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Local and General Anesthetics By Sarah E.. This is all questions! This covers the bulk of the stuff we have to know about anesthetics, but not everything.

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Presentation on theme: "Local and General Anesthetics By Sarah E.. This is all questions! This covers the bulk of the stuff we have to know about anesthetics, but not everything."— Presentation transcript:

1 Local and General Anesthetics By Sarah E.

2 This 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.

3 LOCAL ANESTHETICS First thing’s first.

4 Local Anesthetics List the amides (5) in order of fastest to slowest metabolism 1.Prilocaine (fastest) 2.Lidocaine 3.Mepivacaine 4.Ropivacaine 5.Bupivacaine (slowest)

5 Local Anesthetics Which 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?) – Charged What side of the channel does the anesthetic bind to? (cytoplasmic or extracellular?) – cytoplasmic

6 Local 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

7 Local 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 analgesia How does acidosis (eg. from an abscess) affect a LA? – Decreases diffusion of the LA across the membrane, and also causes tachyphylaxis

8 Local Anesthetics Are local anesthetics weak acids or bases? – Weak bases Which 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? –3–3

9 Local Anesthetics Which are more sensitive: Larger or smaller fibers? – Smaller Myelinated or unmyelinated? – Unmyelinated Central or peripheral fibers in a bundle? – Peripheral A fibers or C fibers? – C (B fibers are between A and C)

10 Local Anesthetics List the types of fibers in order from most to least sensitive: (6) 1.Pain 2.Autonomic 3.Temperature 4.Touch 5.Deep pressure 6.Motor

11 Local Anesthetics List the esters in order of duration of action from shortest to longest (4). 1.Procaine 2.Chloroprocaine 3.Cocaine 4.Tetracaine

12 Local Anesthetics Name 2 anesthetics that would be used for epidurals. Bupivacaine and ropivacaine Why? Because they both bind proteins and therefore do not cross the placenta easily Which one is better? Ropivacaine Why? Because it is less cardiotoxic. (Note: bupivacaine has its cardiotoxic effects BEFORE the CNS effects!)

13 Local Anesthetics Name 2 drugs that are contraindicated for epidurals in pregnant women and why. Mupivacaine because it crosses the placenta and is toxic Tetracaine because it causes motor paralysis (ok for spinal injections during C-section though).

14 Local Anesthetics What would you give to a pregnant woman during emergency delivery? Chloroprocaine Why are pregnant patients more susceptible to toxic effects of epidurals? Increased blood flow to the epidural region

15 Local Anesthetics Name all the local anesthetics we have to know that are hydrolyzed by cytochrome P450. Prilocaine Mupivacaine Lidocaine Ropivacaine Bupivacaine

16 Local Anesthetics Which drugs can lead to the formation of o-toluidine? Prilocaine (and benzocaine)-forms methemoglobin How do you treat that? Give methylene blue Which drugs can lead to the formation of PABA? The esters Why 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.)

17 Local Anesthetics What does giving sodium bicarbonate with a LA do? Raises the local pH Who cares? LAs are weak bases, so at higher pH, more are in the uncharged form and can cross membranes, increasing speed of action.

18 Local Anesthetics What is usually the first sign of LA toxicity? Circumoral numbness What are the steps in between that and death? Tingling, tinnitus, nystagmus, anxiety, agitation, seizures Cardiovascular toxicity occurs late-ish (except with bupivacaine) What are the cardiovascular effects? Autonomic blockade! (so…hypotension, bradycardia, myocardial depression, arrhythmia)

19 Local 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.

20 INHALED ANESTHETICS Moving on.

21 Inhaled Anesthetics Name all seven inhaled anesthetics that we have to know (They are listed below in order of their MAC value). 1.Methoxyflurane (0.16) 2.Halothane (0.75) 3.Isoflurane (1.4) 4.Enflurane (1.68) 5.Sevoflurane (2.0) 6.Desflurane (6-7) 7.Nitrous oxide (105) I DOUBT you will have to know the numbers or the order EXCEPT for nitrous oxide

22 Inhaled Anesthetics Are drugs with higher MAC values more potent or less potent? Less potent—it takes more drug to get the same effect Do drugs with a higher lipid solubility have a higher MAC or a lower MAC? Lower MAC (typically). More lipid solubility means more potency, typically.

23 Inhaled Anesthetics Do 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 drug Does 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)

24 Inhaled 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…)

25 Inhaled Anesthetics Does 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)

26 Inhaled Anesthetics Should 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.

27 Inhaled Anesthetics Which gases can you induce with? (3.5) Nitrous oxide Halothane Sevoflurane Isoflurane sometimes for adults, but pretty pungent. Kids really don’t like it.

