Local anaesthetics

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Lecture slides for undergraduates medical (MBBS) Students. Source material for this presentation is Essentials of Pharmacology, KD Tripathi, Katzung and Goodman and Gillman. It deals with Local anaesthetics with their mechanism of action, pharmacokinetics , adverse effects and therapeutic uses.

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Local anaesthetics

  1. 1. Local Anaesthetics Dr Mayur Chaudhari Assistant Professor Department of Pharmacology Government Medical College, Surat Available at www.slideshare.net 1
  2. 2. At The End Of Class….. • Local Anaesthesia • Mechanism of Action • Pharmacodynamic • Pharmacokinetic • Individual Agents • Techniques and uses 2
  3. 3. Local Anaesthesia 3
  4. 4. Local Anaesthesia • Reversible loss of sensation (Sensory) • In a local area • Without loss of consciousness • Without loss of control of vital functions • Topical/Injection/Infiltration 4
  5. 5. Ideal Local Anaesthetic Non irritant / Negligible Local irritation  Negligible local tissue damage  minimal systemic toxicity Rapid onset of action Prolonged action  water soluble  Sterilizable by heat Without after effects 5
  6. 6. Local Vs General Advantages Disadvantages • • • • • • • Uncooperative patient – No • Minor Surgery only • Some major Surgery • Also Have Side effects Consciousness Localized No Altered Physiology Monitoring of Vitals Safe in poor GC Response can be modified 6
  7. 7. Historical Aspects • South American natives chewed coca leaves for stimulant and euphoric action • Albert Niemann – isolated cocaine in 1860 • Niemann noted that it causes numbing of tounge • Sigmund Freud – tried it for psychic energizing activity unsuccessfully • Carl Koller – used cocaine for Ocular surgery in 1884 • Halstead – infiltration anaesthesia 7
  8. 8. Classification  Injectable  Low Potency, Short Duration Procaine, Chloroprocaine  Intermediate Potency and Duration Lignocaine, Prilocaine  High Potency, long Duration Tetracaine, Bupivacaine, Ropivacaine, Dibucaine  Surface Anaesthetic  Soluble: Cocaine, Lignocaine, Tetracaine, Benoxinate  Insoluble: Benzocaine, Butamben, Oxethazaine 8
  9. 9. Classification - II Ester Linked Amide linked • Cocaine, Procaine, Chloroprocaine, Tetracaine • Lignocaine, Bupivacaine, Prilocaine, Ropivacaine – Short acting – Metabolized by plasma esterase – Can be used in poor liver function – Hypersensitivity - ↑ – Longer acting – Metabolized by liver enzymes – Avoided in poor liver function – Hypersensitivity - ↓ 9
  10. 10. Mechanism Of Action 10
  11. 11. Mechanism Of Action  Prevent generation and conduction of Nerve impulses by acting at the cell membrane:  Decrease the entry of Na+ ions during action potential  Increase in LA conc. decreases the maximum depolarization causing slowing of conduction  Finally depolarization fails to reach threshold potential 11
  12. 12. Mechanism Of Action 12
  13. 13. Mechanism Of Action Degree of blockade is frequency dependent: Greater blockade at higher frequency of stimulation Higher concentration of Ca++ reduces inactivation of Na+ channel Blockade is not due to hyperpolarization RMP is unaltered as K+ channels are not blocked 13
  14. 14. Factors Influencing Action of LA  Lipid Solubility  Lipid solubility helps in nerve penetration, faster action  Non ionized form can easily cross nerve membrane pH  Lower pKa (7.6 – 7.8) – faster acting (lidocaine, mepivacaine)  Higher pKa (8.1 – 8.9) – slower acting (procaine, tetracaine, bupivacaine) 14
  15. 15. Factors Influencing Action of LA  Vasoconstrictors (Adrenaline, Phenylephrine)  Tissue Necrosis, Systemic Side effects  CI in areas with terminal arteries (Fingers, Toe, Nose, Penis) - Hypoxic injury - Tissue Necrosis and May Produce gangrene  Felypressin (Vasopressin Analogue) - Used as vasoconstrictor in CV Dz Patients 15
