LAST: PREVENTION AND
TREATMENT
PART A
PART A: OVERVIEW
•
•
•
•
•
•
•
What are local anesthetics
Classification
MOA
Anesthetic potency
Clearance
Uses
Prolongation of action
PART B: ADVERSE EFFECTS&SYSTEMIC
TOXICITY
• Allergic reaction
• Local toxicity
• Systemic toxicity
What are LA
• Weak bases which produce a transient
and reversible loss of sensation
(analgesia) in a circumscribed region of
the body without loss of consciousness.
• Normally, the process is completely
reversible.
Classification
• Local anesthetics - esters or
amides.
• Major difference is their potential
for producing adverse effects and
the mechanisms of their
metabolism.
Esters
• Eg: Procaine, Cocaine, tetracaine
• The ester linkage is cleaved by plasma
cholinesterase. Short half life( abt 1min).
• Amides:
• Eg: lidocaine, Marcaine(Bupivacaine),
ropivacaine. Amide linkage is cleaved in the
liver. Half life is about 2-3 hrs
MECHANISM OF ACTION
• LA block nerve conduction by impairing
propagation of action potential in axons.
Interact directly with Na+ channels and stop
Na+ ion influx. May also act on K+ & Ca+
channels.
• LA need to diffuse passively in uncharged
state (lipophilic) to reach target-axoplasmic
side of Na+ channel.
HOW MUCH IS TOO MUCH?
ESTERS
Chloroprocaine
MAX
DURATION
DOSE(mg/kg) (HOURS)
0.5 – 1
12
Procaine
12
0.5 – 1
Cocaine
3
0.5 – 1
Tetracaine
3
1.5 – 6
Max Dose
Amides
Duration (h)
(mg/kg)
Lidocaine
4.5/(7 with epi)
0.75 – 1.5
Mepivacaine
4.5/(7 with epi)
1– 2
Prilocaine
8
0.5 – 1
Bupivacaine
3
1.5 – 8
Ropivacaine
3
1.5 – 8
ANESTHETIC POTENCY
• The more LA is lipophilic the more potent it is (
increased rate of diffusion).
• More protein binding prolongs the effect.
Bupivacaine is approximately 95% protein-bound.
• Intermediate-duration LAs (lidocaine and
mepivacaine) have a smaller protein-bound
fraction (60-70%).
• pH; higher pH speeds action (keeps LA
uncharged).
• pKa: lower pKa faster onset.
• Concentration; higher conc. =rapid onset (mass
effect).
CLEARANCE
• ESTERS
hydrolysis via tissue cholinesterase
• AMIDES
metabolism via hepatic enzymes
USES
• Surface anesthesia
• Infiltration anesthesia
• Regional anesthesia
SURFACE ANESTHESIA
• On intact skin –
• eutectic mixture of
Local anesthetics
• (EMLA)
• Slow absorption,
Action up to ½ Hr
INFILTRATION ANESTHESIA
• LA infiltrates locally into tissues to numb the
area.
• Purpose of pain free procedures-before
injections with large needles, lumbar puncture
REGIONAL ANESTHESIA
• Nerve block
• Intravenous
• Epidural/Extradural
• Intrathecal block/ spinal anaesthesia
NERVE BLOCKS
• Inject a drug around
the nerve
• Anaesthetise a region
INTRAVENOUS ANESTHESIA
• 0.5-1% lidocaine
without adrenaline
• Bier’s Block
EPIDURAL
• Thoracic, lumbar,
sacral
• Act on nerve roots
• Less hypotention
SPINAL BLOCK
• Sympathetic nerve
block
• hypotension