question

What are two ways we measure the depth of anesthesia, and what are the main issues with each of these?

answer

MAC - Only 50% won't move on incision! BIS - More likely to have recall if you are using this monitor

question

Who coined the term "anesthesia" after watching a demonstration in the Ether Dome? What year was this? What was his definition?

answer

Oliver Wendall Holmes in 1846 Anesthesia = sleep-like state making painless surgery possible

question

What came first, surgery or anesthesia?

answer

Surgery

question

Who was the first person to recognize a need for the patient to be still during surgery?

answer

Hippocrates in 400 BC. Suggested that all the screaming was distracting to the surgeon.

question

List some trial and error methods for pain relief that existed before the early anesthetic drugs

answer

Opium - fruit of the poppy Alcohol - get them drunk, pass out, won't feel it Coca leaves - chewed for altitude sickness Phlebotomy - bleed them out until they pass out Nerve compression - patient could even do this to themselves Cold - put ice around surgical site

question

What is Dr Liston known for?

answer

He killed 3 people in one surgery. Was amputating a leg (patient died of sepsis) and he cut two fingers off an assisting resident (who died of sepsis) and then cut the coattails off another MD who died of an MI

question

What did the introduction of anesthesia do to the # of surgeries performed? The # of deaths?

answer

Increased both (infection/sepsis caused the increased death #)

question

Why did using medical interns to provide anesthesia fail?

answer

They were distracted by the ongoing surgery and the patient would die from their inattentiveness

question

Discuss the three historical people important in preventing/fighting sepsis in hospitals

answer

Nightingale - promoted cleanliness to decrease infections Pasteur - Germ Theory in 1862 (PCN discovered 1928) Lister - 1867 advocated using carbolic acid to clean hospitals

question

Who was the first Nurse Anesthetist

answer

Sister Mary Bernard

question

Who started the National Nursing Association (eventually became AANA)

answer

Agatha Hodgins

question

Who gave 14,000 anesthetics w/o a single death in the OR?

answer

Alice Magaw (Dr Mayo's nurse)

question

What defined the practice of anesthesia as either medicine or nursing?

answer

Nelson case. Whatever provider is administering it, it falls under that practice.

question

Describe Diethyl Ether (characteristics, etc)

answer

- Made by distilling sulfuric acid with alcohol - Recreational drug used when alcohol taxes increased "Ether Frolicks" - Very slow induction time b/c it is so soluble. Also very long lasting (difficult to wake the person up too) - Cardiac stable drug, and SNS stimulant - Respiratory depression not a big issue

question

Who defined how to prepare diethyl ether? Who wrote about this preparation?

answer

Valerius Cordis His student, Paraclesus (wrote about how chickens in the area responded to it, fell asleep and woke up unharmed)

question

What is Crawford Long known for?

answer

He gave ether to remove neck tumors off a patient, and charged him $2 for it. He cut 2 fingers off a slave child (which caused pain) but the tumor removal didn't cause pain with the ether, and he made the connection between the two.

question

What is William Clark known for?

answer

He used ether on a woman to extract a molar, was reprimanded by his attending for giving a dangerous drug. The anesthetic was excused away as "female hysteria".

question

Describe the first successful demonstration of ether for surgical anesthesia

answer

William Morton in 1846 (student of Horace Wells) 10/16 He had a new denture device that was painful to place, consulted Jackson his chem teacher for advice. Tried to make money off it by flavoring/coloring it and selling it as "lathion" but it didn't work out.

question

Who furthered Morton's work?

answer

Bigelow. He set up a demonstration in the ether dome for a patient with a vascular neck tumor, used an ether inhaler for a slow, controlled delivery of ether.

question

Who was the first person to prepare nitrous oxide? How is it prepared? What else is he known for?

answer

Joseph Priestly (clergyman) He heated ammonium nitrate and iron shavings. He also thought the oxygen in the nitrous would be available for the body to use (false) He discovered photosynthesis He built spas where you could go to breathe in nitrous oxide (air quality was bad back then)

question

What is Humphry Davy known for?

answer

He worked for Priestly Discovered there's a "dose" of gas breathed in Suggested exchange of Co2 for O2 happened in the tissues (respiration occurred in the TISSUES) Wrote a book on how to prepare nitrous, and its use for pain Recognized HR/BP was increasing, but didn't know why (living fast?). Didn't recognize it was due to hypoxia

question

What is Samuel Colt known for?

answer

Invented the 6 shooter revolver, needed money to patent it and sold nitrous oxide as a recreational drug to "live a little faster"

question

Describe Horace Well's contribution to anesthesia

answer

He was a dentist who watched a show where the actors were taking hits of nitrous oxide backstage, then one fell and hurt himself but was not phased by it. His colleague tried it on him, then his intern volunteered for a molar extraction, started groaning = failure. Became addicted to nitrous oxide, died young

question

What do you need for nitrous oxide to be the sole anesthetic?

answer

Need 105% nitrous oxide

question

What was Edmund Andrews known for?

answer

He was the "bodysnatcher" A&P professor who realized the HTN and tachycardia with nitrous oxide was due to hypoxia. He added 20% oxygen Used dissection to teach meds students, would raid Potters field, got arrested, eventually changed laws about donating body to science.

question

Describe properties of chloroform, and who is credited for describing its preparation?

answer

Naturally occurring compound (seaweed). Also used in Teflon, Plexi-glass Not as safe as ether - less CV stable, more resp depression Less n/v compared to ether Narrower therapeutic index compared to ether Caused VTACH b/c it sensitized the myocardium to epi, and if the patient got too light, they got stressed and adrenals released epi. Jean Baptiste Andre Dumas in 1837 was credited for publishing the preparation of this. Suggested using it WITH nitrous oxide for pain relief.

question

Who described pain as coming from actual or potential tissue damage? What anesthetic did he use, and for what?

answer

Sir James Simpson Gave chloroform for relief of pain in childbirth

question

Who was the first anesthesiologist?

answer

Dr John Snow. Gave chloroform to Queen Victoria for the birth of Prince Leopold.

