Anesthhetic Pharmacology (Mod 2) Flashcards
Pharmacodynamics vs Pharmacokinetics?
- Deals the mechanism of drug action (anticholingerics/mimetic and that crap)
- What does the body do to the drug (i.e metabolism)
Define Induction
Transition from an awake state to an anesthetize state
Define Recovery
State of consciousness of an individual when hey are awake or easily arousable and aware of surroundings following the elimination of an anesthetic
What is the purpose of inhaled anesthetic agents?
Inhaled anesthetic are primarily used to maintain the anesthetic state AFTER induction by some other agent (like propofol)
What is the ciruclation/distribution pathway of inhaled anesthetic?
Distributes well to all parts, but becomes most concentrated in the fatty tissue
- this occurs because this area is not as well vascularized
- it gets held because it takes longer to get there and exit (its more like a storage place where it gets saturated as a uptake area)
What is Minimum Alveolar Concentratino (MAC)
- Important
Dose that we’re going to providing, but it is not dose specific. It’s the minimum we need.
- Levels associated with partial pressures to deliver the desired range by varying the inspired partial pressure (Pi)…we set this. measure is not precise
- Controls the depth of anesthesia, anesthesiologist have precise control of the level of anesthetic in the CNS
How is level of anesthetic in the CNS (Pcns) determined?
The CNS partial pressure (Pcns) is monitored via alveolar partial pressure (Palv) because it cannot be directly monitored.
- its a substitute method for Pcns because Pcns tracks palv with only a small lag time
How is alveolar partial pressure (Palv) measured?
Palv is measured directly as the partial pressure of anesthetic in the end tidal exhaled gas, when dead space no longer contributes to the exhaled gas
Why is the potency of anesthetic is related inversely to its Minimum Alveolar Concentration (MAC)
- what doe sit mean?
- edit this is a important point
MAC is alveolar partial pressure that abolishes a movement response to a surgical incision in 50%, so you need to give MORE than you need bc they may not be affected by it
- If the MAC is small, the potency is high and relatively low partial pressure of anesthetic will be sufficient to cause anesthesia
- MAC is associated with how much drug they are getting, partial pressure deals with how it is being delivered??? —> Partial pressure is associated how much more gas is needed to deliver the drug itself, lower MAC needs less partial pressure
What is the alveolar partial pressure that results in the lightest possible anethesia called?
Minimum alveolar concentration (MAC)
What could be indicators of movement response if a paralytic is applied?
Vitals such as HR.
- so the patient may not necessarily grimace or flinch in response to surgical incisions
What MAC concentration do you typically want to aim for?
edit
1.1-1.3
- as you increase the dose, more people will not response to surgical incision
- standard deviation is approx 10% (MAC + 1SD)
- Example: Refer to slide 7. to achieve 68% anesthetic state, you want to multiply the partial pressure MAC (slide 8) of a drug by 1.1
How are separate douses of anesthetic gasses admined overtime over affect?
Effects of anesthetic are additive (they stack)
- 0.5 of 1 in combo w/another 0.5 drug will increase potency to 1 MAC of a single agent
What conditions would require a patient to need a higher MAC (increased MAC) of anesthetic gas?
- aka more mac needed to induce them
- Pt with Hyperthermia
- Chronic alcohol abuse
- Pt with that drug use or amphetamines, and CNS stimulants (they have higher tolerances)
What conditions would require a patient to need a lower MAC (decreased MAC) of anesthetic gas?
- aka less mac needed less to induce them
The following will need less anesthetic drug use:
- Advanced age
- Hypothermia
- Severe hypotension
- Otehr agents; opiates, valium
- Acute drugs or ETOH into
- Pregnancy
- High PCO2 or Low PO2
What is the Meyer Overton Rule?
Oil/gas partition coefficient that helps us understand the potency of the anesthetic gas
- As the oil/gas partition increases, MAC decreases
- The potency of an anesthetic increases as its solubility in oil increases
- The gases do not bind to receptors, they disrupt the nervous system in the body enters the lipid bilayers in the CNS
What are the benefits of using a mixture of inhaled anesthetic gasses? (3)
Allows for:
- Anesthetic potency
- Recovery
- Inhaled agents and IV agent combinations allows for the above goals to be achieved
What are pharmacokinetics characteristics of an ideal inhaled anesthetic? (2)
- Provides a rapid and pleasant induction of surgical anesthesia
- Provides a smooth and rapid recovery to a fully functional and concisions state
what factor limits the transfer of anesthetic in both lungs and the tissue in terms of capillary beds and blood?
