Anaesthetics

• Anaesthetics


  Blocking or removal of sensation
• Anaesthetics


  • Can be provided locally or generally
• Objective of General Anaesthetics

  • Temporary loss of consciousness and sensation
  • Analgesia
  • Muscle relaxation
• MOA - General Anaesthetics


  • Complexity of anaesthetic state (amnesia, unconsciousness, analgesia & immobility)
  • Multiple organ systems
  • Diverse side effects – cardiac, respiratory
  • Animal models
  • The predominant effect is on synaptic transmission rather than action potential propagation
• Excitatory Synaptic Transmission


  Anaesthetics are thought to block excitatory receptors such as glutamatergic, cholinergic & serotonergic
• Inhibitory Synaptic Transmission


  Generally enhance the function of inhibitory synaptic receptors such as GABA-A receptors & TREK potassium channels
• Premedication


  • Sedate patient
  • Reduction of anxiety and pain providing amnesia for post-operative period
  • Prevention of parasympathomimetic effects of anaesthesia (bradycardia, salivation, bronchial secretion, coughing, vomiting)
• Analgesia


  • Opioids remain the mainstay due to severity of surgical pain
  • Used pre and post operatively
  • Morphine, Fentanyl
  • Post operative side effects including constipation, urinary retention, respiratory depression, nausea & vomiting
• Muscarinic Antagonists


  • Prevent excessive cholinergic effects such as salivation and bronchial secretions
  • Protect the heart from arrhythmias caused by some anaesthetics like halothane (Atropine, Hyoscine)
• Antiemetic Drugs


  Prevent post operative vomiting (Metoclopramide, Prochlorperazine)
• Neuromuscular Blockers


  • Prevention of reflex induced muscle contractions for abdominal/thoracic surgery
  • Tracheal intubation
  • NMBs block synaptic transmission at the neuromuscular junction (nACh receptors)
• Non-Depolarising


  • Act by blocking nACh receptors directly (antagonists)
  • Pancuronium, Vercuronium, Atracuronium
• Depolarising


  • Act as agonists at nACh receptors
  • Initial effects is depolarisation (muscle fasciculation) then nerve block due to its sustained presence (not broken down by AChE) and activation of the receptor
  • Succinylcholine
• Sedative/Hypnotic & Anti-Anxiety Agents

  • Benzodiazepines
  • Most important group
  • Provide anxiolysis sedation, reduction in muscle tone, anterograde amnesia, anticonvulsant effects
  • Midazolam
  • Target GABA-A Receptors
• General Anaesthetics


  • Intravenous Anaesthetics
  • Inhalation Anaesthetics
• Intravenous Anaesthetics


  • Injections
  • Anaesthetics or induction agents
• Inhalation Anaesthetics


  • Gasses or vapours
  • Usually halogenated
• General Anaesthetics - Intravenous


  • Used for induction of anaesthesia
  • Act rapidly (~20-30 seconds)
  • Less traumatic for patients
  • Short duration of action – 10 minutes for each dose – not suitable for long-term maintenance of anaesthesia
• Propofol


  • Most widely used
  • Rapidly distributes to brain so quick onset of action
  • Rapidly metabolised soo in some cases can be used for induction and partial maintenance
  • No need for NMB
  • Less post operative drowsiness, nausea and vomiting
  • Both thiopental and propofol cause respiratory depression of cardiac output
• Etomidate


  • Thought to act on GABA-A receptors containing the beta3 subunit
  • Short acting – rapid induction and recovery
  • Used for induction of general anaesthesia or sedation during minor procedures which do not require general anaesthesia
  • Less cardiovascular and respiratory depression
  • No analgesia so use opioids
  • May cause adrenocortical suppression by inhibiting steroidogenesis
• General Anaesthetic - Inhalational

