Exam 3 - PK/PD of Inhaled Anesthetics Flashcards
Pharmacokinetics describes these four things in inhaled anesthetics.
- Uptake from the alveoli into the pulmonary capillary blood.
- Distribution
- Metabolism
- Elimination via Lungs
What factors does aging contribute to the pharmacokinetics of inhaled anesthetics?
- Decreased body mass
- Increase fat mass, increase Vd for lipid-soluble drugs
- Decrease clearance if the pulmonary exchange is impaired
- Increase time constraints d/t lower cardiac output
What is Boyle’s Law?
Example?
- At a constant temperature, pressure and volume of a gas in inversely related
- Anesthetic machine bellows contract increasing pressure in the ventilator and circuit causing gases to move from high pressure (vent) to low pressure (lungs)
What is Fick’s law of diffusion?
Example?
- It describes the rate at which molecules move from an area of high concentration to an area of low concentration.
- Once the molecules get to the alveoli, they move around randomly and begin to diffuse into the pulmonary capillary.
What three things does diffusion of a gas depend on?
- Partial pressure gradient of the gas
- Solubility of the gas (diffusion)
- Thickness of the membrane
What is Graham’s law of diffusion?
Example?
- Proccess in which molecules diffuse through pores and channels without colliding
- Smaller molecules effuse faster (leave their container) depending on solubility (diffusion)
- EX: CO2 is 20x more diffusable than O2 despite having a larger molecular weight
What is alveolar gas pressure indicative of?
How is it measured?
- Depth of anesthesia
- Recovery from anesthesia
- End tidal gas concentration
What does inspired and expired anesthetic gas concentrations tell us?
- If inspired gas concentrations are higher than expired, then the brain is not saturated with anesthetics yet (may be more awake)
- If inspired matches expired, then the gas should be at equilibrium in the body/brain
- If expired is greater than inspired, the gas is offloading from the tissues and the patient will be waking up
What are the 3 partial pressure gradients that affect the induction process?
- Anesthetic machine to alveoli
- Alveoli to blood
- Arterial blood to the brain
What four factors will affect the input of the volatile anesthetic from the anesthetic machine to the alveoli?
- Inspired partial pressure
- Alveolar ventilation
- FRC
- Anesthetic breathing system (rebreathing? → not in modern machines)
What 3 factors will affect the uptake of volatile anesthetics from the alveoli to the blood?
- Blood: gas partition coefficient
- Cardiac output
- Alveolar-to-Venous partial pressure differences
What 3 factors will affect the uptake of volatile anesthetics from the arterial blood to the brain?
- Brain: blood partition coefficient
- Cerebral blood flow (dependent on CO)
- Aterial-to-Venous partial pressure difference
What is the concentration effect and how does it affect induction times?
- The higher the inspired gas concentration (PI) the faster alveolar concentration (PA) will reach the inspired gas concentration
- Higher inspired gas pressure with decrease breaths to unconciousness
- 8 % desflurane will cause unconciousness in less breaths than 1%
Describe over pressurization?
Example?
- Increasing PI by a large amount will result in a rapid loss of conciousness
- Left at these high levels will result in overdose
- 1 vital capacity breath of 7% sevo will result in loss of eyelash reflex
What is the second gas effect?
- Uptake of a high volume gas (N2O) accelerates a concurrently administered companion gas
- A high volume of N2O is highly diffusable and is taken up quickly into the pulmonary capillary
→ this leaves a high concentration of the second gas in the alveoli → second gas will be uptaken more rapidly now due to the gradient created
Nitrous like to diffuse into ____
air-filled cavities (inner ear, intestines, lung)
How much nitrous can diffuse into an air filled space in the first 10-15 mins of administration?
10 L
What effects the magnitude of pressure exerted by nitrous administration?
- Compliant vs non-compliant walls
- Partial pressure of nitrous oxide
- Blood flow to the cavity
- Duration of administration
What 2 specific pathologies are contraindicated for nitrous administration?
- Pneumothorax - will greatly increase size
- Intraocular procedures - will cause retinal artery compression and vision loss
How does increased alveolar ventilation affect induction of anesthesia?
Increased RR increases the speed that alveolar pressure reaches inspired gas pressure, speeding up the rate of induction
Hyperventilation will cause a decrease in __________ which will decrease cerebral blood flow (vasoconstriction) and limit the speed of induction.
PaCO2
Differentiate between spontaneous ventilation and mechanical ventilation of inhaled anesthetics?
Spontaneous ventilation has a dose-dependent depressant effect on alveolar ventilation (negative feedback loop). As a person falls more asleep their CO and ventilation decrease, decreasing the amount of anesthetic offloaded from the alveoli and going to the brain. This causes the gas to move from high (brain) to low (tissues) concentrations and the patient wakes up a little more. As they wake up, they breathe faster, inhaling more gas, causing deeper anesthesia. Bascially, the body can regulate how anesthetized it is.
With mechanical ventilation, the body is not able to provide a negative feedback loop. The ventilator will continue to administer molecules at a set rate and can lead to overdose.
Define solubility of inhaled anesthetics?
What is solubility dependent on?
- A ratio of how the inhlaed anesthetic distributes between two compartments when partial pressures are equalized (capacity of each compartment to hold a volatile).
- Temperature - the higher the temp, the more likely the gas wants to leave the blood and move to the tissues (less soluble in the blood = faster induction)
Rannk the volatiles from least soluble in blood to most soluble?
- Desflurane (most rapid induction/emergence)
- Nitrous
- Sevoflurane
- Isoflurane
- Enflurane
- Halothane (slowest induction/emergence)
Blood:Gas partition coefficient of Halothane?
