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Local anesthetics


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references- sharma & sharma K.D Tripati

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Local anesthetics

  1. 1. Local Anesthetics Dr.K.R.Prabhakar Asst.Professor
  2. 2. Introduction  LA reversibly block the impulse conduction.  Transient loss of sensation in area of contact.  Used for performing minor surgeries.  Neither cause unconsciousness nor need proper maintenance of vital functions during surgery.  Mixed nerve- not only sensory but also motor impulses are interrupted.  Results in muscular paralysis and loss of autonomic control as well.
  3. 3. Susceptibility of nerve fibers to LA blockade  Differs on the basis of size & myelination.  Small unmyelinated C&B fibers blocked first.  Pain, temp & touch sensation are blocked first.  Proprioception disappears in succession.  Small typeA-delta fibers(myelin) are blocked next.  Heavily myelinated A-α, β & ɣ fibers blocked last.  Skeletal muscle tone is lost in the end.  Recovery takes place in reverse order.
  4. 4. Classification Amide type Long acting  Bupivacaine  Levo-Bupivacaine  Ropivacaine  Dibucaine Intermediate acting  Lidocaine (lignocaine)  Mepivacaine  Prilocaine  Articaine Ester type Long acting  Tetracaine (amethocaine) Intermediate acting  Cocaine Short acting  Procaine  Chloroprocaine  Benzocaine  Proparacaine
  5. 5. Miscellaneous  Pramoxine (pramocaine)  Dyclonine  Oxethazaine (mucaine)
  6. 6. Mechanism of action  LA molecules consist of an aromatic part liked by an ester or amide bond to a basic amine side chain.  LA are weak bases  Remain partly ionized at physiological pH.  Unionized form penetrates the N membrane.  In axon- ionized form of LA is active at receptor site.
  7. 7.  LA block the voltage gated Na+ channels..  Blocking action is favored by repetitive stimulation- voltage dependence.  Activation gate (AG) on extracellular site.  Inactivation gate (IG) on intracellular site.  These gates are called voltage sensors.  Voltage sensors movement is regulated by conformational change due to voltage gradient.
  8. 8. Effect of pH on LA action  LA action is strongly pH dependent.  Partly ionized & partly unionized at physiolog pH.  Unionized form diffuses through axon.  Inside axon it is ionized to cationic form BH+  LA are less effective in infected tissue due to- 1. Acidic pH 2. ↑Blood supply at inflamed site. 3. Effectiveness of Adr ↓ at inflamed site. 4. Inflammatory products may oppose LA action.
  9. 9. Prolongation of action by vasoconstrictors  Drugs that delays absorption of LA in to circulation will prolong its action & reduce systemic toxicity.  Adrenaline (1:100,000 to 1: 200,000) in dentistry (1:50,000 to 1: 100,000) MC used with LA- doubles the duration of LA action.  Vasoconstrictor shouldn’t be used for N block of an extremity or end organs e.g. on fingers, toes, nose & penis.
  10. 10.  One ampoule of 1:1000 adrenaline in 1 ml volume.  This equals 1mg in 1 ml  This equals 1000 μg/ml   If one ampoule is diluted to 10ml  This equals 0.1 mg/ml  This equals 100 μg/ml  This is 1:10,000 adrenalin   If one ampoule is diluted to 100ml  This equals 0.01 mg/ml  This equals 10 μg/ml  This is 1:100,000 adrenalin
  11. 11.  Adr can cause cardiac complications.  Felypressin can be used as an alternative.  Preferable in pts with cardiovascular diseases.  Alternatively prilocaine can be used.
  12. 12. Systemic actions C.N.S  Stimulation followed by depression. Symptoms of overdose with clinically used LAs are-  Circumoral numbness,  Abnormal sensation in the tongue,  Dizziness, blurred vision, tinnitus followed by  Drowsiness, dysphoria and lethargy.  Still higher doses produce excitation, restlessness, agitation, muscle twitching, seizures and finally unconsciousness.
