2This is all questions!This covers the bulk of the stuff we have to know about anesthetics, but not everything.Try to answer the questions before you click forward. They are designed to have short answers.
4Local AnestheticsList the amides (5) in order of fastest to slowest metabolismPrilocaine (fastest)LidocaineMepivacaineRopivacaineBupivacaine (slowest)
5Local AnestheticsWhich form of the sodium channel do local anesthetics bind to? (resting, active, or inactive?)Active or inactive (not resting)Which form of the anesthetic binds to the sodium channel? (charged or uncharged?)ChargedWhat side of the channel does the anesthetic bind to? (cytoplasmic or extracellular?)cytoplasmic
6Local Anesthetics What determines the potency of a local anesthetic? Lipid solubility (more lipid soluble=more potent)What determines the speed of onset of a local anesthetic?pKa (lower usually means faster)What can be administered to enhance uptake and prolong absorption of a local anesthetic?epinephrine
7Local Anesthetics What determines the duration of action of an LA? Protein binding! And rate of degradation! (Esters are degraded faster. Amides have to get to the liver first)What do opioids and/or clonidine do in conjuction with a LA?Intensify the analgesiaHow does acidosis (eg. from an abscess) affect a LA?Decreases diffusion of the LA across the membrane, and also causes tachyphylaxis
8Local Anesthetics Are local anesthetics weak acids or bases? Weak basesWhich part of a sodium channel is closed during the resting stage? (h or m?)m (it’s closer to the outside)During the inactive stage?h (it’s closer to the inside)How many nodes of Ranvier have to be blocked by LA to block conduction?3
9Local Anesthetics Which are more sensitive: Larger or smaller fibers? Myelinated or unmyelinated?UnmyelinatedCentral or peripheral fibers in a bundle?PeripheralA fibers or C fibers?C (B fibers are between A and C)
10Local AnestheticsList the types of fibers in order from most to least sensitive: (6)PainAutonomicTemperatureTouchDeep pressureMotor
11Local AnestheticsList the esters in order of duration of action from shortest to longest (4).ProcaineChloroprocaineCocaineTetracaine
12Local Anesthetics Name 2 anesthetics that would be used for epidurals. Bupivacaine and ropivacaineWhy?Because they both bind proteins and therefore do not cross the placenta easilyWhich one is better?RopivacaineBecause it is less cardiotoxic. (Note: bupivacaine has its cardiotoxic effects BEFORE the CNS effects!)
13Local AnestheticsName 2 drugs that are contraindicated for epidurals in pregnant women and why.Mupivacaine because it crosses the placenta and is toxicTetracaine because it causes motor paralysis (ok for spinal injections during C-section though).
14Local AnestheticsWhat would you give to a pregnant woman during emergency delivery?ChloroprocaineWhy are pregnant patients more susceptible to toxic effects of epidurals?Increased blood flow to the epidural region
15Local AnestheticsName all the local anesthetics we have to know that are hydrolyzed by cytochrome P450.PrilocaineMupivacaineLidocaineRopivacaineBupivacaine
16Local AnestheticsWhich drugs can lead to the formation of o-toluidine?Prilocaine (and benzocaine)-forms methemoglobinHow do you treat that?Give methylene blueWhich drugs can lead to the formation of PABA?The estersWhy does PABA matter?Allergies!!! (The preservatives in the anesthetic injection can also cause allergies, and are suspected when someone has a reaction to an amide, since true amide allergies are rare.)
17Local Anesthetics What does giving sodium bicarbonate with a LA do? Raises the local pHWho cares?LAs are weak bases, so at higher pH, more are in the uncharged form and can cross membranes, increasing speed of action.
18Local Anesthetics What is usually the first sign of LA toxicity? Circumoral numbnessWhat are the steps in between that and death?Tingling, tinnitus, nystagmus, anxiety, agitation, seizuresCardiovascular toxicity occurs late-ish (except with bupivacaine)What are the cardiovascular effects?Autonomic blockade! (so…hypotension, bradycardia, myocardial depression, arrhythmia)
19Local Anesthetics When is it ok to use cocaine? In front of the police, you say?No. You will go to jail.TOPICALLY ONLY (opthalmic analgesia)It has inherent vasoconstrictive properties!Do NOT give as an epidural.What else can be used topically (and not necessarily for eyes)?Tetracaine, but it’s less fun than telling your patients that you’re putting crack in their eyes.
