Why is this significant?
A
Oxidative phosphorylation
Fatty acid metabolism
Significance = cells are starved of O2, especially in cardiac and skeletal muscle
19
Q
What are risk factors for propofol infusion syndrome (6)
A
- Propofol dose >4 mg/kg/hr
- Infusion duration > 48 hrs
- Sepsis (inadequate O2 delivery)
- Continuous catecholamine infusions
- High-dose steroids
- Significant cerebral injury
20
Q
Why is contamination concerning with propofol infusion or syringes
A
It supports bacterial and fungal growth
21
Q
How is propofol injection pain minimized (3)
A
Inject into larger more proximal vein
Giving opioid before propofol
Giving lidocaine before propofol
22
Q
What dose of propofol can be an effective antipruritic
A
10 mg IV
23
Q
What dose of propofol can be an effective antiemetic
A
10 - 20 mg IV
24
Q
Fospropofol MOA= Onset= Duration= pKa=
A
MOA= GABA-A agonist
Onset= 5 - 13 minutes
Duration= 15 - 45 minutes
pKa=
25
```
Fospropofol
Clearance=
Active metabolite=
Induction dose=
Repeat dose=
```
Clearance= liver + extrahepatic metabolism
Active metabolite= propofol
Induction dose= 6.5 mg/kg IV
Repeat dose= Max 1.6 mg/kg q4min
26
```
Fospropofol
Respiratory effects=
CV effects=
CNS effects=
Other=
```
Respiratory effects= similar to propofol
CV effects= similar to propofol
CNS effects= similar to propofol
Other= genital and anal burning
27
Class of fospropofol
isopropylphenol
28
How is the formulation for fospropofol different from propofol
It's an aqueous solution which prevents burning on injection and doesn't support microbial growth
29
What is the MOA of fospropofol
It's metabolized to propofol by the enzyme alkaline phosphatase which prolongs onset. It binds to GABA-A increasing Cl- conductance
30
Which receptor does ketamine antagonize
NMDA
31
```
Ketamine
MOA= primary and secondary
Onset= (IV, IM)
Duration=
pKa=
```
```
MOA=
-Primary = NMDA antagonist
-Secondary = binds to secondary receptors i.e. opioid, MAO, serotonin, NE, muscarinic, Na+ channel
Onset
-IV= 30-60 sec
-IM= 2 - 4 min
Duration= 10-20 minutes
pKa= 7.5
```
32
```
Ketamine
Clearance=
Active metabolite=
Induction dose= (IV, IM)
Opioid sparing dose=
```
```
Clearance= liver
Active metabolite= Norketamine
Induction dose=
-IV = 1-2 mg/kg
-IM = 4-8 mg/kg
-PO=10 mg/kg
Opioid sparing dose= 0.1-0.5 mg/kg
```
33
```
Ketamine
Respiratory effects=
CV effects=
CNS effects=
Other=
```
Respiratory effects= maintains respiratory drive, increased oral secretions
CV effects= Increased SNS tone, SVR, HR, CO
CNS effects= Increased ICP, IOP, nystagmus, analgesia. Emergence delirium, lowers SZ threshold.
Other= Avoid with acute intermittent porphyria
34
Chemical name and class of ketamine
Name = 1-(o-Cholophenyl)-2(methylamino) cyclohexanone hydrochloride
Class = Arylcyclohexylamine; phencyclidine derivative
35
What is the formulation or ketamine
Aqueous solution available as 1%, 5%, and 10% solutions
| Racemic mixture
36
Ketamine MOA
NMDA receptor antagonist. Antagonizes glutamate
Dissociates the thalamus (sensory) from the limbic system (awareness)
37
Describe the clearance of ketamine
Liver (P450 enzymes)
| -Chronic ketamine use induces the enzymes that metabolize it
38
How does chronic ketamine use affect the enzymes that metabolize it.
Why is this significant?
