Unit 4 Pharmacology: Volatile Anesthetics 2: Pharmacodynamics Flashcards
(139 cards)
1
Q
N2O is ____ times more soluble than nitrogen. What does this mean?
A
34 x
For every 1 molecule of nitrogen that leaves a closed space, 34 molecules of N2O enter to take it’s place.
2
Q
What is the nitrogen blood:gas partition coefficient?
What is the N2O blood:gas partition coefficient?
A
Nitrogen: 0.014
N2O: 0.46
3
Q
How does N2O affect a compliant airspace? Fixed airspace?
A
Compliant: increase volume
Fixed: increase pressure
4
Q
What are the compliant airspaces in the body that N2O can affect? At what rate are these affected?
A
Pulmonary blebs - fast equilibration between space and blood
Air bubbles in the blood - fast
Sulfa hexafluoride bubble in the eye - fast
Bowel - slow
Pneumoperitoneum - slow
5
Q
What are the fixed airspaces that can be affected by N2O? At what speed?
A
Middle ear - fast equilabration between space and blood
Brain during intracranial procedures - fast
6
Q
Discontinuation of N2O can do what to the ear?
A
Decrease middle ear pressure and result in serous otitis
7
Q
When must N2O be discontinued if placing an SF6ocular gas bubble? How long should it be avoided?
A
D/C: 15 minutes before the SF6 bubble is placed
Avoid N2O for 7 - 10 days after the bubble is placed
8
Q
There are 3 alternatives to SF6 for an intraocular bubble, what are they and how long should N2O be avoided?
A
Air: 5 days
Perfluoropropane: 30 days
Silicone oil: no contraindication to N2O
9
Q
Is N2O flammable?
A
No, but it does suppose combustion
10
Q
How does N2O affect the volume and pressure in anesthetic equipment?
A
It can increase the volume and pressure in:
ETT cuff
LMA cuff
Balloon-tipped pulmonary artery catheter
11
Q
What is the deal with N2O and B12?
A
N2O irreversibly inhibits B12, which inhibits methionine synthase (enzyme required for folate metabolism and myelin production).
12
Q
What are 7 potential side effects of N2O inhibiting B12?
A
- Megaloblasic anemia
- Neuropathy
- Immunocompromise
- Impaired DNA synthesis
- Concern of teratogenicity - clinical data lacking
- Possible risk of spontaneous abortion - many avoid in first 2 trimesters
- Homocysteine accumulation
13
Q
What increases the risk of complications of N2O and B12 inhibition? Examples
A
Prolonged exposure: recreation use
Pre-existing B12 deficiency: pernicious anemia, alcoholism, strict vegan diet
14
Q
Order the volatile agents from lowest to highest potency (4)
A
N2O
DES
SEVO
ISO
15
Q
How is the potency of inhalation anesthetic measured?
A
MAC: this is the concentration of agent that prevents the nociceptive withdrawal reflex following a supramaximal painful stimulus is 50% of the population
16
Q
What is the MAC for a 40 yr old in all 4 agents?
A
ISO: 1.2
SEVO: 2.0
DES: 6.6
N2O: 104
17
Q
What is the essential triad of anesthetic actions?
What else may VAs do?
A
- Amnesia
- Loss of consciousness
- Immobility
VAs may also modulate autonomic function and provide some analgesia
18
Q
What suggests that anesthetics exert their effects in different regions of the CNS?
A
The effects are dose dependent, Supra spinal effects (amnesia and LOC) occur at lower levels, while immobility requires a higher concentration
19
Q
If you add 2 gases together (ie ISO and N2O) what happens to MAC?
A
MAC is additive
0.5 Mac ISO + 0.5 Mac N2O = 1 MAC
20
Q
Define Mac awake. What is its value?
A
MAC-awake is the alveolar concentration at which a patient opens their eyes
~ 0.4 - 0.5 MAC during induction but as low as 0.15 MAC during recovery
21
Q
Define MAC-bar? What is its value?
