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Pharm1 Test2 Inhalationals Barry University

True or false: General anesthetics can include IV and/or inhalational agents. True.
What makes general anesthetics dangerous? They have low therapeutic indices, thus potentially dangerous requiring careful administration and monitoring.
Though SE and other effects differ wildly, all GE have the same basic effect, which is what? Unconsciousness.
"Balanced anesthesia" is using a combination of several agents. Why is this done? To allow reduced dosages, and thus decrease risk of toxicity.
What is the goal of general anesthesia? To produce CNS depression sufficient to cause unconsciousness and lack of response to external stimuli.
What was the original inhalational anesthetic? Diethyl Ether.
Who discovered the original inhalational anesthetic, Diethyl Ether? Morton, in the 1840's, for dentistry.
What was the problem with most inhalational agents prior to the 1950's? They were either flammable or had a high potential toxicity.
Fluorine-containing alkanes were introduced to reduce flammability, but what else did they bring as a SE? Cardiotoxicities.
Ether derivatives of fluorine-containing alkanes were created to reduce cardic toxicity, but what were their major SE? Fluoride-induced nephrotoxicity.
True or False: Newest ether derivatives cause more fluoride-induced nephrotoxicity. False. Newest ether derivatives have decreased fluoride toxicity.
To occur, what two things does Osmosis require? A semi-permeable membrane and a difference in concentration of solutes on each side of the membrane.
How does osmosis affect large and small molecules differently? Allows small molecules to equilibrate concentrations, but not large molecules such as Albumin (MW ~ 69K.
What is Fick's law of diffusion? Diffusion Rate = (P1-P2) (Area) (Solubility)/(Membrane Thickness)( Sq. Root of the Molecular Weight)
According to Fick's law of diffusion, diffusion rate is directly proportional to what three things? The partial pressure gradient, membrane area, and solubility of a gas in the membrane.
What is another way of expressing the partial pressure gradient? P1-P2.
According to Fick's law of diffusion, diffusion rate is indirectly proportional to what two things? Membrane thickness and sq. root of the molecular weight.
What is Graham's law of diffusion? The rate of diffusion of the gases is inversely proportional to the square root of the density of the gas.
What is it called when we assume all gases have the same number of molecules at the same temperature and pressure? Assuming ideal gases.
Assuming ideal gases, the density of a gas is directly proportional to what? The molar mass of the gas.
Since the density of a gas is directly proportional to the molar mass of the gas, then according to Graham's law of diffusion, the rate of diffusion is inversely proportional to what? The square root of the molar mass of the gas.
What is Henry's law? The amount of a gas that will dissolve in a liquid is proportional to the partial pressure of the gas in the gas phase.
What does Henry's law allow us to determine? amounts of gases (O2 and CO2) that dissolve in blood.
What is laminar flow? A smooth, streamline type of viscous flow in which the fluid behaves as a system of orderly layers, with no eddies or irregular fluctuations.
What is turbulent flow? A flow in which the particle movement is not straight or parallel, but chaotic, eddying, etc.
What is turbulent flow due to? More random movement of molecules in flow and interactions with ‘tubing’ walls.
Resistance increases proportionally with... Flow.
Where is turbulent flow more likely to be seen? High flow rates, in rough tubing, in areas of tubing kinks and bends, or sudden changes in tubing diameter
What is Reynolds number used for? A factor used to help predict laminar/turbulent flow.
What is the equation for Reynolds number? Re = Linear Velocity x Diameter x Fluid Density / Fluid Viscosity
What Reynolds numbers are associated with laminar flow? Below 1000.
What Reynolds numbers are associated with turbulent flow? Above 1500.
For what kind of flow can we apply Poiseuille’s Law? Only laminar flow.
What is absolute humidity? The mass of water vapor in a given volume of air.
What is relative humidity(%)? (Actual vapor pressure / Saturated vapor pressure) x 100
As the temperature decreases, what happens to air's ability to hold water vapor? It decreases, and water will condense out of the air.
What is the dew point? The temperature at which water begins to condense out of the air.
What is Ohm's law? E=IR E = energy (in Volts) I = current (in Amperes) R = resistance (in Ohms)
Why do we use Ohm's law? To quickly tell if too much current is being drawn from source.
