1. The document discusses clinical pharmacology of anesthetic drugs used for general anesthesia. It describes the components, practical conduct, monitoring, and tools used for general anesthesia. 2. It discusses various drugs used for premedication, induction, maintenance and recovery from anesthesia including opioids, hypnotics, muscle relaxants, inhalational agents, and reversal agents. 3. The document provides details on the pharmacokinetics, pharmacodynamics and side effect profiles of commonly used anesthetic drugs.

1. Clinical Pharmacology of Anesthetic drugs Dr. Ahsan K. Siddiqui

2. General Anesthesia Definition – Induced, Reversible, controlled, loss of sensation Components : 1. Analgesia 2. Muscle relaxation 3. Amnesia 4. Suppression of excessive autonomic responses

3. Practical Conduct : Pre Anesthetic check up Just preoperative monitoring Induction Maintenance Recovery Post operative Care

4. Monitoring Maintenance Induction Recovery Pre op. Check Post op. Care

5. Anesthesiologist Tools Drugs : Hypnotics, Analgesics, Muscle relaxants & others Gases : Oxygen, Nitrous Oxide Vapors : Halothane, Isoflurane, Sevoflurane Equipments : Anesthetic Machine - Breathing Circuits, Monitors……. Others : iv access, Infusion fluid, Airway equipments……..,…..

6. Premedication Reasons for administration of premedications 1. Reduction of fear and anxiety catecholamine , risks 2. Reduction of saliva secretion 3. Prevention of vagal reflexes (caused by surgical stimulation like squint op., stretching of anal sphincter, or associated with medication e.g., B –blockers 4. As part of anesthetic technique e.g. use of narcotics

7. 5. To produce amnesia - Hyoscine ( Scopolamine) - Benzodiazepines - anterograde amnesia - Diazepam -hyoscine – in 75% pts complete amnesia 6. For specific therapeutic effects - Transdermal glyceryl nitrate patches for angina pts, - Steroids - B – blockers (anterograde amnesia- inability to form new memories, Impairment of memory for events occurring after the onset of amnesia)

8. Drugs : 1. Anxiolysis\ Amnesia: BNZ, Hyosc., Antihist. (H1 Blochers) 2. Analgesia: Opiates 3. Adjuvant to GA : BNZ & Ketamine 4. Anti-emetic : Metoclopramide, Antihist. 5. Antacids : H2 blockers, Antihist., Na Citrate

9. 6. Antihist. : Promethazine,Diphinhydramine 7. Antivagal \ Antisialagogues: Atrop, Hyos.,AntiH 8. Antitromb. / Anticoag.: Heparin, Stockings 9. Antibiotics: Infective Endocarditis Prophylaxis 10: Attention to pre-existing medications: Continue: unless otherwise Stop : MAOI, Contraceptive pills Change : Insulin, oral hypogly., Steroids

10. Common Premadications Drug Dose Route Timing Diazepam 5-15 mg oral 1-2 hr Lorazepam 1-3 mg oral preop. Morphine 5-15 mg IM Hyoscine 0.2-0.4 mg IM 1hr pre Pathedine 50-100mg IM preop Promethazine 12.5-25mg IM Midazolam 2.5-5 mg IM

11. Children Drug Dose Route Timing Diazepam Syrup 0.2mg\kg oral 1 hr Medazolam 70-100 mcg\kg IM preop Promethazine 2-5yr 10-20mg oral 1hr preop 5-10 yr 20-25 mg 1\2dose for IM Morphine 0.1-0.2mg\kg IM Hyoscine 5mcg\kg IM

12. Side effect of premadications : Delayed recovery and interaction of Specific drugs

13. Opioids Act on opioid receptors located through out CNS Identified as mu - mu1 & mu2 keppa (k) delta (d) sigma Most effective as producing analgesia They provide some degree of sedation