A
MAC-Bar is the alveolar concentration required to block the autonomic response following a supramaximal painful stimulus
~1.5 MAC
22
Q
At what MAC can movement be prevented in 95% of the population?
A
1.3 MAC
23
Q
Awareness and recall is generally assumed to be prevented at what MAC?
A
0.4 - 0.5 MAC
24
Q
List 6 drugs that increase MAC
A
Chronic alcohol consumption (Increased CNS neurotranmitters:) Acute amphetamine intoxication Acute cocaine intoxication MAOIs Ephedrine Levodopa
25
List 8 drugs/classes that decrease MAC
```
Acute alcohol intoxication
IV anesthetics
N2O
Opioids - IV and neuraxial
Alpha-2 agonists
Lithium
Lidocaine
Hydroxyzine
```
26
How does the electrolyte Na affect MAC?
Hypernatremia: increases MAC
Hyponatremia: decreases MAC
27
How does the electrolyte K affect MAC?
Hyper- and hypokalemia have no effect on MAC
28
How does the electrolyte Mg affect MAC?
Hyper- and hypomagnesemia have no affect on MAC
29
How does age affect MAC?
MAC is increased in infants from 1 - 6 months of age.
Prematurity decreases MAC.
Older age decreases MAC 6% per decade after the age of 40.
30
How does body temperature affect MAC?
Hyperthermia: increase MAC
Hypothermia: decreases MAC
31
How does red hair affect MAC? By what %?
Increases MAC by 19%
32
How does BP affect MAC?
Hypotension (MAP < 50 mmHg) decreases MAC
| Hypertension has no affect on MAC
33
How does gender affect MAC?
No affect
34
How does thyroid disease affect MAC?
No direct effect
35
How does PaCO2 affect MAC?
PaCO2 > 95 mmHg decreases MAC
| PaCO2 15 - 95 mmHg has no effect
36
How does hypoxia affect MAC?
Decreases MAC
37
How does anemia affect MAC?
Decreases MAC
| <4.3 mL O2/dL blood
38
How does CPB affect MAC?
Decreases MAC
39
How does metabolic acidosis affect MAC?
Decreases MAC
40
How does Hypo-osmolarity affect MAC?
Decreases MAC
41
How does pregnancy affect MAC?
Pregnancy through 24-72 hours postpartum decreases MAC
42
They Meyer-Overton rule states:
Lipid solubility is directly proportional to the potency of an inhalation anesthetic
43
What is the Unitary hypothesis?
States that all anesthetics share a similar mechanism of action, but each may work at a different site
44
General anesthesia is produced by ________ in the _____ & ________.
Membrane bound protein interactions
Brain
Spinal cord
45
As a general rule the volatile anesthetics have what 2 effects on their target receptors?
1. They stimulate inhibitory receptors
| 2. They inhibit stimulators receptors
46
What 3 inhibitory pathways are stimulated by VAs?
GABA-A receptors
Glycine channels
Potassium channels
47
What 4 stimulators pathways are inhibited by VAs?
NMDA receptors
Nicotinic receptors
Sodium channels
Dendritic spine function and motility
48
In the brain what is the most important site of volatile anesthetic action?
GABA-A receptor
49
The GABA-A receptor is what type of receptor?
Ligand gated chloride channel
50
Stimulation of the GABA-A receptor does what?
Increases chloride influx and hyperpolarizes neurons impairing their ability to fire.
They likely increase the duration the chloride channel remains open.
51
In the spinal cord where do VAs produce immobility?
In the ventral horn
52
What are the most important sites of VA action in the spinal cord (3)?
Glycine receptor stimulation
NMDA receptor inhibition
Na+ channel inhibition
53
Where is the site of action for gaseous anesthetics (N2O and Xenon)? (2)
NMDA antagonism
Potassium 2P-channel stimulation
They do not stimulate GABA-A receptor
54
What is the essential triad of general anesthesia?
Unconsciousness
Amnesia
Immobility
55
VAs causes unconsciousness in what 3 sites of action?
