General and Local Anesthetics

Local Anesthetic (Single Target)

Mode of Action

• Reversible Inhibition of Action Potential
    * Inhibits Depolarization causing relaxation and prevents sodium from entering
• Sodium Channel

Side Effects

• CNS Stimulation
    * Causing Tremor
    * Euphoria

• Seizures (Due to High Dosage)

• Example
    * Ester (RCOOR)
      * Short Acting Local Anesthetic
        * Procaine
          * 1st synthetic local anesthetic
        * Chloroprocaine
          * Addition of a functional group Chlorine

    * Intermediate Acting Local Anesthetic
      * Cocaine
        * 1st natural local anesthetic
        * Inhibits Epinephrine or Alpha 1 causing Vasoconstriction
      * Benzocaine

    * Long Acting
      * Tetracaine

  * Amides (RCO)
    * Intermediate Acting Local Anesthetic
      * Lidocaine
        * Most Widely used Anesthetic
      * Prilocaine
        * Congener of Lidocaine
        * Converted into a metabolite called O-Toludine
          * O-Toludine is carcinogenic that causes Methemoglobinemia, that reduces the oxygen carrying capacity of the blood

      * EMLA = Eutectic Mixture Local Anesthetic
        * Specifically Lidocaine
          * This are mixtures that are given as topical administration
            * This is use for children who are afraid in injections

    * Long Acting Local Anesthetic
      * Bupivacaine
        * Causes Cardiotoxic
          * Causes Arrythmia

      * Levobupivacaine
        * Less Cardiotoxic
        * Use for Epidural Anesthesia
          * Pain and Labor during pregnancy
        * Administered Intrathecaly in the spinal cord
      * Ropivacaine
        * Less potent and High Dose
          * Causing less cardiotoxic effect

General Anesthesia

• Stage 1
    * Induction/Analgesia
      * Removing the pain of the patient
      * The patient is aware or awake
• Stage 2
    * Delirium/Disinhibition
      * Avoid this stage
      * Causes severe depolarization
      * Causes muscle excitation
• Stage 3
    * Surgical Anesthesia
      * No Pain
      * Unconscious
      * Relax
      * No muscle movement
• Stage 4
    * Medullary Depression
      * Avoid this stage
      * Causes Respiratory Depression
        * Patient cant breath
      * Causes Cardiovascular Depression

Goal of Anesthesia

• Unconsiousness
• Analgesia
• Amnesia
• Skeletal muscle relaxation
• Loss of muscle reflexes

Mode of Action of Anesthesia

• Stimulate GABA A-Chloride
• Inhibits Sodium Influx
    * Causing depolarization
• Inhibits Calcium Influx
    * To prevent inducing depolarization or muscle movement

Concepts of Anesthesia

• Minimum Alveolar Concentration
    * Minimum concentration of an inhaled anesthetic at 1atm that prevents skeletal movement
    * Determines the Potency
      * High Minimum Alveolar Concentration
        * Low Potency
          * Nitrous Oxide
      * Low Minimum Alveolar Concentration
        * High Potency
          * Most Potent Halothane

• Blood-Gas Partition Coefficient
    * Solubility of inhalation anesthetics in blood
    * High Blood/Gas Ratio increases the solubility in the blood
      * Causes Slow Onset and Recovery
    * High Blood/Gas Ratio
      * Halothane
        * Most Potent
    * Low Blood/Gas Ratio
      * Desflurane
        * Less Potent

NonHalogenated Drugs

• Nitrous Oxide
    * Produce more analgesia
    * No Cardiovascular and Respiratory Depression
    * For minor surgery and dental surgery

• Adverse Effect
    * Megaloblastic Anemia
      * Deficiency of B12 and B9
    * Causes mild euphoria
      * A feeling of great happiness or well-being

Halogenated Anesthetic (Inhalational Anesthetics)

• Halothane
    * Most Potent
    * High Blood/Gas Ratio
    * Slow Onset and Recovery
    * Sensitize the heart to catecholamines
    * Hepatoxicity
    * Malignant hyperthermia or the fast rise of body
      * Treatment is Danthrolene

• Enflurane and Isoflurane
    * Rapid induction and recovery
    * Less metabolic degradation
    * Produce little arrhythmia
    * Causes more respiratory depression
    * Enflurane is used in Asthmatics
    * Isoflurane is used for Neurosurgery

• Desflurane and Sevoflurane
    * 1st line to be administered
    * Has the most rapid rate of induction and recovery
    * Desuflurane can cause irritation in the respiratory tract
    * Sevoflurane is close to an ideal anesthetic
      * Has pleasant odor
      * Low Blood Solubility
      * Less Arrhythmogenic
        * Causes a strong or irregular heart beat (palpitations), chest pain, or shortness of breath

Parenteral Anesthetics (Intravenous Anesthetics)

• Barbiturates (Activate GABA) (Changes the opening of Chloride) (More chloride causes hyperpolarization)
    * Thiopental
    * Methohexital
• Benzodiazepines (Activate GABA) (Changes the opening of Chloride) (More chloride causes hyperpolarization)
    * Midazolam
• Opioids
    * Fentanyl
      * Fentanyl + Droperidol + Nitrous Oxide
        * For Neuroleptic Anesthesia
• Propofol (Fospropofol)
    * Milk of Amnesia
    * Default induction Anesthetic
• Etomidate
    * Rapid Induction to induce Anesthesia for conscious sedation
    * No Cardiovascular Risk
• Ketamine
    * Avoid
    * Addictive
    * Blocks N-methyl-d-aspartate receptors
      * Receptor for Glutamate
    * Produces Dissociative Anesthesia
      * Causes Psychedelic
        * Dissociate from reality
        * Affects mood and perception

Inhalational Anesthetics