2. Contents
• History
• Molecular structure
•Classification
•Mechanism of action
•Characteristics
•Pharmacokinetics
•Uses
•LAST
•REFERENCES
3. History
1.KARL KOLLER introduced COCAINE as the first local anaesthetic in
OPHTHALMOLOGY in 1884
2.First synthetic local anaesthetic was PROCAINE
3.Lidocaine was synthesized by LOFGREN in 1943
7. Mechanism of
Action
1. Site of action : voltage gated
Na+ channels.
2. Inhibits passage of sodium ions
through ion –selective sodium
channels in nerve membranes
thus prevents transmission of
nerve impulses (conduction
blockade)
3. Thereby reducing excitability of
neuronal, cardiac or CNS tissue.
8.
9. MINIMUM EFFECTIVE
CONCENTRATION (Cm)
Minimum concentration of drug necessary to produce conduction
blockade of nerve impulses
Factors affecting Cm
1. Increases with increase in Nerve diameter (Cm of motor fiber is 2x
sensory fiber)
2. Decreases with increase in tissue Ph & nerve stimulation
12. Physiochemical structures
1. The S enantiomers of bupivacaine and mepivacaine are less toxic
than racemic mixture of these LA present commercially
2. Whereas Ropivacaine and Levobupivacaine developed as pure S
enantiomers commercially are less toxic than racemic mixtures or R
enantiomer
13. Alkalinization
• Shortens onset of neural blockade, enhances sensory and neural
blockade, increases epidural blockade
• increases % of LA in lipid soluble form that is available to diffuse
across lipid cellular barriers
• hence, adding sodium bicarbonate increases speed of onset of
peripheral nerve block
15. Absorption
1. MUCOUS MEMBRANE- faster due to weak barrier to LA
penetration, rapid onset of action (eg per rectal )
INTACT SKIN- high concentration of lipid soluble LA to ensure
analgesia ( EMLA for venous cannulation )
16. Systemic Absorption
1.Site of injection : rate of systemic absorption is directly
proportional to vascularity of site of injection :
intravenous>tracheal>intercostal>caudal>paracervical>epidural>
brachial plexus>sciatic>subcutaneous.
2.Presence of vasoconstrictors : addition of epinephrine
/phenylephrine increases neuronal uptake, enhances quality of
analgesia ,prolongs duration of action & limits toxic side effects.
17. Distribution
1.TISSUE PERFUSION- highly perfused tissue take up more drugs
2.TISSUE/BLOOD PARTITION COEFFICIENT- strong plasma protein
binding tends to retain anaesthetic in the blood whereas high lipid
solubility facilitates tissue uptake.
3.TISSUE MASS- more the mass, more is the reservation of LA
18. Metabolism and Excretion
1. Esters : hydrolysed by pseudocholinesterases
water soluble metabolites are excreted in the urine
2. Amides : metabolized by cytochrome P-450 enzymes in liver
Metabolism slower than esters hydrolysis . Metabolites are cleared
through urine.
20. Doses
Drugs
Mepivacaine
Bupivacaine
Ropivacaine
Levobupivacaine
Minor block
50 to 200 mg
12.5 to 100 mg
10 to 100 mg
----------------
Major block
350 to 500 mg
175 to 225 mg
200 to 250 mg
200 to 225 mg
Spinal block
40 to 80mg
15 to 20 mg
(isobaric and
hyperbaric )
15 to 20 (isobaric
and hyperbaric )
15 to 20 mg
(isobaric and
hyperbaric )
Epidural block
350 to 500mg
175 to 225 mg
200 to 250mg
200 to 250 mg
22. Allergic Reactions
1. Allergic reaction with LA is rare.
2. Allergic reaction is due to ester metabolites p amino benzoic acid
3. preservatives like methylparaben structural similarity to p amino
benzoic acid hence result in allergic reaction
23. LAST( local anaesthetic systemic
toxicity)
• It is due to excess plasma concentration of the drug.
• Plasma concentration is determined by rate of drug entrance into systemic
circulation
• Magnitude of systemic absorption depends on :
1. Doses of drug
2. Vascularity of injection site
3. Presence of vasoconstrictor
4. Physiochemical properties of drug