PHARMACOLOGY-Inhaled anesthetics PK Flashcards
(111 cards)
1
Q
What are the 3 categorizations of inhaled anesthetics
A
Ethers
Alkanes
Gases
2
Q
What form do ethers and alkanes take at atmospheric pressure and room temperature
A
Liquids
3
Q
What form do nitrous oxide and xenon take at atmospheric pressure and room temperature
A
Gas
4
Q
How are the halogenated anesthetics differentiated from each other
A
By the number of fluorine atoms
5
Q
How many fluorine atoms does each anesthetic have Halothane Isoflurane Desflurane Sevoflurane
A
Halothane= 3 Isoflurane= 5 Desflurane= 6 Sevoflurane= 7
6
Q
Which halogenated anesthetics have 3, 5, 6, 7 fluorine atoms
A
3= halothane 5= isoflurane 6= desflurane 7= sevoflurane
7
Q
What molecule is added to isoflurane that makes it more potent
A
Chlorine atom
8
Q
Describe the difference between isoflurane and desflurane.
How does this difference affect PK/PD
A
Iso has a chlorine atom replacing 1 fluorine atom.
This extra fluorine reduces des potency and metabolism while increasing vapor pressure
9
Q
Compare the potency of sevoflurane and desflurane
A
Sevo > des
x3 potency
10
Q
What effect does full fluorination of desflurane have potency, vapor pressure and biotransformation
A
Potency = DECREASED, requiring increased MAC
-decreased oil:gas solubility
Vapor pressure = INCREASED d/t decreased intermolecular attraction requiring heated vaporizer
Biotransformation= INCREASED resistance decreasing metabolism
11
Q
Rate the potency of sevoflurane, desflurane, and isoflurane from greatest to least
A
Isoflurane»_space;Sevoflurane»_space;> desflurane
12
Q
What effect does the chlorine atom in isoflurane have on solubility and potency
A
Increases potency
Increases blood and tissue solubility
13
Q
What molecules and chemical alterations make halothane different from the ether anesthetics
A
Lacks an ether bridge (C-O-C)
Presence of Cl and Br
14
Q
Define vapor pressure
A
The pressure exerted by a vapor in equilibrium with its liquid or solid phase inside of a closed container
15
Q
How does vapor pressure relate to temperature
A
Directly proportional
Increased temp = increased VP
16
Q
Define boiling point
A
The temperature where matter transitions from a liquid to gaseous state
17
Q
How does boiling point relate to pressure and tempurature
A
Boiling occurs when VP equals atmospheric pressure
At high altitudes, liquids boil at lower temperatures as a function of reduced atm pressure
18
Q
Define partial pressure
A
The fractional amount of pressure that a single gas exerts within a gas mixture
19
Q
What is Dalton’s gas law
A
Law of partial pressures
Total gas pressure in a container is equal to the sum of the partial pressure exerted by each gas
P total = P1 + P2 + P3…
20
Q
Define evaporation
A
The process where compounds transition from liquid to gaseous stat at a temperature below boiling point
21
Q
When does boiling occur
A
When vapor pressure equals atm pressure
Open container is required
Increased atm P = increased boiling point
Decreased atm P = decrease boiling point
22
Q
What effect does pressure have on boiling point
A
Increased pressure = increased BP
Decreased pressure = decreased BP
23
Q
What determines the depth of anesthesia with gases
A
The partial pressure of the anesthetic agent in the brain NOT the volume precent
24
Q
What can transform volatile anesthetics into toxic compounds (2)
A
Carbon dioxide absorbent
Liver
25
What does stability refer to with anesthetic gases
The ability to resist breakdown or metabolism
26
What can desflurane and isoflurane produce in desiccated soda lime
Carbon monoxide
des>iso
27
What does sevoflurane produce when unstable
compound A
28
```
Vapor Pressure
Sevo=
Des=
Iso=
N2O=
```
```
Sevo= 157 mmHg
Des= 669 mmHg
Iso= 238 mmHg
N2O= 38,770 mmHg
```
29
```
Boiling Point
Sevo=
Des=
Iso=
N2O=
```
```
Sevo= 59*C
Des= 22*C
Iso= 49*C
N2O= -88*C
```
30
```
Molecular weight
Sevo=
Des=
Iso=
N2O=
```
```
Sevo= 200 g
Des= 168 g
Iso= 184 g
N2O= 44 g
```
31
```
Stable in hydrated CO2 absorber (Y/N)
Sevo=
Des=
Iso=
N2O=
```
```
Sevo= N
Des= Y
Iso= Y
N2O= Y
```
32
