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Local Anesthetics, Are nonselective voltage-gated sodium channel blockers …

- - - - Measuring MRD (maximum recommended dose)
        
        MRD in mg = MRD mg/kg X weight in kg
        
        MRD in mL = MRD mg ÷ mg/mL
    - - -low BP
        -depress conduction, excitability, and contractility
        -may progress to ventricular arrhythmia and AV block
  - - - Sodium bisulfite an anti-oxidant in LAs containing vasoconstrictors can cause allergic reactions
      - Reactions:
        -Rash
        -angioedema
        -asthma
        -anaphylaxis
  - - - Can cause Methemoglobinemia:
        -LA metabolites (orthotolwidine) bind hemoglobin and reduce O2 circulation
        -Children and patients with G6PD anemia are most susceptible
        
        Signs and Symptoms:
        -cyanosis (nails, lips)
        -fatigue, weakness
        -nausea
        -sedation
        -seizures
  - - - Only use Lidocaine and Prilocaine in the 2nd trimester
        
        Never use Mepivacaine, Articaine, or Bupivacaine during pregnancy
    - - Bupivacaine can cause toxicity to nursing infants
- - - - Signs and Symptoms:
        -edema
        -skin peeling
        -ischemic necrosis
    - - Signs and Symptoms:
        -transient anesthesia or paresthesia (lips, tongue)
        May take 2-6 months in worst cases
  - - - Effects of Lidocaine overdose
        -dizziness, blurred vision, tinnitus, lethargy, abnormal tongue sensation
  - - - No significant effects in normal doses
        
        -fall in BP
        -local vasodilation
  - - - -Healthy adults: MRD = 0.2mg epinephrine, 1.0mg levonordefrin per visit
        -ASA III patients: MRD = 0.04mg epinephrine
- - - - Factors affecting duration of action:
        
        Protonated LAs: dissociate slower
        
        Dose administered
        
        Addition of a vasoconstrictor (slows absorption)
  - - - Only neutral form can cross neuronal membranes, this prevents LAs from working in cases of infection (acidic pH)
      - Low pH (acidic) = more protonated
        Higher pH (basic/alkaline) = more neutral
  - - - High lipid solubility, lower concentration of LA is required
- - - - Higher Vd = higher elimination half-life = longer to eliminate = high toxicity risk
        
        Example: Bupivacaine has a half-life of 5.5 hours, compared to Lidocaine's 2 hours
  - - - Metabolized in liver by cytochrome P450
        -to be more hydrophilic for excretion mainly by kidneys (urine) or some by liver (bile)
        
        Cytochrome P450 can have isoenzymes: CYP34A and CYP1A2
    - - Metabolized by tissue and plasma pseudocholinesterases into (PABA) and other metabolites to be excreted by kidneys
        
        PABA may trigger allergic reactions especially in atopic patients
  - - - Example: Bupivacaine less likely to diffuse due to its high protein binding capacity