question

List the 11 Standards of Care for Nurse Anesthetists

answer

1 - Perform a pre-anesthesia assessment 2 - Get informed consent 3 - Develop a patient specific plan for anesthesia care 4 - Implement/adjust the care plan as needed 5 - Monitor the patient's physiologic condition "In Constant Attendance". 6 - Timely Documentation 7 - Determine when you can transfer responsibility of care 8 - Safety! Inspect anesthesia machine 9 - Minimize risk of infection 10 - Assess quality of your anesthesia care 11 - Respect/maintain basic patient rights

question

List qualities that would make an anesthetic "ideal"

answer

Fast acting (rapid, smooth) Safe, minimal side effects (no CV/resp depression) 100% reversible Provide all four components of anesthesia Inexpensive No pain on injection, compatible in solution No excitatory activity (skip stage 2) Steep dose/response curve Decreased CMRO2 (cerebral metabolic rate of oxygen) Rapid return to "street readiness"

question

What are the four components of anesthesia?

answer

Physiologic homeostasis Analgesia Amnesia Muscle Relaxation

question

Besides stable vital signs, what does the component of anesthesia "physiological homeostasis" include?

answer

Stable positioning Enough RBC's to carry O2 to the tissues Enough MAP to perfuse the brain Adequate fluid volume status Protecting the patient from the stress response of surgery. Prevent pain stimulus from reaching their brain, so they do not release catecholamines from a fight/flight response.

question

Differentiate between visceral, somatic, and autonomic pain and give examples

answer

Visceral = organ pain. Travels w/SNS nerves up/down chain ganglia from its fetal origin and enters spinal cord w/the dermatome of its original development. Ex: Heart pain felt in L arm/shoulder. Somatic = travels in dermatomes. Ex: Incision Autonomic = travels w/SNS nerves. Sympathetic nerve dystrophies are abnormal upregulation of pain sensation that occurs long after the pain is gone.

question

What is anterograde amnesia?

answer

Wipes out recall/memory from the time the drug reaches the receptor site (and carries forward for many hours)

question

What benefits did we discuss for inducing muscle relaxation?

answer

Facilitate surgical exposure Causes less tissue damage during incision Prevents tracheal injury during intubation

question

How do we determine that the patient is unconscious? Will they have recall? Are they abel to hear you?

answer

When they are not responsive to verbal stimuli They may still have recall or be able to hear you

question

What is the difference between a sedative and a hypnotic?

answer

Sedative = medication to make them "smooth". Ex: Valium, Versed Hypnotic = medication to make them unconscious. Ex: Propofol

question

What is the #1 cause of airway disasters in hospitals?

answer

Sedatives given by non-qualified providers that turns into hypnosis/unconsciousness

question

What is recall? Can you be awake and not have recall?

answer

Retention of memory. Yes

question

What is the difference between being awake and being aware?

answer

Awake = responsive Aware = responsive AND learning/able to remember.

question

List some of the "costs" related to activation of the stress response/SNS activation

answer

Hypermetabolism (catabolism of proteins/fats). Blood sugar increases to stay alert Increased cardiac workload Decreased pulmonary function Increased pain sensation Decreased GI motility Hypercoagulability Immunosuppression Loss of muscle mass Decreased cognition

question

What are the 5 phases of an anesthetic?

answer

Pre-op Induction Maintenance Emergence Post-op

question

Who was Dr Arthur Guedel?

answer

Developed stages of anesthesia by ether observation Developed cuffed ETT so he could have his hands free, and demonstrated it w/his dog "Airway" in a fishtank Developed the Guedel airway

question

Describe Stage 1 of anesthesia

answer

Analgesia/Pain Control/Sedation Awake, responsive RR slightly increased/shallow Voluntary eye activity, intact reflexes, normal muscle tone

question

Describe Stage 2 of anesthesia

answer

Want to get through this QUICKLY!! Delerium/Excitement Loss of consciousness starts here Hypersensitive to stimuli Unable to protect the airway (vomiting/laryngospasm a risk) Nystagmus, hyperactive eyeball activity Hyperreflexic Erratic breathing

question

Describe Stage 3 of anesthesia

answer

Surgical Anesthesia Usually get here straight from Stage 1 (skip stage 2) Smooth, regular breathing Pupils dilate

question

What are some factors affecting how fast a drug will work?

answer

Charge of the drug Lipid solubility Works via ion channels or GPCR % receptors needing to be activated Receptor affinity

question

If you have 70% Nitrous oxide and 2% Sevoflurane, what is going to reach the brain first, and why?

answer

Nitrous will because its concentration gradient is steeper

question

Define volume of distribution

answer

Total amt of the drug / plasma concentration

question

Explain how an elderly patient will have both a small Vd and a large Vd

answer

Small Vd b/c circulating blood volume is less Large Vd b/c of increased adipose tissue %

question

Muscle relaxants are water soluble. What compartment are you concerned about with regard to the volume of distribution?

answer

Plasma/circulating blood volume only.

question

What is the initial, steep drop off seen in a drug distribution curve?

answer

That is from the dilution of the drug in the circulating blood volume, as well as the dilution of the drug in organs with high blood flow

question

What type of receptors do all anesthetics work at?

answer

Ligand gated receptors

question

What is the primary inhibitory NT in the brain? In the spinal cord? What is the primary excitatory NT in the brain?

answer

Brain = GABA Spinal cord = Glycine Excitatory = Glutamate

question

What neurotransmitter is associated with increased consciousness?

answer

ACh

question

Which ligand gated receptor is cation selective and excitatory?

answer

Seretonin

question

What is the effect site equilibration time?

answer

The onset time from when you give the med to when you start to see an effect.

question

Explain redistribution

answer

This is how 90% of our drugs wear off Central compartment = blood Vessel rich group = brain Vessel poor group = fat Concentrated drug enters the blood where it is diluted and quickly diffuses to have an equal concentration in the blood and brain. Slowly starts leaking from the brain to the blood, to fat storage. Once levels in the blood are less than levels in the brain, the drug starts to diffuse back into the blood to make levels equal. Now the drug's effects are wearing off unless you give another dose.

question

Explain why a drug like pentothiol has a short duration of action, but a long half life.

