Dr. RAGHU PRASADA M SMBBS,MDASSISTANT PROFESSOR

DEPT. OF PHARMACOLOGYSSIMS & RC.

LOCAL ANAESTHETICS

Definition

Drugs that cause reversible loss of sensory perception specially of pain in a restricted area of the body, when applied topically or local injection.

LA if applied to a mixed nerve—sensory and motor impulses are interrupted—resulting in muscular paralysis and loss of autonomic control.

How ?

Reversibly block the impulse conduction

Transient loss of sensation

Local anaesthesia blockadeC,B > Aδ > Aα,ß,γ

Classification

AMIDE TYPE Long acting- BUPIVACAINE, LEVO-

BUPIVACAINE, ROPIVACAINE, DIBUCAINE

Intermediate Acting-LIDOCAINE, MEPIVACAINE, PRILOCAINE, ARTICAINE

ESTER TYPE- LONGER ACTING- TETRACAINE,

CLASSIFICATION

Intermediate Acting-COCAINE

Short Acting- PROCAINE, CHLORPROCAINE, BENZOCAINE, PROPARCAINE

Miscellaneous- PRAMOXINE, DYCLONINE,OXETHAZINE

Pharmacokinetic differences

E S T E R S Short duration of action Less intense anesthesia

Higher risk of hypersensitivity -PABA.

Hydrolyzed by Plasma Cholinesterase in blood.

Rarely used for Infiltration anesthesia But useful for topical anesthesia on mucous membranes.

A M I D E S Produce more intense and

longer lasting anesthesiaBind to alpha1 acid glyco-

protein in plasmaRarely cause hypersensitivity

reactions- no cross reactivity with ESTER L A s

Not hydrolyzed by Plasma Cholinesterase, but in liver

Vasodilation

Vasoconstrictor is a substance used to keep the anesthetic solution in place at a longer period and prolongs the action of the drug

Vasoconstrictor delays the absorption which slows down the absorption into the bloodstream

Vasoconstrictor used ---the natural hormone called epinephrine (adrenaline).

L A - Mode of action

Blockage of membrane depolarisation in all excitable tissues, usually intended on peripheral nerve Membrane stabilizer

They prevent the Initiation and propa- Gation of the nerve Impulse by reducing the passage of Na

MOA

Effects of LA: injection as acid (hydrochloric salt)= ionized form at physiological pH dissociation to free base (lipid soluble) passage through cell membrane to interior of axon re-ionisation enter and blockage of Na+-channel and thereby preventing influx of Na+ no generation of AP conduction blockade

They block nerve conduction by reducing the permeability of Na ions during depolarisation

Epinephrine

Should not be coadministered for nerve block in areas such as fingers and toes that are supplied with end-arteries because it may cause ischemia or necrosis

It should be used cautiously in patients in labour and in patients with thyrotoxicosis or cardiovascular disease.

pH influence

Usually at range 7.6 – 8.9 Decrease in pH shifts equilibrium toward the ionized

form, delaying the onset action. Lower pH, solution more acidic, gives slower onset

of action Presence of Pus and inflammation will retard the

action of LA. ( probably low acidic pH)

Lignocaine ( Xylocaine )

Most widely used Amide linked LA and most versatile ana.

Has variety of applications like Local, nerve block, spinal, epidural, IVRA.

When used locally action starts within 3 mts and causes vasodilatation.

Overdose causes muscle twitchings, convulsions, cardiac arrhythmias, fall in BP, coma, respiratory arrest.

Most popular ant arrhythmic drug

Lignocaine ( Xylocaine )

• Standard agent for infiltrations, regional blocks or topical

• Short onset time, intermediate duration of action• Class Ib antiarrhythmic properties• Medium toxicity• Maximal recommended dose: 3 mg/kg, 6 mg/kg with

vasconstrictor

Bupivacaine

A potent long acting ---Amide linked LA available in India, most widely used allover.

Not used for IVRA but all others like local, spinal epidural blocks.

Action lasts for 2 to 3 hours. Strength for epidural is 0.25 to 0.5 % solution.

