Ppt local anaesthetics

1. LOCAL ANESTHESITCS
MODERATOR: DR.JAGADISH
SPEAKER : DR.KARTHIK

2. CONTENTS
• History
• Physiochemical properties of local
anaesthetics.
• Mechanism of action.
• Pharmacology of anesthetics.
• Clinical uses.

3. HISTORY
• Albert Niemann(1834-1861) of Germany isolated the
alkaloid from dried leaves of coca plant in 1856 & gave
the name ‘COCAINE’ to the active drug.
• Vasali von Anrep(1852-1918) was the first to remark on
its local anaesthetic property.
• Sigmund Freud(1856-1939), who first tested the drug
as a substitute for opioids on a colleague who was
addicted to morphine, also noticed its ability to
produce numbness of the tongue.
• Freud introduced it to his junior colleague Carl
Koller(1858-1944) who was interested in producing
local anaesthesia for operations on the eye.

4. • Koller arranged to demonstrate the use of topical
cocaine analgesia at the Ophthalmologic Congress in
Hiedelburg, Germany on September 5, 1884.
• The idea of injecting cocaine into nerve trunks is
credited to William Halsted(1852-1922) and Alfred Hall.
• Carl Schleich(1859-1922) introduced infiltration local
anaesthesia in 1892 as an alternative to direct injection
of nerve trunks.

5. • Tetracaine was introduced in 1932.
• Lidocaine was introduced by Torsten Gordh in
1948.
• Benzocaine(1900), Chlorprocaine(1952),
Mepivacaine(1957), Prilocaine(1960),
Bupivacaine(1963), Ropivacaine(1996),
Levobupivacaine(1997).

6.  Definition-
 A local anesthetic is an agent that interrupts
pain impulses in a specific region of the body
without a loss of patient consciousness.
Normally, the process is completely reversible-
the agent does not produce any residual effect on
the nerve fiber.

 A local anesthetic blocks the conduction of
impulses in an electrically excitable tissue .
 one of the important uses of LA’s is to provide
anesthesia and analgesia by blocking the
transmission of pain sensation along the nerve
fibres.

7. Physiochemical properties
• Local Anaesthetics are weak bases.
• It contains tertiary amine attached to a
substituted aromatic ring by an intermediate
chain that almost always contains either an ester
or an amide linkage.
• Local anesthetics are poorly soluble in water and
therefore are marketed most often as water
soluble hydrocholoride salts.
• These hydrochloride salts are acidic (pH 6)
contributing to the stability of the local
anesthetic.

10. Classification of local anaesthetics

13. Classification based on duration of action
and potency
AMIDES
 Bupivacaine, Etidocaine and Ropivacaine- very
high potency and lipid solubility, very long
duration and protein binding also.
Lidocaine, Prilocaine and Mepivacaine- have
intermediate potency and lipid solubility and
intermediate duration of action and protein
binding.

14. ESTERS
• Chloroprocaine and Procaine- have low potency and
lipid solubility and also low duration and protein
binding.
• Cocaine- has intermediate potency and solubility and
intermediate duration and protein binding.
• Tetracaine- has high potency and lipid solubility along
with a long duration of action and high protein binding.

15. Effect of pH, and pKa
• Pka It is the PH at which a LA is 50% ionized and
50%nonionized. Since LAs are weak bases,agents
with Pka closer to physiological PH will have more
drug in non-ionized form which can diffuse
through axonal membrane and so onset will be
rapid. That is why lignocaine with Pka 7.8 is fast
acting than bupivacaine with Pka 8.1.
• The pKa of amides ranges from 7.6 to 8.1. At
physiologic pH (7.4), most of the local anaesthetic
is in the ionized state.

17. Mechanism of action
• Physiology of nerve conduction:
Neural membrane is able to maintain a voltage difference of
-60 to -90 mV (-70 mV) between the intracellular medium and
the cell’s outside at rest.
This is possible due to the presence of Na+/K+ pump, an active,
energy dependant mechanism, which causes a constant
extrusion of sodium from within the cells in exchange for a net
uptake of K+,with ATP used as an energy source .
Neurons at rest are more permeable to K+ than Na+.

18. Excitation of nerve segments leads to an increase in
permeability of cell membranes to Na+ ions due to transient
widening of transmembrane ion channel
influx of Na+ ions
depolarization of nerve membrane to ‘firing threshold’
(-50mV to -60mV)
increased permeability to Na+
rapid influx of Na+
peak of action potential (+40mV).

19. • Repolarization takes place after that.
• Na+ channels are closed(inactivated) and K+ efflux
occurs causing the potential to reach resting
membrane potential

20. • Within milliseconds after opening, channels undergo a
transition to the inactivated state.
• Fast inactivation is completed within milliseconds & is
sensitive to local anaesthetics.
• Slow inactivation lasting for seconds to minutes is
resistant to the action of local anaesthetics.
• Impulse Propagation: The new electrical equilibrium in
the depolarized segment of the nerve produces local
currents that begin flowing between the depolarized
and the adjacent resting area, causing adjacent area to
undergo depolarization
• wave of depolarization spread in only one direction
because retrograde movement is prevented by the
inexcitable refractory segment.

21. Theories of local anaesthetics
Membrane expansion theory :
• LAs diffuse to the hydrophobic regions of the
excitable membranes producing a general
disturbance of the cell membrane structure,
expanding some critical regions of the membrane
and preventing an increase in the permeability to
Na+ ions.

22. Specific receptor theory:
• states that LAs act by binding to specific receptors on
the sodium channels – most accepted theory
• LAs block the transmission of nerve impulses by
targeting the function of voltage-gated sodium
channels.
• LAs reversibly bind the intracellular portion of the
voltage gated sodium channels.
• Application of local anaesthetics typically produces a
concentration-dependent decrease in the peak
sodium current Known as ‘tonic blockade’, it reflects
the reduction in number of sodium channels for a
given drug concentration present in the open state at
equilibrium.