Why is the Oil:Water partition coefficient important? To cross membranes and explain action in membranes.
Why is the Blood:Gas partition coefficient important? It shows us the ability of the agent to move from the gas phase to the blood.
Define % Inspired Air: The percentage of the inhaled air that is occupied by the anesthetic gas.
True or False: the % inspired air is the same with all anesthetic gases. False. It varies greatly with differing agents.
How is the % inspired air controlled? With the anesthesia machine.
Why do we use alveolar partial pressure? It is used as a determinant of brain partial pressure
Partial pressures are similar to... Concentration of a gas.
Alveolar partial pressures helps us determine... Depth, recovery time, and potency.
How is alveolar partial pressure(PA) determined? Input amounts minus uptake amount.
On what do we base alveolar partial pressure (input amounts minus uptake amount)? Input based on inhaled partial pressure (PI) and alveolar ventilation. Uptake into pulmonary capillary blood depends on tissue solubility, cardiac output and partial pressure differential (PA – PBlood).
What is inhaled partial pressure? Delivery amount by anesthesia gas machine.
How does inhaled partial pressure change over the course of the case? It is normally high at start, until brain equilibration begins, then turned down to match uptake and balance loss.
What does the concentration effect tell us about inhaled partial pressure (PI)? The higher the PI, the more rapidly PA approaches PI.
Why do we want to keep PA(alveolar partial pressure) high at first? To ensure PBlood stays high even with uptake.
What happens when we remove anesthesia gas from lungs? It decreases lung gas volume, which is then filled with additional gas.
How does the "second gas effect" work? The removal of PI(inhaled partial pressure) anesthetic results in smaller lung gas volume which is filled with additional gas, thus concentrating second gas (higher PA) and allowing more to be taken up.
What is MAC (minimum alveolar concentration)? The minimal concentration of the agent (in % of total gas mixture) at 1 atm in the alveolus at steady state that will inhibit pain response to surgical incision in 50% of patients.
What is another word for MAC? ED50(Effective dose for 50% of patients).
True or False: Red headed women take more anesthesia (have a higher MAC)? True.
Why does MAC decrease with age? Less body fat.
MAC is additive with... Each anesthetic agent used in combination.
What do opioids do to MAC? Decrease it.
MAC is used as a measure of anesthetic... Potency.
How does high lipid-solubility of an agent affect MAC? Lowers it.
True or False. MAC value predicts induction time. False. That time is dependent on solubility in blood.
How much population variation is there in MAC? ~10%-15%
For each agent, MAC correlates to how many micromoles per 100mL of membrane at steady state? 500 micromoles per 100mL.
What is the Unitary Theory of Narcosis? All anesthetics have a common method of action.
What is the Meyer-Overton Theory? Strong correlation between lipid solubility and potency.
What data supports the Myer-Overton Theory? more lipid soluble agents are more potent anesthetics, points to a lipophilic action in some region of the brain, most likely site is membrane, affecting fluidity.
What does the Myer-Overton Theory suggest about an agent's action at the membrane? That it is the number of molecules dissolved in the membrane, and not the specific agent which causes the effect.
What data does not support the Myer-Overton Theory? Some agents with similar solubilities (partition coefficients) have different potencies, suggesting other factors, and not all very lipophilic substances are good anesthetics.
What is the Critical Volume Hypothesis(Mullins)? Binding of anesthetic agent into membranes causes membrane to expand.
How does the Critical Volume Hypothesis suggest that expansion of the membrane causes unconsciousness? It alters the action of receptors and/or ion channel proteins locked into membrane.
What does the Critical Volume Hypothesis fail to explain? Why some hydrophobic substances are poor anesthetics.
What are some "other theories" of mechanism of inhalational anesthetics? Larger molecule size increases membrane expansion, and binding of agent to membrane proteins in lipophilic regions alters protein (Na+ ion channel) function.
The Membrane Concentration Rule provides a quantitative explanation of the mechanism of inhalational anesthetics. Define: When membrane excitability is blocked, the concentration of the agent in the membrane is 500 umoles per 100 ml of membrane volume. This equals 3 x 1020 molecules (since Avogadro's number = 6 x 1023 molecules per mole) per 500 umoles.