Perfusion rates rather than difffusion rates
- The transfer of anesthetic is limited by perfusion rather than diffusion
- increasing the rate of diffusion will not increase the rate of induction of anesthesia
In the realm of the pharmkinentics of anesnethic gasses; what does the concept of compartments refer to?
The different spaces agents need access to, to achieve their desired effect
What pathway does anesthetic gas generally diffuse within the body?
- Pt breathes in gas (spontaneous or via vent)
- Anesthetic reaches the alveoli; must diffuse across the AC membrane into the pulmonary capillaries
- Gas should diffuse into the blood
- Blood brain barrier (site of action) aka CNS
Why is partial pressure of alveolar and systemic arterial pressure nearly the same in healthy adults?
edit
- add more to this card aka be more specific
The lungs optimize gas diffusion and Inspired Partial pressure
- The capillary beds in tissues delivery oxygen rapidly to all cells in the body through a series.
- The end goal will be D, but gas will still pass through ABC eventually filling the capacities in this areas
- All compartments will equilibrate to equal Pi
What does a compartments equilibrium depend on?
The volume capacity and flow rate of blood (and subsequent diffusion) -> which is perfusion limited.
- Blood flow refers to level of blood flow delivering anesthetic
- Equilibrium of partial pressure of the compartment with he incoming flow takes place more quickly when the inflow is larger or compartment capacity is smaller
What is the primary determinant of diffusion?
Partial pressure of gas
What are the compartment groups for distribution of blood to tissues? (4)
slide 19
- adjust later
- Vessel Rich Group (VRG)
- Muscle Group (MRG)
- Fat Group (FG)
- Vessel Poor Group (VPG)
When does Movement of agents stop?
when pressure equilibrium is achieved because no pressure gradient exists
Which tissue group receives
How do you speed up induction of anesthetic gas?
Increases MV (via rr and vt)
- Its all about the partial pressure of gas; you have to increase the partial pressure of the inhalant anesthetic
- If Vt increases but partial pressure remains the same, the speed of induction won’t increase
What is the first step of equal ration of partial pressure of VRG (Pvrg)?
Managing Pi (inspired partial pressure)
- Palv results from the balance between delivery by ventilation and removal by uptake into the blood stream (Part); dynamic process.
- Think about the concentration gradient like a cup with a hole. 1 drop for every 3 drops leaving will leave in total water levels dropping
- The Palv is constantly dropping basically
What methods can increase the delivery of anesthetic? (2)
- Increased ventilation
- Increased Pi to raise Palv
What factors could lower anesthetic uptake/affect aka lowers the Palv?
- Increased uptake into the bloodstream caused by a large blood/gas coefficient (Increased solubility of a anesthetic into the blood) —> ask about this point later think about it as peeing in a pool vs a river stream => the pee leaves faster out of the river than the pool
- Increased cardiac output (CO)
Equilibrium of Palv with Pi is faster with what factors? (3)
- Lower blood solubility (Small B/G coefficient)
- Lower CO
- Smaller arterial to venous partial pressure difference
oil gas partition vs partial pressure alveolar equilbrium?
- look into it
- Deals with potency/concentration
- Deals with solubility
What does a small b/g coefficient imply?
- aka what does a low solubility mean?
A low solubility means it doesn’t bind well with the components in the blood (like albumin for example)
What does a large b/g coefficient mean
The anesthetic is soluble in blood
- It takes longer for the blood to become saturated with a large b/g coefficient agent: Palv = Part take longer
- This means that blood can hold more anesthetic agents with a large B/G compared to an agent with a low b/g. it will require more to acquire the anesthetic state
What is equilbrium of tissue with alveolar partial pressures fast?
Changes to Palv are transmitted rapidly to systemic arterioles bc equilibrium across the pulmonary capillaries is fast
- The circulation time from pulmonary veins to issue capillaries is generally less than 10 seconds
What are the implications of a high rate of uptake of anesthetic ino the blood stream?
Prevents Palv from rising rapidly meaning there will be
- Slow induction
- Slow recovery
What must occur for induction to occur?
Palv must equilbrium with Pi
- Palv can only equilbrium with Pi when Pvrg is in equilbrium w/Palv
- Recall: Large blood/gas (b/g) coefficient limits the rate of alveolar uptake (highly soluble in blood) -> if gasses dissolve into the blood, they leave and disrupt equilibrium
- slide 26
Can anesthetic displace oxygen in the blood?
Yes; you need to mix the gasses with oxygen.