It's an enzyme inducer
This causes rapid escalation in tolerance
39
What is the metabolite for ketamine?
| Describe the potency of the metabolite
Active metabolite = norketamine
potency = 1/3 - 1/5 the potency of ketamine
40
How is ketamine excreted
Renal
41
How does ketamine affect the myocardium if SNS isn't intact
It is a myocardial depressant
If catecholamines are depleted or SNS isn't intact, then myocardial depression will be prominent. Can cause severe bradycardia d/t muscarinic action
42
What are respiratory effects of ketamine
- Bronchodilation
- Airway reflexes remain intact
- Respiratory drive remains intact
43
How does ketamine affect the CO2 response curve
Does not significantly shift CO2 response curve
44
What are CNS effects of ketamine
- increased CMRO2
- increased cerebral BF
- increased ICP
- increased IOP
- increased EEG activity
- Emergence delirium
45
How does emergence delirium present with ketamine use?
| What is helpful
Nightmares and hallucinations
Benzodiazepines are effective in preventing emergence delirium
46
How does ketamine affect pain
- Good analgesia with opioid-sparing effects
- Relieve somatic pain > visceral pain
- Blocks central sensitization and effects in the dorsal horn of the SC
- prevents hyperalgesia following remifentanil infusion
47
What conditions should ketamine use be avoided in
CAD
| Acute intermittent porphyria
48
What is an off-label use for ketamine
sub-hypnotic doses can treat MDD resistant to treatment
49
What is the plasma protein binding for ketamine?
| How does this relate to other IV anesthetics?
12%
| MUCH lower
50
```
Etomidate
MOA=
Onset=
Duration=
pKa=
```
MOA= GABA-A agonist
Onset= 30-60 seconds
Duration= 5-15 minutes
pKa=
51
Etomidate
Clearance=
Active metabolite=
Induction dose=
Clearance= Liver + plasma esterases
Active metabolite= none
Induction dose= 0.2-0.4 mg/kg
52
Etomidate
Respiratory effects=
CV effects=
CNS effects=
Respiratory effects= mild respiratory depression
CV effects= minimal
CNS effects= decreased ICP, no analgesia
53
Chemical name and class of etomidate
Chemical name= R-1-methyl-1-(a-methylbenzyl) imidazole-5-carboxylate
Class=Imidazole
54
How does the imidazole etomidate function in different pH's
Acidic pH = imidazole ring opens = INCREASED H2O solubility
Physiologic pH = imidazole ring closes = INCREASED lipid solubility
55
Describe the clearance of etomidate
Liver P450 enzymes and plasma esterases
56
Why does rapid awakening occur with etomidate?
Due to redistribution NOT metabolism
57
What are CV effects and benefits of etomidate
- Hemodynamic stability with minimal change to HR, SV, and CO
- SVR is decreased lowering BP minimally
- Doesn't blunt SNS response to laryngoscopy
58
What are respiratory effects of etomidate
Mild respiratory depression but less than propofol and barbs
59
What are 5 CNS effects of etomidate
1. decreased CMRO2
2. decreased CBF d/t cerebral vasoconstriction
3. decreased ICP
4. Stable cerebral perfusion
5. No analgesia
60
Does etomidate provide analgesia
No
61
Which IV anesthetic can increase mortality in patients with Addisonian crisis?
Why?