Using this rule, predictions of each anesthetic agent hold up well when compared to their anesthetic potency. The Membrane Concentration Rule.
What is the problem with physical theories of the mechanism of inhalational anesthetics? Impossible to explain why some entantiomers (which have exactly the same physical properties) have different anesthetic potencies or effects.
What is an example of two entantiomers of an inhaled anesthetic that have different properties? L-isoflurane more potent than d-isoflurane at enhancing presynaptic potassium conduction which leads to presynaptic inhibition.
What do the differing effects of two entantiomers of an inhalational anesthetic prove? Mechanisms other than just lipid solubility effects must be responsible for activity.
How are inhalational anesthetics currently believed to work? Interactions with specific receptor-binding sites.
Different inhalational anesthetic families act on different... Receptors.
Why do we have problems understanding the mechanisms of inhalational anesthetics? Elucidation of mechanism very difficult due to complexity of CNS.
What are some of the various ways to produce unconsciousness? Via effects on peripheral neurons, spinal cord, brainstem, or other specific brain areas.
What effects are shown to be caused by an inhalational agent's action on the spinal cord? immobilization in response to surgical incision. However this effect is not the likely cause of amnesia or analgesia.
Inhalational agents depress thalamic neurons. What do those neurons normally do? They act as the gateway for sensory information to reach the cerebral cortex, and enter "consciousness."
What happens after damage to the thalamocortical neurons? Permanent unconscious state.
How do IV and inhalational agents cause amnesia? By acting on the hippocampal neurons, which are important in memory formation.
True or False: In the past 15 years, much evidence has been found to discredit the Receptor Interaction theory of inhalational anesthetics. False. Evidence supports this theory.
The inhalational agents are believed to bind to various proteins (such as channel proteins) at specific sites for each agent. What do they do there? Cause activation of GABA-mediated chloride ionophores in the brain which may trigger cell hyperpolarization, thus less likely to be able to be stimulated, thus decreasing passage of signals between neurons.
Where are inhalational agents thought to act outside of the brain? Cell hyperpolarization seen on Glycine-mediated chloride ionophores in brainstem and spinal cord.
True or False: Inhalational agents may inhibit certain glutamate-mediated excitatory calcium channels (NMDA channels)and increase postsynaptic release of some neurotransmitters. False. They may inhibit certain glutamate-mediated excitatory calcium channels (NMDA channels)and ALSO INHIBIT postsynaptic release of some neurotransmitters.
What are the structures of inhalational agents? Alkanes, Ethers, and chlorinated/fluorinated analogs mainly.
What are the stages of anesthesia? Stage 1 from initiation to loss of consciousness Stage 2 called the delirium phase (from loss of consciousness through restlessness to calm state. Stage 3 is stage where surgery performed. Stage 4 is point of imminent death.
What is general anesthesia? The loss of all perception.
What are the characteristics of GA? Sleep, loss of pain sensation, inhibition of visceral reflexes, and muscle relaxation.
What are the characteristics of a perfect GA? rapid induction, good muscle relaxation, amnesia (to allow patient to "forget" the process), analgesia, and rapid emergence.
What is the only true anesthetic "gas" that we use (not a vapor). Nitrous Oxide.
Why do we use the blood:gas partition coefficient? To discuss the agent's solubility between the gaseous phase and solubility into blood.
MAC values are not related to time to reach anesthesia because they are taken when? At equilibrium (steady state).
The onset of anesthesia is related to blood/gas solubility, and is thus more rapid for what kind of agents? Less soluble agents.
Older inhalational agents include ethylene and cyclopropane which we no longer use because... They are flammable.
What does Nitrous Oxide smell like? A non-irritating gas, it has a slightly sweet odor.
Is Nitrous Oxide very flammable. It is not explosive or very flammable.
What is the MAC of Nitrous Oxide? 104% (thus would need a concentration of 104% in inspired air to produce surgical anesthesia).
What are some of the advantages of Nitrous Oxide? It is a good relaxant at 10 - 30% in air, and is an excellent analgesic - as good as morphine.
