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13236530 Anesthesia Pharmacology

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13236530 Anesthesia Pharmacology

  1. 1. Clinical Pharmacology of Anesthetic drugs Dr. Ahsan K. Siddiqui
  2. 2. General Anesthesia <ul><li>Definition – Induced, Reversible, controlled, loss of sensation </li></ul><ul><li>Components : </li></ul><ul><li>1. Analgesia </li></ul><ul><li>2. Muscle relaxation </li></ul><ul><li>3. Amnesia </li></ul><ul><li>4. Suppression of excessive autonomic </li></ul><ul><li>responses </li></ul>
  3. 3. <ul><li>Practical Conduct : </li></ul><ul><li>Pre Anesthetic check up </li></ul><ul><li>Just preoperative monitoring </li></ul><ul><li>Induction </li></ul><ul><li>Maintenance </li></ul><ul><li>Recovery </li></ul><ul><li>Post operative Care </li></ul>
  4. 4. <ul><li>Monitoring </li></ul><ul><li>Maintenance </li></ul><ul><li>Induction Recovery </li></ul><ul><li>Pre op. Check Post op. Care </li></ul>
  5. 5. <ul><li>Anesthesiologist Tools </li></ul><ul><li>Drugs : Hypnotics, Analgesics, Muscle </li></ul><ul><li>relaxants & others </li></ul><ul><li>Gases : Oxygen, Nitrous Oxide </li></ul><ul><li>Vapors : Halothane, Isoflurane, Sevoflurane </li></ul><ul><li>Equipments : Anesthetic Machine - Breathing </li></ul><ul><li>Circuits, Monitors……. </li></ul><ul><li>Others : iv access, Infusion fluid, Airway </li></ul><ul><li>equipments……..,….. </li></ul>
  6. 6. <ul><li>Premedication </li></ul><ul><li>Reasons for administration of premedications </li></ul><ul><li>1. Reduction of fear and anxiety </li></ul><ul><li>catecholamine , risks </li></ul><ul><li>2. Reduction of saliva secretion </li></ul><ul><li>3. Prevention of vagal reflexes (caused by surgical stimulation like squint op., stretching of anal sphincter, </li></ul><ul><li>or associated with medication e.g., B –blockers </li></ul><ul><li>4. As part of anesthetic technique e.g. use of narcotics </li></ul>
  7. 7. <ul><li>5. To produce amnesia </li></ul><ul><li>- Hyoscine ( Scopolamine) </li></ul><ul><li>- Benzodiazepines - anterograde amnesia </li></ul><ul><li>- Diazepam -hyoscine – in 75% pts complete amnesia </li></ul><ul><li>6. For specific therapeutic effects </li></ul><ul><li>- Transdermal glyceryl nitrate patches for angina pts, </li></ul><ul><li>- Steroids </li></ul><ul><li>- B – blockers </li></ul><ul><li>(anterograde amnesia- inability to form new memories, Impairment of memory for events occurring after the onset of amnesia) </li></ul>
  8. 8. <ul><li>Drugs : </li></ul><ul><li>1. Anxiolysis Amnesia: BNZ, Hyosc., Antihist. </li></ul><ul><li>(H1 Blochers) </li></ul><ul><li>2. Analgesia: Opiates </li></ul><ul><li>3. Adjuvant to GA : BNZ & Ketamine </li></ul><ul><li>4. Anti-emetic : Metoclopramide, Antihist. </li></ul><ul><li>5. Antacids : H2 blockers, Antihist., Na Citrate </li></ul>