28 Inhaled Anesthetics Name the 3 most popular inhaled anesthetics, currently. 1.Nitrous oxide 2.Desflurane 3.Sevoflurane What are the two historically important inhaled anesthetics on the list? 1.Nitrous oxide 2.Halothane

29 Inhaled Anesthetics List the 5 components of general anesthesia. 1.Unconsciousness 2.Analgesia 3.Amnesia 4.Muscle relaxation 5.Progressive loss of reflexes Name a drug on the list that does all of these really well. NONE.

30 Inhaled Anesthetics List the 4 stages of general anesthesia. 1.Analgesia (block substantia gelatinosa) 2.Excitation (block inhibitory neurons) 3.Surgical anesthesia (depression of the RAS) 4.Apnea/death (depression of medulla) Where do all these effects happen, generally? The CNS!!

31 Inhaled Anesthetics Name 4 ways to measure consciousness Respiration, reflexes, muscle tone, response to incision Are EEGs useful? If there is just one anesthetic. Otherwise not really.

32 Inhaled Anesthetics What determines which tissues get saturated first when giving inhaled anesthetics? Blood flow! Which tissues have high flow? (4) Brain, heart, liver, kidney Intermediate? (2) Skin and muscle Low? (4) Fat, bone, tendon, connective tissue

33 Inhaled 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.

34 Inhaled Anesthetics Does 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 saturate Are more soluble drugs more or less potent? More potent! (One exception on next slide)

35 Inhaled Anesthetics What are the 2 most insoluble agents on our list? Nitrous oxide and desflurane Of those two, which is more POTENT? Desflurane (even though it is less soluble than nitrous oxide)

36 Inhaled Anesthetics Is 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

37 Inhaled Anesthetics Is 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 rate All are bronchodilatory except Desflurane How do halogenated anesthetics affect blood pressure? Decrease BP ICP? increased

38 Inhaled Anesthetics Name 4 components of balanced anesthesia. 1.pre-anesthetic 2.induction anesthetic 3.maintenance anesthetic 4.neuromuscular blocking agent

39 SPECIFIC INHALED ANESTHETICS Woot.

40 Nitrous 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.

41 Nitrous 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 receptors Any side effects? Megaloblastic anemia due to effects on methionine synthase IN ABUSERS

42 Halothane Can it be used for induction? Yes. Not pungent! Are induction and recovery fast or slow? Fairly fast Cardiac effects? Decreases cardiac output and blood pressure, SENSITIZES TO CATECHOLAMINES, which means ARRHTYMIAS Muscle effects? Only slight relaxation of skeletal. Relaxes smooth muscle, increasing ICP (and decreasing BP)

43 Halothane 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-op When 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

44 Isoflurane 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!

45 Isoflurane Cardiac effects? Decreases BP, Increases HR, same CO Arrhythmias? No. Muscle effects? Potentiates non-depolarizing blockade Metabolism? Much less than halothane. Cost as compared to halothane? More expensive

46 Enflurane 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 relaxation When should you not use this drug? In kids and people with abnormal EEG because it can induce seizures in sensitive patients.

47 Methoxyflurane More or less soluble than halothane? WAY more soluble, more potent Speed 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

48 Sevoflurane More or less soluble than halothane? Less soluble, more potent Mask induction? Yep! Speed of induction and emergence? Fast, and offers excellent control Respiratory? Bronchodilation Metabolism? 3% More or less toxic than isoflurane? More toxic

49 Desflurane 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 little Suitable for pediatric patients? No.

50 More Inhaled Anesthetic Questions Hang in there!

51 Inhaled Anesthetics Which two increase heart rate? Isoflurane and desflurane Which one depresses cardiac function most? Halothane Which one causes bronchodilation? Sevoflurane Which one causes bronchoconstriction? Desflurane

52 Inhaled 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)

53 Inhaled Anesthetics Which three are most toxic? Methoxyflurane Halothane Sevoflurane Which one is your favorite? Just checking to see if you were paying attention. Mine is nitrous oxide.

54 IV ANESTHETICS They’re finally here!

55 IV Anesthetics What makes these guys so great? (2 reasons) 1.Rapid induction (10-15 seconds) 2.Very lipid soluble, so crosses BBB How is the action of these drugs stopped? Redistribution (NOT metabolism) What affects where the drug redistributes? Blood flow!

56 IV 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 minutes Then where? Adipose tissue! (LOW FLOW)

57 IV Anesthetics Why aren’t they metabolized quickly? Highly protein bound Which part of the body is most important for the termination of these drugs’ initial action? Skeletal muscle What 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.

58 IV Anesthetics Does 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

59 Ultra-short acting barbiturates Name the two ultra-short acting barbituates on our list. Thiopental and methohexital Are these drugs good analgesics? No. Do they produce good muscle relaxation? No. Just transient.

