LOCAL ANAESTHETICS – A BRIEF OUTLOOKPRESENTED BY :VISHNU.R.NAIR,FOURTH YEAR PHARM.D,NATIONAL COLLEGE OF PHARMACY (NCP),KERALA UNIVERSITY OF HEALTH SCIENCES (KUHS).

DEFINITION :“ LOCAL ANAESTHETICS (LAs) are agents, which when applied LOCALLY to NERVE TISSUE, in APPROPRIATE CONCENTRATIONS, cause BLOCKADE of ACTION POTENTIALS responsible for NERVE CONDUCTION”……….

CLASSIFICATION :LAs are classified into:A.INJECTABLE ANAESTHETICS :I. LOW POTENCY, SHORT DURATION LAs:- PROCAINE- CHLOROPROCAINEII. INTERMEDIATE POTENCY & DURATION LAs:- LIDOCAINE (LIGNOCAINE)- PRILOCAINE

III. HIGH POTENCY, LONG DURATION LAs:- TETRACAINE(AMETHOCAINE)- BUPIVACAINE- ROPIVACAINE- DIBUCAINE(CINCHOCAINE)

B. SURFACE/ TOPICAL ANAESTHETICS:I. SOLUBLE LAs:- COCAINE- LIDOCAINE- TETRACAINE- BENOXINATE

II. INSOLUBLE LAs:- BENZOCAINE- BUTYLAMINOBENZOATE(BUTAMBEN)- OXETHAZAINE……………………………….

MECHANISM OF ACTION :LOCAL ANAESTHETICS bind to VOLTAGE-GATED SODIUM CHANNELS BLOCK them REDUCES PERMEABILITY of EXCITABLE MEMBRANES to SODIUM PROGRESSION of ANAESTHETIC action in the nerve INCREASES THRESHOLD for ELECTRICAL EXCITABILITY REDUCES ACTION POTENTIAL REDUCES IMPULSE CONDUCTION Thus, NERVE CONDUCTION is REDUCED………………………..

TYPE OF NERVE FIBRE

LOCATION FUNCTION SENSITIVITY TO BLOCK

I. ‘A’ FIBERS:- A(ALPHA) MUSCLES & JOINTS MOTOR &

PROPRIOCEPTION MOTOR(+) ; PROPRIOCEPTION(++)

- A(BETA) MUSCLES& JOINTS MOTOR & PROPRIOCEPTION

MOTOR(+); PROPRIOCEPTION(++)

- A(GAMMA) EFFERENT TO MUSCLE SPINDLES

MUSCLE TONE ++

- A(DELTA) SENSORY ROOTS; AFFERENT PERIPHERAL NERVES

PAIN, TEMPERATURE, TOUCH

+++

II. ‘B’ FIBERS: PREGANGLIONIC; SYMPATHETIC

VASOMOTOR, PILOMOTOR, SUDOMOTOR

++++

III. ‘C’ FIBERS

NOTE:‘C’ FIBERS comprise 2 subdivisions:A. SYMPATHETIC NERVE FIBERB. DORSAL ROOT NERVE FIBER- SYMPATHETIC NERVE FIBER has same location, function & block

sensitivity as ‘B’ fiber- DORSAL ROOT NERVE FIBER has same location, function & block

sensitivity as ‘A DELTA’ fiber………………

ADVERSE DRUG EFFECTS :I. CNS EFFECTS:- Restlessness- Tremor- Clonic convulsions- CNS depression- Coma- Death (due to RESPIRATORY FAILURE)

II. CVS EFFECTS:- Bradycardia - Vascular collapse- Hypotension - Arrhythmias

III. SMOOTH MUSCLE EFFECTS:- Reduced intestinal & bowel contractionsIV. LOCAL SITE EFFECTS:- Delayed wound healing- Tissue necrosis (especially when a potent vasoconstrictor is added)V. HYPERSENSITIVITY EFFECTS:- Rashes - Dermatitis- Angioedema -

Anaphylaxis………………

DRUGS, AT A GLANCE :1. COCAINE:- DRUG acts as LA, along with LOCAL VASOCONSTRICTION blocks nerve

impulses- ADRs:a. DRUG REDUCES REUPTAKE of CATECHOLAMINES in CNS(especially

DOPAMINE) produces EUPHORIAb. MYDRIASIS- USE: TOPICAL ANAETHESIA of UPPER RESPIRATORY TRACT (1%; 4% solutions)………..

2. LIDOCAINE (XYLOCAINE):- FASTER & LONGER ACTING- AMIDE LA- Used for people SENSITIVE to ESTER-TYPE LAs- ADRs:a. Dysgeusiab. Twitchingc. Respiratory depression- USES:a. LAb. Anti-arrhythmic……………………………………

3. BUPIVACAINE (SENSORCAINE):- WIDELY USED AMIDE LA- Causes PROLONGED ANAESTHESIA- ADRs:a. Ventricular arrhythmia (malignant)b. Myocardial depression- USES:a. Prolonged analgesia during laborb. Postoperative analgesia…………………..

IV. ARTICAINE(SEPTOCAINE):- Rapid onset of action (1-6 mins)- Duration of action: 1 hour- Amide LA- Used for DENTAL & PERIODONTAL PROCEDURES…………………

V. CHLOROPROCAINE(NESACAINE):- ESTER LA- Rapid onset- Short duration of action- ADRs:a. Prolonged sensory & motor blockb. Muscular back pain…………………………………….