  13. 13. cvs Heart  No significant effects at conventional doses.  High doses- LAs are cardiac depressants.  Decrease automaticity, excitability, contractility, conductivity and prolong ERP.  Quinidine like antiarrhythmic action.  Procainamide is a class IA antiarrhythmic.  QTc interval is prolonged and LAs can induce cardiac arrhythmias  Bupivacaine is relatively more cardiotoxic  Lidocaine used as an antiarrhythmic.
  14. 14. Blood vessels  ↓ BP due to sympathetic blockade  High conc locally- direct relaxation of arterial SM.  Bupivacaine> Lidocaine> prilocaine  Toxic doses of LAs- cardiovascular collapse.  Cocaine has sympathomimetic property;  ↑sympathetic tone, causes local vasoconstriction, marked rise in BP and
  15. 15. Pharmacokinetics  Ester/amide bond in LA governs its metabolism & ability to cause hypersensitivity reactions.  Ester LA are hydrolysed by plasma esterases & liver esterases.  Spinal fluids contain negligible esterases.  Amide LA are degraded by hepatic microsomes by N-dealkylation & hydrolysis.  Hypersensitivity more common with ester Las.  First pass metabolism is significant for both procaine & lidocaine, not used orally in arrhythmias
  16. 16. Adverse effects CNS Low doses  Tongue numbness  Sleepiness  Mild headache  Visual & auditory disturbances High doses  Nystagmus & muscle twitching.  Convulsions  Cocaine- long lasting CNS stimulation & euphoria.
  17. 17. CVS  Bradycardia,  Hypotension,  Cardiac arrhythmias and  Vascular collapse Blood  Orthotoludine – metabolite of prilocaine.  Oxidises Hb to metHb, ↑levels cause cyanosis.  Rx- reducing agents like methylene blue or ascorbic acid I.V to convert metHb to Hb.
  18. 18. Allergic reactions  Ester LA are metabolized to PABA derivatives .  Responsible for allergic reactions. 1. Rashes, 2. Angioedema, 3. Dermatitis, 4. Contact sensitization, 5. Asthma and 6. Rarely anaphylaxis occur.  Methylparaben added as preservative in certain LA solutions is responsible for allergic
  19. 19. Precautions and interactions  Pts on propranolol are very sensitive to pressor responses of Adr- unopposed 1 action.  Drugs with 1blocking property may lead to hypotension if co-administered with L+A.  Pts on acute alcohol intoxication need higher doses of X+A.  In pts on digoxin- accidental I.V inj of Adr cause arrhythmias.  Propranolol can lead to xylocaine toxicity due to- 1. Inhibition of metabolic oxidation of xylocaine.
  20. 20. Amide group Long duration Bupivacaine & Levo-Bupivacaine (4>lignocaine) 0.25-0.5% Uses: nerve block, epidural & spinal anesthesia  More sensory than motor block.  Least placental transmission- painless delivery.  Intermediate onset of action.  Shouldn’t be used for IV regional analgesia or obstetrical paracervical block anesthesia.
  21. 21. Toxicity  Cardiotoxic- prolongs QTc interval- VT & VA.  Blocks Na channels both in systole & diastole.  Aggrevated by acidosis & hypoxemia.  Levo-bupivacaine equally potent but less toxic.
  22. 22. Ropivacaine (equipotent to bupivacaine) Uses: infiltration, epidural & regional anesthesia.  Continous epidural used for relief of post op & labor pain.  Less cardiotoxic & more motor sparing than bupi.  Intermediate onset of action. Toxicity  Available as S-sterioisomer-  Less affinity for cardiac Na+ channels.  R-isomer is toxic.
  23. 23. Dibucaine (Cinchocaine)  Very potent, longest acting LA.  Slow onset of action. Use: surface anesthetic in anal canal & rectum.  Ocasionally for SA of longer duration. Rarely used Toxicity  More toxic than bupivacaine Other uses  Pseudocholinesterase inhibitor.  Used for dibucaine number test.  Normal dibucaine number is 80.