Etomidate
It is an 11-beta-hydroxylase and 17-alpha-hydroxylase inhibitor which is what cortisol and aldosterone synthesis is dependent on
A single dose of etomidate suppresses adrenocortical function for 5-8 hours
Avoid etomidate in patients reliant on intrinsic stress response because they need alllllll the cortisol (i.e. addison's crisis, severe sepsis)
62
What are 4 undesirable effects of etomidate
1. myoclonus
2. Suppression of adrenocortical function for up to 24 hrs
3. Nausea and vomiting
4. Acute intermittent porphyria
63
What conditions should etomidate use be avoided and why
1. Addison's crisis
2. Severe sepsis
3. Acute adrenal failure
4. Acute intermittent porphyria
d/t depletion of intrinsic cortisol stress response. Don't want to inhibit cortisol production
64
How does myoclonus present following etomidate use
Involuntary skeletal muscle contractions, dystonia, or tremor
65
What effect can etomidate have in patients with a history of seizures
It can increase epileptiform activity and risk of seizures
66
Thiopental
MOA=
Onset=
Duration=
```
MOA= GABA-A agonist
Onset= 30-60 seconds
Duration= 5-10 minutes
```
67
Thiopental
Clearance=
Active metabolite=
Induction dose=
Clearance= Liver
Active metabolite= None
Induction dose= 2.5-5 mg/kg IV
68
Thiopental
Respiratory effects=
CV effects=
CNS effects=
Respiratory effects= decreased drive, bronchoconstriction d/t histamine release
CV effects= HoTN, myocardial depression, baroreceptor reflex preserved
CNS effects= Decreased ICP, hyperalgesia possible
69
What conditions should thiopental use be avoided
Acute intermittent porphyria
70
What can occur with intra-arterial thiopental injection?
| Treatment?
Intense vasoconstriction and crystal formation leading to tissue necrosis
Tx: vasodilator like phentolamine or phenoxybenzamine. Stellate ganglion nerve block for sympathectomy of UE
71
What medication is used for electroconvulsive therapy and why
Methohexital
| Decreases seizure threshold and produces better-quality seizure
72
What chemical are barbiturates derived.
| How is PK/PD altered
Derived from barbituric acid
Substitutions on the barbituric acid ring can modify PK/PD
73
What molecule is added to barbituric acid to form thiobarbiturates
Sulfur molecules in the 2nd position
74
What is an example of a thiobarbiturate
Thiopental
75
What molecule is added to barbituric acid to form oxybarbiturate
Oxygen molecule in the 2nd position
76
Give an example of an oxybarbiturate
Methohexital
| Pentobarbital
77
What chemical substitution on barbituric acid can lower seizure threshold and increase potency.
Name medication
Adding methyl group on nitrogen
Methohexital
78
What chemical substitution on barbituric acid can increase anticonvulsant effects.
Name medication
Adding a phenyl group to the carbon in the fifth position
Phenobarbital
79
How do each of the following drugs affect seizures
Methohexital
Phenobarbital
Methohexital = lower seizure threshold
Phenobarbital = increased anticonvulsant effect
80
Chemical name and class for thiopental
name= 5-ethyl-5-(1-methylbutyl)-2-thiobarbituric acid
Class=barbiturate
81
What is the solubility and pH for thiopental
```
Solubility = water soluble
pH = 9
```
82
Describe the MOA for thiopental
GABA-A agonist depresses the reticular activating system in the brain stem
83
How are the GABA receptors affected by thiopental dosing
Low/normal= increases affinity of GABA for its binding site
High dose= directly stimulates GABA-A receptor
84
Describe the clearance mechanism for thiopental.
| How does repeated dosing affect clearance
Liver P450
| Repeated dosing causes tissue accumulation leading to longer wake-up time and hangover effect
85
What determines awakening following thiopental administration
Determined by redistribution NOT metabolism
86
What is the active metabolite for thiopental
Normal dose = NO active metabolite
High dose= pentobarbital
87
BP effect btween propofol and thiopental
thiopental produces less HoTN than propofol
88
Describe 4 CV effects of thiopental
1. HoTN is d/t venodilation which decreases preload
2. Myocardial depression
3. Non-immunogenic histamine release
4. Baroreceptor reflex preserved cause reflexive tachycardia with HoTN to maintain CO
89
What is the mechanism that causes HoTN with thiopental administration
1. Venodilation causes decreased preload
2. Myocardial depression
3. non-immunogenic histamine release (short-lived)
90
Respiratory effects of thiopental
1. Respiratory depression d/t CO2 response curve shifting right
2. bronchoconstriction d/t histamine release
91
What respiratory condition should thiopental be used with caution and why
Asthma
d/t bronchoconstriction from histamine release
92
Which direction does the CO2 response curve shift with thiopental use?