- potent is kept and maintained at a certain rate to maintain the anesthetic state
What are ventilation factors that limit anaesthetics?
- slide 26
b/g coefficent: Partial alveolar pressure must equilibrate with partial inspired pressure for induction to occur.
- Partial alveolar pressure can only equilibrate with Pi when pressure in the VRG is in equilibrium with partial alveolar pressure
Does a combination of a tissue low capacity and high blood flow result in?
Short equilibration time
what exerts a partial pressure and in turn increases induction in the realm of the blood/gas (b/g) model?
- hint think solubility
Lower capacity; less gasses bind to less proteins which means more gas moves into the plasma. You want a small b/g coefficient.
- Equilibrium occurs faster with more pressure and hence faster induction
- if binded to a protein, it won’t exhibit a pressure; you want a pressure to create the induction affect
Why is a high solubility less desirable in induction? (large b/g)
More gas molecules will bind to proteins and less gas moves into the plasma. causing:
- Less pressure (bc its binded to proteins)
- Will require more gas to increase pressure bc they’re binded to the proteins in the blood
- Remember: free floating gasses in the blood exert pressure (those that move from alv to blood)
True or False: Anesehtics that are less soluble in blood induce anesthesia faster
True
- The more solvable the agent (high b/g coef) the faster the uptake into the blood, the slower the induction (slowly increases the partial pressure within the blood and VR)
Perfusion invited anaesthetics?
- slide 27
Add info from slide 28
(Applications of the uptake model)
Why does partial pressure take a long time to buildup in the scheme of venous return?
Why does hypoventilation slow induction?
Decreases the delivery of anesthetic to the alveoli
- removal of anesthetic from the alveoli continues (if no change to CO)
- Palv rises more slowly and equilbrium to Pi is prolonged
Why would be want anesthetic induced hypoventilation?
Sets up a beneficial negative feedback loop on the depth of anesthesia
- Increased anesthetic depth leads to resp. depression. Depressed ventilation slows the rate of rise of Palv while perfusion continues to remove anesthetic from the lungs at the same rate
- Palv falls and shortly after the Pcns falls in teh relief of resp depression
How does a decreased cardiac output after the uptake model in anesethics?
Decreased CO speeds induction.
- when CO falls, the bloodstream removes anesthetic from teh alveoli at a slower rat resulting in an increase in Palv
Why is cardiac depression dangerous in the realm of anaesthetics (consider the uptake model)
Can set up a harmful positive feedback loop
- Increasing Pcns depresses cardiac function which further increases Palv which further increases Pcns which further depresses cardiac function
- counter w/a beta 1 agonist
Why does induction occur faster in children than adults?
Relative to adults, a greater proportion of the blood flow serves the VRG in children
- The increased cardiac output and lower capacity of the tissues for anesthetic in children relative to adults both accelerate the rate at which tissues become saturated with anesthetic
True or False: Do adults induce faster under anaesthetics than children?
False; children induce faster
What are induction and depth of anesthesia largely affected by?
Changes in ventilation and cardiac output (In the realm of partial pressure of inspired gas delivered)
- The particular general anesthetic, the surgery and other physiologic or pathophysiologic process can effect ventilation and cardiac output
What is Partial pressure of mixed venous return (Pmvr)
The weighted average of the partial pressure in each compartment (tissue group)
- Pvrg makes the largest contribution because VRG receives the majority of cardiac output (CO)
Why do changes in ventilation and cardiac output have a greater affect early rather than later in the course of anesthesia?
Partial pressure of mixed venous return (Pmvr)
- The gas will still be in circulation via venous return
True or False: The affect of induction is largely dependant on Palv and Pvrg being at equilbrium?
True
What happens when Pmvr approaches Pi?
The blood stream can’t remove much anesthetic from the lungs; changes to ventilation and perfusion will have little effect on Pcns
MAC vs B/G coefficient?
- Depth of Anesthesia
- Speed to induction
Does Hemorrhagic shock have a faster or slower than usual induction?
Faster
- Decreased Cardiac Output: Accelerate the raise of Palv
- Hyperventilation: Accelerate the raise of Palv
- PMVR increases since shock states increase perfusion to PVRG
Does V/Q mismatch (COPD) have a faster or slower Than Usual Induction?
Slower.
- Over perfused (under ventilated) alveoli contribute a larger percentage to the overall perfusion;
- The weighted average partial pressure of anesthetic in the blood leaving the lung is decreased
- Gas is not entering the arterial blood cause its not exiting the alveoli
How do you displace the residual gas that remains during emergence/recovery post anesthetic state?
