Local Anesthesia (Nagelhout)

2 classes of LA's
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Terms in this set (73)
2 classes of LA's
Esters
Amides
Ester LA's
Cocaine
Procaine (Novocaine)
Chloroprocaine (Nesacaine)
Tetracaine (Pontocaine)
Benzocaine (Anbesol, Cepacol, Lanacane etc)
Amide LA's
Lidocaine (Xylocaine)
Prilocaine (Citanest)
Ropivicaine(Naropin)
Bupivicaine (Marcaine, Sensorcaine)
Articaine (Septocaine)
Mepivicaine (Carbocaine)

Amides = two "i's"
Miscellaneous
EMLA cream (topical cream), others
Hyaluronidase (Wydase, Vitrase, others)
(an additive to LA to help it spread; more commonly used for Botox)
The only naturally occurring local anesthetic is ________.
cocaine

(adult max = 200mg; blocks the re-uptake of Norepi into the sympathetic nerves, therefore has sympathomimetic effects)
The 1st man made local anesthetic is _______.
Procaine (Novocaine)
The 1st synthesized LA and most widely used LA is _______.
Lidocaine (Xylocaine)
What are the 3 chemical properties that a local anesthetic must have for it to be a LA?
1) Lipophilic portion (Benzene ring)
2) Hydrophilic portion (Quaternary amine)
3) Intermediate chain (Ester or Amide linkage)
Image: What are the 3 chemical properties that a local anesthetic must have for it to be a LA?
Which portion of the LA is lipid soluble?
Lipophilic = Benzene ring
Which portion of the LA is water soluble?
Hydrophilic = Quaternary Amine
Structure of 2 Local Anesthetics: The AminoAMIDE Lidocaine and the AminoESTER Procaine.Ester metabolism is catalyzed by plasma and tissue ______________ via hydrolysis; occurs throughout the body and is rapid.cholinesteraseTrue or False: Esters have a lower allergy potential than Amides.*False* Although local anesthetic allergy is uncommon, esters have a *higher allergy potential*, and if patients exhibit an allergy to any ester drug, all *other esters should be avoided*Ester drugs tend to be LONGER or SHORTER acting.Shorter acting due to ready metabolism; tetracaine is the longest acting esterAmides are metabolized in the __________ by CYP1A2 and CYP3A4 and thus a significant blood level may develop with rapid absorption.liverTrue or False: There is no cross allergy among the amide class or between the ester and amide agents.True Allergy to amides is extremely rareAmide drugs are LONGER or SHORTER acting.Longer acting because they are *more lipophilic and protein bound* and require transport to the liver for metabolism.______________ of an LA is what causes it's offset.AbsorptionNerve fiber characteristics and sensitivity to local anestheticsThe fatter the nerve, the harder it is to block. Myelinated are harder to block than non-myelination. Last to get blocked are usually the motor nerves bc they're so large & myelinated.Local anesthetic access to the sodium channelWhat is the mechanism of action of local anesthetics?they *block voltage-dependent Na+ channels*, therefore *block nerve conduction*Esters are metabolized by ___________.Plasma cholinesterasesAmides are hydrolyzed in the ____________.liverWhich portion of the LA diffuses more readily *into the membrane*?the *lipophilic* portionWhich portion of the LA diffuses more readily *through the cytoplasm*?the *hydrophilic* portionLocal anesthetic distributionAll LA's are ACIDS or BASES.*bases*One of the most important determinants of onset of action = ________it's *pKa*The lower the pKa, the FASTER/SLOWER the onset.The lower the pKa, the *faster* the onset. lower pKa = closer to 7.4 (of body)The closer the pKa to 7.4, the larger the fraction that's ______________.non-ionized (and in order to get inside the nerve, it needs to be *non-ionized*)True or False? If the pKa of the drug equals the pH of the solution, then it's 50/50 ionized/non-ionized.TrueWhat characteristic of local anesthetics is most closely related to the *duration of action*?*% protein binding*The more protein bound, the _____________ the duration of action.The more protein bound, the *longer* the duration of action.Effect of dose of local anesthetic and Epinephrine on clinical propertiesVasoconstrictors, usually *epinephrine* (5mcg/mL or 1:200,000), are frequently included in local anesthetic solutions to ___________________ ?*decrease the rate of vascular absorption* (so that it won't be removed as quickly) This allows more anesthetic molecules to reach the nerve membrane and thus improve the depth and duration of anesthesia.Manufacturer's Recommended Single-Injection DoseMax dose of Lidocaine?7 mg/kgionized = ? non-ionized = ?ionized = *water soluble* non-ionized = *lipid soluble* NOTE: ionized = charged = can't cross BBBIn the event of local anesthetic overdose, associated respiratory depression may occur resulting in ________ and ________. The acidosis resulting from hypoxia may INCREASE/DECREASE the ionized fraction of local anesthetic within the cerebral circulation thereby decreasing its ability to cross the blood/brain barrier, leave the brain and reenter the systemic circulation. This phenomenon may prolong and enhance the CNS toxicity of local anesthetics.In the event of local anesthetic overdose, associated respiratory depression may occur resulting in *hypoxia* and *acidosis*. The acidosis resulting from hypoxia may *increase* the ionized fraction of local anesthetic within the cerebral circulation thereby decreasing its ability to cross the blood/brain barrier, leave the brain and reenter the systemic circulation. This phenomenon may prolong and enhance the CNS toxicity of local anesthetics.Fetal pH being lower than the maternal pH can cause __________________.local anesthetic accumulationThe lipid solubility of LA's is diminished