6.3 Local anesthetics and general anesthetics

Local and general anesthetics are crucial in pain management and surgical procedures. Local anesthetics block nerve signals in specific areas, while general anesthetics induce unconsciousness. Both types work by interfering with nerve cell communication, but their effects and applications differ significantly.

Understanding these drugs is essential for safe and effective pain control. Local anesthetics offer targeted relief for minor procedures, while general anesthetics enable complex surgeries. Proper selection and administration of these agents are key to minimizing risks and maximizing patient comfort.

Mechanisms of Action for Local Anesthetics

Sodium Channel Blockade and Molecular Structure

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• Local anesthetics block voltage-gated sodium channels in neuronal membranes preventing action potential generation and propagation in sensory nerve fibers
• Molecular structure consists of three components contributing to lipid solubility and membrane penetration
  • Aromatic ring
  • Intermediate chain
  • Amine group
• Exist in two forms allowing membrane penetration and channel binding
  • Uncharged base form penetrates nerve membranes
  • Charged cationic form binds to sodium channels intracellularly

Physicochemical Properties and Anesthetic Effect

• Onset, duration, and potency influenced by physicochemical properties
  • Lipid solubility affects membrane penetration (higher solubility increases potency)
  • Protein binding impacts duration of action (higher binding prolongs effect)
  • pKa determines speed of onset (lower pKa leads to faster onset)
• Provide reversible regional anesthesia by interrupting pain signal transmission from injury site to central nervous system
• Vasoconstrictors (epinephrine) added to prolong action and reduce systemic absorption
  • Decreases local blood flow
  • Slows drug clearance from injection site

Pharmacological Properties of Local Anesthetics

Classification and Common Agents

• Classified into two groups based on chemical structure
  • Amino esters (procaine, tetracaine)
  • Amino amides (lidocaine, bupivacaine, ropivacaine)
• Commonly used local anesthetics with distinct profiles
  • Lidocaine: fast onset, moderate duration
  • Bupivacaine: slow onset, long duration
  • Ropivacaine: similar to bupivacaine with reduced cardiotoxicity
  • Prilocaine: fast onset, short duration, reduced systemic toxicity

Therapeutic Uses and Administration Techniques

• Used in various medical and dental procedures
  • Minor surgeries (wound closure, biopsies)
  • Dental extractions and root canals
  • Regional nerve blocks for acute and chronic pain management
• Administration techniques
  • Topical application (EMLA cream, lidocaine patches)
  • Infiltration (subcutaneous injection)
  • Nerve blocks (brachial plexus block, femoral nerve block)
  • Neuraxial anesthesia (spinal and epidural)
• Factors influencing choice of anesthetic and technique
  • Desired onset and duration of action
  • Anatomical location of procedure
  • Type of procedure being performed
• Combination with other agents to enhance efficacy
  • Opioids (fentanyl, morphine) for prolonged analgesia
  • Alpha-2 agonists (clonidine, dexmedetomidine) for extended duration

Adverse Effects of Local Anesthetics

Systemic Toxicity and Allergic Reactions

• Systemic toxicity (LAST) characterized by CNS and cardiovascular effects
  • Causes include accidental intravascular injection or overdose
  • Manifests as seizures, arrhythmias, and cardiovascular collapse
  • Treatment involves supportive measures and lipid emulsion therapy
• Allergic reactions range from mild to severe
  • More common with amino ester compounds (procaine, tetracaine)
  • Can present as skin reactions or anaphylaxis
  • Management includes discontinuation and appropriate allergy treatment

Tissue Toxicity and Safety Considerations

• Neurotoxicity and myotoxicity associated with prolonged exposure or high concentrations
  • Can lead to persistent numbness or muscle weakness
  • More likely with long-acting agents (bupivacaine)
• Contraindications for use
  • Patient allergies to specific local anesthetics
  • Infection at the injection site
  • Coagulation disorders for certain regional techniques (epidural anesthesia)
• Safety considerations for administration
  • Proper dosing based on patient factors (age, weight, liver function)
  • Use of test doses to detect intravascular injection
  • Adherence to maximum recommended doses to prevent systemic toxicity

Types of General Anesthetics

Inhalational and Intravenous Agents

• Inhalational agents
  • Volatile liquids: sevoflurane, desflurane, isoflurane
  • Gases: nitrous oxide
  • Primarily enhance inhibitory GABA-A receptor activity and suppress excitatory NMDA receptors
• Intravenous agents
  • Propofol: potentiates GABA-A receptor activity
  • Ketamine: acts as NMDA receptor antagonist
  • Etomidate: enhances GABA-A receptor function
  • Barbiturates (thiopental): potentiate GABA-A receptors and inhibit glutamate receptors

Mechanisms and Effects

• Meyer-Overton hypothesis correlates anesthetic potency with lipid solubility
  • Exceptions exist (e.g., nonimmobilizers)
  • Additional mechanisms contribute to overall anesthetic effect
• General anesthetics produce multiple effects
  • Unconsciousness through actions on thalamocortical and brainstem arousal systems
  • Amnesia by affecting hippocampal function
  • Analgesia via spinal cord and supraspinal mechanisms
  • Immobility through spinal cord actions
• Minimum alveolar concentration (MAC) used to compare potency
  • Defined as the concentration preventing movement in 50% of patients to surgical incision
  • Guides clinical administration and dosing of inhalational agents

Factors Influencing General Anesthetic Selection

Patient and Procedure Considerations

• Patient factors affecting choice and dosing
  • Age: elderly patients require lower doses
  • Weight: obesity affects drug distribution and elimination
  • Comorbidities: liver or kidney disease alters drug metabolism
  • Genetic variations: malignant hyperthermia susceptibility contraindicates volatile anesthetics
• Procedure-related factors
  • Type of surgery: ambulatory vs. major procedures
  • Duration: short-acting vs. long-acting agents
  • Desired speed of induction and recovery

Pharmacokinetics and Perioperative Management

• Pharmacokinetic properties affecting anesthetic profile
  • Distribution: lipid solubility influences onset and offset
  • Metabolism: hepatic clearance affects duration of action
  • Elimination: context-sensitive half-time impacts recovery
• Drug interactions in perioperative setting
  • Opioids: synergistic effects on analgesia and respiratory depression
  • Neuromuscular blocking agents: potentiation of muscle relaxation
• Monitoring for safe anesthetic management
  • Vital signs: blood pressure, heart rate, oxygen saturation
  • Depth of anesthesia: bispectral index (BIS) monitoring
  • End-tidal anesthetic gas concentrations for inhalational agents
• Emergence considerations
  • Residual drug effects: delayed awakening or respiratory depression
  • Airway protection: ensuring return of protective reflexes
  • Prevention of postoperative complications (nausea, vomiting, delirium)