```
Stable in dehydrated CO2 absorber (Y/N)
Sevo=
Des=
Iso=
N2O=
```
```
Sevo= N
Des= N
Iso= N
N2O= Y
```
33
```
Toxic by-product
Sevo=
Des=
Iso=
N2O=
```
```
Sevo= compound A
Des= carbon monoxide
Iso= carbon monoxide
N2O= none
```
34
Define solubility of inhalation anesthetics
The ability of the anesthetic agent to dissolve into blood and tissue
35
What does the blood:gas partition coefficient describe
The relative solubility of an inhalation anesthetic in blood vs. in the alveolar gas when the partial pressures between the two compartments are equal
36
```
Blood:gas coefficients for
Sevo=
Des=
Iso=
N2O=
```
```
Sevo= 0.65
Des= 0.42
Iso= 1.46
N2O= 0.46
```
37
What does the partition coefficient measure
solubility
| The relative solubility of a solute in 2 different solvents (blood vs alveolar gas)
38
What is the likelihood of anesthetic uptake in the blood with a low blood:gas solubility
Less likely to be taken up into the blood (less blood soluble)
39
What is the distribution of anesthetic agent with low blood:gas solubility (blood, alveolus, brain)
More agent is available to exert partial pressure in alveoli and brain
40
What is the likelihood of anesthetic uptake in the blood with a high blood:gas solubility
More likely to be taken up in the blood (more blood soluble)
41
What is the distribution of anesthetic agent with high blood:gas solubility (blood, alveolus, brain)
Less agent is available to exert a partial pressure in the alveoli and brain
42
```
Blood:Gas partition coefficient
Sevo=
Des=
Iso=
N2O=
```
```
Sevo= 0.65
Des= 0.42
Iso= 1.46
N2O= 0.46
```
Iso > Sevo > N2O >Des
43
```
Brain:Blood partition coefficient
Sevo=
Des=
Iso=
N2O=
```
```
Sevo= 1.7
Des= 1.3
Iso= 1.6
N2O= 1.1
```
Sevo > Iso > Des > N2O
44
```
Muscle:Blood partition coefficient
Sevo=
Des=
Iso=
N2O=
```
```
Sevo= 3.1
Des= 2.0
Iso= 2.9
N2O= 1.2
```
Sevo > Iso > Des > N2O
45
```
Fat:blood partition coefficient
Sevo=
Des=
Iso=
N2O=
```
```
Sevo= 47.5
Des= 27.2
Iso= 44.9
N2O= 2.3
```
Sevo > Iso > Des > N2O
46
```
Oil:gas partition coefficient
Sevo=
Des=
Iso=
N2O=
```
```
Sevo= 47
Des= 19
Iso= 91
N2O= 1.4
```
Iso > Sevo > Des > N2O
47
Equation for partition coefficient
partition coefficient = ([anesthetic dissolved in BLOOD*]/[anesthetic inside ALVEOLUS*])
48
How is an anesthetic state induced with volatile anesthetics
Building up a partial pressure of anesthetic agent in the brain and spinal cord
49
How de the alveolar and brain concentrations of anesthetic agents correlate
Agent in the alveoli is proportional to its concentration inside the brain
50
What measurable anesthetic value is a surrogate for anesthetic partial pressure in the brain
Alveolar partial pressure (FA)
51
What determines the amount of anesthetic agent inside the alveoli
The balance between input (vaporizer setting) and uptake in blood
52
What 3 factors determine anesthetic uptake in the blood
1. Agent solubility
2. Partial pressure difference between alveoli and blood
3. Cardiac output
53
How does an anesthetics solubility affect FA/FI equilibration
Low solubility = decreased blood uptake = increase rise of concentration = faster equilibration of FA/FI = faster onset
High solubility = increased blood uptake = slower rise in concentration = slower equilibration of FA/FI = slower onset
54
How does alveolar concentration of an anesthetic correlate to blood and brain concentrations
Alveolar concentration is proportional to the concentration in blood which is proportional to concentration in the the brain
55
What is FI in relation to the FA/FI curve
Inhaled fraction of anesthetic
56
What does the FA/FI curve describe
the speed at which alveolar partial pressure equilibrates with partial pressure leaving the vaporizer
57
What does a decreased rate of rise of FA/FI mean for induction
slower induction
58
How is the rate of rise of the FA/FI curve decreased
Increased CO
Increased FRC
Decreased FGF
59
What does an increased rate of rise of FA/FI mean for induction
faster induction
60
How is the rate of rise of the FA/FI curve increased
Decreased time constant
