local anesthetics

Question 1

for classification of local anesthetics, what are esters?

Answer 1

ESTERS
cocaine, benzocaine (topical), procaine, tetracaine
hydrolyzed by pseudocholinesterases
plasma and tissue esterases
Hydrolysis is rapid
Cocaine partially metabolized in liver
hypersensitivity reactions are more common than with amides
Structural similarity to p-aminobenzoic acid (PABA)
Safe to use amides if there is reaction to esters

Question 2

for classification of local anesthetics what are amides?

Answer 2

AMIDES
lidocaine, bupivacaine, ropivacaine
metabolized by hepatic microsomal enzymes
N-dealkylation and hydroxylation
Metabolism much slower than esters
Dependent on liver function
Systemic toxicity more likely than esters

Question 3

what is the mechanism of action of local anesthetics?

Answer 3

Prevent conduction of nerve impulse
PROTONATED FORM blocks sodium channels from the CYTOSOLIC side of the membrane
NON-PROTONATED FORM penetrates axon

Question 4

what are factors affecitng local anesthetic action?

Answer 4

-  pH and pKa:
pKa = 7.7 - 8.9 
local anesthetics are weak bases
-  acidosis eg. infection
-  alkalosis eg.carbonated solutions
-  Lipid Solubility
Bupivacaine, lipid soluble / high protein binding 
 long acting
Lidocaine, less lipid soluble -- short acting
-  Blood Flow
Systemic absorption / vasodilation
use of vasoconstrictors eg. epinephrine

Question 5

what is blocked in the nerve fibers and what does the axon have to do with it?

Answer 5

• What is blocked?
  Sensation (pain, touch, etc.)
  Motor
  Sympathetic
• Small axons more sensitive than large axons
  temp > pain > touch, pressure > motor
  Allows for the concept of differential blockade

Question 6

what adverse effects can local anesthetics have?

Answer 6

• Systemic toxicity: amides > esters
• Toxic range
  Different for different local anesthetics
  Eg. Lidocaine 3-5 mg/kg plain, 5-7 mg/kg with epinephrine
• CNS
  inhibitory neurons affected more
  Perioral numbness, restlessness, dizziness, seizures, coma
• CVS
  myocardial depression
  vasodilation
  Arrhythmias
• Hematologic
  Methemoglobinemia (esp. benzocaine, prilocaine)

Question 7

what is the treatment for adverse effects?

Answer 7

• ABC’s (Airway, Breathing, Circulation)
• Raise seizure threshold
  Benzodiazepine, hyperventilation
• Supportive care
  Oxygen, secure airway if need
  Support circulation if cardiovascular effects
• Lipid emulsion / albumin to bind local anesthetic?
  Intralipid TM

Question 8

what are techniques for local anesthetics uses?

Answer 8

• Topical
  Skin: eutectic mixture of local anesthetics (EMLA)
  Wounds: tetracaine adrenaline cocaine (TAC)
  Mucosa
• Infiltration
  -Peripheral Nerve Blockade
  -Intravenous Regional Anesthesia / Bier Block
• Neuraxial Anesthesia/Analgesia
  Epidural
  Spinal
• Intravenous

Question 9

what are the advantages of local anesthetics?

Answer 9

Less disturbance of coexisting disease
Fewer systemic side effects: respiratory and cardiovascular
May be used for postoperative analgesia
Inexpensive
potentially improved outcome: major abdominal, thoracic, orthopedic, transurethral resection of the prostate, cesarean section

Question 10

what to know!!!

Answer 10

Differentiate between amide and ester local anesthetics
Understand site of action and which form has the greatest effect
Know the toxicity / adverse effects