Anesthetics Drugs

• General Anesthesia


  Neurophysiological state: unconsciousness, amnesia, analgesia, inhibition of autonomic reflexes, and skeletal muscle relaxation
• Balanced anesthesia care technique


  Use of combination of intravenous and inhaled drugs
• Mechanism of General Anesthetic Action

  Affect neurons at various cellular locations but the primary focus is on the synapse:

  • Pre-synaptic action - alter the release of neurotransmitters
  • Post-synaptic action - change the frequency or amplitude of impulses exiting the synapse
  • Organ level - effect may result from strengthening inhibition or from diminishing excitation within the CNS
• Cl channels and K channels


  Remain the primary inhibitory ion channels considered legitimate candidates for anesthetic action
• Benefits of General Anesthesia

  • Sedation and reduced anxiety
  • Lack of awareness and amnesia
  • Skeletal muscle relaxation
  • Suppression of undesirable reflexes
  • Analgesia
• Components of Balanced Anesthesia


  • Relieve of anxiety: facilitated by Benzodiazepines
  • Sedation: facilitated by Barbiturates
  • Prevention of allergic reactions: facilitated by Anti-histamines
  • Prevention of aspiration of stomach contents and post-surgical N &V: facilitated by Anti-emetics
  • Provide analgesia: facilitated by Opioids
  • Prevent bradycardia and secretion of fluids into respiratory tract: facilitated by Anticholinergic drugs
  • Facilitation of intubation and relaxation: facilitated by Muscle relaxants
• Three Stages of Anesthesia


  1. Induction

  2. Maintenance of Anesthesia

  3. Recovery
• Induction


  Thiopental to produce induction, IV agent like Propofol to produce unconsciousness in 30-40 seconds, additional inhalation or IV drugs may be given to produce desired depth of anesthesia (Rocuronium, Vecuronium or Succinylcholine to facilitate tracheal intubation)
• Maintenance of Anesthesia


  Vital signs and response to stimuli are monitored continuously to balance amount of drug inhaled and/or infused with depth of anesthesia, maintained by the administration of volatile anesthetics (+ Fentanyl for pain), IV infusions of various drugs may be used during this stage
• Recovery


  POST-OPERATIVE: Anesthetic admixture is withdrawn and patient is monitored for return of consciousness, redistribution from the site of action underlies recovery, normal physiological functions (spontaneous respiration, acceptable BP and HR, intact reflexes, and no delayed reactions such as respiratory depression)
• Depth of Anesthesia


  • Stage I - Analgesia
  • Stage II - Excitement
  • Stage III - Surgical Anesthesia
  • Stage IV - Medullary paralysis
• Adjuncts to Anesthetic: Pre-Anesthetic Medications

  • Anticholinergics
  • Anti-emetics
  • Anti-histamines
  • Barbiturates
  • Benzodiazepines
  • Opioids
• Mechanism of Action of General Anesthetics


  Increase the sensitivity of the γ-aminobutyric acid (GABA) receptors to the inhibitory neurotransmitter GABA, Increase in Cl ion influx and hyperpolarization of neurons, Diminished post-synaptic neuronal excitability and CNS activity

  
• Inhaled Anesthetics


  • Used primarily for the maintenance of anesthesia after administration of an IV agent, Changing the inhaled concentration rapidly alters the depth of anesthesia, Very steep dose-response curves and very narrow therapeutic indices, Delivered in a recirculation system containing absorbents that remove CO2 and allow rebreathing of the agent
• Common Features of Inhaled Anesthetics

  • Non-flammable, non-explosive, Decrease cerebrovascular resistance - increased brain perfusion, Cause bronchodilation but also decrease both spontaneous ventilation and hypoxic pulmonary vasoconstriction

  
• Potency of Inhaled Anesthetics


  Minimum alveolar concentration (MAC) is small for potent anesthetics (Sevoflurane) and large for less potent agents (Nitrous oxide), More lipid soluble - lower the concentration needed to produce anesthesia hence higher potency
• Uptake and Distribution of Inhaled Anesthetics

  Alveoli are the "windows to the brain" for inhaled anesthetics, The partial pressure of an anesthetic gas at the origin of respiratory pathway is the driving force moving the anesthetic into the alveolar space and hence into the blood which delivers the drug to the brain and other body compartments, Taken up through gas exchange in the alveoli of the lung
• HALOTHANE