2.54 - More blood soluble, slower induction and emergence
Blood:Gas partition coefficient of Enflurane?
1.90 - More blood soluble, slower induction/emergence
Blood:Gas partition coefficent of Nitrous?
0.46 - poorly blood soluble, quick induction and emergence
Blood:Gas partition coefficient of Isoflurane?
1.46 - More blood soluble, slower induction/emergence
Blood:Gas partition coefficent of Desflurane?
0.42 - poorly blood soluble, quick induction and emergence
Blood:Gas partition coefficent of Sevoflurane?
0.69 - poorly blood soluble, quick induction and emergence
Which gas would be better for a morbidly obese patient, sevoflurane or desflurane?
Desflurane- Sevoflurane has a almost 2x the fat:blood partition coeffient, meaning emergence will take longer due to resedation from gas stored in fats
Emergence depends on the rate of decrease in ____
This process begins when the inspired partial pressure of volatile gas is ____
Pbr
0 mmHg
What increases washout of anesthetics from the brain?
- High cardiac output
- Anesthetics not highly soluble in the brain (nitrous 1.1, and des 1.3)
Why does length of anesthetic administration matter for emergence?
- Drug is sequestered in tissues
- Anesthetics may continue to rise in the fat and muscles despite the gas being turned off due to pressue gradients
- This can cause prolonged recovery due to redistrubution back into the blood/brain
Which inhaled anesthetic might you use for a patient that will remain intubated after surgery?
Isoflurane - has a longer emergence which will help keep the patient comfortable during transport to ICU
Which inhaled anesthetics are we more concerened with duration of anesthesia?
The more blood soluble volatiles (halothane, isoflurane)
What is the definition of MAC?
Minimum alveolar concentration (MAC)
The concentration at 1 atm that prevents skeletal muscle movement in response to supramaximal, painful stimulation in 50% of patients.
Same as ED50
What MAC is required to prevent movement in response to painful stimulation in 99% of people?
1.3 MAC
What is the value for MACawake
0.3 - 0.5 MAC
What is the value for MACbar
1.7 - 2.0 MAC
BAR- Blunt Autonomic Responses - very bad
MAC % is based upon what constants?
- 30-55 y/o
- 37 ℃
- 760 mmHg
What is 1 MAC of nitrous oxide?
104 %
What is 1 MAC of Halothane?
0.75 %
What is 1 MAC of Enflurane?
1.63 %
What is 1 MAC of Isoflurane?
1.17 %
What is 1 MAC of Desflurane?
6.6 %
What is 1 MAC of Sevoflurane?
1.8 %
How can you calculate what to turn your vaporizor to?
MAC % of gas ✖️ 1.3
What is the most important factor that alters MAC?
Body temperature
How does age alter MAC?
- MAC peaks at 1 y/o
- For every decade below constant range (30-55) increase by 6 %
- For every decade after constant range (30-55) decrease by 6 %
List the 4 things that increase MAC?
- Hyperthermia
- Excess pheomelanin production (redheads)
- Drug induced increase in catecholamines (cocaine, meth)
- Hypernatremia (membranes depolarize faster)
Factors that decrease MAC? (there are lots)
Hypothermia
Pre-op Meds (BZD), intraop opioids (synergism)
Alpha-2 agonist (decreases SNS)
Acute EtOH ingestion
Pregnancy
Post partum (12-72 hours)
Lidocaine
PaO2 < 38 mmHg
Mean BP < 40 mmHg
Cardiopulmonary Bypass
Hyponatremia
Age
Renal failure
Factors that do not affect MAC.
Chronic EtOH abuse
Gender
Duration of anesthesia
PaCO2 15-95 mmHg
PaO2 > 38 mmHg
Hyper/hypokalemia
Thyroid gland dysfunction
How do volatiles cause spinal immobility?
- Depress excitatory AMPA and NMDA (glutatmate receptors)
- Enhance inhibitory glycine receptors (strychnine - glycine antagonist)
- Blocks presynaptic release of glutamate via sodium channels
How do volatiles cause loss of conciousness?
- Inhibtory transmission of GABA - especially in RAS
- Potentiates activation of glycine in the brainstem
- Does not affect AMPA, NMDA, or kainate receptors
What are the colors associated with the following volatile gasses?
Isoflurane:
Sevoflurane:
Desflurane:
Isoflurane: Purple
Sevoflurane: Yellow
Desflurane: Blue
What is Dalton’s Law?
The total pressure exerted by a gas mixture is equal to the sum of the individual gas partial pressures
What is vapor pressure?
- The pressure at which vapor and liquid are in equilibrium
- Evaporation = condensation
- A higher vapor pressure means the gas is more likely to evaporate (lower boiling point, more volatile)
What affects vapor pressure?
Temperature - heat increases vapor pressure and cool decreases vapor pressure
What is the vapor pressure of Halothane?
243 torr
What is the vapor pressure of Enflurane?
175 torr
What is the vapor pressure of Isoflurane?
238 torr
What is the vapor pressure of Desflurane?
669 torr
Means will evaporate readily at sea level
What is the vapor pressure of Sevoflurane?
157 torr
How can you calculate volume percent of an anesthetic?
partial pressure / total pressure
How does a variable bypass vaporizer work?
A control dial is turned that opens pores to allow fresh gas to mix with gas in the vaporizing chamber- the higher it is turned up, the more fresh gas is allowed in and higher anesthetic taken to the patient
How does a flow over vaporizer work?
- Increases efficency of vaporization by increasing the gas-liquid interface (allows fresh gas to mix more with the anesthetic)