answer

It quickly reaches equilibrium between the blood and the brain (due to redistribution), putting the patient to sleep. However once the blood levels drop, the drug moves back from the brain into the blood and now the patient wakes up. However, it is continually building up in the fat of the patient if you keep re-dosing, and then once you stop giving the drug, it will move out of the fat and back into the blood (and brain!)

question

What is the "K" value of a drug?

answer

It is the movement of the drug between compartments, it is a constant. The higher the concentration gradient, the higher the K value, the faster the diffusion into the different compartments.

question

True or False: Almost all anesthesia meds stop working before they are significantly metabolized.

answer

True

question

What factors would make it easier for an anesthetic to get into the brain, and reach therapeutic levels quickly?

answer

uncharged (non-ionized) ↑ lipid solubility ↑ blood flow to the brain ↑ rate of delivery of the drug ↓ protein binding

question

What would make the central compartment smaller? What would make the vessel poor compartment larger?

answer

Smaller central compartment = dehydration/volume loss, ↓ cardiac output Larger vessel poor compartment = obesity, older age

question

Why do drugs move into the brain faster than they move into the adipose tissue?

answer

The brain has faster blood flow, and a smaller mass

question

Differentiate between C steady state and the partition coefficient

answer

C steady state = The concentration of free drug that is able to move within that compartment when the concentrations (mg/mL) of all compartments are equal Partition Coefficient = Measured in a ratio of (lipid:water). Amount of drug (mg) in the specific compartment at steady state.

question

What is elimination half time?

answer

How fast the body gets rid of the drug (either from metabolism or redistribution). How long the effect of the drug would last

question

What would you use to determine how often you would have to dose the patient to maintain a steady state concentration of that drug?

answer

Elimination half time

question

What is the effect site equilibration time?

answer

The amount of time it takes to see the effect from the drug (not peak effect, just the onset of effect)

question

Describe the first pass effect in the lungs. What drugs are subject to this?

answer

Lungs act like a storage compartment for redistribution later when the plasma concentration starts to drop Meds: Fentanyl, Su and Al fentanyl, Meperidine, Lidocaine & Propranolol

question

Differentiate between half-life, half-time, and clearance

answer

Half-life = when concentration of the drug drops by 50% in the body Half-time = when concentration of the drug drops by 50% in the plasma Clearance = the amount totally cleared from the plasma in some unit of time (L/min)

question

What do you need to wait for before you give another dose of drug to prevent overdosing?

answer

Need to wait for the peak time! Otherwise you won't know how strong that dose is.

question

Define context sensitive half time and it's relationship to when the patient will become conscious/responsive

answer

Half time of an infused drug When the concentration of the drug drops by 50% in the plasma after discontinuing the infusion. Patient's return of consciousness/responsiveness is dependent on what the plasma drug concentration has to drop to for consciousness to return.

question

How would you describe a drug that has a high context-sensitive half time?

answer

It will take the patient a long time to recover from one dose because it is stored away in lipids, or is not protein bound at all.

question

What would give a drug a shorter context sensitive half time?

answer

If it was protein bound (not moving into the lipids to be stored)

question

If Sufentanil is more lipid soluble than Fentanyl, how do you explain the fact that Sufentanil has a shorter context-sensitive half time?

answer

Sufentanil is very highly protein bound, so it remains in the plasma

question

If the rate of propofol clearance remains constant regardless of dose, how would you change the administration of propofol from being a general anesthetic to being used for a shorter case? Would you need to give a different drug?

answer

Give a smaller dose. Both the general anesthetic dose and the sedation dose are being cleared at the same time, but it will take less time for the smaller dose to return to "awake" concentrations in the blood. You would not necessarily need to give a different drug

question

If you gave one dose of a drug, what level will drop first the plasma concentration of the drug, or the level of drug in the brain? Why?

answer

The plasma concentration b/c it immediately starts being metabolized and moving out of the blood once it is given. The level of drug in the brain only drops once the plasma concentration has already dropped (the drug then moves back into the plasma)

question

Explain what is meant by a drug having a high partition coefficient

answer

A high partition coefficient = there are more parts in lipid vs parts in water. Very lipid soluble, faster onset, however will be stored in tissues.

question

Why are drugs with low partition coefficients not the best anesthetics?

answer

Low partition coefficients = more parts per water than lipid. Water soluble Difficult to get across the biological membranes and into the brain where they need to work. Slow onset.

question

When pH of a solution is = to the pKa of a drug, what does that mean?

answer

There is an equal amount of ionized and non-ionized drug in the system. 50/50

question

When given the pH of a solution, and the pKa of a weak acid, how do you figure out if the drug will be ionized or not in that solution?

answer

You put the pKa of the acid after the pH and subtract pH - pKa = ________ If it is a negative number, it will be > 50% unionized (lipid soluble) and will cross easily across biological membranes

question

When given the pH of a solution, and the pKa of a weak base, how do you figure out if the drug will be ionized or not in that solution?

answer

You put the pKa of the base before the pH and subtract pkA - pH = ________ If it is a negative number, it will be > 50% unionized (lipid soluble) and will cross easily across biological membranes

question

Are opioids and local anesthetics weak acids or weak bases?

answer

Weak bases

question

How do local anesthetics work? Do they need to be water or lipid soluble?

answer

They have to get inside the cell to block the ion channel, however no local anesthetic is > 50% non-ionized (lipid soluble) at a normal pH

question

Do drugs need to be put in a solution with a basic pH or an acidic pH for IV use?

answer

Basic pH because when placed in the human pH of 7.4, you want them to be ionized, and water soluble.

question

What happens if you put an acidic drug and a basic drug into an IV with a neutral pH?

answer

Salt will form (precipitate)

question

If you have a patient who is vascularly overloaded and alkalotic, how would you adjust your pentothiol dose?

answer

Vascularly overloaded = central compartment size ↑ Alkalotic = ↑pH Pentothiol = acid If you gave the normal dose of Pentothiol, due to the high pH in alkalosis, there would be an increased % of drug that is ionized so you would need to ↑ the dose to get the same effect. Additionally, his central compartment size has ↑'d, so you would need to give more drug.

question

Do acids or bases tend to accumulate in the plasma? The tissues?