  • Anesthetic of choice due to its rapid induction and quick recovery
• Intravenous Anesthetics


  • Rapid induction often occurring within one "arm-brain circulation time" or the time it takes to travel from the site of injection (usually the arm) to the brain where it has its effect
  • Can be used as sole agents for short procedures or administered as infusions to help maintain anesthesia during longer cases
  • At low doses, used for sedation
• Induction


  • % of drug binds to plasma proteins and the rest are free
  • Drug is carried by venous blood to the right side of the heart through pulmonary circulation and via the left heart into systemic circulation
  • A high proportion of initial drug bolus is delivered to cerebral circulation then passes along a concentration gradient from blood to brain
• Recovery


  • Due to redistribution from sites in the CNS
  • Drug diffuses into other tissues with less blood supply, secondary tissue uptake by the skeletal muscle
  • Plasma concentration of the drug falls, drug diffuses out of the CNS
• Reduced Cardiac Output (CO) to IV anesthetics


  • Low CO, body compensates by diverting more CO to cerebral circulation, greater amount of IV anesthetic enters the cerebral circulation, dose of drug must be reduced
  • Decreased CO, prolonged circulation time, longer time for induction drug to reach the brain and exert its effects
• Local Anesthetics


  • Abolish sensation
  • At higher concentration, motor activity is also abolished
  • No loss of consciousness
  • Delivery techniques: topical, infiltration, peripheral nerve blocks, and neuraxial (spinal, epidural, or caudal) blocks
  • Block nerve conduction of sensory impulses and in higher concentrations, motor impulses from periphery to the CNS
  • Block Na ion channels, prevent transient increase in permeability of nerve membrane for Na that is required for action potential, no transmitted sensation
• Characteristics of Local Anesthetics


  • Esters (Procaine, Chloroprocaine, Tetracaine, Cocaine)
  • Amide (Lidocaine, Bupivacaine, Ropivacaine, Mepivacaine, Prilocaine)
• Local Anesthetic Drugs


  • Procaine
  • Chloroprocaine
  • Tetracaine
  • Lidocaine
  • Mepivacaine
  • Bupivacaine
  • Ropivacaine
• Procaine


  • Low potency
  • Rapid onset
  • Short duration
• Chloroprocaine


  • Low potency
  • Rapid onset
  • Short duration
• Tetracaine


  • High potency
  • Slow onset
  • Long duration (spinal)
• Lidocaine


  • Low potency
  • Rapid onset
  • Intermediate duration
• Mepivacaine


  • Low potency
  • Moderate onset
  • Intermediate duration
• Bupivacaine


  • High potency
  • Slow onset
  • Long duration
• Ropivacaine


  • High potency
  • Moderate onset
  • Long duration
• Goal of Balanced anesthesia care technique

  increase safety of patient, convenience to patients
• Effects of balanced anesthesia

  • relieve anxiety
  • relax muscles
  • prevent secretion of fluids into the respiratory tract
  • rapid induction of anesthesia
  • prevent post surgical nausea and vomiting
• Patient Factors in the selection of Anesthesia

  • Liver and Kidney: release of F, Br, and other metabolic products of halogenated HCs that can affect these organs
  • Respiratory system: for inhalation anesthetics
  • Cardiovascular system: for Halothane (sensitizes the heart to the arrhythmogenic effects of sympathomimetic agents)
  • Nervous system: existence of neurological disorders influences selection of anesthetic
  • Pregnancy: Nitrousoxide (aplastic anemia in unborn child); Benzodiazepines (oral clefts); Diazepam (when used in labor can cause temporary hypotonia-floppy baby syndrome
• Induction [stages of anesthesia]


  essential to avoid Stage II delirium (excitatory phase)
• Maintenace of Anesthesia [stages of anesthesia]


  patient is surgically anesthetized
• Recovery [ stages of anesthesia ] 


  reverse of induction
• Stage 1 [Analgesia]

  • Loss of pain sensation
  • Patient progresses from conscious and conversational to drowsy
  • Amnesia and reduced awareness of pain as stage II is approached
• Stage 2 [excitement]

  • Patient experiences delirium and violent combative behavior; rise and irregularity in BP and respiration along with laryngospasm
  • Note: Thiopental is given to avoid this stage