How does this affect respiratory drive?
Curve shifts RIGHT
Causes respiratory depression
93
CNS effects of thiopental (6)
1. Decreased CMRO2
2. Decreased CBF from vasoconstriction
3. Decreased ICP
4. Decreased EEG activity
5. No analgesia
6. Neuroprotection with focal ischemia
94
How can thiopental be useful when performing an EEG
It can cause burst suppression or isoelectric EEG
95
How can thiopental affect acute intermittent porphyria
By inducing ALA synthase which accelerates the production of heme precursors and their accumulation
96
What are the symptoms of acute intermittent porphyria
GI
CNS
PNS
```
GI= severe abd pain, N/V
CNS= Anxiety, confusion, seizures, psychosis, coma
PNS= skeletal muscle weakness, bulbar weakness (both can lead to respiratory failure)
```
97
List medications that should be avoided with acute intermittent porphyria (7)
1. Barbiturates
2. Etomidate
3. Ketamine
4. Ketorolac
5. Amiodarone
6. CCBs
7. BCPs
98
Anesthetic management for acute intermittent porphyria (6)
1. Liberal hydration
2. glucose supplementation reduces ALA synthase activity
3. Heme arginate reduces ALA synthase activity
4. Prevent hypothermia
5. Administer ALP safe medications
6. Avoid regional anesthesia
99
Methohexital induction dose
1-1.5 mg/kg
100
```
Dexmedetomidine
MOA=
Onset=
Duration=
pKa=
```
```
MOA= alpha-2 agonist
Onset= 10-20 minutes
Duration= 10-30 minutes
pKa= 7.1
```
101
```
Dexmedetomidine
Clearance=
Active metabolite=
Loading dose=
Maintenance dose=
```
Clearance= Liver
Active metabolite= None
Loading dose= 1 mcg/kg over 10 minutes
Maintenance dose= 0.4-0.7 mcg/kg/hr
102
```
Dexmedetomidine
Respiratory effects=
CV effects=
CNS effects=
Other=
```
Respiratory effects= Respiratory drive preserved
CV effects= Bradycardia, HoTN, HTN w/ rapid administration
CNS effects= Sedation, analgesia, no ICP effects, limited effects on evokes
Other= Antishivering, decreased emergence delirium
103
Chemical name and class for dexmedetomidine
Chemical name = (S)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole monohydrochloride
Class = imidazole
104
Is dexmedetomidine lipid or water soluble
Water
105
Describe the MOA of dexmedetomidine
Alpha-2 agonist
Binds to presynaptic alpha-2 receptors decreasing cAMP which inhibits the locus coeruleus in the pons leading to sedation
106
Describe the mechanism that produces HTN with rapid dexmedetomidine administration
Rapid administration produces peripheral alpha-2 effects before the central effects that reduce SNS tone. Peripheral effects include alpha-2 stimulation in vasculature causing vasoconstriction.
107
How does dexmedetomidine affect the CO2 response curve
It doesn't!