  16. 16. Factors Influencing Action of LA Inflammation  Acidic environment  ionized LA, Penetration decreased  Alkalization  Hasten onset of nerve block  Limited increase in unionized form  precipitation of LA 16
  17. 17. Pharmacodynamics Functions lost by LA (Local)  Pain perception  Temperature  Touch sensation  Proprioception  Skeletal muscle tone 17
  18. 18. Pharmacodynamics Sensory > Motor Nonmyelinated > Myelinated Small fibres > Large fibres Autonomic fibres > Somatic Fibres 18
  19. 19. Pharmacodynamics (Systemic) CNS • Inhibition of inhibitory neurons • Euphoria, Dysphoria, Muscle twitches • Stimulation – Restlessness, tremors, Convulsions • Respiratory depression in high doses • Respiratory failure - death 19
  20. 20. Pharmacodynamics (Systemic) CVS • ↓ Automaticity, Conductivity, Excitability, Contractility, Conductivity • ↑ Effective refractory period • Prolonged QTc interval • Ventricular Tachycardia, Ventricular Fibrillation • ↓ in Blood Pressure by Sympathetic blockade • Cocaine ↑ Blood pressure 20
  21. 21. Pharmacodynamics (Systemic) Smooth Muscle • ↓ contraction of bowel • Relaxation of vascular and bronchial smooth muscle  Sympathetic System • Blockade – Spinal, Epidural anaesthesia, local infiltration in peritoneal cavity  Neuromuscular Junction • Block NMJ, Inhibit ganglionic transmission 21
  22. 22. Pharmacokinetics • Surface anesthetics from mucus membrane and abraded areas • Depends on Blood flow to the area, total dose and specific drug characteristics • Widely distributed in the body: (lipophilic) • Enters brain, heart, liver and kidney • Followed by muscle and other viscera 22
  23. 23. Pharmacokinetics • Ester linked LA – inactivated by hydrolysis by plasma esterases, cholinesterase • Spinal anaesthesia – absorbed into systemic circulation • Amide linked LA – Degraded in liver by CYP450 • Use restricted in Liver disease 23
  24. 24. Pharmacokinetics • Amide linked LA – bind with α1 acid glycoprotein • α1 acid glycoprotein (↑) – MI, Trauma, Cancer, Surgery, Smoking • α1 acid glycoprotein (↓) – Oral Contraceptive Pill, Infants • Termination of action depends on rate of absorption and elimination 24
  25. 25. Break Time Available at www.slideshare.net 25
  26. 26. Toxicity  CNS  Numbness in circumoral area and tongue  Metallic taste  Drowsiness, Lightheadedness, Restlessness  Visual and auditory disturbances, Nystgmus  Respiratory depression, convulsions  Death due to respiratory failure 26
  27. 27. Toxicity CVS  Hypotension, Bradycardia, Cardiac Dysrhythmia  CV Collapse Methaemoglobinaemia  Prilocaine and Benzocaine  AE due to Vasoconstrictor 27
  28. 28. Toxicity Hypersensitivity  Esters> Amides (Methyl Paraben)  Asthmatic attack  Allergic dermatitis 28
  29. 29. Prevention of Toxicity  Proper History, Allergy Testing  4 hour fasting, Premedication  Avoid in Hepatic and cardiac disease  Administration at Proper site  Wait for development of effect  Look for signs of toxicity  Observation post operatively 29
  30. 30. Cocaine Natural alkaloid from Erythroxylon coca Medical use limited to surface or topical anesthesia Avoid with adrenaline A toxic action on heart may induce rapid and lethal cardiac failure Marked pyrexia is with cocaine overdose Not used presently 30
  31. 31. Procaine  Topically ineffective  Used for infiltration because of low potency and short duration  Most commonly used for spinal anesthesia  Produces significant vasodilation. Adrenaline used to prolong effect  Systemic toxicity negligible because rapidly destroyed in plasma  Procaine penicillin 31