Increase oxygenation (so that it can mix in with the remaining gas)
- ensures oxygen can still make it into the blood when all the gasses displace
diffusion hypoxia
Why does Hemorrhagic shock increase induction of anesthetic?
- Decreased cardiac output: accelerates the raise of partial alveolar pressure
- Hyperventilation: accelerate the raise of partial alveolar pressure
- pressure in the muscle rich groups: Increases since shock states increase perfusion to pressure in the VRG
What is the most effective method to remove anesthetic from the blood stream in recovery?
Increased ventilation accelerate recovery and 100% or mixed oxygen
In recovery, what is the concentration gradient of partial pressure of gasses in the system?
Pmvr is the weighted average of Pvrg, Pmg, and Pfg
- Pvrg making up the largest contribution
What can occur during recovery due to the concentration effect?
The diffusion effect
- caused by the outflow of high partial pressure of nitrous oxide into the lung
- Since N2O go in fast, they exit fast. They leave a void usually upkept w/a volatile gas
TLDR of second gas effect, how are potent gasses affected?
Potent gasses with slower induction times have a faster uptake when paired with a gas with a quicker induction time…why?
- bc the concentration of gasses remaining in the alveoli is increased (i.e N2O leaves quickly)
How do you counter diffusion hypoxia?
Provide 100% hypoxia for a few minutes to reduce the displacement of oxygen being pushed out by other gasses
What is Diffusion hypoxia?
Occurs when anesthesia is terminated
- nitrous gas diffuses out of the blood into the alveoli at a high rate bc of the high partial pressure difference between 2 compartments
- volume of nitrous oxide displaces up to 1L/min of air that would otherwise have been inhaled which leads to a reduction in alveolar and arterial partial pressures of oxygen
why is a IV route faster acting that a oral route?
Oral routes need to work through the stomach and the liver. IV goes directly to the CNS/brain
- They also can’t be removed by the body via ventilation
Why is it favourable to use a IV anesthetic?
Fast distribution to the site of action (brain/CNS) = fast induction
What is the titration of dose to effect?
How IV anesthetics should be intimated and maintained
- Dose can be slowly increased until the desired effect is achieved then maintained by slow continuous infusion.
- What impact does it have on the pt?
What is Tissue Up Take of IV anaesthetics dependant on?
Rate and amount of drug absorption is propionate to the blood flow and the tissue mass
- high perfusion or vessel rich organs receive peak concentrations of drug within 30-60 seconds
Why is continuous infusions monitoring and maintaince important
- hint consider tissue up take
As time passes, concentration of drug in the large muscle mass can exceed that of the brain (5 to 10 minutes) therefore continuous infusion is necessary.
- Lipid soluble agents will also be taken-up by fat tissue. The rate may be slow (poorly perfused) but the high mass will cause continued absorption by this tissue, and later, expect slower recovery or more residual effect after administration is discontinued.
How are IV drugs removed from the body?
Metabolism and excretion
What is a balanced anesthesia
A combination of several inhaled and/or IV drugs used to produce the anesthetic state
- no single drug hits all the goals of anesthesia
- effects of simultaneously administered general anesthetic are additive
0.5 MAC of one inhaled anesthetic in combination with 0.5 MAC of another is equivalent in terms of potency of 1 MAC of either anesthetic as a single agent (edit this point)
What does a mixture of inhaled anesthetics allow?
- Anesthetic potency
- Recovery
- IV and inhaled agent combos allow for the above as well
What affects can be expected with a IV and inhaled agent combo?
Short acting IV agents can be used to induce stage 3 anesthesia
- Anesthetic depth can be maintained w/inhaled anesthetics the could be removed by ventilation
- IV agents act additively with inhaled anesthetics; less than 1 MAC of inhaled anesthetic will be required as long as IV agent present
How is MAC affected for inhaled gasses when paired with IV agents?
Bc IV agents act addivtely w/inhaled anesthetics
- less than 1 MAC of inhaled agent will be required as long as the IV agent is present
What is the main benefit of balanced anesthesia?
Allows for more control since a separate drug is used to mediate each desired effect
i.e
- If the surgeon requires more muscle relaxation the anesthesiologist can administer more NMB without having to increase the depth of anesthesia (and risking cardiopulmonary depression).
- A bolus of short acting opioid can be administered immediately before a particularly painful surgical maneuver
What will speed induction?
- Hyperventilation
- Decreased cardiac output
- Children
- Hemorrhagic shock (Pmvr increases)
What will slow down induction?