answer

Acids tend to accumulate in the plasma, bases tend to accumulate in the tissues

question

What ions do acids typically bind to? Bases?

answer

Acids = Na+, K+, Mg++, Ca++ Bases = Cl-, SO4-

question

Which compound prefers acid, albumin or AAG? What is AAG?

answer

Albumin AAG = alpha-acid glycoprotein

question

In a stress state, will albumin or AAG accumulate?

answer

AAG

question

Explain how protein saturation and competition for binding sites effects the % of free drug available

answer

If proteins are saturated and the drug is highly protein bound, then less drug is bound by protein, free % ↑ If there are two drugs competing for binding at the same proteins, there will be ↑ free drug % of the less competitive drug.

question

How do low protein states effect the plasma concentration of the drug in both the acute and steady state?

answer

Acutely you will have more free drug, quicker onset (need to give a lower dose). In steady state conditions the unbound and bound concentrations will even out, and you will have a lower total drug concentration.

question

Do highly lipophilic drugs (like aneshetics) have low or high volumes of distribution?

answer

HIGH. The greater the affinity of tissues for a drug (in comparison to the blood) the greater the volume of distribution.

question

If you increased the volume of distribution of a drug, what will happen to its elimination-half life?

answer

It will increase

question

What three things does the speed of liver metabolism depend on?

answer

Blood flow to the liver The liver's ability to eliminate the drug The amount of drug that is "free" and not bound to proteins

question

Differentiate between Phase I and Phase II reactions in the liver. What enzymes conduct Phase II reactions?

answer

Phase I - exposing a charged group, making the drug more polar and water soluble Phase II - adding a functional group on that makes the drug more polar, water soluble. Done by transferases

question

What changes will you see regarding Phase II reactions in someone on antiseizure medication? What could you do to avoid this problem?

answer

Transferases undergo induction and will be upregulated. Drug metabolism will occur faster (chew through drugs). Need a higher dose, or you could give a drug that is metabolized via ester hydrolysis because esterases do not undergo induction.

question

Explain why Phase II reactions will be different in the elderly and children

answer

Infants aren't born with many transferases, elderly have less transferases so both groups will have ↓ metabolism of the drug. Need a lower dose.

question

Differentiate between first order and zero order kinetics. Which one do inhaled anesthetics follow?

answer

First order - constant fraction(%) of a drug is being cleared with each half life. Zero order - limited capacity to eliminate the drug (can only go so fast!). If you can only clear 10mg of drug/hr, that's it. Dose doesn't matter. Inhaled anesthetics reach zero order almost instantly!

question

Why will the onset of pro-drugs be delayed?

answer

They have to be metabolized before they are active and can work

question

What element when added to a drug will cause it to burn?

answer

Phosphorus

question

What are active metabolites? List two drugs that degrade into these.

answer

Metabolism of the drug produces these active breakdown products that can still be very potent. Increases the length of effect seen from the drug Ex: Tylenol and Demerol (dangerous metabolites!)

question

Describe the difference in metabolism of drugs between a chronic alcoholic and someone in end-stage liver disease

answer

Chronic ETOH - their enzymes of metabolism are induced (upregulated). They will need more drug ESLD - they are now enzyme deficient and will need less drug.

question

What is the difference between oxidation and reduction? What enzymes do this?

answer

CYP450 do this Oxidation - removing an electron, adding OH and producing water. You need oxygen to do this! Most common reaction Reduction - less common, only used when there's no oxygen. Adding an electron to charge the drug so it is excreted via the kidney.

question

Would you suspect an oxidation or a reduction reaction to occur in a situation where there is surgical stress?

answer

Reduction! The liver gets 75% of its blood supply from the splanchnic circulation which blood gets shunted away from during surgery. This ↓ liver blood flow, and in anaerobic conditions reduction is more likely to occur.

question

What two enzymes did we talk about that can undergo induction?

answer

CYP450 Transferases

question

What kind of enzyme is CYP450? What two subtypes are we most concerned with?

answer

Heme containing protein CYP3A4 + 3A5. Over 50% of our drugs are metabolized this way CYP2D6. 25% of our drugs are metabolized this way

question

Would a woman given a drug metabolized by CYP3A4 need a higher or lower dose of drug than a man?

answer

Higher b/c she has more CYP3A4 enzymes

question

When might you consider using a drug that is metabolized via ester hydrolysis?

answer

If the patient has upregulation of CYP450's (chronic ETOH, on antiseizure medication), because esterases do not undergo induction.

question

Describe esterases and give one example

answer

They metabolize drugs via ester hydrolysis They cause RAPID termination of drugs and cause drugs to be very titratable They break down drugs like Sux, Cisatracurium, Esmolol Ex: Plasmacholinesterase (Psuedocholinesterase, Type 2 cholinesterase)

question

How are H2 blockers and TCA's broken down?

answer

By FMOs (Flavin Containing Monooxygenase)

question

Describe the infant's metabolism. What does Debra mean when she calls them "little sacs of water"?

answer

They metabolize proteins, have a fully functional liver 0-6 months = SLOW metabolism of drugs 6mo-1yr = FAST metabolism of drugs Little sacs of water = the drug dilutes out FAST. They need a higher plasma concentration for onset to occur

question

When the flow to the liver drops, what happens to the kinetics of drugs? What happens to drugs with high extraction rates? Low extraction rates?

answer

Low flow to the liver = Drug metabolism moves to zero order kinetics quicker than usual. High extraction rates - Overall metabolism of the drug is slowed Low extraction rates - Nothing changes! Still only metabolizing xmg/hr

question

How does low cardiac output effect high and low extraction drugs?

answer

High extraction drugs - you will need to ↓ the dose, there will be more of them around than usual Low extraction drugs - not affected

question

What drugs have a low hepatic extraction rate?

answer

Thiopental Diazepam Lorazepam Rocuronium Methadone Theophylline

question

Where is the source of blood for the liver? What makes the liver vulnerable?

answer

75% of blood comes from the portal vein 25% of blood comes from the hepatic artery When MAP ↓, so does hepatic blood flow (no autoregulation) Liver is vulnerable when there's ↓splanchnic blood flow (surgical stress!)