  24. 24. Medium duration Lidocaine (Lignocaine) or Xylocaine  Most widely used multipurpose LA Uses:  Topically on mucous membrane- Aq.sol, jelly etc.  Infiltration, nerve block & epidural anesthesia.  Spinal analgesia- high conc 5% made hyperbaric with 7.5% dextrose is used.  Rapid onset of action, lasts for 1-2 hrs.  Opiods are synergistic for intrathecal & epidural.  Transdermal patch- for post herpetic
  25. 25. Toxicity  CNS: dizziness, paresthesia & euphoria.  High doses- confusion, vertigo, tinnitus & nausea.  Severe toxicity ppt seizures.  Overdose- arrhythmias, ↓BP, coma, resp arrest.  Propranolol enhances toxicity by ↓ clearance. Other uses  Ventricular arrhythmias during MI.
  26. 26. Mepivacaine (50% potent as lignocaine)  Similar to lidocaine  Not effective as topical anesthetic.  Can be used without epinephrine. Articaine (almost equipotent to lidocaine)  Rapid onset of action (5min)  Recently approved for dental & periodontal procedures. Contains epinephrine.  Also used for spinal & epidural anesthesia  Mainly metabolized by liver, partly by plasma cholinesterase.
  27. 27. Prilocaine (equipotent to lidocaine) Uses: mostly for dental procedures.  Administered by infiltration or nerve block.  Can be used without epinephrine. Toxicity  Similar to lidocaine  Metabolite orthotoludine causes metHb.  CI in obstetric practice.
  28. 28. Eutectic lidocaine/prilocaine  Anaesthetise intact skin after surface application.  Eutectic mixture refers to lowering of melting point of two solids when they are mixed.  Lidocaine and prilocaine are mixed in equal proportion at 25°C.  The resulting oil is emulsified into water to form a cream
  29. 29. Use:  Applied under occlusive dressing for 1 hr before 1. I.V. cannulation, 2. Split skin graft harvesting and 3. Other superficial procedures.  Anaesthesia up to a depth of 5 mm lasts for 1–2 hr after removal.  It has been used as an alternative to lidocaine infiltration.  PRILOX 5% cream.
  30. 30. Ester group Long duration Tetracaine or Amethocaine (4> lignocaine) Uses: topically on eye, nose, troat & tracheobronchial tree.  Eye: no effect on pupil, accomdation & IOP.  Very suitable for SA of long duration.  Onset of action is slow. Toxicity:  Slowly metabolized  Being PABA ester may antaonise- sulfonamides.  I.V doses may produce arrhythmias.
  31. 31. Medium duration Cocaine (50% potent as lidocaine)  Earlier it was used as ocular anesthetic.  Vasoconstrictor, Adr not necessary.  Protoplasmic poison, causes necrosis on injection. Toxicity  CNS stimulant- euphoria, delays fatigue, strong psychological dependence  Bradycardia, ↑BP, ↑temp  Nausea & vomiting
  32. 32. Short duration Procaine (25% potent as lidocaine)  No longer used  Slow onset of action, Ineffective topically Toxicity  Bradycardia, vasodilation, ↓CO.  Anxiety, restlessness & shivering.  Hydrolysed to PABA Other uses  Procaine + Benzylpenicillin= procaine penicillin  Procainamide- class IA antiarrhythmic.
  33. 33. Chloroprocaine (slightly > procaine)  Better & safer than procaine.  Use: infiltration, nerve block, caudal & epidural block.  Rapid onset of action.  Not effective topically.  Less toxic than procaine.
  34. 34. Benzocaine & Proparacaine  Used as topical (surface) anesthetics.  Included in preparations of ointment, lozenges & suppositories- ulcer, sore throat & inflammation.  Proparacaine preferred in minor ocular procedures. Non irritant & less antigenic. Toxicity  PABA derivatives- antagonize sulfonamides.  Too toxic for injection
  35. 35. Miscellaneous group
  36. 36. Uses and techniques of LA Surface anaesthesia  Applied topically on mucous membranes and abraded skin.  Superficial layer is anaesthetised and motor function not affected.  Onset and duration -site, the drug, conc and form.  Lidocaine (10%) sprayed in the throat acts in 2–5 min and produces anaesthesia for 30–45 min.
