Local Anesthetics

Question 1

Local anesthesia general definition/mechanism

Answer 1

• = loss of sensation in circumscribed area of the body
• results from block of AP initiation or propogation @ nerves
  
  • block voltage-gated Na⁺ @ peripheral nerves

Question 2

Chemical structure of local anesthetics

Answer 2

1. lipophilic aromatic portion
2. intermediate alkyl chain
   
   1. ester vs. amide group
3. hyrdophilic amine portion
4. naming
   
   1. “-caine”
   2. one i = intermediate ester (cocaine)
   3. two i’s = intermediate amine (lidocaine)

Question 3

Effect of pH on local anesthetic action

Answer 3

• local anesthetics = weak base
  
  • pK_a ~7.7 - 9.0
• thus, local anesthetics are partly ionized @ pH 7.4 ==> more drug molecules are charged vs. neutral
• both forms are needed for proper action
• changes in tissue pH ==> ratio of neutral/charged ==> alter effectiveness of local anesthetics

Question 4

MOA of local anesthetics

Answer 4

• binding site = @ wide region of water-filled pore of Na⁺
  
  • route of access = intracellular pore entrance
  • binding site accessed when channel is open
• cross plasma membrane when in neutral form
  
  • lipophillic portion ==> membrane solubility
• charged (cationic) form of binds with more affinity w/in Na⁺ channel pore
  *

Question 5

Characteristics of use-dependent block

Answer 5

• more the channel is open, thre greather degree of local anesthetic binding and block

Question 6

Physiocochemical properties ==> potency, onset of drug action

Answer 6

• lipid solubility ==> potency
• pKa determines speed of drug to target ==> onset of action
  
  • lipid solubility correlates w/pKa and onset
• protein binding ==> longer duration of action

Question 7

Procaine: potency, onset, duration, pKa, lipid solubility, protein binding

Answer 7

• low potency
• slow onset
• short duration
• high pKa
• low lipid solubility
• low protein binding

Question 8

Lidocaine: potency, onset, duration, pKa, lipid solubility, protein binding

Answer 8

• medium potency
• intermediate onset
• medium duration

Question 9

Etidocaine: potency, onset, duration, pKa, lipid solubility, protein binding

Answer 9

• high potency
• fast onset
• long duration
• low pKa (7.7)
• high lipid solubility
• high protein binding

Question 10

Methods of local anesthetic application

Answer 10

• topical anesthesia
• infiltration anesthesia
• nerve block anesthesia
• IV regional anesthesia
• Spinal anesthesia
• epidural anesthesia

Question 11

Topical anesthesia mechanism/disadvantage

Answer 11

• directly onto skin, cornea, mucous membranes of nose, mouth, etc.
• disadvantage: considerable amount can get into circulation ==> toxic effects

Question 12

Infiltration Anesthesia

Answer 12

• Injection of local anesthetic into tissue without consideration of the location of cutaneous nerves.
• advantage = very superficial anesthesia but function of underlying organs is unaffected
• Disadvantage is that large doses are needed and there may be significant absorption into the circulation.

Question 13

Nerve block anesthesia

Answer 13

• injection of a high concentration of local anesthetic near a peripheral nerve or nerve plexus
• advantage of this technique = larger body regions can be anesthetized as compared to infiltration anesthesia.

Question 14

IV regional anesthesia

Answer 14

• blood is squeezed out of a limb or part of a limb using a very tight elastic bandage, and a tourniquet is placed proximally.
• Local anesthetic is then injected via a catheter, and limb anesthesia develops within 5-10 minutes.
• Tourniquet pain and ischemic injury limit the use of this method to a maximum duration of 2 hours.

Question 15

Spinal anesthesia technique + advantages/disadvantages

Answer 15

• injection of a local anesthetic into the cerebrospinal fluid bathing the lumbar section of the spinal cord.
• advantage = large body regions can be anesthetized while maintaining a low plasma level of drug
• disadvantage = useful for surgical procedures of the lower abdomen, perineum and lower extremities.

Question 16

Epidural anesthesia technique + advantages/disadvantages

Answer 16

• injection of a local anesthetic just outside the dura-enclosed spinal canal, and at the base of the canal.
• advantage = can use catheters, allowing repeated bolus or continuous application of anesthetic.
• disadvantage vs. spinal anesthesia = plasma levels of anesthetic are higher, which can lead to toxicity (e.g. cardiovascular).

Question 17

Vasoconstrictor use with local anestheti

Answer 17

• vasoconstrictor prolongs the duration of conduction blockade (by a factor of perhaps 2) by reducing blood flow in the vicinity of the injection,
  
  • ==> slower systemic absorption of the anesthetic
• vasoconstrictor also helps to prevent plasma anesthetic levels from rising to potentially toxic levels.
• Epinephrine (5 μg/ml) is usually the chosen vasoconstrictor

Question 18

Side effects of local anesthetics

Answer 18

• convulsion
  
  • action @ inhibitory interneurons @ CNS
• interfere w/autonomic nervous system fxn
• CV = actions @ heart
  
  • can be pro-arrhythmic
  • some (e.g. lidocaine) are used as antiarrhythmics
• arteriolar dilatation
  
  • action @ vascular smooth muscle
• impact fetus by crossing placenta
• inhibit neuromuscular transmission
  
  • block nicotinic ACh receptors
• possibility of hypersensitivity

Question 19

Local anesthetics vs. Tetrodotoxin and Saxitoxin

Answer 19

• TTX blocks NaV channels from extracellular side, not selective at all or use dependent
• LA are use dependent and attack from cytoplasm.
• Bottom line TTX and SAX are NOT SELECTIVE; no descrimination at all