Term
| What are the 3 structural components of local anesthetics? |
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Definition
lipophilic portion - benzene ring
hydrophilic portion - amine group
intermediate chain - ester linkage or amide linkage |
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Term
| Do ester or amide local anesthetics have 2 "i"s in their name? |
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Definition
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Term
Are ester or amide LA metabolized primarily in the liver by CYP P450?
What is the major excretory route for unchanged drug and metabolites |
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Definition
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Term
| Are ester or amide LA hydrolyzed in plasma by plasma cholinesterases? |
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Definition
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Term
| What is the metabolite formed associated with ester-type LA that can cause an allergic/anaphylactic-typre reaction? |
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Definition
| para-aminobenzoic acid or PABA |
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Term
| pts with _____________ may experience prolonged effects & exaggerated toxicity when administered ester-type LA |
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Definition
| atypical pseudocholinesterase |
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Term
ALL local anesthetics have the following structural components EXCEPT:
Lipophilic portion
Benzene ring
Ester linkage
Hydrophilic portion
Hydrocarbon side chains |
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Definition
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Term
Nerve cell membrane relatively permeable to ____; IMPERMEABLE to ___.
Resting membrane potential ___ mVolts.
Interior is (positive or negative) compared to extracellular.
Active transport outward of ___ ions
Voltage gated ___ channels allow influx of ___ ions when excited |
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Definition
Nerve cell membrane relatively permeable to K+; IMPERMEABLE to Na+
Interior is NEGATIVE compared to extracellular
Active transport outward of Na+ ions
Voltage gated Na+ channels allow influx of Na+ ions when excited |
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Term
After excitation, influx of _____ causes depolarization of action potential (phase 0)
At max. depol, conductance reverses & movement of ____ out repolarizes cell.
Ionic gradients reestablished by __________. |
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Definition
After excitation, influx of Na+ causes depolarization of action potential (phase 0)
At max. depol, conductance reverses & movement of K+ out repolarizes cell.
Ionic gradients reestablished by Na/K ATP pump. |
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Term
LAs bind to ___________ in inactivated state, preventing Na+ influx.
LAs DO NOT alter Resting membrane potential or Threshold level, but slow the ______________.
Action potential is not propagated b/c _________ is never attained |
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Definition
Na+ channels
rate of depolarization
threshold |
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Term
When bupivacaine is applied to a nerve cell which of the following is changed?
Na+/K+ ATP pump function
Rate of depolarization
Resting membrane potential
Threshold potential |
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Definition
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Term
ALL of the following anesthetics are metabolized mainly by cholinesterases EXCEPT:
2-Chloroprocaine
Lidocaine
Tetracaine
Benzocaine
Cocaine |
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Definition
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Term
| What are 2 things that matter in terms of sensitive of nerve fibers to local anesthetic? |
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Definition
Myelinaton (Myelinated > Non-myelinated)
Size (Small >>> Large) |
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Term
| In two small nerve fibers of equal diameter, the (myelinated or unmyelinated) fiber is blocked FIRST |
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Definition
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Term
| Diffusion of LA away from the nerve (adds or reduces) to systemic toxicity. |
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Definition
| adds to (It has to sit there as it slowly diffuses through all these layers to get to the core. That increases the chance of systemic uptake and chance of toxicity because it can go to places you don’t want it to go) |
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Term
| What are the physical and chemical properties of LAs that affect their ability to shut down nerve cell function? |
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Definition
Lipid solubility = POTENCY
Protein binding = DURATION
Ionization = ONSET
Stereochemistry = TOXICITY |
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Term
What property determines potency (ability to do what you want it to do) of a LA?
What structure of LA determines potency? |
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Definition
Lipid solubility
Benzene ring + substitutions |
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Term
| What property determines duration of action of LA (along with pharmacokinetics)? |
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Definition
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Term
Will a highly protein bound LA be (short or long) acting?
What are the most frequent plasma proteins bound? |
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Definition
long acting (Bupiv and ropiv)
albumin and alpha-1-acid glycoprotein |
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Term
| What determines the onset of action of local anesthetics? |
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Definition
| ionization (the ability of an agent to loss or gain a proton or a charge. It’s directly related to the pKa of the local anesthetic) |
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Term
| Would a LA with a pKa close to 7.4 have a (slow or fast) onset? |
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Definition
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Term
| What property determines toxicity? |
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Definition
| stereochemistry (mix of enantiomers in a solution- D is less desirable) |
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Term
| Is the Dextro-isomer (R) or Levo-isomer (S) have higher cardiac Na+ channel affinity --> more toxic, shorter duration? |
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Definition
Dextro-isomer (R)
Heart has similar Na+ channels as nerve cells so can't tell the difference and binds more tightly |
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Term
| Is the Dextro-isomer (R) or Levo-isomer (S) less toxic, longer duration? |
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Definition
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Term
| Is Ropivacaine or bupivacaine less cardio-toxic? Why? |
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Definition
| Ropivacaine is a pure S enantiomer; less cardio-toxic than bupivacaine |
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Term
Based on the following pKa information (Tetracaine -8.5; Ropivacaine- 8.1; Lidocaine-pKa 7.9; Etidocaine-pKa 7.7; Mepivacaine-pKa 7.6) which of the following is TRUE:
Tetracaine is more potent than lidocaine
Lidocaine has a longer duration than etidocaine
Ropivacaine is more toxic than mepivacaine
Etidocaine is faster in onset than ropivacaine |
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Definition
Etidocaine is faster in onset than ropivacaine
(pKa refers to onset of action) |
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Term
Explain what will happen to LA in the following scenarios:
If you increase volume and concentration
If you add a vasoconstrictor (epinephrine)
If you inject in a highly vascular site
If you add bicarbonate to a LA
If you combine certain drugs |
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Definition
increase volume and concentration: faster onset of action
add a vasoconstrictor (epinephrine): reduce amount of anesthetic swept away
If you inject in a highly vascular site: increases toxicity
If you add bicarbonate to a LA: ionization-increase onset time
If you combine certain drugs: can combine faster onset drug with longer duration of action |
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Term
| What are external factors that can affect LA? |
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Definition
Volume and concentration
Vasoconstrictor
Site of injection
Bicarbonate and carbonation
Temperature
Combination of drugs |
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Term
| Is the CNS or Cardiovascular system more susceptible to the toxic effects of LA? |
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Definition
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Term
| If a patient starts to feel dizzy, have a metallic taste, lethargy and quivering, what may they be experiencing? |
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Definition
| anesthetic toxicity of CNS --> can progress to cardia arrhthmias, asystole, and even death |
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Term
| If a patient is experience toxicity due to local anesthetics, what should you do? |
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Definition
CPR, ABC (airway, breathing, circulation)
often have cardiac arrhythmias that are very resistant to electric cardioversion and fibrillation, so often times we have to use intralipid rescue to ensure successful resuscitation |
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Term
| What agent is used for IV feed and is thought to extract plasma or cardiac tissue LA into an intravenous lipid depot. |
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Definition
| intralipid rescue (soybean oil, egg yolk, glycerin) |
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Term
| Local anesthetics block nerve conduction by blocking _________. |
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Definition
| Local anesthetics block nerve conduction by blocking sodium ionophores. |
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