Local Anesthetics

Question 1

What is local anesthesia?

Answer 1

• Loss of sensation in a circumscribed area of the body
  
  • No loss of consciousness
  • Block of action potential initiation or block of action potential conduction in nerves
  • Blocking voltage gated Na channels in peripheral nerves

Question 2

What’s the basic structure of local anesthetics?

Answer 2

• Lipophilic aromatic portion
  
  • Intermediate alkyl chain
  • Hydrophilic amine portion

Question 3

Drug names with two I’s are what?

Answer 3

• Amides

* Lidocaine is an amide with two I’s

Question 4

Drug names with a single “I” are what?

Answer 4

• They are esters

* Cocaine, one I, esters

Question 5

Local anesthetics have what pKa values? How does pH effect them?

Answer 5

• They are basic, with pKas in the 7.7 - 9 range
  
  • At 7.4 are only partly ionized
  • More are charged than neutral, but both are needed for action as cation is what binds sodium channel but neutral crosses membrane
  • Thus, during infection the tissue is acidic and higher dose needed

Question 6

What has to be true about the sodium channel for a local anesthetic to work?

Answer 6

• Block initiation and conduction of nerve impulses by blocking VSSC
  
  • VSSC are responsible for upstroke of AP
  • Closed, (fast) open, (slow) inactivated
  • Local anesthetics block the pore, and thus only bind an open conformation

Question 7

Local anesthetics don’t just block the pore of VSSCs, they do what in addition?

Answer 7

• Stabilize the inactivated conformation
  
  • Increases the lifetime of the inactivated state of Na channel
  • Refractory period is prolonged

Question 8

Why do local anesthetics affect pain perception first?

Answer 8

• Pain fibers fire for longer duration at higher frequency
  
  • Essentially their sodium channels are open for longer
  • The use-dependent drug sops up the more open pain VSSCs first before the larger myelinated motor axons

Question 9

What two factors primarily affect potency of local anesthetics?

Answer 9

What primarily affects speed of onset of a local anesthetic?
• Speed of onset is primarily pKa dependent
• Lower pKa and higher lipid solubility means faster action onset

Question 10

What primarily affects speed of onset of a local anesthetic?

Answer 10

• Speed of onset is primarily pKa dependent

* Lower pKa and higher lipid solubility means faster action onset

Question 11

What is the primary factor in duration of action of the local anesthetics?

Answer 11

• Protein binding capacity
• More drug bound to protein pore, more action for longer
• More binding of plasma protein, longer reserve of drug bouncing off to bind the target
• Alpha-1-acid glycoprotein is major binder
○ Only bind amides thus amides tend to have longer duration

Question 12

would cocaine or lidocaine have a longer duration of action

Answer 12

just looking at the number of “i”s, lidocaine is an amide and thus is protein bound and thus has longer duration of action

Question 13

Where are amide and ester local anesthetic drugs metabolized?

Answer 13

• Esters by esterase in the plasma AND liver
  
  • Amides only in the liver
  • Hepatic insufficiency, use of amide-linked local anesthetics is not a great idea

Question 14

Where are local anesthetics excreted?

Answer 14

• Renal elimination, excretion in the kidney

* Needs to be ionic form for elimination by that route

Question 15

Which anesthetics are best for topical anesthesia

Answer 15

• Tetracaine
• Lidocaine
• Cocaine
○ Side effects from absorption to blood stream
• Lidocaine and prilocaine make up EMLA cream which allows for further skin penetration to 5mm depth

Question 16

What drugs are used for nerve block anesthesia?

Answer 16

• Injection of high concentration of local anesthetic near a peripheral nerve or nerve plexus
• Larger body regions can be anesthetized, but requires some anatomoical knowledge
○ Lidocaine (2-4 hours) and bupivacaine (longer)

Question 17

What local anesthetics are used for the purpose of infiltration anesthesia?

Answer 17

• Lidocaine
• Procaine
• Bupivacaine
○ Large doses, no care for underlying cutaneus nerves just let it diffuse

Question 18

Benzocain is good for wounds why?

Answer 18

• It has a terminal amino group and has low water solubility

* Slow absorption reduces risk of toxicity so they are suited for wounds

Question 19

What is Bier’s block?

Answer 19

• Intravenous regional anesthesia
• Blood is squeezed out of a limb or part of limb with tight elastic bandage
• Tourniquet placed proxiamlly
• Local anesthetic is injected via catheter
• Entire limb is numb in 5-10 minutes
• Ischemic injury limits to 2 hour duration
• Lidocaine most commonly used here
○ Bupivacaine is cardiotoxic, don’t inject this into bloodstream

Question 20

What is spinal anesthesia?

Answer 20

• Injection of local anesthetic into the CSF bathing the lumbar section of the spinal cord
• Large body region anesthetized with low plasma level
• Only useful for lower abdomen perineum and LE
• Lidocaine is used for short duration
• Bupivacaine for intermediate duration
• Tetracaine is the long lasting ester drug for long procedures
○ Also, little to no plasma esterase in CSF

Question 21

What is epidural anesthesia?

Answer 21

• Injection of local anesthetic just outside the dura at the base of canal
  
  • Advantage is ability to use cathetars so you can do continuous application
  • Plasma levels aer higher though and thus possible toxicity (cardio)
  • Lidocaine is used for short
  • Bupivacaine longer duration
  • Pregnancy - lower dose bupivacaine often with fentanyl (opioid) co-adimin

Question 22

When administering local anesthetic, what other drug is often co-administered?

Answer 22

• A vasoconstrictor with local anesthetic will reduce blood flow to area and increase duration about 2-fold
○ Also reduces plasma levels
• Epinephrine is usually used
• Cocaine has a vasoconstrictive property of it’s own by messing with NE reuptake
• Most other anesthetics reduce sympathetic done and vasodilate

Question 23

What are some toxic side effects of local anesthetics?

Answer 23

• They can inhibit action potentials in any neuron or cell that has them
• Cardiac toxic effects
• Convulsions in CNS
• Interefere with ANS by reducing symp tone
• Cross placenta and affect fetal circulation
• NMJ problems by blocking N-m receptors
• Rarely - allergic response
○ PABA, by-product of pseudochoniesterase is usually the hypersensitivity culprit
○ Thus the esters are more likely than amides to cause allergic reaction

Question 24

What do you use if a patient is allergic to all local anesthetics?

Answer 24

• Promethazine, which is an antihistamine at lower doses