  9. 9. <ul><li>6. Antihist. : Promethazine,Diphinhydramine </li></ul><ul><li>7. Antivagal Antisialagogues: Atrop, Hyos.,AntiH </li></ul><ul><li>8. Antitromb. / Anticoag.: Heparin, Stockings </li></ul><ul><li>9. Antibiotics: Infective Endocarditis Prophylaxis </li></ul><ul><li>10: Attention to pre-existing medications: </li></ul><ul><li>Continue: unless otherwise </li></ul><ul><li>Stop : MAOI, Contraceptive pills </li></ul><ul><li>Change : Insulin, oral hypogly., Steroids </li></ul>
  10. 10. <ul><li>Common Premadications </li></ul><ul><li>Drug Dose Route Timing </li></ul><ul><li>Diazepam 5-15 mg oral 1-2 hr </li></ul><ul><li>Lorazepam 1-3 mg oral preop. </li></ul><ul><li>Morphine 5-15 mg IM </li></ul><ul><li>Hyoscine 0.2-0.4 mg IM 1hr pre </li></ul><ul><li>Pathedine 50-100mg IM preop </li></ul><ul><li>Promethazine 12.5-25mg IM </li></ul><ul><li>Midazolam 2.5-5 mg IM </li></ul>
  11. 11. <ul><li>Children </li></ul><ul><li>Drug Dose Route Timing </li></ul><ul><li>Diazepam Syrup 0.2mgkg oral 1 hr </li></ul><ul><li>Medazolam 70-100 mcgkg IM preop </li></ul><ul><li>Promethazine </li></ul><ul><li>2-5yr 10-20mg oral 1hr preop </li></ul><ul><li>5-10 yr 20-25 mg 12dose </li></ul><ul><li>for IM </li></ul><ul><li>Morphine 0.1-0.2mgkg IM </li></ul><ul><li>Hyoscine 5mcgkg IM </li></ul>
  12. 12. <ul><li>Side effect of premadications : </li></ul><ul><li>Delayed recovery and interaction of Specific drugs </li></ul>
  13. 13. <ul><li>Opioids </li></ul><ul><li>Act on opioid receptors located through out CNS </li></ul><ul><li>Identified as mu - mu1 & mu2 </li></ul><ul><li>keppa (k) </li></ul><ul><li>delta (d) </li></ul><ul><li>sigma </li></ul><ul><li>Most effective as producing analgesia </li></ul><ul><li>They provide some degree of sedation </li></ul>
  14. 14. <ul><li>IV opiates </li></ul><ul><li>Drugs Dose Onset Duration </li></ul><ul><li>Morphine 0.1-0.2mgkg slowest long </li></ul><ul><li>Pathedine 1-2 mgkg slow long </li></ul><ul><li>Fentanyl 1-2mcgkg rapid short </li></ul><ul><li>Alfentanil 10-20mcgkg v. rapid v. short </li></ul><ul><li>Sufentanil 0.2-0.4mcgkg rapid short </li></ul>
  15. 15. <ul><li>Induction </li></ul><ul><li>Check: pt machine Monitors </li></ul><ul><li>Monitoring: </li></ul><ul><li>Basic Monitoring: </li></ul><ul><li>Anesthetics, clinical, Air way </li></ul><ul><li>EKG,NIBP,SpO2, Capnography </li></ul><ul><li>Add.: PNSTemp. CVP </li></ul><ul><li>Agent for induction : IV vs. Inhalational </li></ul><ul><li>Analgesia: Opiates </li></ul>
  16. 16. <ul><li>IV Induction Agents </li></ul><ul><li>The ideal intrav. Agent reliably and pleasantly induces full anesthesia within one arm-brain circulation time </li></ul><ul><li>- is free of side effects </li></ul><ul><li>- completely wears off in a few minutes </li></ul><ul><li>- it must be capable of infusion to maintain </li></ul><ul><li>anesthesia without problems. </li></ul>
  17. 17. <ul><li>I.V. anesthetic agents may be used for </li></ul><ul><li>1. Induction of anesthesia </li></ul><ul><li>2. As a sole agent for operation (TIVA) </li></ul><ul><li>3. To supplement volatile anesthesia or regional </li></ul><ul><li>anesthesia </li></ul><ul><li>4. For sedation </li></ul>
