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Dr rowan molnar anaesthetics study guide part iv

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Dr rowan molnar anaesthetics study guide part iv
Identifies (hopefully confirms!) anaesthetic agent being used
Measures inspiratory & expiratory concentrations
Expiratory (alveolar) concentration enables calculation of MAC fraction or multiple – i.e. estimation of anaesthetic depth.
Now mandatory when inhalational anaesthetic agents are used.
Dr Rowan Molnar,
Dr Rowan Molnar Anaesthetics,
Dr Rowan

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Dr rowan molnar anaesthetics study guide part iv

  1. 1. DR ROWAN MOLNAR ANAESTHETICS STUDY GUIDE PART IV Anaesthetic Drugs: Pharmacology, Use & Related Issues
  2. 2. CLASSIFICATION OF DRUGS USED FOR ANAESTHESIA “The Big Five “  Inhalation anaesthetic agents – gasses/vapours  IV anaesthetic agents alias “Hypnotics” or “induction agents”  Narcotic (& other) analgesics  Muscle relaxants – neuromuscular blocking agents  Local anaesthetic agents Other agents are often given as part of anaesthesia – e.g. antiemetics & autonomic agents, but are not conventionally regarded as anaesthetic agents per se.
  3. 3. PHARMACOLOGY 1: INHALATIONAL ANAESTHETIC AGENTS  Inhaled – therefore delivered via apparatus  Gasses or volatile liquids  Moderate to high lipid solubility – “solvents”  Effects related to physical properties (rather than to a generic chemical structure)  Effects on multiple organ systems  Actual mode of action not yet fully elucidated, but thought to be by dissolving into cell membranes & causing secondary changes in configuration of ion channels.
  4. 4. CURRENTLY USED INHALATIONAL ANAESTHETICS (SHOWN IN THEIR INTERNATIONAL COLOUR CODES):  Nitrous oxide (N20)– a gas. Insufficiently potent to produce full anaesthesia on its own, but is rapid acting, pleasant to inhale & is the only currently used agent that is also analgesic.  Sevoflurane  Desflurane all liquids that are flourinated ethers  Isoflurane Earlier volatile agents such as ether, chloroform & halothane have been superceded due to issues such as flammability, slow recovery, & toxicity.
  5. 5. PRACTICAL PHARMACOLOGY OF INHALATIONAL AGENTS  Used for induction sometimes (predominantly in children) & maintenance of anaesthesia in the majority of cases - either alone, or in combination with narcotics & muscle relaxants.  Modern flourinated agents are good hypnotics, & provide a degree of muscle relaxation at high doses, but not analgesia.  In contrast, nitrous oxide is analgesic, but doesn’t decrease muscle tone, and is a poor hypnotic except at very high (i.e. hypoxic) concentrations.  The combination of a volatile agent, e.g. sevoflurane, with a 50:50 nitrous oxide/oxygen mix is a useful combination that combines the attributes of both agents.
  6. 6. PRACTICAL PHARMACOLOGY OF INHALATIONAL AGENTS (2)  Sevoflurane has superceded isoflurane as probably the most widely used agent, & has also superceded halothane as the agent of choice for inhalational induction in children.  All currently used agents have relatively low solubility in blood & tissue – meaning that their partial pressures rise & fall quickly, producing more rapid induction & emergence.  The classical stages of anaesthesia are still seen with modern agents – including the delerium phase – characterised by restlessness & risk of laryngospasm. This stage is usually seen on emergence, or with inhalational inductions in children.
  7. 7. PRACTICAL PHARMACOLOGY OF INHALATIONAL AGENTS (3)  Nitrous oxide, as a gas is delivered by a flowmeter (as are O2 & air – the 3 flowmeters on a typical modern anaesthetic machine). A linkage between the N20 & oxygen flowmeters stops the delivery of any mixture <25%O2. Most anaesthetic machines also only allow delivery of either N20/O2 or air/O2, not all 3 & none allow air/N2O (a hypoxic mixture).  Volatile agents are delivered by vapourisers – devices which add a precise percentage of vapour to the gas mixture. Modern vapourisers are agent specific and colour coded/labelled accordingly. They have numerous mechanisms to ensure accurate delivery, plus safety measures such as “keyed” filling systems that match only the correct bottle; and machines that can have more than one vapouriser fitted must have interlocks that prevent more than one being turned on.
  8. 8. PHARMACOLOGY 2: IV ANAESTHETIC “INDUCTION” AGENTS Used for:  Induction of anaesthesia  Sole agent for brief procedures  By infusion for longer procedures - in place of inhaled agents – i.e. total intravenous anaaesthesia “TIVA”
  9. 9. CLASSIFICATION OF INTRAVENOUS AGENTS Barbiturates – Thiopentone Benzodiazepines – Midazolam Dissociative agents – Ketamine Others- Propofol + Alpha-2 agonists – Dexmetomidine . . . maybe “the next big thing”
  10. 10. GENERAL FEATURES OF IV AGENTS  Lipid soluble  High volume of distribution (Vd)  Initial distribution to VRG  Offset of (initial) effect predominantly by redistribution  More complex when used as infusions (Computerised multicompartment pharmacokinetic modelling required)