Cerebral cortex
Thalamus
Reticular Activating system
56
VAs cause amnesia in what 2 sites of action?
Amygdala
| Hippocampus
57
VAs cause immobility in what site of action?
Ventral horn
58
VAs cause analgesia in what site of action?
Spinothalmic tract
59
VAs cause autonomic modulation in what 2 sites of action?
Pons
| Medulla
60
In cardiac muscle and vascular smooth muscle, VAs decrease what ions influx?
Ca+2 - through the sarcolemma and reduce Ca+2 release from the sarcoplasmic reticulum
61
How do halogenated agents affect BP? How?
Decrease MAP in a dose dependent fashion.
Primary cause: decreases intracellular Ca+2 in vascular smooth muscle -> systemic vasodilation -> decreased SVR and venous return
Secondary cause: decreases intracellular Ca+2 in the cardiac myocyte -> myocardial depression -> decreased inotropy
62
How does N2O affect BP?
No change / possible increase
Hemodynamic effects can be explained by SNS activation. N2O + VA causes less BPP reduction when compared to the MAC equivalent of VA alone
63
How do halogenated agents affect HR?
They directly affect cardiac conduction in a dose dependent fashion.
- decrease SA node automaticity
- decrease conduction velocity though AV node, His-purkinje system, and ventricular conduction pathways
- increase duration of myocardial repolarization by impairing the outward K+ current, this increases action potential duration and prolongs the QT interval
- altered baroreceptor function
64
Do all of the halogenated agents increase HR? How much does it increase and why?
No. SEVO does not cause tachycardia.
DES and ISO increase HR from baseline by 5-10%. Most likely due to respiratory irritation. -> SNS activation -> increase NE release -> beta 1 stimulation
65
How can the tachycardia from VAs be minimized/abolished?
It can be minimized by not abolished.
| Opioids, alpha-2 agonists, beta-1 antagonists
66
How does N2O affect HR?
N2O activates the SNS and increases HR
67
How is contractility affected by halogenated agents?
There is a small decrease in baseline contractility, however the myocardium remains preload responsive.
Myocardial depression is dose dependent.
68
N2O + _____ can cause myocardial depression
Opioid
69
How do VAs affect SVR?
Decrease.
| Decreases intracellular Ca+2 in vascular smooth muscle -> systemic vasodilation -> decreased SVR
70
Which VA causes the least reduction in SVR?
SEVO
71
How does N2O affect SVR?
Increases
72
How do VAs affect coronary vascular resistance?
VAs increase coronary blood flow in excess of myocardial oxygen demand. They preferentially dilate the small cardiac vessels
73
List the 3 VAs in order of potency of coronary artery vasodilation from greatest to least:
ISO > DES > SEVO
74
What is the hearts oxygen extraction % ?
~75 %
75
As myocardial demand increases, health vessels dilate, the heart cannot significantly increase its )O2extraction ratio, so what does the heart do?
It increases its own blood flow to satisfy its O2 requirement.
76
What is coronary steal?
Diseased coronary vessels are not able to dilate much more, so health ones do and blood flow is preferentially directed to healthy tissue
77
Which VA is link to Coronary Steal, though current thinking is that this doesn’t really contribute to steal?
ISO
78
The central chemoreceptors in the medulla monitor what value to determine minute ventilation?
PaCO2
79
Every 1 mmHg in PaCO2 above baseline changes minute ventilation how?
Increases minute ventilation by 3 L/min
80
What are VA pulmonary effects?
Dose dependent depression of the central chemoreceptors and the respiratory muscles
81
What are the 3 mechanism by which VA contribute to hypercarbia?
1. Altering the respiratory pattern
2. Impair the response to CO2
3. Impair motor neuron output and muscle tone to upper airway and thoracic muscles
82
How do VAs alter the respiratory pattern?
Decrease Vt
| Increase RR partially compensates fo the reduction in Vt, although not enough to prevent a rise is PaCO2
83
What happens to the CO2 response curve with VAs?
