Medical Archive

Overview

• LAs have a lipophilic group linked with a hydrophilic group 
• Ester group
  • Metabolized in the serum by esterases
  • Have a higher risk of causing allergic reactions or systemic toxicity 
• Amide group
  • Metabolized in the liver
  • Safer than the ester agents 
  • Should be used when patients are allergic to esters

	??	??????	??????
Ester	?? esterase	???	??? (paraaminobenz-oic acid)	Cocaine Procaine Chlorprocaine Tetracaine
Amide	? enzyme (CYP 450)	??	?? ??? (methylparaben)	Lidocaine Mepivacaine Bupivacaine Etidocaine Ropivacaine

	Local anesthetics	Onset	Duration of action
Ester group	Procaine	~5m	Short (<90m)
	Chloroprocaine	6-12m	Short (<60m)
	Benzocaine		Short
	Tetracaine	Rapid	Long (2-6hr)
Amide type	Lidocaine	Rapid	Intermediate (50-120m)
	Pilocaine		Intermediate
	Mepivacaine	Rapid	Intermediate (2-2.5hr)
	Bupivacaine	~10m	Long (4-8hr)
	Etidocaine		Long
	Ropivacaine		Long

• ?? ?? ?? ?? ?? ?? – Na+ block – ??? ?? ??
• Epinephrine ??? ???? ?? ? ???? ??. (?? ?? ??) But Terminal artery organ? ?? ??.
• ?? ???? ?? ?? (acidic?? ionization ?, alkaline ???? ??? ???)
• BBB ???? ??? ??? ??? ? ?????.

Lidocaine
Maximal safe dose: 5mg/kg (? 300mg), epinephrine ??? 7-8mg/kg
?? ??? ?? ?: ??? ??? ? ?? ?? ?? + ?? ? ????? 100% O2 ??.

Order of nerve blockade
Small myelinated fibers > small unmyelinated fibers > large myelinated fibers > large unmyelinated fibers.

Order of loss
Pain > temperature > touch > pressure 

Pharmacodynamics

• Pain pathway: thermal, mechanical, or chemical stimuli ? nociceptor stimulation ? conversion of stimulus to an electric signal (action potential) ? neural conduction of electric signal to the CNS ? perception of pain
• LAs bind to the inner portion of voltage-gated sodium channels of the nerve fibers  ? reversibleblockage of sodium channels ? inhibition of nerve excitation and impulse conduction (pain signals)? local anesthesia in the area supplied by the nerve
• LAs with 3° amine structure infiltrate membranes in their uncharged form, then bind to ion channels in their charged form.
• The susceptibility of nerve fibers to LA depends on their firing rate, size, and myelination. 
  • Rapidly firing neurons are blocked more effectively than slow-firing neurons.
  • Small diameter nerves are the first to be anesthetized. 
  • Myelinated nerves are blocked faster than unmyelinated nerves. 
  • Because size is thought to outweigh myelination, nerve fibers are blocked in the following order:
    1. Small myelinated fibers
    2. Small unmyelinated fibers
    3. Large myelinated fibers
    4. Large unmyelinated fibers
  • Loss of sensation occurs in the following order:
    1. Pain
    2. Temperature
    3. Touch
    4. Pressure
• Factors that affect the efficacy of LA 
  • Use of vasoconstrictors (e.g., adrenaline) reduces bleeding and systemic absorption of LAs, leading to a prolonged anesthetic effect.  
  • Inflamed/infected tissue: decreased efficacy of LAs 
    • LAs are composed of a lipophilic group and a hydrophilic group, and permeability depends on which group is predominant.
    • Because inflamed tissue has an acidic environment, alkaline anesthetics are charged and the hydrophilic group predominates ? ? ability to penetrate the nerve cell membranes ? ? efficacy

Adverse effects

• Complications are uncommon
• Allergy
  • Acute: anaphylaxis (rare)
  • Delayed: pruritic rash with blisters at site of LA injection within 72 hours of administration
• Vasovagal syncope
• Systemic toxicity 
  • Central nervous system
    • Tinnitus, metallic taste, perioral paresthesia
    • Seizures
  • Cardiovascular system (especially with bupivacaine)
    • Bradycardia  , decreased cardiac contractility , atrioventricular block 
    • Ventricular arrhythmias (especially cocaine)
    • Can cause hypertension or hypotension
    • Cardiogenic shock
  • Hematologic: methemoglobinemia (especially benzocaine) ? cyanosis, gray skin color, fatigue

Indications

• Local anesthetic agents have a wide range of clinical uses
• Topical application (lidocaine, tetracaine, prilocaine) 
  • Useful in children before performing minor invasive procedures (e.g., venipuncture, intravenous catheter placement)
  • As a gel: prior to catheterizing the bladder (as a lubricant and as an LA)
  • As a mouth gargle/spray: prior to performing indirect laryngoscopy, endoscopy, etc.; in pharyngitis with odynophagia
• Infiltration 
  • Into the skin/subcutaneous tissue: for skin surgery (skin biopsy, suturing, foreign body extraction, etc.)
  • Into the epidural space for epidural anesthesia
  • Into the subarachnoid space for spinal anesthesia