How do the analgesic effects of NO2 compare to Morphine? It is as good as Morphine.
What is believed to be the main action of NO2? Inhibiting NMDA glutamate excitatory receptors, not by GABA enhancement.
What are the effects of Nitrous Oxide's very low solubility in the blood? It rapidly reaches equilibrium, and is rapidly eliminated (excreted unchanged in lungs).
Why do we use NO2 in conjunction with other agents? This allows lower doses of those anesthetic agents to be used, with fewer risks.
What are some adverse effects of long term use/abuse of Nitrous Oxide? Inactivation of vitamin B12, which can then lead to various blood disorders such as megaloblastic anemia, leukopenia, and thrombocytopenia.
Diethyl Ether is a good anesthetic but is no longer used in the US. What are some of its problems? Stimulates catecholimine release, very irritating to the bronchioles, explosive.
What is the problem with Diethyl Ether stimulating catecholimine release? While it helps maintain BP, it can cause arrhythmias.
What is the problem with Diethyl Ether irritating the bronchioles? It causes increased secretions.
Halogenated alkanes and ethers appear to have multiple effects on the CNS. How do they affect receptors? Inhibit post-synaptic excitatory responses and enhances post-synaptic inhibitory response.
How do the halogenated alkanes and ethers act post-synaptically? Potentiates GABA and Glycine effects at post-synaptic receptor channels – shifts curve left.
How do the halogenated alkanes and ethers act pre-synaptically? Pre-synaptic effects leading to inhibition of neurotransmitter release by decreasing calcium inflow into nerve terminal and thus decreasing neurotransmitter release.
Halothane(Fluothane) is D/C'd in the US. What are some of its physical properties? Pleasant smelling, non-irritating and non-explosive.
How does Halothane(Fluothane) affect rubber parts? It is soluble to some extent in rubber, and thus is taken up into some parts and tubing of anesthetic equipment.
How does the body rid itself of Halothane(Fluothane)? Approximately 80% cleared by lungs, with remainder undergoing liver biotransformation.
What is the MAC of Halothane(Fluothane)? 0.76%.
How does Halothane(Fluothane) affect respiration? Produces some respiratory depression and a decrease in tidal volume, resulting in short rapid breaths during anesthesia.
How does Halothane(Fluothane) affect BP? Decreases blood pressure due to cardiac depression and relaxation of vascular smooth muscle (some).
Like all alkanes, Halothane(Fluothane) sensitizes the heart to catecholimines. What does that mean? Arrhythmias can be triggered if catecholamine release is stimulated or exogenously supplied.
Can Halothane(Fluothane) trigger MH? Yes.
True or False: Halothane(Fluothane) has poor muscle relaxant properties, so higher doses of neuromuscular blockers are required. False. While Halothane(Fluothane) does have poor muscle relaxant properties, it potentiates neuromuscular blockers so LOWER doses are needed.
Halothane(Fluothane) toxicity is low, but what adverse outcome has been reported? Hepatitis.
Why has Methoxyflurane(Penthrane) been D/C'd from the US market? Liver metabolism, via P-450 2E1 isomer mainly, (50% of dose) releases free fluoride, which can lead to kidney toxicity.
What causes Methoxyflurane(Penthrane) nephrotoxicity? Actual cause of nephrotoxicity not believed due to liver metabolism, but instead release of free fluoride in nephron by kidney metabolism.
Isoflurane(Forane) is widely used and non-explosive. What does it smell like? It has a pungent odor which may limit its use for induction, somewhat irritating but less then Desflurane.
What are the induction and maintaince concentrations of Isoflurane(Forane)? Induction concentration used - 2-4% (v/v). Maintenance concentration 1 - 2% (v/v).
A very small amount of Isoflurane(Forane) is metabolized. About how much? Less than 1%.
What is the MAC of Isoflurane(Forane)? 1.16%.
Isoflurane(Forane) has mild analgesic effects. How does it assist with muscle relaxation? It potentiates neuromuscular blockers.
How does Isoflurane(Forane) affect the heart? Cardiac depression (some) and decreased blood pressure, but no sensitization of the myocardium to catecholamines (ether structure).