- Hypoventilation
- Increased cardiac output
- Older adults
- VQ mismatch- COPD (over perfused alveoli)
What happens when Pi = Pmvr?
Bloodstream will have a harder time to remove anesthetic from lungs.
- Ventilation and perfusion will have limited effect
What happens when Palv is lower than Pi
Pmvr is much lower and bloodstream is capable of taking the anesthetic from lungs to tissues. Equilibrium has not been reached yet.
What is Partial pressure mixed return venous return (Pmvr)?
Pmvr is the average of the partial pressure of all compartments
Ventilation limited anesthetics
Large BG coefficient; high uptake rate of anesthetics into the bloodstream prevent partial alveolar pressure from rising rapidly.
- Increased solubility will prevent Palv from rising as Palv cannot equilibrate with Pvrg fast enough
Perfusion limited anesthetics
small BG coefficient; low solubility allows to Palv to rise fast and Palv = Pi faster
How can depth of anesthesia be changed?
Changes in ventilation and cardiac output
Beneficial negative feedback loop anesthetic induced hypoventilation
- how does hypoventilation slow anesthesia?
Increased anesthetic depth causes respiratory depression, slower RR will slow anesthetic delivery, allowing for anesthetic to be removed from lungs at the same time
- Palv slowly falls and PCNS falls resulting in resuming ventilation
- used sometimes for intubation
harmful positive feedback anesthetic induced cardiac depression
increasing PCNS will depress cardiac function, causing slowed CO, resulting in faster delivery of anesthetic, causing further increase of PCNS to depress cardiac function even more
Recovery order?
Opposite from induction
- PMVR - Palv - Pi
How to speed recovery post op anesthesia?
Increase ventilation to remove anesthetic form alveoli faster (and flood 100% o2)
Input of anesthetic depends on
- Pi
- Alveolar ventilation rate
- Breathing system used
Uptake of anesthetic depends on?
- solubility (BG coefficient)
- Cardiac output
- Pressure gradient between alveolar and venous
Second gas effect
- High Pi of first gas N2O quickly goes into bloodstream, leaving a large concentration gradient.
- In new breath, new second gas concentration will add on top and increase the alveolar concentration of second gas.
What pathologies and disorders would slow induction?
- COPD
- Hypoventilation: Anesthetic induced hypoventilation sets up a negative feedback loop on the depth of anesthesia
- Old age
If we set a partial pressure to a set mat that induces the patient, what do we have to ensure occurs for induction?
We have to ensure CNS partial pressure equilibrates with what we set
- Partial pressure is dynamic, we maintain partial pressure in the system, for everything leaving the same amount is going in to equalize the partial pressure
How is partial alveolar pressure raised?
By increased delivery of anesthetic from either increased ventilation or an increased Pi.
- partial alveolar pressure results from the balance between delivery by ventilation and removal by uptake into the bloodstream
How does a large b/g coefficient as a result of increased uptake into the blood stream affect partial alveolar pressure?
Lowers partial alveolar pressure because there is an increased solubility of an anesthetic into the blood, that or a increased cardiac output has occurred.
- high solubility of anesthetic binds to components of the blood and doesn’t create partial pressure, free flowing in plasma creates a partial pressure
Why does increased cardiac output slow induction time for anesthetics?
Increased CO slows the time to induction because a increased flow of blood moves through the lungs more quickly, taking the partial pressure drop much faster
- It delivers quicker but its a dynamic system so whats going in quickly comes out quickly
How is induction time affected by a unresponsive person?
Unresponsive person will reach equilibrium faster, meaning anesthetic affect occurs quicker
High blood gas coefficient vs low blood gas coefficient?
- A higher blood gas co-efficient means more inhaled anesthetic will dissolve in the bloodstream as it passes the lungs reducing partial pressure of the anesthetic in the alveoli (slower induction)
- Lower blood gas coefficient increase partial pressure in the lungs because it is less soluble in blood so it will dissolve less readily into the blood stream and more of the inhaled anesthetic will be in the lungs
(facilitates faster onset of action and recovery)
Equilibrium of partial alveolar pressure with partial inspired pressure is faster with: (3)
- small b/g coefficient
- lower cardiac output
- Smaller arterial to venous partial pressure difference
Why do VRG like the CNS equilibrate faster?
he combination of low capacity and high blood flow results in a very short equilibration time.
Why does P(MVG) rise faster in kids compared to adults?
A greater proportion of CO reaches the VRG causing P(MVG) to rise faster