  • Used for maintenance of anaesthesia
  • Administered in gaseous form
  • No need for metabolism before elimination by lungs – preferred for maintaining anaesthesia
  • Elimination occurs via expired air – rapid decrease of brain and cardiac concentration and reversal of anaesthetic effect
  • Administered at a particular gas or vapour pressure rather than a dose
  • At steady state, gas concentration in lung correlates with brain concentration - monitor end-expiratory gas concentration to monitor brain concentration
• Nitrous Oxide


  • Many advantageous features for anaesthesia - widespread use
  • Rapid in action
  • Is analgesic in sub-anaesthetic doses. 50% mixture with oxygen is used when analgesia is required (e.g. Childbirth)
  • Not potent enough to be used alone so often combined with lower concentrations of other agents
  • Has little effects on cardiac and respiratory system – low side effect profile
• Isoflurane


  • Widely used
  • Produces anaesthesia, analgesia as well as muscle relaxation
  • Binds to GABA, Glutamate receptors. Also affects potassium channels.
  • Causes hypotension due to vasodilatation though less than Halothane
  • Does not sensitize the heart to adrenaline like halothane
  • Muscle relaxation
  • Can irritate mucous membranes
  • Preferred inhalational anaesthetic in obstetrics
• Desflurane


  • Chemically similar to isoflurane
  • Lower potency than isoflurane
  • Recovery from anaesthesia is rapid due to its low solubility
  • Not recommended for induction due to its irritant nature to upper respiratory tract
• Sevoflurane


  • More potent and less respiratory tract irritation than desflurane
  • Rapid acting and more potent than Desflurane
  • Rapid recovery from anesthesia
  • Non-irritant so can be used for induction
  • Has little effect on heart
• Local Anaesthesia


  • Interruption of pain impulses in a specific region of the body without a loss of patient consciousness
  • Completely reversible - the agent does not produce any residual effect on the nerve fiber
• Local Anaesthesia - Mechanism of Action

  • Local anesthetics block nerve conduction by reducing the influx of sodium ions into the nerve cytoplasm
  • Sodium ions cannot flow into the neuron; thus the potassium ions cannot flow out, thereby inhibiting the depolarization of the nerve
  • If this process can be inhibited for just a few Nodes of Ranvier along the way, then nerve impulses generated downstream from the blocked nodes cannot propagate to the ganglion
• Types of Local Anaesthesia

  • Local Infiltration
  • Surface Anaesthesia
  • Topical Block
  • Nerve Block
  • Epidural Anaesthesia
  • Spinal Anaesthesia
• Local Infiltration


  • Nerve endings in the skin and subcutaneous tissues are blocked by direct contact with a local anesthetic
  • Used primarily for surgical procedures involving a small area of tissue (for example, suturing a cut)
  • Lidocaine, Benzocaine, Tetracaine
• Surface Anaesthesia


  • Application of a local anesthetic to skin or mucous membranes
  • Surface anesthesia is used to relieve itching, burning, and surface pain (for example, as seen in minor sunburns)
  • Lidocaine, Benzocaine, Tetracaine
• Topical Block


  • Anesthetic agent applied directly to mucous membrane surface (cornea; respiratory tract; oral mucosa)
  • Used during examination procedures (often in spray form)
  • Lidocaine, Benzocaine, Tetracaine
• Nerve Block


  • Local anesthetic is injected around a nerve that leads to the operative site
  • More concentrated forms of local anesthetic solutions are used for this type of anesthesia
  • Used for surgery or dentistry
  • Lidocaine, Bupivacaine
• Epidural Anaesthesia


  • Accomplished by injecting a local anesthetic into the epidural space
  • The epidural space is above the dura and surrounds the spinal cord
  • Lidocaine, Bupivacaine
• Spinal Anaesthesia


  • Local anesthetic is injected into the subarachnoid space of the spinal cord to act on spinal roots and spinal nerves
  • Acts more quickly than epidural anesthesia
  • Used for surgery to abdomen, pelvis or leg if GA is contra-indicated
  • Mainly lidocaine