Local Anesthetics

Question 0

Procaine

Answer 0

• Prototype ester local anesthetic
• Low potency, short duration
• Decreased use
• Used for infiltration anesthesia
  
  • Occasionally diagnostic nerve blocks
• Route of administration: injection
• Metabolism: hydrolyzed to PABA in vivo
  
  • Hydrolyzed by plasma cholinesterase (very short half life)
  • Can inhibit action of sulfonamides
• Toxicity:
  
  • CNS: stimulation->seizure->depression->death
  • GABAergic neurons have high firing frequency
  • Decrease myocardial electrical excitability (decrease BP)
  • high doses cause neurotoxicity
  • Hypersensitivity rxn

Question 1

Cocaine

Answer 1

• Ester local anesthetic
• Use: nerve conduction blockade
  
  • topical anesthesia in nose, nasopharynx, mouth, throat, ear
• Route of administration: mucus membrane & skin
• Vasoconstriction due to inhibition of NE uptake
• Metabolism: in liver & plasma
• Excreted in urine
• Side effects: toxicity & abuse
  
  • due to inhibition of catecholamine reuptake
  • CNS: stimulation->seizure->depression->death
  • mood & behavioral alteration
  • Increases HR &BP

Question 2

Benzocaine

Answer 2

• Ester local anesthetic
• Topical use only
• Used directly on wound and ulcers
• OTC topical preparations
• Route of administration: mucus membranes & skin
• Long duration due to low water solubility
• Metabolism: Hydrolyzed by plasma cholinesterase
  
  • very short half life
• Toxicity:
  
  • CNS: stimulation->seizure->depression->death
  • GABAergic neurons have high firing frequency
  • Decrease myocardial electrical excitability (decrease BP)
  • high doses cause neurotoxicity
  • Hypersensitivity rxn
  • Methemoglobinemia-oxidized to o-toluidine which converts hemglobin to methemaoglobin

Question 3

Lidocaine

Answer 3

• Prototype amide local anesthetic
• Greater potency & longer duration than procaine
• Widely used clinically
  
  • intermediate duration
• Also used as an Antiarrhythmic
• Route of administration: mucus membranes, skin patch, injection
• Metabolism: slowly by liver CYP450
  
  • Can build up in body: more toxicities than esters
• Toxicity:
  
  • CNS: stimulation->seizure->depression->death
  • GABAergic neurons have high firing frequency
  • Decrease myocardial electrical excitability (decrease BP)
  • high doses cause neurotoxicity
  • Hypersensitivity rxn

Question 4

Bupivacaine

Answer 4

• Amide local anesthetic
• Greater potency than lidocaine
• Longer duration than lidocaine
• More toxic than lidocaine
• Route of administration: injection
• Metabolism: slowly by liver CYP450
  
  • Can build up in body: more toxicities than esters
• Toxicity:
  
  • CNS: stimulation->seizure->depression->death
  • GABAergic neurons have high firing frequency
  • Decrease myocardial electrical excitability (decrease BP)
  • high doses cause neurotoxicity
  • Hypersensitivity rxn

Question 5

Mechanism of action of local anesthetics

Answer 5

• Bind specific site in intracellular region of Na+ channel pore
  
  • Block Na+ influx
• Selectively block transient rise in Na+ permeability responsible for conduction in excitable membranes
• Increases threshold & decrease rate of rise & amplitude of AP
• Decrease conduction velocity & finally blocks AP generation
• Doesn’t alter resting potential except at high concentrations, then affects K+ channel
• Bind Na+ channels in open state
  
  • block via voltage, time, & frequency dependent mechanism
  • Stabilize the inactive state & slow recovery from inactivation
• Susceptibility to block: C>Aδ>Aß>A∂
• Sensation lost in order:
  
  • Pain->temp->touch->deep pressure->motor

Question 6

Tetracaine

Answer 6

• Ester local anesthetic
• greater potency and longer duration than procaine
• Route of administration: injection
• MetabolismL Hydrolyzed by plasma cholinesterase
  
  • very short half life
• Toxicity:
  
  • CNS: stimulation->seizure->depression->death
  • GABAergic neurons have high firing frequency
  • Decrease myocardial electrical excitability (decrease BP)
  • high doses cause neurotoxicity
  • Hypersensitivity rxn