Pharmacology 0f Local Anaethetics.

2. Local Anaesthetics
LA’s are the drugs which upon the Topical application
/injection causes reversible loss of perception, esp.
Pain, in a restricted area of the body.
When it is used on specific nerve pathways local
anaesthetic nerve block, paralysis (loss
of muscle power) also can be achieved.

3. Classification:
(I) Injectable Anaesthetics:
(a)Low potency, Short duration:
Procaine , Chlorprocaine
(b) Intermediate potency & duration:
Lidocaine , Prilocaine.
(c) High potency & Long duration:
Teracaine Bupivacaine,
Rupivacaine,Dibucaine.

4. (II) Surface Anaesthetics:
(a) Soluble:
Cocaine, Tertacaine, Bupivacaine,Lidoacine.
(b)In Soluble:
Benzocaine,
Butylaminobezoate,
Oxethazaine.

5. MECHANISM

6. Local Anaesthetics block initiation & propagation of Action
potential by preventing voltage-dependent increase NA+2
Conductance. Finally, local depolarization fails to reach the
threshold potential & conduction block ensues.
These interact with a receptor situated with in voltage
sensitive Na+2 channel & raise the threshold of channel
opening.
Impulse conduction is interrupted when the Na+2 channels
over a length of Nodes of Ranvier are blocked.

7. Pharmacokinetics
Lidocaine & Tetracaine Rapidly absorbed from Mucus membrane
but from intact skin is poor.
Procaine Does not penetrate mucus membrane , bound to plasma
proteins.
LA’s are Lipophilic –widely distributed & rapidly enters highly
perfused organs Brain, Kidneys, Liver, Muscle & others.
Amide LA’s bound to Alpha-1 glycoprotein degraded in liver by
Dealkylation & Hydroxylation.
Ester LA’s rapidly hydrolysed by “plasma pseudocholinesterse” &
Remaining by esterases in Liver.

8. Pharmacological Actions
Local Actions: Injected around a Nerve-cause Anaesthesia of skin &
paralysis of voluntary muscle supplied by nerve.
The order of blockade is: Pain—Temperature– Touch senses
-- Deep pressure senses.
CNS: Produces sequence of Stimulation followed by Depression.
Cocaine is a powerful CNS stimulant acts in a sequence Euphoria–
xcitement – Mental confusion– Resstlessness – Tremors & Twitchings
-- Covulsions—Unconsiousness—Rep.depression—Death.
Lidocaine : Initially, causes Drowsiness & Lethargy. But @ higher doses
produces Xcitation followed by Depression.
CVS: on Heart Cardiac depressant action @ higher doses on I.V injection
Decreases Automaticity,xcitabilty,Cotractility,Conductivity.
on BloodVessels: Decresed Blood pressure, More Vasodilatory than
Lidocaine.@ Toxic doses Causes Cardiovascular collapse.

9. Adverse Effects
Restlessness, Tremor, Light-headedness, Dizziness, Auditory &Visual
disturbances, Euphoria, Mental confusion, Shivering,
Twitchings,Involuntary movements, Respiratory arrest.
Myocardial depression, Vasodilation,Inhibition of sodium current in
cardiac muscle reduces muscle contarctilty.Reduces force of
contraction.
COCAINEIt doesn’t have depression action on CVS, becoz of its
ability to inhibit NA uptake,produces an enhancement of sympathetic
activity Tachycardia, Cardiac output, Vasoconstriction, Increased
Arterial pressure.
Hypersensitivity reactions: Rashes ,Angioodema, Dermatitis, Contact sensitization,Asthma.

10. Uses:
Surface Anaesthesia: By topical application to mucus membrane &
abraded skin.
Lidocaine,Tetracaine,Dibucaine,Benzocaine---Nose,Mouth,Bronchial
tree,Cornea,Urinary tract.
Infiltration Anaesthesia: Blocks sensory endings.
Lidocaine,Bupivacaine---In minor surgeries.
Nerve block: Produces loss of sensation peripherally.
Lodcaine,Pilocaine--- Surgeries,Densistry,Analgesia.
Spinal Anaesthesia: Injected in Sub-arachnoid space between
L2-3/L3-4 i.e; Below lower end of spinal cord.
Lidocaine--- For surgery of Abdomen, Pelvis,Leg.
Epidural Anaesthesia: Injected in Epidural space blocking spinal roots.
Lidocane, Bupivacaine---For painless childbirth.