  18. 18. <ul><li>IV Induction Agents </li></ul><ul><li>Propofol – </li></ul><ul><li>- Mechanism of action – facilitation of inhibitory neurotransmission mediate by GABA </li></ul><ul><li>- Not water soluble </li></ul><ul><li>1% solution aqueous solution is available for IV use as an oil-in-water emulsion containing </li></ul><ul><li>- soybean oil </li></ul><ul><li>- egg lecithin </li></ul><ul><li>- glycerol </li></ul>
  19. 19. <ul><li>Only for IV administration </li></ul><ul><li>Rapid on set ( one arm brain circulation time) </li></ul><ul><li>12 life 2-8 min. ( recovery rapid, no hangover) </li></ul><ul><li>V. high clearance rate( 10 time that of thiopentone) </li></ul><ul><li>Conjugation in liver results in inactive metabolites </li></ul><ul><li>Excretion – in urine </li></ul><ul><li>Can be used in Chr. Renal F, hepatic ds. </li></ul>
  20. 20. <ul><li>Thiopent. Propofol Ketamine </li></ul><ul><li>barbiturate phenol phencyclidine </li></ul><ul><li>Pain - - + - - </li></ul><ul><li>Phleb. Less more less </li></ul><ul><li>Rapid onset ++ +++ + </li></ul><ul><li>BP decrease decrease increase </li></ul><ul><li>Analgesia -- -- + </li></ul><ul><li>Bronch ppt Asthma -- + </li></ul><ul><li>Mech. GABA GABA Desociat. </li></ul><ul><li>of act. </li></ul>
  21. 21. <ul><li>Recovery Hang over clean headed Emerg. </li></ul><ul><li>Delir. </li></ul><ul><li>PONV + - Antiemetic + </li></ul><ul><li>antipruritic </li></ul><ul><li>Duration 10 min 10 min < 10min </li></ul><ul><li>Route iv i.v i.v i.m </li></ul>Thiopent. Propofol Ketamine Commul. ++ - -
  22. 22. <ul><li>Life Support During Induction </li></ul><ul><li>A. Airway : Support: manual Atrif. Airway </li></ul><ul><li>B. O2 FM + circuit +- An. Agent </li></ul><ul><li>Chest expansion bag monitor </li></ul><ul><li>C. Circulatory Support </li></ul><ul><li>D. Definitive Airway : Guedel`s Airway </li></ul><ul><li>Laryngeal Mask Airway </li></ul><ul><li>ETT MR + Circuit + IPPV </li></ul>
  23. 23. <ul><li>MAINTENANCE </li></ul><ul><li>Anesthesia ( Tetrad) : </li></ul><ul><li>Unconsciousness : Inhal. Vs TIVA </li></ul><ul><li>Analgesia : N2O + Opioids / LA </li></ul><ul><li>Relaxation : M.R. </li></ul><ul><li>Autonomic : Pares. : Anticholin. </li></ul><ul><li>: Symp. : GA </li></ul><ul><li>Opioids </li></ul><ul><li>CVS drugs </li></ul>
  24. 24. Inhalational Anesthetics <ul><li>The greater the uptake of anesthetic agent, the greater the difference b w the inspired and alveolar conc. And slower the rate of induction. </li></ul><ul><li>Three factors affect anesthetic uptake </li></ul><ul><li>1. Solubility in the blood </li></ul><ul><li>2. Alveolar blood flow </li></ul><ul><li>3. partial pressure difference bw alveolar gas </li></ul><ul><li>and venous blood. </li></ul>
  25. 25. <ul><li>The relative solubility's of an anesthetic in air, blood, and tissues are expressed as Partition Coefficients </li></ul><ul><li>Partition Coefficients </li></ul><ul><li>N2O 0.47 ( insoluble in blood) </li></ul><ul><li>Halothane 2.4 </li></ul><ul><li>Isoflurane 1.4 </li></ul><ul><li>Desflurane 0.42 </li></ul><ul><li>Sevoflurane 0.65 </li></ul><ul><li>(Factors that speed induction also speed recovery) </li></ul>
