Local anaesthetics cause reversible loss of sensation in a specific area by altering the functioning of nerve cells. They are absorbed and distributed throughout the body after administration but only cause anaesthesia locally due to their ability to selectively affect nerve cells. Local anaesthetics are metabolized in the liver and excreted by the kidneys, and have the potential for toxicity if blood levels become too high, which can lead to seizures, respiratory depression, hypotension, and other adverse effects.

1. PHARMACOLOGY OF LOCAL
ANAESTHETICS
VISHAL GOHIL

2. WHAT IS LOCAL ANAESTHESIA?
• Local anaesthesia has been defined as loss of
sensation in a circumscribed area of the body
caused by depression of excitation in nerve
endings or inhibition of the conduction process
in peripheral nerves.

3. WHAT IS LOCAL ANAESTHETIC?
• Local anaesthetic is a drug that causes
reversible local anaesthesia.

4. • After administration of LA,
Eventually it enters into the circulation &
reaches to all the organs.
Then,
WHY IT CAUSES LOSS OF SENSATION IN
ONLY TARGET ORGAN?
Because it has ability to alter the functioning of
some of these cells.

6. UPTAKE :
• When injected into soft tissues, it exerts
pharmacologic action on blood vessels in the
area.
• All LA possess a degree of vasoactivity,
Most LA produces vasodilation but
degree of vasodilation may vary &
May produce vasoconstriction.
( to be continued…)

7. • This effects may be concentration dependent.
• PROCAINE : The most potent vasodilator
• COCAINE : Only LA which produces
vasoconstriction consistently
-Initial action : Vasodilation
followed by,
an intense & prolonged vasoconstriction
HOW?
By inhibiting uptake of catecholamines into tissue
binding sites ( especially norepinephrine )

8. ROUTES FOR ADMINISTRATION OF
LA :
1) ORAL ROUTE
2) TOPICAL ROUTE
3) INJECTION

9. 1) ORAL ROUTE :
• All LA are absorbed poorly except cocaine
• Reason : High first pass metabolism

10. 2) TOPICAL ROUTE :
• Absorbed at different rates after application to
mucous membranes.
• Whenever no layer of skin is present, topically
applied LA can produce an anaesthetic effect.
• Application to intact skin : no anaesthetic action

11. 3) INJECTION :
• Commonly used route for administration of LA
• Uptake of LA after parentral administration
depends on :
I. Vascularity of the injection site
II. Vasoactivity of the drug

12. DISTRIBUTION :
• Once it enters the blood, then distributed to all
tissues
• Brain, head, liver, lungs, kidneys & spleen have
high levels of local anaesthetics
WHY?
Due to their high level of perfusion
• Skeletal muscle has the highest level because it
has the largest mass of tissue in the body

13. The blood level of local anaesthetics
is influenced by :
 Rate at which the drug is absorbed into the
CVS
 Rate of distribution from the vascular
compartment to the tissues
 Elimination of the drug through metabolic or
excretory pathways

14. ELIMINATION HALF LIFE :
• The rate at which a local anaesthetic is removed
from the blood, the time necessary for 50%
reduction in the blood level.
ALL LA CAN CROSS THE BLOOD BRAIN
BARRIER & PLACENTA.

15. METABOLISM OR BIOTRANSFORMATION
1) PABA ( Paraaminobenzoic acid) metabolism :
- Hydrolyzed in plasma by enzyme pseudo
cholinesterase
- Rate of hydrolysis is related to the degree of
toxicity
- SLOW HYDROLYZATION= INCREASE IN
TOXICITY

16. 2 ) AMIDE LOCAL ANAESTHETICS :
• Primary site of metabolism : Liver
• Prilocaine is metabolized in the liver & lung
• Rate of metabolism is greatly affected by ,
1. Liver function
2. Hepatic perfusion
Articaine has a shorter half life than other
amides because a portion of its metabolism
occurs in the blood by plasma cholinesterase.

17.  Metabolism by-products of
amide local anaesthetics can
possess clinical activity if allowed
to accumulate in blood.
All local anaesthetics have the
ability to cause sedation.

18. EXCRETION :
• Major excretory organ : Kidneys
• ESTERS : Almost completely hydrolyzed in
plasma,
Thus, appear in small concentrations in the
urine.
In patients undergoing dialysis :
Unable to excrete the unchanged portion of the
esters or amides thus increasing toxicity.

19. • PROCAINE : Appear in urine as 90% PABA &
2% unchanged.
• COCAINE : Appear in urine as 10% unchanged.

21. CNS :
• In one word : DEPRESSION
• At high levels, LA will produce tonic-clonic
convulsions
• Procaine, Lidocaine etc produce ANTI-
CONVULSANT properties.
• This drugs are used for management of grand
mal & petit mal seizures
• The depressant action of LA raise the seizure
threshold by decreasing the excitability of
cortical neurons in epileptic patients.

22. PRECONVULSIVE SIGNS & SYMPTOMS :
• Numbness of the tongue & circumoral regions
• If excitation or sedation occurs in the first 5 or
10 minutes after administration of LA, it should
consider as a warning that convulsive activity
could be possible.
• Shivering, slurred speech, muscular twitching,
visual/auditory disturbances, dizziness,
drowsiness, disorientation & tremor.

23. CONVULSIVE PHASE :
• Duration of seizures is related to blood level of
LA &
inversely related to arterial pCO2 levels.
• Seizures last less than or equal to one minute.
• In seizure, 1) cerebral blood flow & 2) cerebral
metabolism increase

24. 1 ) CEREBRAL BLOOD FLOW :
LONGER SEIZURE
INCREASE IN VOLUME OF BLOOD FLOW
BEING DELIEVERED TO BRAIN
INCREASED CEREBRAL BLOOD FLOW

25. 2 ) CEREBRAL METABOLISM :
PROLONGS THE SEIZURE
ACIDOSIS
INCREASED CEREBRAL METABOLISM

26. RESPIRATORY SYSTEM :
• DUAL EFFECTS :
1. Non-overdose levels : Direct relaxant action on
bronchial smooth muscle
2. Overdose levels :
DEATH
RESPIRATORY ARREST
GENERALIZED CNS DEPRESSION

27. CVS :
• Direct action on myocardium & peripheral
vasculature.
• Increased LA blood levels result in
decreased myocardial depolarization
• Decrease in myocardial excitation, decrease in
conduction rate & decrease in the force of
contraction
• Produces hypotension ( direct relaxation effect
on vascular smooth muscle )

28. LOCAL TISSUE TOXICITY :
• Skeletal muscle will heal within 2 weeks of being
injected with local anaesthetic.
• Longer acting LA produces more damage to
skeletal muscle than shorter acting LA.

29. MISCELLANEOUS ACTIONS :
1) NEUROMUSCULAR BLOCKADE
2) DRUG INTERACTIONS
3) MALIGNANT HYPERTHERMIA

30. MALIGNANT HYPERTHERMIA :
• Pharmacological disorder in which a genetic
variant alters the person’s response to certain
drugs.
• Tachycardia, tachypnea, unstable BP, cyanosis,
fever muscle rigidity & death