Local anaesthetics , pharmacology , mechanism of action ,actions ,

3. Introduct
ion:• Local anaesthetics (LAs) are drugs which
upon topical application or local
injection cause reversible loss of sensory
perception, especially of pain, in a
restricted area of the body.
• They block generation and conduction of
nerve impulse at all parts of the neurone
where they come in contact, without
causing any structural damage.

4. Nerve
fibres???

7. Action
Potential???

9. LA ???? GA????

11. In 1860, German chemist Albert Niemann
successfully isolate the active principle of
coca leaf; he named it cocaine.
History

12. Classification

13. Classification– Ester-linked
• procaine (Novocaine)
• tetracaine (Pontocaine)
• Benzocaine
• Cocaine
– Amide-linked
• lidocaine (Xylocaine)
• mepivacaine (Carbocaine)
• bupivacaine (Marcaine)
• etidocaine (Duranest)
• ropivacaine (Naropin)
REMEMBER: All are weak Bases!

14. Classification
– Ester-linked
• Short acting
• Metabolized in the plasma and tissue fluids
• Excreted in urine
– Amide-linked
• Longer acting
• Metabolized by liver enzymes
• Excreted in urine

15. Chemistry/Structure of LA

16. • As you know, entry of
Na+ is essential for
Action potential
• Two things happen:
– Rate and rise of AP and
maximum depolarization
decreases – slowing of
conduction.
– Finally, local depolarization
fails to reach threshold
potential – conduction block.
Mechanism of Action

19.  Injected around a mixed nerve they cause anaesthesia of
skin and paralysis of the voluntary muscle supplied by
that nerve.
 Sensory and motor fibres are inherently equally sensitive.
The sensitivity is determined by diameter of the fibres as
well as by fibre type.
If Diameter remaining the same, myelinated nerves are
blocked earlier than nonmyelinated.
Smaller fibres are more sensitive than larger fibres.
Local actions

20. Autonomic fibres are generally more
susceptible than somatic fibres.
Among the somatic afferents order of
blockade is: pain—temperature-
sense—touch—deep pressure sense.
Since pain is generally carried by
smaller diameter fibres than those
carrying other sensations or motor
impulses, pain in the first modality to
be affected.

21. Lipid solubility
• All local anesthetics have weak bases. Increasing the lipid solubility leads to faster
nerve penetration, block sodium channels, and speed up the onset of action.
Influence of pH
• Lower pKa (7.6 – 7.8) – faster acting (lidocaine, mepivacaine)
• Higher pKa (8.1 – 8.9) – slower acting (procaine, tetracaine, bupivacaine)
Vasoconstrictors
• Cocaine itself is vasoconstrictor
• Adrenaline
– Potential adverse effects of vasoconstrictors
• DON’T use in areas of toes, fingers, ear lobes, necrosis
Inflammation tends to produce lower pH in tissues therefore
• LA are more ionized - don’t penetrate very well
• Blood flow
• Decreased ability of LA to produce effects
Influencing factor of LA
action

22. CNS Stimulation:
• Cocaine is a powerful CNS stimulant causing in sequence
euphoria—excitement—mental confusion—restlessness—tremor
and twitching of muscles—convulsions—unconsciousness—
respiratory depression—death, in a dose-dependent manner.
• Lidocaine - can initially cause drowsiness and lethargy, but
higher doses produce excitation followed
by depression like others.
• Premonitory signs include:
ringing in ears, metallic taste,
numbness around lips
Systemic action

23. C.V.S.
Heart
LAs are cardiac depressants, but no
significant effects are observed at conventional
doses. At high doses or on inadvertent i.v.
injection, they decrease automaticity, excitability,
contractility, conductivity and increase effective
refractory period (ERP). They have a quinidine like
antiarrhythmic action.

24. Blood Vessels
LAs tend to produce fall in BP.
This is primarily due to sympathetic blockade,
but high concentrations, as obtained locally at
the site of injection, do cause direct relaxation of
arteriolar smooth muscle.
BUPI – LIDO - PRILO