Decreased anatomic dead space
Increased alveolar ventilation
61
What are 5 factors that influence the rate of anesthetic delivery to the alveoli
1. Setting on the vaporizer
2. Time constant of the delivery system
3. Anatomic dead space
4. Alveolar ventilation
5. Functional residual capacity
62
What 3 factors influence removal of anesthetic from the alveoli
1. Agent solubility
2. Partial pressure difference between the alveoli and blood
3. Cardiac output
63
How do anesthetic wash in or uptake increase or decrease FA/FI
Greater wash-in and reduced uptake increase FA/FI
Reduced wash-in or increased uptake decrease FA/FI
64
Which direction does the FA/FI curve move when onset is faster
Curve is pushed up because of increased FA/FI
65
What 5 factors increase anesthetic wash-in
How does this affect anesthetic onset and FA/FI curve
1. High FGF
2. High alveolar ventilation
3. Low FRC
4. Low time constant
5. Low anatomic dead space
Faster onset and increased FA/FI
66
What 3 factors decrease anesthetic uptake
How does this affect anesthetic onset and FA/FI curve
1. Low solubility
2. Low CO
3. Low Pa-Pv difference
Faster onset and increased FA/FI
67
What 5 factors decrease anesthetic wash-in
How does this affect anesthetic onset and FA/FI curve
1. Low FGF
2. Low alveolar ventilation
3. High FRC
4. High time constant
5. High anatomic dead space
Slower onset and decreased FA/FI
68
What 3 factors increase anesthetic uptake
How does this affect anesthetic onset and FA/FI curve
1. High solubility
2. High CO
3. high Pa-Pv difference
Slower onset and decrease FA/FI
69
What percentage of body weight is accounted for by vessel rich group
How much CO does it receive
10%
75%
70
What 4 tissue groups are considered for distribution of anesthetic
VRG
Muscle group
Fat group
Vessel poor group
71
What 3 factors is tissue uptake dependent on
1. Tissue blood flow
2. Solubility of the anesthetic in the tissue
3. Arterial blood:tissue partial pressure gradient
72
What 5 organs make up the vessel rich group
```
Heart
Brain
Kidneys
Liver
Endocrine glands
```
73
What percentage of body mass is the muscle/skin group
How much CO does it receive
50% of mass
20% of CO
74
What percentage of body mass is the fat group
How much CO does it receive
20% of mass
5% of CO
75
What percentage of body mass is the vessel poor group
How much CO does it receive
20% of mass
<1% CO
76
Which tissue group is first to equilibrate with FA and why
The VRG
because it receives 75% of CO
77
After the VRG is fully saturated which group is responsible for the majority of continued tissue uptake
Muscle group
78
Why is the muscle group slower to saturate than the VRG
larger mass/capacity and lower CO
79
Why is the fat group capable of storing large amounts of anesthetic agent
Because halogenated agent
80
How does N2O into tissue groups differ from halogenated anesthetics
It partitions nearly the same into all compartments
It quickly diffuses into the GAS containing areas of the body, such as the GI tract and middle ear
81
What 3 ways are inhaled anesthetics eliminated from the body
1. Elimination from the alveoli (primary)
2. Hepatic biotransformation (secondary)
3. Percutaneous loss (minimal)
82
What percentage of each halogenated anesthetic is transformed by the liver
```
Halothane= 20%
Sevo= 2%
Iso= 0.2%
Des= 0.02%
N2O= 0.004%
```
Halo > Sevo > Iso > Des > N2O
83
Compare the hepatic metabolism of the inhaled anesthetics from greatest to least
Halo > Sevo > Iso > Des > N2O
DISH (from lowest to highest)
84
What metabolic by-product is a result of des and iso metabolism
Trifluoroacetic acid
85
What metabolic by-product is a result of sevo metabolism
Free fluoride ions
86
How are halogenated anesthetics metabolized in the liver
By the P450 system carried out by CYP2E1
87
What inhaled anesthetic by-product can precipitate immune-mediated hepatic dysfunction
Trifluoroacetic acid
by-product of halothane metabolism
88
What anesthetic by-products are produced inside the body vs outside the body (soda lime)
Inside = free fluoride ions, TFA
Outside = compound A, carbon monoxide
89