VI. ETIDOCAINE(DURANEST):- Long acting AMIDE LA- Used in SURGERY, involving INTENSIVE SKELETAL MUSCLE RELAXATION- ADR : Cardiotoxicity……………

VII. MEPIVACAINE(POLOCAINE):- AMIDE LA- Intermediate acting- More toxic to NEONATES, than ADULTS, so it should be avoided in

OBSTETRICAL ANAESTHESIA………………………

VIII. PRILOCAINE(CITANEST):- AMIDE LA- Intermediate acting- Lesser incidence of CNS TOXICITY- ADR : METHEMOGLOBINEMIA(in such conditions, treat with METHYLENE

BLUE, at a dose of 1-2 mg/kg)………………………

IX. PROCAINE(NOVOCAIN):- FIRST SYNTHETIC LA- AMINO ESTER- Has less potency and duration of action- Drug metabolizes into PABA(Para-amino benzoic acid) thus avoid

usage in patients having SULFONAMIDES- USES:a. Infiltration anesthesiab. Diagnostic nerve blocks…………………………

X. ROPIVACAINE (NAROPIN):- Long lasting AMIDE LA- Low incidence of CARDIOTOXICITY- Used in EPIDURAL & REGIONAL ANESTHESIA……………

XI. TETRACAINE(PONTOCAINE):- Long acting AMINO ESTER- Increased POTENCY, & DURATION OF ACTION- Used mainly in SPINAL ANESTHESIA- Has high risk of SYSTEMIC TOXICITY………………………………..

XII. DIBUCAINE(NUPERCAINAL):- Used as SPINAL ANESTHETIC- Also used as CREAM & OINTMENT for TOPICAL USE- Not used as injection(due to increased TOXICITY)………………………

XIII. DYCLONINE HYDROCHLORIDE(DYCLONE):- Has rapid onset of action- Increased duration of action- USES:a. Topical anesthesia during ENDOSCOPY(0.5-1% solution)b. For oral mucositis pain, due to radiation/ chemotherapyc. Anogenital proceduresd. Sore throat(as lozenges)e. Contact dermatitis(0.75% solution)………………….

XIV. PRAMOXINE HYDROCHLORIDE (ANUSOL):- Too toxic for eye/ nose application- Mainly used as 1% TOPICAL APPLICATION …………………..

XV. BENZOCAINE(AMERICAINE):- Poorly soluble- Used on WOUNDS & ULCERATED SURFACES for sustained LOCALIZED

ACTION- ADR : Methemoglobinemia………………………………..

XVI. PROPARACAINE(ALCAINE):- Reduced irritation- Used in patients SENSITIVE TO ESTER LAs- Mainly restricted to OPTHALMOLOGICAL USE…………………………

XVII. TETRODOTOXIN & SAXITOXIN:- Block SODIUM CHANNEL PORE- Derived from JAPANESE PUFFER FISH- ADRs:a. Respiratory muscle paralysisb. Hypotension……………………………………

GENERAL USES OF LAs :Comprise:1. SURFACE ANESTHESIA2. INFILTRATION ANESTHESIA3. CONDUCTION BLOCK4. SPINAL ANESTHESIA5. EPIDURAL ANESTHESIA6. I.V REGIONAL ANESTHESIA

1. SURFACE ANESTHESIA:- Drugs used include:a. LIDOCAINEb. PRILOCAINE, etc………….

2. INFILTRATION ANESTHESIA:- Dilute solution of LA infiltrated under SKIN in area of OPERATION

BLOCKS SENSORY NERVE ENDINGS- Drugs used include:a. LIDOCAINEb. BUPIVACAINE etc………………..

3. CONDUCTION BLOCK:- LA injected around nerve trunks area, FAR from site of injection is

ANESTHETIZED & PARALYZED- Mainly FIELD BLOCK & NERVE BLOCK is achieved- Drugs used include:a. LIDOCAINEb. BUPIVACAINE, etc…………………………

4. SPINAL ANESTHESIA:- LA injected in SUBARACHNOID SPACE, in between L(2-3) / L(3-4) , below

lower part of SPINAL CORD LOWER ABDOMEN & HIND LIMBS are ANESTHETIZED & PARALYZED- Drugs used include:a. LIDOCAINEb. BUPIVACAINEc. TETRACAINE, etc- Complications include:a. RESPIRATORY PARALYSISb. HYPOTENSIONc. HEADACHEd. SEPTIC MENINGITIS

e. NAUSEA & VOMITINGf. CAUDA EQUINA SYNDROME (Prolonged loss of control over bladder & bowel sphincters)………………

5. EPIDURAL ANESTHESIA:- LA injected into SEMILIQUID FAT of SPINAL DURAL SPACE causes

MULTIPLE PARAVERTEBRAL BLOCKS- Sites of injection include:a. Thoracicb. Lumbarc. Caudal- Drugs used include:a. Lidocaineb. Bupivacaine………………………

6. I.V REGIONAL ANESTHESIA:- Also known as INTRAVASCULAR INFILTRATION ANESTHESIA- LIDOCAINE is used here………………………………..

REFERENCE/ BIBLIOGRAPHY :• Catterall.A.W; Mackie.K; “Chapter 14: Local Anesthetics”; Goodman &

Gilman’s Pharmacological Basis of Therapeutics; 11th edition; McGraw-Hill Publications; Page: 369-386• Tripathi.D.K; “Chapter 26: Local Anesthetics”; Essentials of Medical

Pharmacology; 7th edition; Jaypee Publishers; Page: 360-371

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