21Inhaled AnestheticsName all seven inhaled anesthetics that we have to know (They are listed below in order of their MAC value).Methoxyflurane (0.16)Halothane (0.75)Isoflurane (1.4)Enflurane (1.68)Sevoflurane (2.0)Desflurane (6-7)Nitrous oxide (105)I DOUBT you will have to know the numbers or the order EXCEPT for nitrous oxide
22Inhaled AnestheticsAre drugs with higher MAC values more potent or less potent?Less potent—it takes more drug to get the same effectDo drugs with a higher lipid solubility have a higher MAC or a lower MAC?Lower MAC (typically). More lipid solubility means more potency, typically.
23Inhaled AnestheticsDo drugs with a higher Blood:Gas partition coefficient equilibrate more quickly or more slowly)More slowly—it takes a long time to saturate the blood since the blood can hold so much drugDoes this matter?It could lengthen induction time, but not necessarily. Some drugs have effects before they reach equilibrium (ie. the blood doesn’t have to be saturated)
24Inhaled Anesthetics Why can’t you use nitrous oxide alone? It sucks. Actually it doesn’t. It just has a MAC value of over 100%.So why do we use it at all?It has very few side effects, so use in combo with lower doses of stronger (more toxic) anesthetics to decrease the likelihood of adverse effects.So what ARE the side effects of nitrous oxide?Megaloblastic anemia due to effects on methionine synthase (ABUSERS ONLY)accumulation in air spaces (blocked up middle ears, etc…)
25Inhaled AnestheticsDoes nitrous oxide enhance other inhaled anesthetics? How or how not?Yes. It absorbs into the blood quickly early on, increasing the relative concentration of the other anesthetics in the inhaled air. (second gas effect, minor clinically)What is diffusion hypoxia?The reverse of the second gas effect. Nitrous oxide can come out of the blood and into the alveolus and decrease the relative concentration of oxygen. (minor, clinically)
26Inhaled AnestheticsShould you give loading doses of inhaled anesthetics?No. Your patient will die (probably). The therapeutic indices for these drugs are low.What should you do?Give IV anesthetics for rapid induction, if so desired.
27Inhaled Anesthetics Which gases can you induce with? (3.5) Nitrous oxideHalothaneSevofluraneIsoflurane sometimes for adults, but pretty pungent. Kids really don’t like it.
28Inhaled AnestheticsName the 3 most popular inhaled anesthetics, currently.Nitrous oxideDesfluraneSevofluraneWhat are the two historically important inhaled anesthetics on the list?Halothane
29Inhaled Anesthetics List the 5 components of general anesthesia. UnconsciousnessAnalgesiaAmnesiaMuscle relaxationProgressive loss of reflexesName a drug on the list that does all of these really well.NONE.
30Inhaled Anesthetics List the 4 stages of general anesthesia. Analgesia (block substantia gelatinosa)Excitation (block inhibitory neurons)Surgical anesthesia (depression of the RAS)Apnea/death (depression of medulla)Where do all these effects happen, generally?The CNS!!
31Inhaled Anesthetics Name 4 ways to measure consciousness Respiration, reflexes, muscle tone, response to incisionAre EEGs useful?If there is just one anesthetic. Otherwise not really.
32Inhaled AnestheticsWhat determines which tissues get saturated first when giving inhaled anesthetics?Blood flow!Which tissues have high flow? (4)Brain, heart, liver, kidneyIntermediate? (2)Skin and muscleLow? (4)Fat, bone, tendon, connective tissue
33Inhaled Anesthetics What does the term “Fa/Fi” stand for? Fa= the gas concentration of a drug in the alveolus AFTER gas exchange has occurred.Fi= gas concentration of a drug in the alveolus INITIALLY (before absorption happens)What does it mean when this term is 100%?The drug is at equilibrium. Nothing more can be absorbed into the blood because it is saturated.