  11. 11. PROPOFOL  Most widely used agent now  Rapid(ish) onset & offset  Shorter elimination halftime  Less CVS & respiratory depression  Doesn’t predispose to laryngospasm  ED50 for induction: ~ 2 mg/kg  Suitable kinetics for infusion
  12. 12. OTHER IV AGENTS THIOPENTONE  First widely used agent  Rapid onset & initial offset by redistribution  Long elimination halftime  CVS & resp depressant  Laryngospasmogenic  ED50: ~ 5mg/kg  Still used for RSI “The correct dose of thiopentone is enough” (and no more!!) MIDAZOLAM  Low CVS & resp depressant  Anxiolytic, good initial adjuvant agent, not often used as sole agent KETAMINE  “Dissociative” agent  Phencyclidine derivative  Cardiorespiratory stimulant (in vivo)  Maintains airway reflexes  Analgesic in subanaesthetic doses “The disaster anaesthetic”
  13. 13. TOTAL INTRAVENOUS ANAESTHESIA “TIVA”  Not practical until introduction of propofol , with its short elimination half life, meaning minimal accumulation with infusion.  Usually target controlled infusion using computerised algorithm in syringe pump software. Operator enters patient weight, age, & desired blood level.  Often used in combo with remifentanil & cisatracurium infusions for long cases (these also have good kinetics for use by infusion).
  14. 14. TIVA –GOOD & BAD Advantages  Good for cases of long or uncertain duration  Less effects on CBF & ICP than volatile agents  Less likely to cause PONV then either volatiles or N2O. Disadvantages  Long setup time  More expensive  Multiple syringe pumps required  No direct measure of blood or effect site concentration
  15. 15. PHARMACOLOGY 3: NARCOTIC ANALGESICS & ACUTE PAIN MANAGEMENT A Definition of Pain: “An unpleasant localised sensory experience perceived as actual or potential tissue damage.” May be acute or chronic
  16. 16. CLASSIFICATION OF ANALGESICS Conduction blockade Opiods Paracetamol NSAIDs & COX2s Miscellaneous agents  Complementary/Non pharmacological
  17. 17. AN OPIOD IS A DRUG THAT EXHIBITS AGONIST ACTIVITY AT OPIATE (ENDORPHIN/ENKEPHALIN) RECEPTORS. A CLASSIFICATION OF OPIODS INCLUDES:  Opiates (naturally occuring constituents of opium) & their derivatives: e.g. morphine, codeine, diamorphine (heroin)  Synthetic opiods e.g. pethidine, fentanyl cogeners, oxycodone  Partial agonists e.g. pentazocine “Fortral”, buprenorphine N.B. This classification does not include the narcotic antagonists e.g. naloxone “Narcan” & naltrexone; however these are closely related, being n-allyl substituted derivatives (hence their names)of opiods
  18. 18. PROPERTIES OF OPIODS  Analgesia Spinal ( μ/κ) & supraspinal (μ)  Respiratory depression  Sedation/euphoria (addiction potential)  Emesis  Depression of GI motility  Pruritis  Urinary retention No difference in respiratory depression between equi-analgesic doses of any narcotic agonists } Neuraxial route predominantly
  19. 19. SO THE DIFFERENCES BETWEEN OPIODS ARE LESS IN THEIR ANALGESIC EFFICACY THAN IN:  Onset  Duration  Potency/dose  Histamine release  Autonomic effects  Chest wall rigidity  Effective routes of administration
  20. 20. ROUTES OF ADMINISTRATION OF OPIODS:  Intravenous: (a) Boluses – titrated to effect – e.g recovery pain protocol (b) Infusions – require close monitoring due to potential for overdose as narcotic requirements fall away. (c) PCA – now widely used. Intrinsically safer than infusions, plus positive psychological effect of patient knowing they are in control.  Neuraxial - Epidural or intrathecal (spinal) – usually in combination with regional anaesthesia, but may also be stand alone technique for postoperative analgesia. Risk of late onset respiratory depression if agent migrates into intracranial CSF in significant amount (highest with morphine, but this is also the longest acting)  IM/SC – decreasing importance with availability of PCA & better oral agents, & multimodal therapy.  Oral – variable bioavailability: e.g. oxycodone high, morphine ~ 15% due to first pass metabolism.  Sublingual(buprenorphine) /Intranasal(fentanyl) – lipid soluble agents fairly rapidly absorbed & this route avoids first pass effect (& injection)  Transcutaneous – e.g. fentanyl patches for chronic pain
  21. 21. PROBLEMS WITH OPIODS  Respiratory depression/cough suppression  Tolerance  Abuse/addiction potential  Accountability/access/supply difficulties - consequent to abuse potential.  Nausea & vomiting  Constipation
  22. 22. MULTIMODAL ANALGESIA OPTIONS  Regional/local blockade (if possible)  Paracetamol  NSAID or COX2  Basal opiod (e.g. oxycontin); or tramadol (or both)  prn or PCA opiod  Other Clonidine or ketamine
  23. 23. PHARMACOLOGY 4: NEUROMUSCULAR BLOCKERS  Purely paralysing agents – no analgesic or hypnotic activity.  Two types based on modes of action: Depolarising (Suxamethonium) Versus Nondepolarising (NDNMBs, several available)
  24. 24. WHY USE PARALYSING DRUGS AT ALL?  Permit procedures at a lighter plane of anaesthesia – hence less CVS depression  Intubation & ventilation  Surgery  Permit IPPV without interference  Lower airway pressures by increasing chest wall compliance.  Lower O2 consumption in critical periods

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