question

The kidneys have great autoregulation, so renal blood flow doesn't change with small ↑or↓ in MAP, but what will impact urine output?

answer

Peritoneal Insufflation - extra pressure on the kidneys

question

Differentiate between pharmacogenetics and pharmacogenomics

answer

Pharmacogenetics - you give a drug, and discover a disease process b/c of how they metabolize the drug. Pharmacogenomics - attempts to develop drugs that act on specific receptors for specific populations

question

What is the #1 complication of a patient coming to the OR?

answer

Weight

question

List the variations that need to be considered when choosing a drug and the dose for each patient

answer

Age Weight Sex - men/women have different Vd's Co-exisiting Diseases Concurrent Meds Nutritional Status

question

What do the multiple patient variations cause in regard to dosing and effects of anesthetics? What class of drugs has the biggest variability? The least?

answer

A huge variation in dosing and the effect that is seen. It is normal to see a 5 fold change in variation with doses/effects Opioids - most variability Inhaled gases - least variability

question

What types of compounds usually aren't racemic mixtures? What anesthetic gas isn't?

answer

Naturally occurring compounds Sevoflurane

question

On a dose response curve, where would you see the most efficacious drug? The most potent? What does a steep incline tell you?

answer

Most efficacious will have the highest rise Most potent will be the farthest to the left of the graph Steep incline - the drug is very titratable! You need very little additional drug to see a big change in effect.

question

What happens if you give a reversal to your patient, then have to re-administer the original muscle relaxant?

answer

They will both be competing for the same receptor site! You will have to give more muscle relaxant to out-compete the antagonist

question

What effect will you see from a drug if you give a non-competitive antagonist + a drug?

answer

You will never see the maximal effect of the drug

question

What is the difference between a non-competitive antagonist and a competitive antagonist?

answer

The competitive antagonist reversibly binds to the receptor at the same site as the drug The non-competitive antagonist irreversibly binds to the receptor, and not at the same site as the drug

question

How could an antagonist be "indirect"?

answer

If it is a physiologic antagonist. It produces the opposite effect, but has an entirely different receptor site.

question

What is the difference between tolerance and tachyphylaxis? Give an example of tachyphylaxis

answer

Tolerance - develops over time Tachyphylaxis - QUICK tolerance to a drug (ephedrine for hypotension). Ex: When pain is allowed to break through during local anesthesia, pain receptors are upregulated.

question

What is the difference between synergistic and additive effects?

answer

Synergistic - two different drugs that work together (but differently) towards the same outcome Additive - two different drugs that work the same way to create a stronger response/effect

question

What two things should you do to test loss of consciousness in a patient? What should you hold off on doing until you are SURE they are unconscious?

answer

1 - Verbal Stimuli (ask them to take a breath) 2 - Touch their eyelashes, see if they blink Hold off on breathing for them until you are sure they are unconscious.

question

What are the reasons speculated for why we need sleep? Is sleep active or passive?

answer

We need sleep for neuroplasticity, laying down memory pathways There is an active part of sleep

question

What is the Ascending Reticular Activating System?

answer

It has two arousal branches: thalamic and hypothalamic It connects sensory input coming up the cord to the cortex

question

What part of the brain is where consciousness, awareness, comprehension occurs?

answer

The cortex

question

Describe the thalamic branch of the ascending reticular activating system

answer

Cholinergic neurons (ACh) are used to promote awakenss/arousal/consciousness

question

Describe the hypothalamic branch of the ascending reticular activating system

answer

Monoamines are used to promote wakefulness (norepi, seretonin, histamine) Norepi = locus ceruleus Seretonin = raphe nucleus Histamine = tuberomamillary nucleus Also inhibits the VLPO (Ventrolateral Preoptic Nucleus) which is the "sleep" switch in the brain.

question

Describe how the VLPO operates

answer

Ventrolateral Preoptic Nucleus It produces gabaminergic neurons (GABA and Galanin) which are inhibitory, and these inhibit the thalamic and hypothalamic branches

question

What brain waves are present in the quiet, but awake brain?

answer

Alpha

question

When you are in deep anesthesia, what brain waves are seen? Describe these. What type of "sleep" is anesthesia? What waves are seen?

answer

Delta. Taller, smoother, slower, and more uniform. Anesthesia = NON-REM sleep. Delta/Theta waves

question

Are active alpha and beta brain waves found during REM sleep or non-REM sleep? If these are also found during a sleep state, how can you tell if the patient is awake?

answer

REM sleep (active cortex!) You can tell that they are in REM sleep and not awake because muscle tone will be drastically decreased.

question

What brain waves do children exhibit?

answer

Theta waves

question

If you were using a BIS monitor, what levels would be "awake"? What would be considered anesthetic levels? What happens to the waves during anesthesia?

answer

Awake = 80-100 Anesthesia = 40-60. Waves are less frequent, more synchronous, more uniform

question

How is spectral entropy different than a BIS?

answer

It adds the muscle component to the BIS monitor.

question

Why wouldn't you feel pain transmission when you are asleep?

answer

The same parts of the brain that are suppressing cortical activity (VLPO) also sends messages down the cord to suppress transmission of anything back up.

question

What are the two sources of energy for the brain? What are the two things we need this energy for? What is the most energy hogging process, and how can we inhibit it?

answer

Glucose and oxygen Need energy for keeping cells alive, and for neuron-neuron communication. Most energy hogging process = neuron-neuron communication (60%) and we can inhibit this w/anesthesia (burst suppression)- but we can't do more than that.

question

If you wanted to inhibit neural activity beyond burst suppression, what would you have to use?

answer

Hypothermia

question

What % of our sleep is spent in REM sleep?

answer

25%

question

Why is our skeletal muscle tone drastically diminished during REM sleep?

answer

The VLPO is suppressing messages coming up the cord

question

Difficulty maintaining temperature, and irregular breathing patterns are seen in what stage of sleep?

answer

REM

question

When would you check evoked potentials? What are the most common? The hardest and easiest to interfere with?

answer

Check them if you want to make sure messages are still getting up/down the cord Most common = somatosensory (nerve stimulator) Easiest to interfere with = visual Hardest to interfere with = auditory

question

Why is it difficult to skip stage 2 of anesthesia?