60 Ultra-short acting barbiturates What should you supplement these drugs with for pain control? Nitrous oxide or opioid analgesic What is the mechanism of action of this class? GABA A receptor activation (hyperpolarization by Chloride ion influx) This independent of endogenous GABA (compare to benzodiazapines)

61 Thiopental Speed of induction? Rapid Duration of action? Short (because of redistribution) Metabolism Very slow Cardiovascular effects? Depression due to decreased contractility and vasodilation Respiratory effects? Depressant

62 Thiopental Name 2 problems with this drug. Poorly soluble so it could come out of solution on injection Unpredictable 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.

63 Methohexital Name 3 reasons this drug is better than Thiopental. 1.3x as potent 2.2x shorter duration of action (fewer side effects) 3.More rapid recovery

64 Benzodiazepines Name the benzodiazepine on our list. Medazolam Why is this drug better than Valium for IV use? (2 reasons) More soluble and shorter half-life Do these drugs provide analgesia? No. Can you reverse an overdose of these drugs? Yes. Give the antagonist Flumazenil

65 Benzodiazepines How do these drugs affect the cardiovascular and respiratory systems as compared to barbiturates? They have less of an effect How does the recovery time compare to the barbiturates? Takes longer Why is this class useful as a pre-op medication? Induces anterograde amnesia What is the mechanism of action of these drugs? Activates GABA A by potentiating endogenous GABA

66 Ketamine Is this a barbiturate? No. It is related to PCP Mechanism of action? Inhibits NMDA receptors What kind of anesthesia does this drug produce? “dissociative anesthesia” in which patient is in a trance, appears awake, but does not respond to sensory stimuli Is this freaky? Yes.

67 Ketamine Does it produce generalized relaxation? No Does this drug induce apnea? No. Does this drug induce loss of airway reflexes? No. Is this drug a good analgesic. Yes. (treat burns!)

68 Ketamine 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 out Increases ICP (and intraocular) pressure

69 Etomidate Name two advantages of this drug. Preserves respiratory stability and preserves cardiac output Is this drug an analgesic? No. Name three disadvantages of this drug. Pain on injection Commonly causes myoclonus Adrenal suppression Do you use this drug for induction, maintenance, or both? Induction only because of adrenal suppression Mechanism of action? Activates GABA A

70 Propofol 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)

71 Propofol What are the respiratory effects? Extremely depressive (can cause apnea) What are the cardiovascular effects? Transient large reduction in BP due to vasodilation Name 2 other problems with this drug. Pain on injection, stored with lipid vehicle (leads to microorganism contamination) Mechanism of action? Activates GABA A

72 Narcotics as IV anesthetics How do you get these drugs to work as anesthetics? Give higher doses Cardiovascular effects? Minimal depression Respiratory effects? Severe depression, even post-op (support!) Name one complication. Muscle rigidity

73 Narcotics as IV anesthetics Name one drug on our list that is in this class. Fentanyl Is this drug a good analgesic? Yes. It’s a narcotic. Why use this over other opioids? It has a shorter half-life Is there an antagonist available for reversal? Yes. Naloxone

74 Droperidol 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 environment What is Innovar? Combination of fentanyl and droperidol-induces neuroleptanalgesia? How do you convert to neuroleptanesthesia? Add 65% nitrous oxide

75 Droperidol 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.

76 Dexmedetomidine 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 properties Does this drug cause sedation? yes Does this drug cause analgesia? Yes

77 Conscious and deep sedation What 3 properties do you need for conscious sedation? Amnesic, sedative, analgesic But 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

78 Conscious and deep sedation Name a combination of three drugs that you can combine for conscious sedation. 1.propofol 2.fentanyl 3.midazolam (These are the ones listed in the syllabus)

79 Conscious and deep sedation Are you currently deeply sedated? Yes. Is this over? Yes. Unless you want a quick IV anesthetic review. Then click again.

80 IV anesthetics What can you cure with flumazenil? Midazolam overdose What can you cure with naloxone? Fentanyl overdose Which of the IV drugs cause analgesia? (3) Fentanyl, ketamine, dexmedetomidine Which is a neuroleptic? droperidol

81 IV anesthetics Which are anti-emetics? Droperidol, propofol Which drug induces dissociative anesthesia? Ketamine Which drug commonly causes myoclonus? Etomidate Which drug is associated with microorganisms growing in it? propofol

82 IV anesthetics Which drug can be administer intramuscularly? Ketamine Which drug has faster recovery: methohexital or thiopental? Methohexital Which one will you need to recover from this powerpoint? Cocaine? Go home.


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