It shifts down and to the right
84
What other effect occurs when VAs impair the response to CO2?
Apneic threshold is increased: the PaCO2 at which a patient is stimulated to breathe.
85
Where is the apneic threshold usually?
3 - 5 mmHg below the PaCO maintained during spontaneous ventilation
86
What is the significance of the apneic threshold when considering assisted ventilation?
If ventilation is assisted to below the apneic threshold, the patient simply will not breathe. To reduce PaCO2 further one would need controlled ventilation.
87
What does a right shift of the CO2 response curve imply? What does this create?
That for a given PaCO2 the minutes ventilation would be less than predicted?
This creates respiratory acidosis.
88
What does a left shift of the CO2 response curve imply? What does this create?
That for a given PaCO2 the minute ventilation would be more than predicted.
This creates a respiratory alkalosis
89
List 4 causes of a right shift of the CO2 response curve:
```
(Depresses ventilation)
General anesthetics
Opioids
Metabolism alkalosis
Denervation of peripheral chemoreceptors
```
90
List 7 causes of a left shift of the CO2 response curve:
```
(Stimulates ventilation)
Anxiety
Surgical stimulation
Metabolic acidosis
Increased ICP
Salicylates
Aminophylline
Doxapram
```
91
Impairment of genioflossus or tensor palatine leads to what?
These are airway dilator muscles, impairment would lead to upper airway obstruction
92
Impairment of the pulmonary muscles decreases _____ and the effectiveness of ______
FRC
| ventilation
93
What effect on the bronchi do halogenated agents have? What is the relationship with airway resistance?
Bronchodilation.
| In the absence of increased airway resistance the effect is minimal.
94
Which VA impairs the hypoxic ventilatory response the LEAST?
Desflurane
95
Where is PaO2 monitored in the body?
Peripheral chemoreceptors in the carotid bodies monitor for hypoxemia and are important in the the hypoxic ventilatory drive, also in the aortic bodies
96
The carotid bodies relay afferent input to the respiratory center via what nerve?
Glossopharyngeal nerve - CN IX
97
The aortic bodies relay afferent traffic via what nerve?
The vagus nerve - CN X
98
The carotid bodies are more sensitive to change is what?
| Whereas the aortic bodies are more sensitive to changes in what?
Carotid bodies: changes in arterial gas tensions (PaO2, PaCO2) and H+ concentration
Aortic bodies: changes in BP
99
VAs also depress ventilation by inhibiting muscles in the: (3)
Upper airway
Diaphragm
Intercostals
100
How long after anesthesia are the peripheral chemoreceptors impaired after VAs?
Up to several hours after anesthesia
101
The impaired response to acute hypoxia occurs at what MAC? But what does this NOT occur?
0.1 MAC
| Response to PaCO2
102
What cells in the carotid bodies provide the sensory arm of the hypoxic drive? Why are these important?
Glomus type I cells
| It is hypothesized that VAs create a reactive oxygen species that impairs the Glomus type I cells
103
Metabolism is the source of the reactive oxygen species that impairs the glomus type I cells, so those agents that undergo the ______ amount of biotransformation in the body inhibit the hypoxic drive the most. List the VA in the greatest to least hypoxic drive impairment.
Greatest.
| SEVO > ISO > DES
104
Does N2O impair the carotid bodies response to hypoxemia?
Yes, but likely for a different reason
105
What type of patients is impairment of the hypoxic drive especially important?
This who rely on the hypoxic drive to breathe: emphysema, sleep apnea
106
Do pain and surgical stimulation reverse the depression of the hypoxic ventilatory drive caused by VAs?
No.
107
What affect do VAs have on cerebral metabolic rate? (CMRO2)
VAs reduce CMRO2, but only to the extent that they reduce electrical activity, once isoelectric they can not reduce CMRO2 further.
108
What MAC is required to produce isoelectric state?
1.5 - 2.0 MAC
109
What 2 things is CMRO2 dependent on?