answer

It is easier to put inhibitory neurons to sleep compared to excitatory neurons.

question

List some undesired effects from anesthetics. What is the #1 complaint from patients?

answer

Post op nausea/vomiting <---- #1 complaint Post op amnesia Hallucinations Dizziness, HA Prolonged sedation Active metabolites

question

Where is GABA produced? How could we increase GABA activity? What happens when GABA binds to its receptor?

answer

Produced by neurons in the VLPO To ↑GABA activity, ↑VLPO activity After GABA binds, Cl- goes through its ion channel, hyperpolarizing the cell which inhibits post-synaptic depolarization

question

What sorts of things can bind to the GABA receptor?

answer

GABA Barbiturates Benzos ETOH Steroids

question

What causes REM sleep? What causes non-REM sleep?

answer

REM sleep (active, alpha, beta, decreased muscle tone) caused by cholinergic transmission going to the cortex non-REM sleep (delta, theta, anesthesia) caused by VLPO decreasing activity of the thalamic/hypothalamic branches via suppression with GABA.

question

What two compounds make barbituric acid? When you add to this "base" compound, what properties does the side chain give you?

answer

Urea + Malonic Acid Adding to the 5 chain barbituric acid = sedative activity + lipid solubility

question

What are the two types of barbiturates? Give examples of drugs for each type. What is a big difference between the two?

answer

Oxybarbiturate - has an oxygen atom, Methohexital. Causes seizure activity Thiobarbiturate - has a sulfur atom, Thiopental. No seizure activity.

question

What is the basic mechanism of action regarding barbiturates?

answer

They ↑GABA activity through ↑ how long the Cl channel is open, and ↓dissociation of GABA from its receptor

question

What is the only class of anesthetics that can activate the GABA receptor without GABA being present?

answer

Barbiturates

question

Besides acting through GABA, how else do Barbiturates promote sleep? How else are they beneficial to the CNS?

answer

By antagonizing the neuronal ACh receptors They depress the reticular activating system, causing ↓SNS transmission which ↓metabolic demand due to an active SNS

question

If you had a drug that was in 15% solution, how many mg/cc is that?

answer

150mg/cc

question

If you had a drug that was 300mg/cc, what % solution is that?

answer

30%

question

Which barbiturate has a high clearance?

answer

Methohexital (makes sense since they developed this one to have a faster emergence than thiopental)

question

Which barbiturate has 4 isomers? Which one can cause seizures (and why)?

answer

Methohexital (for both). Seizures caused with smaller doses due to the methyl group.

question

Which barbiturate is more potent, Methohexital or Thiopental? Which one is stronger acting in the brain (and why)?

answer

Methohexital (1.5mg/kg dose compared to 4mg/kg of Thiopental) Thiopental is stronger acting in the brain due to the sulfur group

question

Which barbituate would you use for cardioversion, and why?

answer

Methohexital b/c it has a rapid onset/offset

question

List the reasons why Propofol made Methohexital less popular

answer

Methohexital is epileptogenic, caused myoclonus (muscle activity that looks like a seizure)

question

How can Methohexital both stop seizures and cause them?

answer

In low doses it causes seizures (good for neurosurgery) In high doses it causes burst suppression

question

What is the max that you can decrease the CMRO2 to? How can you decrease the CMRO2 in the brain to that max?

answer

40% (inducing hypothermia will decrease it further) Burst suppression

question

How is cerebral blood flow autoregulated?

answer

Regulated globally based on NEED. More metabolically active areas require higher blood flow

question

What induction medications have analgesic properties? Which ones have the opposite effect?

answer

Ketamine = analgesia Barbiturates = anti-analgesia

question

What induction medications would you use for someone with high ICP, and why? Which ones would you avoid?

answer

Barbiturates offer neuroprotection by cerebral vasoconstricting local areas, preventing ischemia from happening as quickly as it would normally Could use Propofol, but only if you keep BP stable! Otherwise you will drop your CPP You definitely would NOT want to give Ketamine since it ↑CMRO2 and CBF (and ICP) You would want to avoid Etomidate since it will ↓ CBF more than the oxygen demand (Dexmedetomidine does the same)

question

What is porphyria and why do we care? What drugs could you induce these people with?

answer

Genetic disorder where heme is not made properly. Too many porphyrins (which are proteins that are heme precursors) are made. Symptoms = bruising ALA synthetase (Amino-levulinic acid synthase) is what ramps up the production of porphyrins. Too much = abdominal cramps, seizures, neuropathy, depression/anxiety, arrhythmias, death People with porphyria need to avoid meds SVLTBEP Sulfonamides,Valium,Lidocaine,Tolbutamide,Barbiturates,Etomidate/ETOH,Phenytoin Induce with Propofol, Ketamine. (Dexmedetomidine also ok, but not an induction drug)

question

If your patient needs an emergency C section, what would you use to induce her? What about someone in liver or renal failure?

answer

Thiopental for OB Propofol for liver/renal failure

question

What happens if Thiopental is mixed with Morphine? What if you give it in an A-line? What would you do in each situation?

answer

Mix Thiopental + Morphine = CEMENT. Throw out tubing A-line? Can cause intense spasms, ischemia Flush it in, add heparin (prevent clots), lidocaine (decreases pain, muscle spasms), alpha blocker (helps spasms, relaxes vessel), sympathetic block

question

If your patient was on Coumadin, what drug would you avoid giving for induction?

answer

Methohexital. It increases the free levels of Coumadin.

question

What is hypoxic pulmonary vasoconstriction? Which drugs blunt this response? Which drugs maintain this reflex?

answer

Vasoconstriction to hypoxic areas so that the blood supply is shunted away from those O2 deprived areas, and goes towards the well oxygenated areas. Propofol blunts this response, Barbiturates maintain it (Etomidate and Ketamine too)

question

Does pentothiol block the baroreceptor response? Why is this tricky? What induction drug does?