34Inhaled AnestheticsDoes a more soluble drug reach equilibrium more quickly?No. It takes longer to “fill up” the blood.What value is inversely proportional to solubility?MAC value! (as solubility increases, the effective inhaled concentration decreases (it gets into the blood more quickly, even if it takes longer to saturateAre more soluble drugs more or less potent?More potent! (One exception on next slide)
35Inhaled Anesthetics What are the 2 most insoluble agents on our list? Nitrous oxide and desfluraneOf those two, which is more POTENT?Desflurane (even though it is less soluble than nitrous oxide)
36Inhaled AnestheticsIs induction faster with more soluble or more insoluble agents?Tricky question. More soluble drugs tend to be more potent, though it takes a long time to saturate the blood. Remember that you don’t need to saturate the blood to get the effects. Seems that most of the time, insoluble agents act faster.Is emergence from anesthesia faster with more soluble or more insoluble agents?More INSOLUBLE because they don’t like being in the blood. The patient breathes them out faster
37Inhaled AnestheticsIs induction faster in a patient with a higher cardiac output?No. It takes longer to saturate the blood.How do halogenated anesthetics affect respiration?Decrease volume, increase rateAll are bronchodilatory except DesfluraneHow do halogenated anesthetics affect blood pressure?Decrease BPICP?increased
38Inhaled Anesthetics Name 4 components of balanced anesthesia. pre-anestheticinduction anestheticmaintenance anestheticneuromuscular blocking agent
40Nitrous Oxide Can it be used for induction? Yes, but not alone. Are induction and recovery fast or slow?Fast (because it’s pretty insoluble in the blood)Analgesia?Yes! It’s very good.
41Nitrous Oxide Metabolism? Breath it back out. No significant metabolism.When should you NOT use this drug?When patients have pockets of trapped gas(eg. Middle ear occlusion, pneumothorax, intestinal loop, etc…)Mechanism of action? (yes, this one is known)Blocks NMDA receptorsAny side effects?Megaloblastic anemia due to effects on methionine synthase IN ABUSERS
42Halothane Can it be used for induction? Yes. Not pungent! Are induction and recovery fast or slow?Fairly fastCardiac effects?Decreases cardiac output and blood pressure, SENSITIZES TO CATECHOLAMINES, which means ARRHTYMIASMuscle effects?Only slight relaxation of skeletal. Relaxes smooth muscle, increasing ICP (and decreasing BP)
43Halothane Analgesia? Only slight analgesia Metabolism? ~20%. The rest is breathed out.Any side effects?Toxic metabolite: Fluoride ion, decreases renal function!Halothane hepatitis! -1/35000 cases, 2-5 days post-opWhen should you NOT use this drug?(On days that end in “y”?) Pretty much nobody uses this drug anymore because there are much better options
44Isoflurane Can it be used for induction? Yeah, but not for pediatric patients.How does its potency and solubility compare to halothane?Less potent, less soluble.How does speed of induction and emergence compare to halothane?Faster!
45Isoflurane Cardiac effects? Decreases BP, Increases HR, same CO Arrhythmias?No.Muscle effects?Potentiates non-depolarizing blockadeMetabolism?Much less than halothane.Cost as compared to halothane?More expensive
46Enflurane Can it be used for induction? No. Too pungent. Speed of induction and emergence?So-so. There’s better, less soluble stuff.Cardiac effects as compared to halothane?All are less bad, even ICP (but still there)Muscle effects as compared to halothane?More skeletal muscle relaxationWhen should you not use this drug?In kids and people with abnormal EEG because it can induce seizures in sensitive patients.
47Methoxyflurane More or less soluble than halothane? WAY more soluble, more potentSpeed of induction and emergence?VERY SLOW (because it’s so soluble)When should you not use this drug?(When the next best option is to just get your patient really really drunk?) This drug is no longer in clinical use because of it’s slow speed and high toxicity
48Sevoflurane More or less soluble than halothane? Less soluble, more potentMask induction?Yep!Speed of induction and emergence?Fast, and offers excellent controlRespiratory?BronchodilationMetabolism?3%More or less toxic than isoflurane?More toxic
49Desflurane Mask induction? Absolutely not. Causes laryngospasm and irritation.Faster or slower induction than sevoflurane?Faster. (5-10 min. recovery! Ambulatory surgery)Respiratory?Bronchoconstriction (from all that irritation!)Cardiac?Increases heart rate and CO! (because increased catecholamine release)Metabolism?Very littleSuitable for pediatric patients?No.