108
Describe the CNS effects of dexmedetomidine
1. decreased CBF
2. No change in CMRO2
3. No change in ICP
4. Sedation d/t decreased SNS tone and reduced arousal
109
How does dexmedetomidine affect shivering
It impairs the thermoregulatory response producing antishiver effects
110
How is analgesia produced with dexmedetomidine
The alpha-2 receptors are stimulated in the dorsal horn of the spinal cord. This decreases substance P and glutamate release (excitatory NT)
111
Pediatric nasal or buccal dose of dexmedetomidine
3-4 mcg/kg
112
Compare the elimination half-lives of midazolam, diazepam and lorazepam
Diazepam > lorazepam > midazolam
113
Why is the elimination half-life of diazepam so long
It undergoes enterohepatic recirculation
| t1/2 = 43 hours
114
```
Midazolam
MOA=
Onset=
Duration=
pKa=
```
MOA= GABA-A agonist
Onset= 30-60 seconds
Duration= 20-60 minutes
pKa=
115
```
Midazolam
Clearance=
Active metabolite=
Sedation dose
IV=
PO=
```
```
Clearance= Liver
Active metabolite= 1-hydroxymidazolam
Sedation dose
IV= 0.01-0.1 mg/kg
PO= 0.5-1 mg/kg
```
116
Midazolam
Respiratory effects=
CV effects=
CNS effects=
Respiratory effects= Minimal but synergistic respiratory depression with other sedatives
CV effects= Minimal
CNS effects= Anterograde amnesia, anticonvulsant properties, anxiolysis, antispasmodic
117
Midazolam class
Class = benzodiazepine
118
What is the formulation for midazolam and how is affected by pH
Formulation = imidazole ring
Acidic pH= imidazole ring OPENS and increases WATER solubility
Physiologic pH= imidazole ring CLOSES
119
Describe the MOA of midazolam
GABA-A agonist increases the frequency of channel opening. This increases chloride conductance and neuronal hyperpolarization
120
Describe the active metabolite for midazolam.
1-hydroxymidazolam
0.5x potency
Rapidly conjugated to inactive compound
Renal failure prolongs effects of active metabolite
121
CV effects of midazolam
Minimal effects with sedation dose
HoTN and decreased SVR with induction dose
122
Respiratory effects of midazolam
minimal effects with sedation dose
Respiratory depression with induction dose
Opioids potentiate respiratory depressant effects
COPD pts are more sensitive to the respiratory depressant effects
123
CNS effects of midazolam (6)
1. Minimal effect on CMRO2 and CBF with sedation dose
2. Decreased CMRO2 and CBF with induction dose
3. Anterograde amnesia
4. Anticonvulsant
5. Anxiolysis
6. Spinally mediated skeletal muscle relaxation (antispasmodic)
124
CNS effects of diazepam
1. Antispasmodic agent by reducing skeletal muscle tone at the level of the spinal neurons
2. Anticonvulsant
125
CNS effects of lorazepam
1. Amnestic effects last up to six hours
| 2. Anticonvulsant properties with slow onset
126
Compare the relative potency of midazolam, lorazepam, and diazepam from greatest to least potent
Lorazepam > midazolam > diazepam
127
Why do diazepam and lorazepam cause irritation with injection
The additive to enhance water solubility, propylene glycol, causes venous irritation
128
Indications, induction dose, and maintenance dose for remimazolam
```
Indications = Procedural sedation <30 minutes
Induction= 5 mg IV over 1 minute
Maintenance= 2.5 mg IV over 15 seconds q2 minutes
```
129
Remimazolam
Peak sedation=
t1/2=
Peak sedation= 3-3.5 minutes after administration
t1/2 = 0.5-2 minutes
130
Metabolism of remimazolam
non-specific plasma esterases
131
Excretion of remimazolam
Urine
132
Benefits of remimazolam in procedural sedation
Faster onset of action, deeper sedation, and faster recover
133
How does remimazolam compare to propofol for procedural sedation
Less respiratory depression and better cardiopulmonary stability
134
What patients should not received remimazolam
Patients with a history of severe hypersensitivity to dextran 40
135
MOA of flumazenil
GABA-A receptor competitive antagonist
Higher affinity for receptor but shorter duration
136
Initial flumazenil dose
| Repeat dose
```
Initial = 0.2 mg IV
Repeat = 0.1 mg q1 minute
```
137
Duration of flumazenil and significance for dosing
30-60 minutes
| Repeat doses may be required d/t longer benzo half-life
138
Flumazenil side effects and cautions
1. benzo-dependent patients may have signs of withdrawal or sz with administration
2. Does not increases SNS tone, anxiety, or neuroendocrine stress
3. Tends to reverse sedative effects over amnestic ones