14. IV opiates Drugs Dose Onset Duration Morphine 0.1-0.2mg\kg slowest long Pathedine 1-2 mg\kg slow long Fentanyl 1-2mcg\kg rapid short Alfentanil 10-20mcg\kg v. rapid v. short Sufentanil 0.2-0.4mcg\kg rapid short

15. Induction Check: pt \ machine\ Monitors Monitoring: Basic Monitoring: Anesthetics, clinical, Air way EKG,NIBP,SpO2, Capnography Add.: PNS\Temp.\ CVP Agent for induction : IV vs. Inhalational Analgesia: Opiates

16. IV Induction Agents The ideal intrav. Agent reliably and pleasantly induces full anesthesia within one arm-brain circulation time - is free of side effects - completely wears off in a few minutes - it must be capable of infusion to maintain anesthesia without problems.

17. I.V. anesthetic agents may be used for 1. Induction of anesthesia 2. As a sole agent for operation (TIVA) 3. To supplement volatile anesthesia or regional anesthesia 4. For sedation

18. IV Induction Agents Propofol – - Mechanism of action – facilitation of inhibitory neurotransmission mediate by GABA - Not water soluble 1% solution aqueous solution is available for IV use as an oil-in-water emulsion containing - soybean oil - egg lecithin - glycerol

19. Only for IV administration Rapid on set ( one arm brain circulation time) 1\2 life 2-8 min. ( recovery rapid, no hangover) V. high clearance rate( 10 time that of thiopentone) Conjugation in liver results in inactive metabolites Excretion – in urine Can be used in Chr. Renal F, hepatic ds.

20. Thiopent. Propofol Ketamine barbiturate phenol phencyclidine Pain - - + - - Phleb. Less more less Rapid onset ++ +++ + BP decrease decrease increase Analgesia -- -- + Bronch ppt Asthma -- + Mech. GABA GABA Desociat. of act.

21. Recovery Hang over clean headed Emerg. Delir. PONV + - Antiemetic + antipruritic Duration 10 min 10 min < 10min Route iv i.v i.v \ i.m Thiopent. Propofol Ketamine Commul. ++ - -

22. Life Support During Induction A. Airway : Support: manual \ Atrif. Airway B. O2 FM + circuit +- An. Agent Chest expansion\ bag \ monitor C. Circulatory Support D. Definitive Airway : Guedel`s Airway Laryngeal Mask Airway ETT MR + Circuit + IPPV

23. MAINTENANCE Anesthesia ( Tetrad) : Unconsciousness : Inhal. Vs TIVA Analgesia : N2O + Opioids / LA Relaxation : M.R. Autonomic : Pares. : Anticholin. : Symp. : GA Opioids CVS drugs

24. Inhalational Anesthetics The greater the uptake of anesthetic agent, the greater the difference b \ w the inspired and alveolar conc. And slower the rate of induction. Three factors affect anesthetic uptake 1. Solubility in the blood 2. Alveolar blood flow 3. partial pressure difference b\w alveolar gas and venous blood.

25. The relative solubility's of an anesthetic in air, blood, and tissues are expressed as Partition Coefficients Partition Coefficients N2O 0.47 ( insoluble in blood) Halothane 2.4 Isoflurane 1.4 Desflurane 0.42 Sevoflurane 0.65 (Factors that speed induction also speed recovery)

26. MAC – the alveolar conc. of an inhalational anesthetic that prevents movement in 50% in response to surgical stimulus. - a measure of potency MAC% Nitrous oxide 105 Halothane 0.75 Isoflurane 1.2 Sevoflurane 2.0 Desflurane 6.0

27. ISOFURANE – dilates coronary arteries ( but less potent than nitroglycerine or adenosine). - Can cause (coronary steal syndrome) regional myocardial ischemia) DESFLURANE – Low solubility of desflurane in blood and tissues causes a very rapid wash in and wash out of anesthetic. SEVOFLURANE – Excellent choice for rapid and smooth inhalational induction. ( b\c of non pungency and rapid increases in alveolar anesthetic conc.)