1. Electrical activity - 60%
| 2. Cellular homeostasis - 40%
110
SEVO at what MAC can produce seizure activity? What exacerbates this? Where is it more common?
2.0 MAC
Hypocapnia
Pediatric inhalation induction
111
How does the brain match blood flow with metabolic requirement?
When metabolic demand increases, the blood vessels dilate - cerebrovascular resistance decreases.
When metabolic demand decreases, the blood vessels constrict - CVR increases.
112
How do VAs affect cerebral vessel tone?
VAs are cerebral vasodilators, the decrease CVR
113
What 2 competing factors occur in the cerebral vessels when using VAs? What is the net effect?
Vasoconstriction from the reduction in CMROs and vasodilation from the anesthetic agent.
The net effect is a dose dependent increase in CBF, cerebral blood volume, and ICP
114
What 4 techniques can be used to partially offset the vasodilators effect of VAs?
Mild hyperventilation and/or concurrent administration of propofol, opioids, or barbiturates
115
What affect does N2O have on CMRO2? Cerebral blood flow?
N2O increases CMRO2 and cerebral blood flow
116
What is the equation for cerebral perfusion pressure?
CPP = DBP - LVEDP (or PAOP)
117
What is cerebral autogregulation? What is its normal value?
Cerebral vasculature continuously adjusts vessel diameter to maintain a constant cerebral blood flow.
CPP: 50 -150 mmHg
118
How do VAs affect cerebral autoregulation?
VAs disrupt cerebral autoregulation in a dose dependent fashion, CBF becomes increasingly dependent on blood pressure as the concentration of VA is increased.
119
How do VAs affect CSF volume? (Production and absorption)
ISO: no effect on production, increases absorption
DES: increases/no effect on production, no effect on absorption
SEVO: decreases production, unknown about absorption
120
The tendency of the VAs to affect CSF dynamics is greatly overshadowed by their ability to increase ______.
CBF
121
What are evoked potentials used to monitor?
The integrity of neural pathways.
122
What are the 4 types of EPs?
Somatosensory (SSEP)
Motor (MEP)
Visual (VEP)
Brainstem auditory (BAEP)
123
What do SSEPs monitor?
The integrity of the dorsal column (medial lemniscus)
124
What perfuses the dorsal column of the spinal cord?
Posterior spinal arteries
125
What do MEPs monitor?
Integrity of the corticospinal tract
126
What perfuses the corticospinal tract?
Anterior spinal artery
127
Are SSEPs and MEP interchangable?
No. SSEPs do not monitor the anterior cord
128
What are the 2 important components of EPs?
Amplitude - strength of nerve response
| Latency - speed of nerve conduction
129
VAs affect EPs by doing what to amplitude and latency? What affect does adding N2O have?
Decreasing amplitude and increasing latency.
| N2O makes this worse
130
Losing an EP signal, or recording a diminished response suggests what?
Ischemia to the neural pathway being monitored.
131
As a general rule, you should be concerned about nerve ischemia when what occurs with amplitude and latency, and by how much?
Amplitude decreases by 50% or more
| Latency increases by 10% or more
132
What are 3 other confounding factors that affect amplitude and latency besides VAs?
Hypoxia
Hypercarbia
Hypothermia
133
What is the best anesthetic technique to preserve EPs?
TIVA without N2O
134
If you do use a VA while trying to monitor EPs, what is the recommended MAC to use and technique?
0.5 MAC or less
| Supplement with IV agents - propofol, opioid
135
During MEP monitoring what drug(s) should be avoided?
NMB - short acting is ok for induction
136
What IV agent enhances the EP signals?
Ketamine
137
What EPs are most resistant to the effects of anesthetics? Can any technique be used then?
BAEPs
| Yes, any technique can be used.
138
What EPs are the most sensitive to the effects of anesthetic agents?
VEPs
139
If EP signal dismisses or goes away during surgery, what are anesthetic goals to improve neural tissue perfusion?
Increase BP, volume expansion, transfusion (if anemic). Normalizing gas tensions may also help.