50More Inhaled Anesthetic Questions Hang in there!
51Inhaled Anesthetics Which two increase heart rate? Isoflurane and desfluraneWhich one depresses cardiac function most?HalothaneWhich one causes bronchodilation?SevofluraneWhich one causes bronchoconstriction?Desflurane
52Inhaled Anesthetics Which one can cause seizures? Enflurane Which one has the highest solubility in the blood?Methoxyflurane (it’s as soluble as ether!)Which one has the lowest solubility in the blood?Desflurane (even lower than nitrous oxide, but more potent)
53Inhaled Anesthetics Which three are most toxic? Methoxyflurane HalothaneSevofluraneWhich one is your favorite?Just checking to see if you were paying attention.Mine is nitrous oxide.
55IV Anesthetics What makes these guys so great? (2 reasons) Rapid induction (10-15 seconds)Very lipid soluble, so crosses BBBHow is the action of these drugs stopped?Redistribution (NOT metabolism)What affects where the drug redistributes?Blood flow!
56IV Anesthetics Where do they distribute first? Brain, heart, liver, kidneys (HIGH FLOW regions)Then where?Skeletal muscle and skin (MEDIUM FLOW)Accumulation peaks around 30 minutesAdipose tissue! (LOW FLOW)
57IV Anesthetics Why aren’t they metabolized quickly? Highly protein boundWhich part of the body is most important for the termination of these drugs’ initial action?Skeletal muscleWhat about the patient do you use to calculate dosage?Lean body mass! (not necessarily weight)How does obesity affect the metabolism of these drugs?Obese patients take longer to recover because of storage and release of the drug from fat.
58IV AnestheticsDoes more or less drug get delivered to the brain under conditions of reduced cardiac output?MORE (takes longer to redistribute)Who has reduced CO?The elderly, people with CHF, people with hemorrhage
59Ultra-short acting barbiturates Name the two ultra-short acting barbituates on our list.Thiopental and methohexitalAre these drugs good analgesics?No.Do they produce good muscle relaxation?No. Just transient.
60Ultra-short acting barbiturates What should you supplement these drugs with for pain control?Nitrous oxide or opioid analgesicWhat is the mechanism of action of this class?GABAA receptor activation (hyperpolarization by Chloride ion influx)This independent of endogenous GABA (compare to benzodiazapines)
61Thiopental Speed of induction? Rapid Duration of action? Short (because of redistribution)MetabolismVery slowCardiovascular effects?Depression due to decreased contractility and vasodilationRespiratory effects?Depressant
62Thiopental Name 2 problems with this drug. Poorly soluble so it could come out of solution on injectionUnpredictable allergies because it contains sulfur!Can this drug be co-injected with a weakly basic drug?No! Thiopental is a weak acid in a weakly basic solution and will be even more likely to come out of solution.
63Methohexital Name 3 reasons this drug is better than Thiopental. 3x as potent2x shorter duration of action (fewer side effects)More rapid recovery
64Benzodiazepines Name the benzodiazepine on our list. Medazolam Why is this drug better than Valium for IV use? (2 reasons)More soluble and shorter half-lifeDo these drugs provide analgesia?No.Can you reverse an overdose of these drugs?Yes. Give the antagonist Flumazenil
65BenzodiazepinesHow do these drugs affect the cardiovascular and respiratory systems as compared to barbiturates?They have less of an effectHow does the recovery time compare to the barbiturates?Takes longerWhy is this class useful as a pre-op medication?Induces anterograde amnesiaWhat is the mechanism of action of these drugs?Activates GABAA by potentiating endogenous GABA
66Ketamine Is this a barbiturate? No. It is related to PCP Mechanism of action?Inhibits NMDA receptorsWhat kind of anesthesia does this drug produce?“dissociative anesthesia” in which patient is in a trance, appears awake, but does not respond to sensory stimuliIs this freaky?Yes.