answer

NO. However pentothiol causes histamine release which vasodilates and causes reflex tachycardia (which increases cardiac output) Propofol blunts the baroreceptor reflex (and SNS response to intubation)

question

What are the induction doses (and concentrations) of the barbiurates? Compare their elimination half lives

answer

Thiopental = 4mg/kg in 25mg/cc Methohexital = 1.5mg/kg in 10-20mg/cc Thiopental is 11 hours, Methohex is 4

question

Which induction drugs have high protein binding? What does this mean?

answer

Propofol and Precedex High protein binding means their free drug levels are elevated in conditions with low plasma proteins

question

Some induction drugs are racemic mixtures. Which ones? Which ones do we isolate the isomer that we use?

answer

Racemic = barbiturates, ketamine Methohexital = 2 alpha isomers Etomidate = D isomer

question

What would you avoid inducing your COPD patient with? What one would you choose? Which one would you use for you awake fiberoptic intubation? What if you couldn't get IV access?

answer

Avoid barbiturates, give Propofol Awake fiberoptic = Dexmedetomidine No IV access = Ketamine

question

Which induction drug would cause the least amount of trauma during intubation?

answer

Propofol b/c it blunts the laryngeal reflexes.

question

Which induction drug induces saliva secretion? Which drug blocks it?

answer

Ketamine induces it Dexmedetomidate blocks it

question

Which induction drugs drop the HR? BP?

answer

HR drop seen with Propofol and Dexmedetomidine HR increase seen with Barbiturates, Ketamine BP drop seen with Propofol (the most) then Dexmedetomidine, milder with Barbiturates. Most CV stable = Etomidate

question

Which induction drug has the worst respiratory depression? Which is the safest?

answer

Worst = Propofol Safest = Dexmedetomidine (not an induction drug though!) Ketamine also has very minimal respiratory depression

question

What induction drug would you give to cause a seizure in seizure mapping? Which induction drug causes burst suppression, which one ends status epilepticus, and which one is just an anticonvulsant? Of all the drugs we discussed, which is the BEST for anticonvulsant use? What are the limitations?

answer

Etomidate = seizure mapping Burst suppression = barbiturates (thiopental and high dose methohexital) & Etomidate Ends status = Etomidate Just anticonvulsant = Ketamine BEST anticonvulsant = Benzos (more specific) Limitations = Ceiling effect prevents burst suppression

question

What is the number one drawback to using Dexmedetomidine?

answer

Hypotension

question

Why doesn't Propofol accumulate in the peripheral tissues?

answer

HIGH protein binding!

question

Which induction drugs are painful on injection? Which ones aren't?

answer

Pain = Methohexital, Propofol, Etomidate No pain = Thiopental, Ketamine, Dexmedetomidine

question

What induction drug changes from water soluble in the preparation to lipid soluble when it hits the plasma?

answer

Etomidate.

question

Describe the mechanism of action of Ketamine and Dexmedetomidine

answer

Ketamine = NMDA (glutamate) antagonist, direct mu agonist. Dissociative anesthetic that blocks thalamocortical and stimulates limbic system. Acts as a Ca channel blocker, cerebral vasodilation and cholinergic effects Dexmedetomidine = alpha 2 agonist in locus ceruleus that ↓cAMP, VG-Ca channels, causing hyperpolarization and preventing Subs. P release, SNS transmission (stops VLPO inhibition) and ↓pain transmission up the cord. Also widens thermoreg. range

question

What are the doses for induction, sedation, and TIVA for propofol? What group needs more propofol? How is it supplied?

answer

Induction = 2mg/kg Sedation = 25-100mcg/kg/min TIVA = 100-300 mcg/kg/min More propofol for kids! 1% 10mg/cc

question

How are Etomidate, Ketamine, and Precedex supplied?

answer

Etomidate = 2mg/cc Ketamine = 10,50,100mg/cc Dexmedetomidine = need to mix! 100mg/cc (2cc vial) + 48ml NS = 4mg/cc

question

Which induction agents are the least effected by low protein states?

answer

Ketamine, Etomidate, Barbiturates

question

What induction agents are acids? Which one has the biggest effect on lowering intraocular pressure?

answer

Barbiturates and Propofol = acids Propofol drops IOP the most

question

What sucks about Etomidate? What are you concerned about with Etomidate if your patient was on a maintenance gtt?

answer

Etomidate = E-vomidate (PONV severe) Adrenocortical suppression

question

How are Propofol and Ketamine neuroprotective?

answer

Propofol drops ICF Calcium, decreasing apoptosis Ketamine IS NOT neuroprotective b/c it blocks NaKATPase channels opened by gas anesthesia which normally provides cerebral vasoconstriction for focal ischemic areas

question

List three problems with giving Propofol to kids

answer

Opisthotonos Bradycardia - kids VERY prone to this Propofol infusion syndrome

question

How would you know that propofol infusion syndrome was happening in the OR?

answer

HR would increase, you would have a metabolic acidosis with a base excess

question

If Propofol is safe with renal/liver failure, why is liver failure still an issue with Propofol?

answer

Liver failure interferes w/protein binding b/c of the high uremic acid. Proteins don't bind to as much drug (more free Propofol)

question

Which other drug(s) have a similar mechanism of action as Propofol?

answer

Barbiturates. Propofols main MOA is acting as a GABA agonist, lengthening the time the Cl channel stays open. However, it cannot activate GABA by itself like barbiturates can. Propofol also has NMDA antagonist activity (similar to Ketamine) and A2 agonist activity (similar to Dexmedetomidine) but these are not the main MOA.

question

What is Propofol Infusion Syndrome?

answer

Bradycardia that progresses to asystole, no response with atropine. LOW blood pressure causes slowed lipid metabolism leading to a high lipid content in the blood. This interferes w/mitochondrial respiration, causes metabolic acidosis, rhabdo, fatty infiltrates, hepatomegaly, and myoglobinuria

question

List two uses for Propofol outside of anesthesia

answer

Antiemetic (non-hypnotic doses) Antipruritic (good to ↓ itching with spinal opioids

question

Why was Fospropofol invented? Why didn't it take over for Propofol? Where is it used?