What about Isoflurane(Forane) causes it to NOT sensitize the heart to catecholimines? It has an ether structure.
Enflurane(Enthrane) is an isomer to... Isoflurane(Forane).
Enflurane(Enthane) is not widely used in the US. High doses can stimulate the CNS, leading to... Seizure-like twitching of the muscles.
What is the MAC of Enflurane(Enthane)? 1.68%.
About 2% of Enflurane(Enthane) is metabolized. What does this lead to the release of? Free fluoride ions.
Fluoride ions are freed up by the slight (2%) metabolism of Enflurane(Enthane). What SE can they cause in a long case? Kidney toxicity.
What does the low solubility of Desflurane(Suprane) mean? Rapid induction and emergence.
What is the MAC of Desflurane(Suprane)? 6.0%.
The high vapor pressure (~700 mmHg at 20oC) of Desflurane(Suprane) requires what kind of special vaporizer? A heated vaporizer.
Why don't we use Desflurane(Suprane) often for induciton? It has a pungent odor.
Desflurane(Suprane) is an ether, so it does not sensitize the heart to catecholimines. What is its affect on the cardiovascular system? It depresses BP.
Very little Desflurane(Suprane) is metabolized. About how much? Less than 0.02%.
What is the newest inhalational agent approved in the US? Sevoflurane(Ultane).
What are the benefits of Sevoflurane(Ultane)'s low solubility? Rapid induction and emergence.
What is the MAC of Sevoflurane(Ultane)? 1.71%.
Sevoflurane(Ultane) decreases BP but does not sensitize the heart to catecholimines because of its (blank) structure. Ether.
Approximately 3% of Sevoflurane(Ultane) is metabolized to hexafluoroisopropanol and releasing free fluoride, but why is it not very nephrotoxic? Location where free fluoride is produced appears to be responsible. If fluoride released in nephron by kidney metabolism, it appears to be more toxic. Most free fluoride produced by Sevoflurane is due to liver metabolism.
Why is Sevoflurane(Ultane) less likely to causes hepatotoxicity? It is not metabolized into reactive metabolites.
What does Xenon, an inert gas, smell like? It is odorless and non-pungent.
What is the MAC of Xenon? 63-71%.
Does Xenon cause MH? No.
The mechanism of Xenon is by inhibition of excitatory NMDA glutamate receptors, which makes it similar to what IV drug? Ketamine.
Xenon does not depress (blank), making it different from all other inhaled agents. Hemodynamic functions.
True or False: Like other NMDA inhibitors (Ketamine and Nitrous Oxide), Xenon can be neurotoxic. False. Ketamine and Nitrous Oxide can be neurotoxic, but Xenon is neuroprotective.
Why don't we use more Xenon? High costs and inadequate proof of great benefit have limited current use.
Carbon dioxide absorbents are used in gas machines to allow rebreathing and save anesthetic. What can they do to the halogenated agents? Can chemically break them down.
Below 40 degrees C, there is little carbon dioxide absorbent breakdown of modern anesthetics except for... Sevoflurane(Ultane).
What happens in the CO2 absorbent to allow the temperature to increase to 40-60 degrees C, allowing breakdown of the agents? This temp increase is caused by reaction of soda lime or Baralyme with water vapor and CO2.
What do inhaled agents react with in the CO2 absorbent to break them down? NaOH or KOH in the absorbent.
What happens with significant degradation of the inhaled agents in the CO2 absorber? Anesthetic concentration can be lowered.
What do we do to prevent Sevoflurane(Ultane) from forming the nephrotoxic Compound A? Higher gas flow rates and limited anesthesia times.
If Isoflurane or Desflurane react with dry CO2 absorbent, what bad substance can they produce? Carbon Monoxide.
Why is the risk of inhaled agent reacting with CO2 absorber to form Carbon Monoxide higher on Monday mornings? Because the CO2 absorber has dried out over the weekend and hasn't been changed.
Which inhalational agent is most likely to form CO when reacting with CO2 absorber? Desflurane.
This condition is caused by inhaling CO. Carboxyhemoglobinemia.
Created by: 1592042303



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