General anaesthetic agents

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General anaesthetic agents

  1. 1. General Anesthetic Agents
  2. 2. ANESTHESIA: loss of sensation General Anesthesia : Renders the patient 1.amnesic 2.unconscious while causing muscle relaxation 3.suppression of undesirable reflexes
  3. 3. Anesthesia In the “old days” the following were used for anesthesia. – Alcohol – Ice for numbing – Blow to the head – Strangulation
  4. 4. ADJUNCT AGENTS • Benzodiazepines • Barbiturates • Anticholinergics • Antihistamines • Antiemetics • Muscle relaxants = atracurium,vecorunium,succinylcholine
  5. 5. INTRAVENOUS • BARBITURATES • thiopental,thiamylal,methohexital • BENZODIAZEPINES • Diazepam,lorazepam,midazolam, • ETOMIDATE • OPIODS – fentanyl,morphine
  6. 6. INTRAVENOUS • NEUROLEPTIC – droperidol + fentanyl • KETAMINE • PROPOFOL
  7. 7. Theories of anesthesia • Anesthetic potency is closely correlated with lipid solubility • Postulated interaction with the lipid membrane bilayer. • Interaction with ligand-gated membrane ion channels. • Most anesthetics enhance the activity of inhibitory GABA A-receptors • Many inhibit activation of excitatory receptors, such as glutamate and nicotinic acetylcholine receptors.
  8. 8. Stages of Anesthetic Activity • Stage I - Analgesia – conscious but drowsy. – responses to painful stimuli reduced • Stage II - Excitement – lose consciousness – no longer responds to non-painful stimuli – responds in a reflex fashion to painful stimuli • Stage III - Surgical anesthesia – movement ceases and respiration becomes regular • Stage IV - Medullary paralysis – respiration and vasomotor control cease – death occurs
  9. 9. Properties of Ideal Inhalational Anesthetics • Rapid & pleasant anesthetic induction & recovery • Rapid changes in anesthetic depth • Adequate relaxation of skeletal muscles • Wide margin of safety • Absence of toxic effects or other adverse properties in normal doses
  10. 10. MOA • Increase neuronal threshold for firing leading to a decrease in neuronal activity • Hyperpolarization of neurons via activation of K+ currents
  11. 11. POTENCY –Clinical potency can’t be predicted by chemical structure –Potency correlates w/ lipid solubility • Defined by MAC
  12. 12. • MAC: • -concentration of anesthetic gas needed to eliminate movement among 50% of patients challenged by standardized skin incision
  13. 13. • INVERSE of MAC is an index of potency • *the more lipid soluble, the LOWER the concentration needed to produce anesthesia • The lower the MAC, the more potent is the anesthetic
  14. 14. Highest to lowest MAC • NO • Ether • Enflurane • Isoflurane • halothane
  15. 15. Solubility to blood • Based on blood/gas partition coefficient • Lowest to highest • NO • Isoflurane • Enflurane • halothane
  16. 16. Types of Anesthesia •General • Local
  17. 17. Individual Inhalation Anesthetics Nitrous oxide: – low potency, therefore must be combined with other agents – rapid induction and recovery – good analgesic, WEAK anesthetic properties – risk of bone marrow depression with prolonged administration. – Laughing gas – Can retard O2 uptake during recovery,thus 20% of O2 is always needed
  18. 18. NO • can cause diffusion hypoxia • Least hepatotoxic • safest
  19. 19. HALOTHANE • Prototype • Weak analgesic; POTENT anesthetic • Usually co-administered w/ N2O, opioids, or local anesthetics • Metabolized to tissue-toxic hydrocarbons (trifluroethanol) & bromide ion
  20. 20. HALOTHANE • Disadvantages: • Reduced myocardial contractility & causes hypotension • Arrhythmias
  21. 21. Individual Inhalation Anesthetics • Enflurane: – halogenated anesthetic similar to halothane – less metabolism than halothane; therefore, there is less risk of toxicity – faster induction and recovery than halothane (less accumulation in fat) – some risk of epilepsy-like seizures. Cns excitation – Metabolized to flouride ion,excreted in the kidney
  22. 22. ISOFLURANE • Does NOT induce cardiac arrhythmias and does NOT sensitize the heart to cathecolamines • Stable molecule
  23. 23. ISOFLURANE • Disadvantages: – More pungent odor than halothane – Progressive respiratory depression & hypotension
  24. 24. Individual Inhalation Anesthetics • Desflurane and sevoflurane – similar to isoflurane – have faster onset and recovery – lack of respiratory irritation – commonly used clinically
  25. 25. METHOXYFLURANE • potent, high lipid solubility • Used in child birth • Disadvantages: Metabolized to flouride; Respiratory and circulatory depression
  26. 26. HALOTHANE ENFLURANE ISOFLURANE NITROUS OXIDE ARRHYTHMIA INCREASED SENSITIVITY TO CATHECHOLAMI NES INCREASED SLIGHT INC. CARDIAC OUTPUT DECREASED DEC BUT RECOVERS DECREASED BP DECREASED DEC BUT RECOVERS DECREASED RESPI REFLEX INHIBITED INHIBITED HEPATOTOXICITY HIGH RISK SOME RISK
  27. 27. Intravenous Anesthetics • Thiopental – barbiturate with very high lipid solubility – GABA- mimetic – rapid action because of rapid transfer across blood-brain barrier – short duration (about 5 minutes) because of redistribution, mainly to muscle – Potent anesthetic, weak analgesic effect – Little muscle relaxation – Laryngospasm,not for asthma pt,not w/ porphyria