28. VOLATILE ANESTHETICS Halothane Isoflurane Sevoflurane hydrocarbon -----------halogenated ether------------- Pleasant ++ -- +_ Smell MAC 0.75% 1.2% 2% HR No change arrhythmia minimal SVR +_ - - - - Contractility - minimal - minimal BP - - - - - CO +_ or +_ or minimal minimal

29. Halothane Isoflurane Sevoflurane Catachol. + + + - - sensitisation Bronchi Dilatation less less Uterus Relaxation less less Hepatic Tox. + - - - - Renal Tox. -- - +

30. Neuromuscular Blocking Agents( Ms relaxants) ( no anesthesia, amnesia or analgesia) Depolarizing Nondepolarizing Acetyl-choline competitive antagonist receptor agonist Nondepolarizing Muscle relaxants are not significantly metabolized ( except mivacurium metabolized by pseudocholinestrase & atracurium – metabolized by hofmann elimination and ester hydrolysis ) Need reversal agents ( Cholinesterase inhibitors) that inhibit acetylecholinesterase enzyme activity.

31. Muscle Relaxants Sux Dtc. Panc. Vecur. Atrac. Type Depol ------Non --- Depolarising---------- Onset 30 S. ---3-5 min---- --------2-3 min---- Dur. V. Short ----Long ----- --intermediate --- (3-5 min) ( 30-60min) ( 20-30min) Dose 1 0.2-0.4 0.6-0.1 0.05-0.1 0.25-.5 ( mg\kg) Hist. Min. +++ - - + G.B. - ++ - - - Vagal - - + - - Block

32. Sux Dtc. Panc. Vecur. Atrac Symp. - - + - - HR or +_ +_ BP ? +_ +_ +_ Elim. Ps. Ch Es. ----kidney\liver- –liver-- Hoff + ester Notes ; Sux . apnoea, K/ ICL/IOP, Dysrhythmia, MH+, Myalgea ( fasciculation)

33. Reversal Agents Cholinesterase inhibitors ( Anticholinesterse)

34. Characteristics of cholinergic receptors Nicotinic Muscarinic Location Autonomic Ganglia Glands ( Lacrimal Sympathetic & salivary, gastric) parasympathetic Smooth muscle ganglia (Bronchial, GIT , Skeletal muscle bladder, bld vessels ) Heart( SA node,AV node ) Agonists Acetylcholine Acetylcholine Nicotine Muscarine Antagonist N D P M relaxants Antimuscarinics ( Atropine, Scopolamine, Glycopyrrolate)

35. RECOVERY : Titrate : Reversal : (Muscle relaxant) Atropine + Neostegmine opiate : Nalaxone Benzodiazepine : flumazinil Extubation \ Airway oxygenation Consciousness

36. Pharmacological character of anticholinerg. Dg . Atropine Scopolamine Glycopyrrolate Tachycardia +++ + ++ Bronchodilat. ++ + ++ Sedation + +++ 0 Antisialagogue ++ +++ +++ effect

37. Post- Operative Care : R. Room : A. Airway, recovery position B. O2 C. CVS : Consciousness Analgesia

38. MONITORING COMPLECATION IN THE RECOVERY ROOM HYPOTENTION-HYPERTENSION-ARRHYTHMIA RESPIRATORY : Airway Obstruction, Hypoxia, Hypoventilation Delayed recovery Pain PONV

39. Complication in recovery room CVS : Hypotension – hypertension – arrhythmia Respiratory : Airway obstruction, Hypoxia, Hypoventilation Delayed Recovery Pain PONV

40. RECOVERY : Stop Anaesthesia # Titrate : Reversal : MR : Prostig. + Atropine. Opioids : naloxone A. Extubation \ Airway B. O2 C. Consciousness

41. Thank you