3. Introduction
Local anesthesia: loss of sensation in a limited region of the body
Primary goal: achieve loss of sensation (anesthesia), less of pain (analgesia)
May be used as a sole agent or as adjuncts to general anesthesia
4. Class
Divided broadly into two classes
Amino esters- ester links between the intermediate chain and aromatic acid
Examples: cocaine
Procaine(Novocain)
Tetracaine (pentocaine)
Amino amides-amide links the intermediate chain and aromatic chain
Lidocaine(xylocaine)
Mebivacaine (carbocaine isocaine)
Robivacaine
Bupivacaine
Articaine
7. Pharmacodynamics
Mode of action: blockade of Na voltage-gated channels preventing excitation of
neurons.
8. Pharmacokinetics
Absorption: more lipid soluble local anesthetics are more potent, have longer
duration of action but have slower onset of action.
Factors that determine absorption:
Dosage
Site of injection
Drug tissue binding characteristics
Local tissue blood flow
Use of vasoconstrictors (e.g. epinephrine)/ local properties of the drug- Adrenaline
hastens onset, prolongs duration of action and permits a higher dose limit
9. procaine lidocaine bupivacaine
potency low intermediate high
duration 15-30 mins 1-2 hrs 3-8 hrs
onset fast Fast intermediate
Peak plasma time 15-30 mins
Plasma bound 60-80% 95%
10.
11. Metabolism
Aminoamides : liver
Converted to more water soluble metabolites through hydroxylation and N-dealkylation
by liver microsomal cytochrome p450 enzymes.
prilocaine (fastest) > lidocaine > mepivacaine > ropivacaine = bupivacaine =
levobupivacaine (slowest)
Amino esters : plasma
Hydrolyzed rapidly in in blood by circulating butyryllcholinesterase to inactive
metabolites
Excretion: urine
12. Toxicity
Local:
Nerve injury,
pain at point of injection,
transient neurologic syndrome- syndrome of transient pain or dysesthesia
Cauda equina syndrome- back pain, loss of bowel and bladder control, anal numbness
Systemic
CNS: sedation, lightheadedness, visual auditory disturbances, restlessness
Early symptoms: tongue numbness and metallic taste
Higher concentrations: nystagmus and muscular twitching, tonic-clonic convulsions
13. Cont…
Cardiotoxicity: arrhythmias, cardiac arrest, bradycardia, heart block, hypotension
Respiratory depression, dyspnea
NB: appropriately skilled personnel, resuscitation equipment, and oxygen should
always be available with local anesthetic use because of the potential risks of life-
threatening complications.
16. interactions
TCAs: prevent reuptake of serotonin and norepinephrine. Addition of epinephrine may result in
abnormally high levels of catecholamine's resulting in a hypertensive effect.
Drugs inhibiting liver microsomal enzyme e.g. cimetidine may allow accumulation of high(possibly toxic)
concentrations of lidocaine.
Reduction of hepatic blood flow by drugs or hypotension will decrease the hepatic clearance of amide
local anesthetics.
Summation interactions with local anesthetics ;e.g. lidocaine with bupivacaine ;local anesthetic toxicity is
additive when these drugs are used in combination.
Ester local anesthetics with sulfonamide antibiotics e.g. procaine with sulfamethoxazole ;The procaine
metabolite p-amino benzoic acid may transiently reduce sulfonamide antibiotic efficacy.
Local anesthetics with opioid sedation ;e.g. mepivacaine with meperidine :sedation with opioids may
increase the risk of local anesthetic toxicity.
Other interactions; beta blockers, MAO inhibitors, phenothiazines, lithium, benzodiazepines.