Has high lipid solubility, distributes more in tissues than in blood

PRILOCAINE

It is similar to Bupivacaine

One of the metabolites are toxic and can cause Methamoglobinemia

Used for Nerve Blocks and IVRA.

Bupivacaine

Causes more sensory block, than motor block the advantage taken in during Caesarean Section. (Walking Epidural)

Bupivacaine is more prone to prolong QTc interval and induce ventricular tachycardia or Cardiac depression----( Membrane Stabilization action ) ( toxic doses and accidental entry into vessel)-should not be used for IVRA.

Longest acting LA available in India now.

Therapeutic Uses

1. Surface anesthesia2. Infiltration anesthesia3. Conduction block a. Field block b. Nerve Block4. Spinal anesthesia5. Epidural anesthesia6. I V R A (Bier’s Block)

Surface anesthesia

Amethocaine ---eye, throat, urethra, rectum and skin.

Benzocaine and Lidocaine hydrochloride—same ---except for eye.

Procaine is unsuitable as a surface ana. Because of its poor penetrating power

Lignocaine --4 % topical solution, 2 % Jelly 2 % vials for injections

E M L A Cream : Eutectic Mixture of Local Anesthetic

Eutectic : Lowering of melting point of two solids when they are mixed.

combination of Lidocaine and Prilocaine. For Pediatric purpose. It can penetrate intact skin. I v .cannula inserting. Split skin graft harvesting Other superficial procedures.

Infiltration anesthesia

Mech. of action : Nerve endings as exposed to the drug there by action.

Procaine, Lignocaine 2 % are used either with or without Adrenaline 1 : 2,00,000

C/I : blocking where end arteries are involved either for Penis, or for Digits, C A D patients.

Nerve block or Conduction block

Drug is injected close to the nerve or big nerve trunks eg. Brachial Block, Sciatic, Femoral Nerve, Radial, Ulnar Nerves.

Spinal Anesthesia

LA is injected into the subarachnoid space. Injection is made heavy by adding dextrose or light by adding saline.

When the anesthetic in injected outside the dura, the technique is known as Epidural anesthesia.

Lignocaine, Bupivacaine the two agents most commonly used regularly in anesthesia practice.

EPIDURAL

EPIDURAL

EPIDURAL

I V R A (Bier’s Block)

Intravenous regional anesthesia Agent of choice------ Lignocaine (Xylocaine ) 20 to 40 ml of 0.5 % Lidocaine is used Used for only for Upper Limb orthopedic surgeries

and others on Up. Limb.

Systemic Actions

We have seen all Local actions of LA s Systemic action when given IV : Bupivacaine is

relatively more cardiotoxic , produces ventricular tachycardia or fibrillation.

Lidocaine has little effect on contractility and conductivity, used as antiarrhythmic.

The prominent cardiac action of Xylocaine is suppression of automaticity in ectopic foci.

Systemic Toxicity

Depression of function of CNS and CVS when high plasma concentrations are reached

CNS toxicity : usually before cardiovacular effectsFirst signs of excitation due to initial blockade of inhibitory pathwaysmild: circumoral tingling, metallic taste, tinnitus, visual disturbance, slurred speechmoderate: altered consicous state, convulsionsLater sings of generalized CNS depression with potentially fatal toxicity: coma,respiratory arrest

Complications of Spinal Anesthesia

1.Bradycardia, 2.Hypotension 3.Headache

4.Cauda Equina syndrome 5.Septic meningitis

EPIDURAL ANESTHESIA : Here the drug is injected outside the dura. Drug

spread is restricted to a specific region causes fewer complications.

Other side effects

Allergic reactions: common with ESTERS like Procaine, caused by para-aminobenzoic acid (also found to cause arachnoiditis), less common with AMIDES, then mostly through preservatives

Drug interactions: i.e. Anticholinesterases, other competing drugs hydrolyzed by Plasma CE

Attention with heavy sedation with anticonvulsants: may mask early signs of toxicity

Methaemoglobinaemia: after large doses Prilocaine