in an acidodic environment due to ______________________.The lipid solubility of local anesthetics is diminished in an acidotic environment due to *an increased concentration of the ionized, water-soluble form of the drug*. The loss of lipid solubility prevents absorption into the nerve thereby preventing access to the site of action.Carbonation of local anesthetics (adding CO2) does what to the onset and intensity of action?Carbonation of local anesthetics *speeds the onset and intensity of action* of neural blockade.How does CO2 speed onset of the LA?CO2 readily diffuses into the nerve *lowering the pH within the nerve* --> *Increasing the ionized fraction* within the neuron produces a *higher concentration* of the active form of the anesthetic *available at the Na+ channel*, the site of actionCarbonization makes the inside of the nerve MORE/LESS acidic.Carbonization makes the inside of the nerve *MORE* acidic.True or False? Adding bicarb to your LA's speeds onset.*true* it makes more non-ionized portion *outside* the nerve --> therefore, it's able to penetrate the nerve better NOTE: HCO3 also takes away the sting of the LA injectionAddition of sodium bicarbonate to the local anesthetic mixture INCREASES/DECREASES the pH of the solution thereby increasing the concentration of the non-ionized, lipid soluble form of the drug. Improving the __________ solubility of the local anesthetic improves diffusion of the local anesthetic through the neuronal membrane leading to a more rapid onset of action.Addition of sodium bicarbonate to the local anesthetic mixture *increases* the pH of the solution thereby increasing the concentration of the non-ionized, lipid soluble form of the drug. Improving the *lipid* solubility of the local anesthetic improves diffusion of the local anesthetic through the neuronal membrane leading to a more rapid onset of action.What makes the *inside* of the nerve more acidic?CO2What makes the *outside* of the nerve more basic?HCO3 (makes more non-ionized drug outside of the nerve, which increases penetration/amount that can cross the lipid membrane)Fetal-maternal arterial lidocaine ratios during acidemiaFetal local anesthetic ion trappingLAST: Local Anesthetic Systemic ToxicityLAST: *CNS s/s*LAST: *CV s/s*When does LAST occur?Recommendations for Preventing LAST 1Recommendations for Preventing LAST 2Recommendations for Preventing LAST 3Recommended Lipid Emulsion Dosing for Treatment of Local Anesthetic CV ToxicityFor patients experiencing signs or symptoms of local anesthetic systemic toxicity (lAST): Part IFor patients experiencing signs or symptoms of local anesthetic systemic toxicity (lAST): Part IILocal anesthetics are _________.bases If you put them into a basic pH, they're not gonna be charged. If you put them in an acid pH, they're going to be ionized.Local anesthetics block _______________ thereby interrupting the initiation and propagation of nerve impulses.Na+ channelsTrue or False? LA's need to be lipid soluble to cross the membrane and get into the nerve and then water soluble inside the nerve to block the Na+ channels.TrueTrue or False? Pregnancy enhances the effect of local anesthetic agents.True Pregnant women are more sensitive to the effects of LA's.True or False? Local anesthetics, as used clinically, are teratogenic.False: Local anesthetics, as used clinically, are *NOT* teratogenic._____________ of a local anesthetic makes onset of neural blockade faster.*Alkanization* of a local anesthetic makes onset of neural blockade faster.What are the two reasons we mix our local anesthetics?1) to speed onset 2) to prolong durationIf you want to mix Lidocaine and Bupivicaine, what is the max dose you can give?Normal max dose of Lidocaine = 7mg/kg Normal max dose of Bupivicaine = 3mg/kg If you're mixing, need to cut it in half. Lidocaine 3.5mg/kg max + Bupivicaine 1.5mg/kg maxThe spread and depth of epidural and spinal anesthesia in are LESS/GREATER in pregnancy.Greater What affects this? - mechanical factors associated w/pregnancy (i.e. dilated epidural veins decrease the volume of the epidural and subarachnoid spaces) - direct effects of hormones*The dosage of local anesthetics should be INCREASED/DECREASED in patients in all stages of pregnancies.decreased/reducedWhat is tumescent anesthesia?A technique of local anesthesia most commonly used by plastic surgeons during liposuction procedures involves the *subcutaneous injection of large volumes of dilute local anesthetic* in combination with epinephrine and other agents. Dilute the LA down, and HCO3 to it, so that they can give larger volumes of it. The *maximum safe dose* of lidocaine with epinephrine in tumescent anesthesia for liposuction is probably between from *35 to 55 mg/kg* with a suggested safe dose of 28mg/kg. After tumescent infiltration for liposuction, serum lidocaine concentrations peak between 12 and 16 h after injection.EMLA is a mixture of ___________ and ___________ and is used mostly for ______________ ?EMLA is a mixture of Lidocaine 2.5% and Prilocaine 2.5% and is used mostly for starting IV's in kids.What is *hyaluronidase*? What is it used for? What type of setting is it used in?An enzyme that breaks down the tissue matrix so that things can spread around various tissues --> breakdown hyaluronic acid (which is a normal body thing) *If you put it into a solution, helps it spread through tissues farther than it normally would have.* Used by *opthamologist* -- needle in, inject LA with hyaluronidase, it helps the LA spread to a large. Also used for botox/lip plumping. Would increase onset time and duration of action. Probably higher chance of toxicity.