Local anaesthetics (l)

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Pharmacology lecture for MBBS students

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Local anaesthetics (l)

  1. 1. 10/5/2013RK 1
  2. 2. • Anesthesia literally means “no sensation” • Derived from the Greek verb for “to perceive” : Oliver Wendell Holmes, 1846 10/5/2013RK 2
  3. 3. LOCAL ANAESTHESIA • Loss of sensory perceptions by reversibly inhibiting the propagation of signals along nerve pathways in a specific area of the body. • LAs block generation and conduction of impulse at all parts of neurons where they come in contact. 10/5/2013RK 3
  4. 4. HISTORY • Cocaine : • First local anaesthetic • Discovered by German, Albert Niemann (1860) • Isolated from the leaves of coca • First clinical use in 1884 by Sigmund Freud and Karl Kollar in ophthalmology as a topical ointment 10/5/2013RK 4
  5. 5. INJECTABLE • Low potency & short duration • Procaine • Chloroprocaine • Intermediate potency & duration • Lignocaine • Prilocaine • High potency & long duration • Tetracine • Bupivacaine • Ropivacaine SURFACE • Soluble • Cocaine • Lignocaine • Tetracaine • Insoluble : Benzocaine 10/5/2013RK 5
  6. 6. GENERAL STRUCTURE 10/5/2013RK 6
  7. 7. • Lignocaine • Mepivicaine • Prilocaine • Bupivacaine More intense and longer lasting anaesthesia • Cocaine • Procaine • Tetracaine • Chlorprocaine • Benzocaine Short DOA, less intense analgesia Esters Amides 10/5/2013RK 7
  8. 8. • These get metabolized in the liver to inactive agents • Binding to amides is provided by alpha 1 glycoprotein in plama • No allergies associated with amides • Hydrolysed in the plasma by a pseudo cholinesterase • One by-product of this reaction Para-Amino Benzoic Acid (PABA) • Allergic reaction are associated with PABA Esters Amides 10/5/2013RK 8
  9. 9. MECHANISM OF ACTION • Inhibits sodium influx through sodium-specific ion channels in the nerve cytoplasm • Sodium ions cannot flow in, so potassium ions cannot flow out, thereby preventing the depolarization of the nerve • Rate of rise of AP and depolarisation decreases with increase in concentration of LAs • To do this the anaesthetic molecules must actually enter through the cell membrane of the nerve. This is where the differences in the time of onset and duration of the various local anaesthetics lies. 10/5/2013RK 9
  10. 10. 10/5/2013RK 10
  11. 11. FACTORS THAT AFFECT ACTION OF LOCAL ANESTHETICS • pH • Cationic form binds to receptor site. The uncharged form penetrates membrane . Efficacy of drug can be changed by altering extracellular or intracellular pH 10/5/2013RK 11
  12. 12. FACTORS THAT AFFECT ACTION OF LOCAL ANESTHETIC • Lipophilicity • Main determinant of anesthetic potency. • Compounds with high lipophilicity penetrate the nerve membrane easily. • This means less molecules are needed to inhibit the blockade of sodium ions. This leads to enhanced potency. Lipid solubility and potency Drug Relative potency Lipid solubility Procaine =1 100 Prilocaine 1.8 129 Lignocaine 2 366 Bupivicaine 8 3420 10/5/2013RK 12
  13. 13. • Blood absorbs the unused anesthetic. In order to slow down this process many anesthetics are administered with a vasoconstrictor. • These constrict the vessel and slow down the absorption of the anesthetic, by allowing less blood to enter/leave the site 10/5/2013RK 13
  14. 14. ADVANTAGES OF LIGNOCAINE ADRENALINE COMBINATION • Decrease systemic toxicity (uptake by up to 1/3) • Prolong local anesthesia (by ~50%) • Decrease local bleeding (improve visualization of surgical field DIS ADVANTAGES: • Makes injection more painful • Increases chances of local injury and necrosis. • May raise BP and promote arrhythmias in susceptible individuals 10/5/2013RK 14
  15. 15. PROGRESSION OF LOCAL ANESTHESIA • Loss of: • 1. Pain • 2. Cold • 3. Warmth • 4. Touch • 5. Deep pressure • 6. Motor function 10/5/2013RK 15
  16. 16. PHARMACOLOGICAL ACTIONS • CNS : • All can produce CNS stimulation followed by depression. • Cocaine: • Euphoria-excitement-mental Confusion-tremors- muscle Twitching-convulsions- Unconciousness - resp. Depression. • Procaine, Lignocaine: safe at clinical doses • CVS : • Cardiac depressant at iv doses • Antiarrhythmic action (procainamide) 10/5/2013RK 16
  17. 17. TECHNIQUES OF ADMINISTRATION • Topical Anesthesia • Infiltration • Conduction block Field block Nerve block • Peridural • Spinal anesthesia 10/5/2013RK 17
  18. 18. TOPICAL ANESTHESIA • Done by the administering the anesthetic to mucous membranes or skin. Relieves itching, burning and surface pain, i.e. sunburns. 10/5/2013RK 18
  19. 19. INFILTRATION • Occurs by directly injecting a local anesthetic to block the nerve endings under the skin or in the subcutaneous tissue. Used mainly for surgeries, i.e. cavities being filled. 10/5/2013RK 19
  20. 20. CONDUCTION BLOCK 10/5/2013RK 20
  21. 21. • This is accomplished by injecting a local anesthetic into the peridural space, a covering of the spinal cord 10/5/2013RK 21
  22. 22. • Here, the local anesthetic is injected into the subarachnoid space of the spinal cord 10/5/2013RK 22
  23. 23. TOXICITY • CNS Toxicity: • Systematic absorption can lead to excitement (tremors, shivering, convulsions), • If absorbed in even higher amounts can lead to depression (coma, respiratory arrest and death) • Cardiovascular toxicity: • If absorbed in excess systematically can lead to depression of the cardiovascular system • Hypersensitivity: Rashes to anaphylaxis • Local reactions: Combination with vasoconstrictor (combination should be avoided-feet, fingers, toes, pinna, penis) 10/5/2013RK 23
  24. 24. Cocaine  Ester, tendency to cause allergy  Cardiovascular and CNS stimulant  Addictive  Used in ENT as a vasoconstrictor  Metabolised by plasma esterases 10/5/2013RK 24
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