  26. 26. <ul><li>MAC – the alveolar conc. of an inhalational anesthetic </li></ul><ul><li>that prevents movement in 50% in response to </li></ul><ul><li>surgical stimulus. </li></ul><ul><li>- a measure of potency </li></ul><ul><li>MAC% </li></ul><ul><li>Nitrous oxide 105 </li></ul><ul><li>Halothane 0.75 </li></ul><ul><li>Isoflurane 1.2 </li></ul><ul><li>Sevoflurane 2.0 </li></ul><ul><li>Desflurane 6.0 </li></ul>
  27. 27. <ul><li>ISOFURANE – dilates coronary arteries ( but less potent than nitroglycerine or adenosine). </li></ul><ul><li>- Can cause (coronary steal syndrome) regional myocardial ischemia) </li></ul><ul><li>DESFLURANE – Low solubility of desflurane in blood and tissues causes a very rapid wash in and wash out of anesthetic. </li></ul><ul><li>SEVOFLURANE – Excellent choice for rapid and smooth inhalational induction. </li></ul><ul><li>( bc of non pungency and rapid increases in alveolar anesthetic conc.) </li></ul>
  28. 28. <ul><li>VOLATILE ANESTHETICS </li></ul><ul><li>Halothane Isoflurane Sevoflurane </li></ul><ul><li>hydrocarbon -----------halogenated ether------------- </li></ul><ul><li>Pleasant ++ -- +_ </li></ul><ul><li>Smell </li></ul><ul><li>MAC 0.75% 1.2% 2% </li></ul><ul><li>HR No change </li></ul><ul><li>arrhythmia minimal </li></ul><ul><li>SVR +_ - - - - </li></ul><ul><li>Contractility - minimal - minimal </li></ul><ul><li>BP - - - - - </li></ul><ul><li>CO +_ or +_ or </li></ul><ul><li>minimal minimal </li></ul>
  29. 29. <ul><li>Halothane Isoflurane Sevoflurane </li></ul><ul><li>Catachol. + + + - - </li></ul><ul><li>sensitisation </li></ul><ul><li>Bronchi Dilatation less less </li></ul><ul><li>Uterus Relaxation less less </li></ul><ul><li>Hepatic Tox. + - - - - </li></ul><ul><li>Renal Tox. -- - + </li></ul>
  30. 30. <ul><li>Neuromuscular Blocking Agents( Ms relaxants) ( no anesthesia, amnesia or analgesia) </li></ul><ul><li>Depolarizing Nondepolarizing </li></ul><ul><li>Acetyl-choline competitive antagonist </li></ul><ul><li>receptor agonist </li></ul><ul><li>Nondepolarizing Muscle relaxants are not significantly metabolized ( except mivacurium metabolized by pseudocholinestrase & atracurium – metabolized by hofmann elimination and ester hydrolysis ) </li></ul><ul><li>Need reversal agents ( Cholinesterase inhibitors) that inhibit acetylecholinesterase enzyme activity. </li></ul>
  31. 31. <ul><li>Muscle Relaxants </li></ul><ul><li>Sux Dtc. Panc. Vecur. Atrac. </li></ul><ul><li>Type Depol ------Non --- Depolarising---------- </li></ul><ul><li>Onset 30 S. ---3-5 min---- --------2-3 min---- </li></ul><ul><li>Dur. V. Short ----Long ----- --intermediate --- </li></ul><ul><li>(3-5 min) ( 30-60min) ( 20-30min) </li></ul><ul><li>Dose 1 0.2-0.4 0.6-0.1 0.05-0.1 0.25-.5 </li></ul><ul><li>( mgkg) </li></ul><ul><li>Hist. Min. +++ - - + </li></ul><ul><li>G.B. - ++ - - - </li></ul><ul><li>Vagal - - + - - </li></ul><ul><li>Block </li></ul>