How can compound A buildup in circuits be prevented
Minimum FGF of 1 L/min for up to 2 MAC-hrs
| 2 L/min after 2 MAC-hrs
90
What is a MAC-hr
1 x MAC that prevents movement in response to noxious stimuli in 50% of subjects given 1 MAC-hr
91
Why is the rate of rise for N2O FA/FI curve faster than des
The concentrating effect
92
What 4 factors alter the speed of anesthetic induction and emergence
Concentration effect
Concentrating effect
Augmented gas inflow effect
Ventilation effect
93
Describe concentration effect
The higher the concentration of inhalation anesthetic delivered to the alveolus, the faster its onset
aka overpressuring
Most prominent with N2O and higher soluble agents
94
What two components rate to the concentration effect
ConcentratING effect
| Augmented gas inflow effect
95
Define concentrating effect
Alveolar shrinking due to displacement of nitrogen with nitrous oxide causing a relative increase in FA to the reduced alveolar volume
96
How does the concentrating effect occur
- Nitrogen is the primary gas in the alveolus at RA
- Nitrous oxide is 34 times more soluble in blood than nitrogen
- When nitrous oxide is introduced into the lung, the volume of N2O going from alveolus to pulmonary blood is greater than nitrogen moving in the opposite direction
- This causes alveolar shrinkage, reducing volume and increasing relative FA increase
97
Why does the concentrating effect explain the difference in nitrous oxide vs desflurane rate of FA/FI rise
Even though desflurane is less soluble than nitrous oxide, N2O causes a shrinking effect of the alveoli, decreasing alveolar volume and increasing the relative FA.
This makes the FA/FI curve increase faster
98
Define augmented flow
Following the concentrating effect and reduced alveolar volume, subsequent breath causes increased inflow of tracheal gas with anesthetic. The new breath replaces the lost alveolar volume and increases alveolar ventilation AUGMENTING FA
99
Describe the ventilation effect
Describes how changes in alveolar ventilation can affect the rate of rise of FA/FI
100
How does the ventilation effect alter rate of rise of FA/FI
The greater the alveolar ventilation, the greater the FA/FI rise
In spontaneous ventilating patients, as anesthetic deepens, alveolar ventilation decreases
Reduced anesthetic agent is input to alveolus
101
Define the second gas effect
Administering one gas during anesthetic induction (N2O) will hasten the onset of a second gas (volatile anesthetic)
102
Define diffusion hypoxia
Movement of N2O from the tissue back into the alveoli during emergence
This dilutes alveolar O2 and CO2 which leads to transient hypoxemia and hypocarbia
103
Describe how the second gas effect works
When N2O is given with a second gas, the srhinkage of the alveoli d/t rapid N2O uptake causes relative increase in 2nd gas concentration in alveoli
104
Which volatile anesthetics benefit most from the second gas effect
those with higher blood:gas solubility
| Iso > sevo > des
105
Up to how much N2O can be absorbed in the gas-containing areas of the body
30 L in 2 hrs
106
What causes diffusion hypoxia with N2O
The temporary dilution of O2 and CO2 in the alveolus by large volumes of eliminating N2O
107
How is diffusion hypoxia treated
Give lower FiO2
| 100 FiO2 may cause absorption atelectasis from higher O2
108
On induction, which volatile agents are affected most by right-to-left cardiac shunt and why
Lower solubility gases
Because it takes longer for the FA/FI to equilibrate d/t poor uptake of lower soluble agent
Des > sevo > iso
109
Why is inhaled induction slower when a right-to-left shunt is present
Because a fraction of blood bypasses lungs. This blood does not pick up O2 or anesthetic agents and dilutes the non-shunted fraction of oxygenated/anesthetized blood
110
What are 5 examples of right-to-left shunt
1. Tetralogy of Fallot
2. Foramen ovale
3. Eisenmenger's syndrome
4. Tricuspid atresia
5. Ebstein's anomaly
111
How is an inhaled vs IV induction affected by left-to-right shunting
IV induction will be slower d/t recirculation of agents in the lungs