answer

Wanted something that didn't burn on injection (this just causes perineal burning) so they developed this water soluble pro-drug It's onset time is too long (6-7 min) and b/c the bioavailable Propofol in the drug follows non-linear pharmacokinetics, it isn't reliable. Used outside the OR for IV sedation

question

If you need to induce someone with hypovolemia, CHF, or anyone needing cardiac stability, which induction drug would you pick and what is the dose you would give? How fast would it act? What would be your second choice?

answer

Etomidate 0.3mg/kg, onset 1 min Ketamine would be a second choice (don't use w/neuro patients)

question

What is the only induction agent that blunts the SNS response to intubation? What does this mean?

answer

Propofol. It means you do not need to give an opioid with it to intubate, however you do need to give a benzo with it to ensure amnesia

question

Which drugs do NOT release Histamine?

answer

Etomidate, (Propofol, Ketamine??)

question

If you accidentally gave an induction agent intra-arterially, which one would you hope you gave? Which one would you hope you didn't give?

answer

Hope you gave Etomidate! Better not give Thiopental!

question

If you have to go back to the OR for multiple inductions back to back, what induction agent would you avoid and why?

answer

Etomidate b/c of the adrenocortical suppression

question

Why is Ketamine desirable in day surgery?

answer

It will decrease the opioid need

question

What is the induction dose of ketamine? For analgesia? How is it supplied?

answer

Induction = 1.5mg/kg Analgesia = 0.2-0.5mg/kg Supplied in 5% (also 1% and 10%)

question

What would you do if you were giving Ketamine and wanted to avoid the n/v and respiratory depression?

answer

Add Propofol

question

What induction drug will ↑ the # of circulating epi/norepi? How is it doing this? What group would this be an issue with?

answer

Ketamine It is a norepi/epi reuptake inhibitor Don't give to people on MAOI's or cocaine.

question

What induction agent would you use for an asthmatic or someone prone to bronchospasm?

answer

Ketamine

question

How does Precedex cause analgesia in the spinal cord?

answer

By encouraging release of enkephalins and ACh in the spinal cord (Ach is inhibitory in the spinal cord)

question

Why are Benzos not popular for use as sole induction agents?

answer

Effects last too long They don't blunt the SNS response to intubation

question

List the doses for sedation for Midazolam, Diazepam, and Lorazepam. What does this indicate about their potency?

answer

Midazolam = 0.05mg/kg IV Diazepam = 0.1mg/kg IV Lorazepam = 0.04mg/kg IV Lorazepam is the most potent, then Midazolam, then Diazepam.

question

What are the pediatric Midazolam doses? The maintenance IV dose?

answer

Intranasal = 0.2mg/kg PO = 0.5mg/kg IV = 0.05mg/kg Maint = 0.25-1mcg/kg/min

question

How is Midazolam supplied? Lorazepam? What else is different about how they are supplied?

answer

Midazolam = 1mg/cc and 5mg/cc Lorazepam = 2mg/cc and 4mg/cc Lorazepam = VERY THICK and painful

question

Which benzo has the fastest onset? How long do you have to wait to re-dose? Which benzo has the shortest elimination 1/2 life?

answer

Diazepam (1 min). Have to wait 5 min to re-dose. Midazolam has the shortest elimination 1/2 life

question

Which benzo is best for the elderly and those w/renal failure? Why?

answer

Lorazepam b/c it does not use the CYP450 enzyme system.

question

If you needed to choose a benzo to give PO which would you pick?

answer

Diazepam (has the best PO bioavailability)

question

Do benzodiazepines have analgesic properties? Which benzo is the most amnestic?

answer

NO. They may decrease the analgesic properties of opioids Lorazepam is the best amnestic

question

Are benzos neuroprotective?

answer

No b/c there's a ceiling effect (can only quiet the CNS so much)

question

Which benzos are at risk for causing apnea?

answer

ANY benzo at ANY dose. Never give a benzo and leave your patient.

question

Which benzos are safest for the obese? COPD patients?

answer

Obese = Diazepam and Lorazepam COPD = NONE. All blunt the hypoxic drive to breathe, use caution.

question

Which benzo has the least CV effects? What type of patients would benefit?

answer

Lorazepam Hypovolemia, trauma, any CV instability

question

What areas of the brain are involved in sedation? Anxiolysis? Amnesia? Building new memories?

answer

Sedation = brainstem/cortical Anxiolysis = (HAL) limbic, amygdala, hippocampus Amnesia = forebrain, hippocampus Memories = (HAF) hippocampus, forebrain, amygdala

question

What is the generic name of the date rape drug? How fast is the onset, peak, and duration?

answer

Flunitrazepam (Rohypnol) 20 min onset, peaks 2 hours, lasts 8 hours

question

What is it that makes benzos lipid soluble?

answer

The benzo ring structure. Imidazole ring becomes lipid soluble at pH of 7 b/c the ring closes. It's open at the preparation pH of 4 (water soluble)

question

How protein bound are benzos?

answer

Very highly protein bound

question

Why does it take awhile to develop addiction to benzos? What are some problems with chronic benzo use?

answer

They are very lipid soluble. Chronic use causes suppression of the adrenal axis, ↓cortisol levels, making the person sensitive to wound breakdown and infection. Also creates a need for a higher dose of benzo for surgery.

question

When you just give someone Midazolam for sedation, what happens to their BP?

answer

Drops 20 points

question

What drugs inhibit CYP450? How do these effect benzos?

answer

Cimetidine, Erythromycin, Ca channel blockers, Antifungals These inhibit CYP450, so they increase the free drug level of benzos. Need to ↓ your dose

question

What explains Diazepam being a drug of abuse?

answer

It works on the limbic system (reward system) of the brain

question

If you needed to reverse your benzo, what would you give? How is this supplied?

answer

Flumazenil (Romazicon) 0.2mg IV, then if that didn't work after 2 min would give another 0.1mg IV Q1min up to 3mg total, then would try something else. Supplied in 0.1mg/cc vials

question

Why do you have to give multiple doses of Flumazenil sometimes?

answer

The duration of action of Flumazenil is 30-60 min which is shorter than the drug it is antagonizing!

question

Why would you want to cause burst suppression in the OR? What drugs accomplish this?

answer

To ↓ the O2 demand in the brain to the max (neurosurg) Barbiturates, Etomidate

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