  32. 32. Lignocaine  Effective by all routes.  Faster onset (3 Vs 15 min), more intense, longer lasting  Good alternative for those allergic to ester type  Quicker CNS effects than others  Overdose (muscle twitching, cardiac arrhythmia, fall in BP, coma and respiratory arrest)  Antiarrhythmic  Available as Injections, topical solution, jelly and ointment etc. 32
  33. 33. Bupivacaine  No topical effect  Slower onset and one of longer duration agents  Used for infiltration, spinal, nerve block and epidural  Unique analgesia without significant motor blockade (popular drug for analgesia during labor)  High lipid solubility, high distribution in tissues and less in blood (benefit to fetus)  More cardio toxic than other LA (prolong QT interval) 33
  34. 34. Eutectic Lignocaine/Prilocaine  Eutectic Mixture – Lowering of melting point of two solids when they are mixed  Lignocaine+Prilocaine at 25o C in equal proportion  Oil is emulsified in water to form a cream  Occlusive dressing prior to procedure  IV Canulation, Split Skin graft harvesting, Superficial Procedure  Up to 5mm  last for 1-2 hour 34
  35. 35. Benzocaine, Butamben  Low aqueous solubility – Not absorbed from mucosa or broken skin  Long lasting anaesthesia without systemic toxicity  Lozenges for stomatitis, Sore throat  Dusting powder on wounds/ Ulcerated surfaces  Suppositories for anorectal lesions 35
  36. 36. Techniques Surface Anaesthesia  Mucous membranes and abraded skin  Nose, mouth, bronchial tree, cornea and urinary tracts  Lignocaine, Tetracaine 36
  37. 37. Infiltration Anaesthesia  Injection of LA directly into tissues irrespective of the course of nerve  Superficial or deeper structure  Amides are preferred  Should not be injected into tissues supplied by end arteries  Adequate anaesthesia without affecting normal function  Dose required is more  Chances of Systemic Toxicity 37
  38. 38. Field Block  Injection of LA subcutaneously  Anaesthetize the region distal to the site of injection  Anaesthesia starts 2-3 cm distal to site of injection  All nerves coming to the field are blocked  Dose required is less, Prolonged duration  Forearm, anterior abdominal wall, scalp and lower extremity  Knowledge of neuroanatomy is required 38
  39. 39. Nerve Block  LA injected around individual Nerve/ Plexus..Not in the Nerve  Sensory and motor block distal to site of injection  Block depends on Proximity, Conc. And Volume of LA  Degree of ionization and Time  Trigeminal nerve blocks (face)  Cervical plexus block and cervical paravertebral block (shoulder and upper neck) 39
  40. 40. Spinal Anaesthesia  Subarachnoid space  between L2-3 or L3-4  Site of action – nerve root in the cauda equina  Level of anaesthesia –  vol. & speed of injection;  Baricity of drug soln. with CSF  Posture of patient  Order of anaesthesia – sympathetic > motor 40
  41. 41. Spinal Anaesthesia  Uses – lower limbs, pelvis, lower abdomen, prostatectomy fracture setting and obstetric procedures  Spinal headache, hypotension, bradycardia and respiratory depression, cauda equina syndrome and nausea-vomiting  Drugs - Lidocaine, Tetracaine 41
  42. 42. Epidural Anaesthesia  Site- sacral hiatus (caudal) or lumber, thoracic or cervical region  Catheters are used for continuous infusion  Used like spinal and also painless childbirth.  Side effect similar to Spinal, Less Chances  Lidocaine, bupivacaine, Ropivacaine 42
  43. 43. Regional anaesthesia (IV)  Injection of LA in a vein of a tourniquet occluded limb  Mostly limited to upper limb  Orthopedic procedures 43
  44. 44. Summary -Caine … Na+ Channel Blockers Esters and Amides Local and Systemic Actions (Toxicity)  Techniques Available at www.slideshare.net 44

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