  32. 32. <ul><li>Sux Dtc. Panc. Vecur. Atrac </li></ul><ul><li>Symp. - - + - - </li></ul><ul><li>HR or +_ +_ </li></ul><ul><li>BP ? +_ +_ +_ </li></ul><ul><li>Elim. Ps. Ch Es. ----kidneyliver- –liver-- Hoff + </li></ul><ul><li>ester </li></ul><ul><li>Notes ; Sux . apnoea, K/ ICL/IOP, Dysrhythmia, </li></ul><ul><li>MH+, Myalgea ( fasciculation) </li></ul>
  33. 33. <ul><li>Reversal Agents </li></ul><ul><li>Cholinesterase inhibitors ( Anticholinesterse) </li></ul>
  34. 34. <ul><li>Characteristics of cholinergic receptors </li></ul><ul><li>Nicotinic Muscarinic </li></ul><ul><li>Location Autonomic Ganglia Glands ( Lacrimal </li></ul><ul><li>Sympathetic & salivary, gastric) </li></ul><ul><li>parasympathetic Smooth muscle </li></ul><ul><li>ganglia (Bronchial, GIT , </li></ul><ul><li>Skeletal muscle bladder, bld vessels ) </li></ul><ul><li>Heart( SA node,AV node ) </li></ul><ul><li>Agonists Acetylcholine Acetylcholine </li></ul><ul><li>Nicotine Muscarine </li></ul><ul><li>Antagonist N D P M relaxants Antimuscarinics </li></ul><ul><li>( Atropine, Scopolamine, </li></ul><ul><li>Glycopyrrolate) </li></ul>
  35. 35. <ul><li>RECOVERY : </li></ul><ul><li>Titrate : Reversal : (Muscle relaxant) </li></ul><ul><li>Atropine + Neostegmine </li></ul><ul><li>opiate : Nalaxone </li></ul><ul><li>Benzodiazepine : flumazinil </li></ul><ul><li>Extubation Airway </li></ul><ul><li>oxygenation </li></ul><ul><li>Consciousness </li></ul>
  36. 36. <ul><li>Pharmacological character of anticholinerg. Dg . </li></ul><ul><li>Atropine Scopolamine Glycopyrrolate </li></ul><ul><li>Tachycardia +++ + ++ </li></ul><ul><li>Bronchodilat. ++ + ++ </li></ul><ul><li>Sedation + +++ 0 </li></ul><ul><li>Antisialagogue ++ +++ +++ </li></ul><ul><li>effect </li></ul>
  37. 37. <ul><li>Post- Operative Care : </li></ul><ul><li>R. Room : A. Airway, recovery position </li></ul><ul><li>B. O2 </li></ul><ul><li>C. CVS : Consciousness </li></ul><ul><li>Analgesia </li></ul>
  38. 38. <ul><li>MONITORING </li></ul><ul><li>COMPLECATION IN THE RECOVERY ROOM </li></ul><ul><li>HYPOTENTION-HYPERTENSION-ARRHYTHMIA </li></ul><ul><li>RESPIRATORY : Airway Obstruction, Hypoxia, </li></ul><ul><li>Hypoventilation </li></ul><ul><li>Delayed recovery </li></ul><ul><li>Pain </li></ul><ul><li>PONV </li></ul>
  39. 39. <ul><li>Complication in recovery room </li></ul><ul><li>CVS : Hypotension – hypertension – arrhythmia </li></ul><ul><li>Respiratory : Airway obstruction, Hypoxia, </li></ul><ul><li>Hypoventilation </li></ul><ul><li>Delayed Recovery </li></ul><ul><li>Pain </li></ul><ul><li>PONV </li></ul>
  40. 40. <ul><li>RECOVERY : </li></ul><ul><li>Stop Anaesthesia </li></ul><ul><li># Titrate : Reversal : MR : Prostig. + Atropine. </li></ul><ul><li>Opioids : naloxone </li></ul><ul><li>A. Extubation Airway </li></ul><ul><li>B. O2 </li></ul><ul><li>C. Consciousness </li></ul>
  41. 41. <ul><li>Thank you </li></ul>

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