1. Dr. Naila Abrar

2. After this session you should be able to:  define local anesthesia;  classify local anesthetics;  describe pharmacokinetic properties of commonly used local anesthetics;  describe the mechanism of action;  comprehend the structure-activity characteristics of local anesthetics; and  describe the toxicity of local anesthetics.

3. DEFINITION Loss of sensory perception due blockade of sodium channels in neuronal cell membrane in a restricted/localized area of the body.

5. CHARACTERISTICS  Topical application or local injection  Peripheral nerves  Consciousness not altered  No amnesia  Vital functions not affected  No change in physiological functions  Recovery is spontaneous, predictable & without residual changes

6. ACCORDING TO CHEMISTRY ESTERS  Cocaine  Procaine  Tetracaine  Benzocaine AMIDES  Lignocaine  Prilocaine  Mepivacaine  Bupivacaine  Ropivacaine

7. ACCORDING TO DURATION OF ACTION SHORT  Procaine, Chlorprocaine MEDIUM  Cocaine, Lidocaine, Mepivacaine, Prilocaine LONG  Tetracaine, Bupivacaine, Levobupivacaine, Ropivacaine

8. ACCORDING TO THERAPEUTIC USES SURFACE ANESTHESIA  Cocaine, lignocaine, tetracaine, benzocaine FEILD BLOCK & INFILTRATION ANESTHESIA  Procaine, lignocaine, bupivacaine NERVE BLOCK  Procaine, lignocaine, bupivacaine, tetracaine, ropivacaine SPINAL ANESTHESIA  Lignocaine, bupivacaine, tetracaine EPIDURAL ANESTHESIA  Lignocaine, bupivacaine OPHTHALMOLOGICAL ANESTHESIA  Proparacaine

9. ESTERSAMIDES  Cocaine  Procaine  Tetracaine  Benzocaine  Lidocaine  Mepivacaine  Bupivacaine  Ropivacaine  Articaine

10. ABSORPTION  Dosage  Site of injection intercostal>caudal>epidural>brachial>sciatic  Drug-tissue binding  Local tissue blood flow  Use of vasoconstrictors- epinephrine  Physiochemical properties of the drug Termination of action Systemic effects

11. USE OF VASOCONSTRICTORS  EPINEPHRINE used  Blood supply limited  Absorption restricted  More time of contact-more pronounced effect  Delayed healing & tissue necrosis   2 receptors- decrease release of substance P- clonidine

12. DISTRIBUTION  Amides widely distributed  Initial rapid distribution phase  Slower distribution phase

13. METABOLISM & EXCRETION  Converted to more water soluble forms liver- amides Prilocaine>lidocaine>mepivacaine>ropivacaine plasma- esters (butyrylcholinesterase)  Toxicity of amide type increased in liver disease

14. MECHANISM OF ACTION voltage- gated sodium channels Block Reversible Diffusion into nerve fibre (only in non- ionizable form)

15. Threshold for excitation increasesImpulse conduction slowsRate of rise AP decreasesAbility to generate AP is abolished Propagation blocked if Na current blocked over a critical length

17.  Higher affinity for inactivated phase  Voltage & time dependent  Less affinity for resting state  More effect on high frequency firing  Use dependent block  Resting potential not significantly altered

18.  Biological toxins-batrachotoxin, aconitine, scorpion venoms  Bind to receptors within Na channel and prevent inactivation  Prolonged influx of Na & depolarization  Marine toxins tetrodotoxins & saxitoxin have effects similar to LA

19.  LIPID SOLUBILITY  pKa  CARBON DIOXIDE  HYDROPHOBIC NATURE  TACHYPHYLAXIS

20. SUSCEPIBILITY OF NERVE FIBRES TO LOCAL ANESTHETICS  Firing frequency  Size  State of myelination  Fibre diameter  Fibre position  Pain sensation>temperature>touch>deep pressure> motor

21. TOXICITY 1. SYSTEMIC EFFECTS  Absorption from site of administration 2. DIRECT NEUROTOXICITY  Local effects when high concentrations are administered in close proximity to the spinal cord and other major nerve trunks

22. TOXICITY A. CNS  Circumoral & tongue numbness, metallic taste  Nystagmus, muscle twitching, tonic- clonic convulsions  Depression of cortical inhibitory pathways-unopposed activity of excitatory neuronal pathways  Generalized CNS depression  Death due to respiratory failure

23. TOXICITY B. NEUROTOXICITY  More with chloroprocaine and lidocaine  Transient radicular irritation or neuropathic pain  Interference with axonal transport and disruption of calcium homeostasis

24. TOXICITY C. CARDIOVASCULAR SYSTEM  Direct effects on cardiac & smooth muscle membranes Myocardial depression Arteriolar dilation-hypotension  Indirect effects on ANS  Bupivacaine is more cardiotoxic than others- slow idioventricular rhythm & broad QRS complexes  Cocaine blocks norepinephrine reuptake- vasoconstriction & hypertension, cardiac arrythmias

25. TOXICITY D. HEMATOLOGIC EFFECTS  Prilocaine – metabolite O-toluidine  An oxidizing agent converts Hb to met Hb

26. TOXICITY E. ALLERGIC REACTONS  Esters converted to p -aminobenzoic acid (PABA) derivatives

27.  Sympathomimetic action  Potent vasoconstrictor  Cardiac stimulation  Marked pyrexia with overdose

28.  Low aqueous solubility  Topical local anesthetic – not absorbed  Relief of pain & irritation  Anesthesia of mucous membranes  PABA derivatives – antagonize effect of sulfonamides locally

29.  Most widely used  Effective by all routes but oral BA low  High 1 st pass metabolism  Fast onset, more intense & lasting effect  Alternative for ester allergic pts  Toxicity equal to procaine but more sedative than others

30.  Not effective topically  Slower onset, longer acting  Unique property of sensory & motor dissociation  Popular for anesthesia during labor  More cardiotoxic

31. SURFACE ANESTHESIA  Ear, eye, nose, throat, abraded skin  Only superficial layer  Soluble LA – rapid systemic absorption  Eutectic lidocaine/prilocaine – intact skin

32. INFILTRATION ANESTHESIA  Dilute solution infiltrated under skin  Immediate onset & DoA is short  Minor operations: incisions, excisions

33. FIELD BLOCK or NERVE BLOCK  Injected around nerve trunk  Area distal to injection is anesthetized and paralyzed  Lidocaine  Bupivacaine for longer

35. BIER BLOCK  INTRAVENOUS REGIONAL BLOCK  Short surgical procedures  Upper or lower extremities

36. SPINAL ANESTHESIA  Subarachnoid space L2-3 or L3-4 – cauda equina  Abdominal or pelvic surgery  Effective analgesia & muscle relaxation  Complications: respiratory paralysis, hypotension (sympathetic reflexes inhibited), headache, cauda equina syndrome, infection, neurotoxicity

38. EPIDURAL  Injection into epidural space at L2-3  Used in obstetrics, lower abdomen & pelvic surgery  Unwanted effects similar to spinal but less because longitudinal spread is reduced  Lidocaine, bupivacaine, ropivacaine