67Ketamine Does it produce generalized relaxation? No Does this drug induce apnea?No.Does this drug induce loss of airway reflexes?Is this drug a good analgesic.Yes. (treat burns!)
68Ketamine Can this drug be give intramuscularly? Yes What are the cardiovascular effects?Stimulant! (increase blood pressure and heart rate!)Name 2 adverse effects.Hallucinatory phenomena on emergence, patient freaks outIncreases ICP (and intraocular) pressure
69Etomidate Name two advantages of this drug. Preserves respiratory stability and preserves cardiac outputIs this drug an analgesic?No.Name three disadvantages of this drug.Pain on injectionCommonly causes myoclonusAdrenal suppressionDo you use this drug for induction, maintenance, or both?Induction only because of adrenal suppressionMechanism of action?Activates GABAA
70Propofol Is this a good drug? Yes. Propofol is propular. One of the most common IV agents.Is this drug expensive?Yes.Why so popular? (name three reasons)Anti-emetic, quick induction and emergence, and patients “feel better” (same-day surgery)
71Propofol What are the respiratory effects? Extremely depressive (can cause apnea)What are the cardiovascular effects?Transient large reduction in BP due to vasodilationName 2 other problems with this drug.Pain on injection, stored with lipid vehicle (leads to microorganism contamination)Mechanism of action?Activates GABAA
72Narcotics as IV anesthetics How do you get these drugs to work as anesthetics?Give higher dosesCardiovascular effects?Minimal depressionRespiratory effects?Severe depression, even post-op (support!)Name one complication.Muscle rigidity
73Narcotics as IV anesthetics Name one drug on our list that is in this class.FentanylIs this drug a good analgesic?Yes. It’s a narcotic.Why use this over other opioids?It has a shorter half-lifeIs there an antagonist available for reversal?Yes. Naloxone
74Droperidol What class of drugs does this belong to? Neuroleptics What kind of anesthesia does it produce?Neuroleptanesthesia-patient is conscious and can communicate, but is totally detached from environmentWhat is Innovar?Combination of fentanyl and droperidol-induces neuroleptanalgesia?How do you convert to neuroleptanesthesia?Add 65% nitrous oxide
75Droperidol Is this drug an anti-emetic? Yes Does this drug cause seizures?No. It is an anti-convulsant.Does this drug cause fibrillation?No. It prevents them to some extent.
76Dexmedetomidine Can you say the name of this drug correctly? Me either.What is the mechanism of action of this drug?Alpha-2 agonist! With extra propertiesDoes this drug cause sedation?yesDoes this drug cause analgesia?Yes
77Conscious and deep sedation What 3 properties do you need for conscious sedation?Amnesic, sedative, analgesicBut NO loss of consciousness!How can you tell that your patient is under deep sedation? (3 things)Loss of reflexes, lack of verbal response to surgical stimulus, can’t maintain patent airway
78Conscious and deep sedation Name a combination of three drugs that you can combine for conscious sedation.propofolfentanylmidazolam(These are the ones listed in the syllabus)
79Conscious and deep sedation Are you currently deeply sedated?Yes.Is this over?Yes. Unless you want a quick IV anesthetic review. Then click again.
80IV anesthetics What can you cure with flumazenil? Midazolam overdose What can you cure with naloxone?Fentanyl overdoseWhich of the IV drugs cause analgesia? (3)Fentanyl, ketamine, dexmedetomidineWhich is a neuroleptic?droperidol
81IV anesthetics Which are anti-emetics? Droperidol, propofol Which drug induces dissociative anesthesia?KetamineWhich drug commonly causes myoclonus?EtomidateWhich drug is associated with microorganisms growing in it?propofol
82IV anesthetics Which drug can be administer intramuscularly? Ketamine Which drug has faster recovery: methohexital or thiopental?MethohexitalWhich one will you need to recover from this powerpoint?Cocaine?Go home.