  37. 37.  Adr no affect on duration of topical anaesthesia.  Phenylephrine can cause mucosal vasoconstrion.  Absorption of soluble LAs from mucous membranes is rapid, may attain IV conc.  Eutectic lidocaine/prilocaine is capable of anaesthetizing intact skin.
  38. 38. Sites & uses of SA
  39. 39. Infiltration anaesthesia  Dilute sol of LA is injected under the skin to reach sensory nerve terminals.  Uses; minor surgical procedures like incisions & excisions.  Onset of action is almost immediate.  Duration:lidoc 30-60 min, bupiva 90-180 min.  Motor function is not affected.
  40. 40. Conduction block anesthesia  LA injected around the nerve trunk.  Area distal to injection site is anesthetized & paralysed.  Lidocaine (1–2%) with intermediate duration of action is most commonly used,  Longer lasting anaesthesia bupivacaine may be selected. Two types  Field block  Nerve block
  41. 41. Field block  LA is injected SC in a manner that all nerves coming to a particular field are blocked.  Uses: herniorrhaphy, appendicectomy, dental procedures, scalp stitching, operations on forearms and legs, etc.  Larger area beginning 2–3 cm distal to the line of injection can be anaesthetised with lesser drug compared to infiltration.  The same concentration of LA as for infiltration is used for field block.
  42. 42. Nerve block  LA injected around the appropriate nerve trunks or plexuses.  Latency of anaesthesia depends on the drug and the area to be covered.  Frequently performed nerve blocks are— lingual, intercostal, ulnar, sciatic, femoral, brachial plexus, trigeminal, facial, phrenic, etc.  Used for tooth extraction, operations on eye, limbs, abdominal wall, fracture setting, trauma to ribs, neuralgias, persistent hiccup, etc
  43. 43. Spinal anaesthesia  LA is injected in the subarachnoid space between L2–3 or L3–4.  Nerve roots in the cauda equina are targeted.  Adr may be enhancing spinal anaesthesia by reducing spinal cord blood flow or  By its own analgesic effect exerted through spinal α2 adrenoceptors.  Intrathecal clonidine, an α2 agonist, produces spinal analgesia by itself.
  44. 44.  Spinal anaesthesia is used for operations on the-lower limbs, pelvis, lower abdomen, e.g. prostatectomy,  Fracture setting, obstetric procedures, caesarean section, etc  Advantages of spinal anaesthesia over GA are: (i) It is safer. (ii) Produces good analgesia and muscle relaxation without loss of consciousness. (iii) Cardiac, pulmonary, renal disease and diabetes pose less problem
  45. 45. Complications of spinal anaesthesia Respiratory paralysis  Due to Hypotension and ischaemia of respiratory centre. Hypotension  due to blockade of sympathetic outflow to blood vessels & venous pooling.  Raising the foot end overcomes the hypotension.  Prevented by ephedrine, mephentermine. Headache Septic meningitis
  46. 46. Cauda equina syndrome  Prolonged loss of control over bladder and bowel sphincters.  It may be due to traumatic damage to nerve roots or chronic arachnoiditis caused by  inadvertent introduction of the antiseptic or particulate matter in the subarachnoid space. Nausea and vomiting  Due to reflexes triggered by traction on abdominal viscera.  Premedication with opioid analgesics prevents it.
  47. 47. Epidural anaesthesia  LA injected in dural space, acts on nerve roots. Thoracic  Injection is made in the midthoracic region.  Epidural space in this region is relatively narrow.  Analgesia obtained in middle and lower thoracic dermatomes. Lumbar  epidural space is wide.  Produces anaesthesia of lower abdomen, pelvis and hind limbs.  Use is similar to that of spinal anaesthesia.
  48. 48. Caudal  Injection is given in the sacral canal through the sacral hiatus.  Produces anaesthesia of pelvic and perineal region.  Used mostly for vaginal delivery, anorectal and genitourinary operations. Complications  Cardiovascular complications are similar to spinal.  Headache & neurological complications are less.
  49. 49. Intravenous regional anaesthesia