  28. 28. • Onset: 40 sec • Recovery:30min • Dose: 50mg • Use: induction anesthesia • Toxicity: respi and circulatory depression
  29. 29. Intravenous Anesthetics • Etomidate - potent non barbiturate , hypnotic, no analgesic –similar to thiopental but more quickly metabolized –less risk of cardiovascular depression
  30. 30. may cause involuntary movements during induction possible risk of adrenocortical suppression.  Hypnotic, lacks analgesic
  31. 31. Intravenous Anesthetic Agents • Ketamine – analogue of phencyclidine, w/ similar properties (psychotic reactions) – effect on NMDA-type glutamate receptors – onset of effect is relatively slow (2-5 minutes) – produces “dissociative” anesthesia, in which patient may remain conscious and insensitive to pain – can increase intracranial pressure – Causes cardiovascular stimulation but not respiratory depression
  32. 32. Intravenous Anesthetics • Propofol – rapidly metabolized – very rapid recovery; no cumulative effect – useful for day-case surgery – causes more respiratory and cardiovascular depression than barbiturates – Lowers intracranial pressure
  33. 33. propofol (Diprivan) • Used for maintenance of anesthesia, sedation, or treatment of agitation • Has antiemetic properties – Drowsiness – Respiratory depression – Motor restlessness – Increased blood pressure
  34. 34. fentanyl • Dosage Forms – IV (Sublimaze) – patch (Duragesic) – lozenge (Actiq) for children • Used extensively for open-heart surgery due to lack of cardiac depression
  35. 35. Summary of Intravenous Anesthetics DrugDrug Speed of induction andSpeed of induction and recoveryrecovery Main unwanted effectsMain unwanted effects NotesNotes ThiopentalThiopental Fast (cumulation occurs,Fast (cumulation occurs, giving slow recovery)giving slow recovery) Cardiovascular andCardiovascular and respiratory depressionrespiratory depression Widely used as inductionWidely used as induction agent for routineagent for routine purposespurposes    HangoverHangover       etomidateetomidate Fast onset, fairly fastFast onset, fairly fast recoveryrecovery Excitatory effects duringExcitatory effects during induction and recoveryinduction and recovery Less cardiovascular andLess cardiovascular and respiratory depressionrespiratory depression than with thiopentalthan with thiopental       AdrenocorticalAdrenocortical suppressionsuppression Causes pain at injectionCauses pain at injection sitesite propofolpropofol Fast onset, very fastFast onset, very fast recoveryrecovery Cardiovascular andCardiovascular and respiratory depressionrespiratory depression Rapidly metabolizedRapidly metabolized          Possible to use asPossible to use as continuous infusioncontinuous infusion          Causes pain at injectionCauses pain at injection sitesite KetamineKetamine Slow onset, after-effectsSlow onset, after-effects common during recoverycommon during recovery Psychotomimetic effectsPsychotomimetic effects following recoveryfollowing recovery Produces good analgesiaProduces good analgesia and amnesiaand amnesia       Postoperative nausea,Postoperative nausea, vomiting and salivationvomiting and salivation    MidazolamMidazolam Slower than other agentsSlower than other agents    Little respiratory orLittle respiratory or cardiovascularcardiovascular
  36. 36. Local Anesthesia Relieves pain without altering alertness or mental function.
  37. 37. • . Local anesthesia • - MOA: blocks sodium channels in nerves • - provides analgesia without loss of consciousness
  38. 38. Local Anesthesia Variety of Dosage Forms – Topical – Superficial injection (infiltration) – Nerve block – IV – Epidural – Spinal
  39. 39. • Administration: • Topical, injected into nerves, epidural or subarachnoid space (spinal) • Notes: • Reduced pH, as in inflamed tissues reduces effectiveness (cationic form predominates) • Co-administered with vasoconstrictor epinephrine (1:100,000)
  40. 40. esters • - hydrolyzed by blood esterases; short half-life
  41. 41. esters • Benzoic acid derivatives • P-aminobenzoic acid derivatives
  42. 42. Benzoic Acid Derivatives • Cocaine • Cyclomethicaine • Hexylcaine • Isobucaine • Meprylcaine • Piperocaine
  43. 43. P-aminobenzoic acid Derivatives • Benzocaine • Butacaine • Benoxinate • Propoxycaine • Procaine • Proparacaine • Chlorprocaine • Tetracaine
  44. 44. • 2. Amides • - lidocaine (Xylocaine), mepivacaine (Carbocaine, Mepivastesin), bupivacaine (Marcaine, Sensorcaine, Senpivac), prilocaine (Citanest, Emla), Etidocaine (Duranest), Ropivacaine (Naropin), Levobupivacaine (Sensibloq), Articaine (Ubistesin) • - metabolized in the liver; long half-life • More stable to hydrolysis than esters
  45. 45. • Adverse effects • Cardiovascular depression hypotension • Hepatotoxicity- halothane • Nephrotoxicity- enflurane, methoxyflurane • Malignant hyperthemia (esp. with succinylcholine)- hyperthermia, muscle rigidity (Antidote: dantrolene) • Arrhythmia due to sensitization of heart to cathecholamines

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