P5

• Local Anesthetics


  Drugs that produce a reversible loss of sensation in a localized area of the body
• Ideal Local Anesthetics


  • Fast onset of action
  • Longer duration of action
  • Reduced chances of systemic side effects
  • Reduced local tissue irritation
• How local anesthetic works

  1. Reversibly block voltage gated sodium channels

  2. Reversibly block action potential responsible for nerve conduction

  3. Lead to sensory and/or motor paralysis in the innervated area
• Determinants of physiological activities of local anesthetics

  • pH of surrounding tissue
  • Lipid solubility
  • pKa
  • Bond and length of intermediate chain
  • Protein binding
• pH


  Lower pH (acidic) reduces potency as more of the drug is in the ionized state
• Lipid solubility

  Higher lipid solubility increases potency, faster onset, and longer duration
• pKa


  Lower pKa means more unionized fraction present, leading to faster onset
• Intermediate chain length


  Longer chain increases potency
• Protein binding


  Higher protein binding leads to longer duration of effect
• Chemical structure of local anesthetics

  • Aromatic ring (lipophilic group)
  • Intermediate chain (ester or amide)
  • Tertiary amine (ionizable group)

  
• Classification of local anesthetics

  • Amides
  • Esters

  
• Amides


  Metabolized in the liver via CYP450, risk of toxicity in liver disease
• Esters


  Rapidly hydrolyzed in plasma by pseudocholinesterase enzymes, risk of toxicity in pseudocholinesterase deficiency
• Amide local anesthetics


  • Lidocaine
  • Bupivacaine
  • Levobupivacaine
  • Ropivacaine
  • Etidocaine
  • Mepivacaine
  • Prilocaine
• Ester local anesthetics


  • Tetracaine
  • Benzocaine
  • Cocaine
  • Procaine
  • Chloroprocaine

  
• Lidocaine


  Prototypical amide local anesthetic, produces fast, intense anesthesia with intermediate duration
• Bupivacaine


  Widely used, potent, long duration, good sensory and motor block, but cardiotoxic
• Levobupivacaine


  Slightly less potent than bupivacaine, less cardiotoxic, similar duration with less motor blockade
• Tetracaine


  Potent and long-acting ester, used in spinal anesthesia
• Benzocaine


  First synthetic local anesthetic, low potency, slow onset, short duration, metabolized to PABA
• Cocaine


  Ester LA with local vasoconstriction, not used clinically due to toxicity and abuse potential
• Clinical uses of local anesthetics

  Produce loss of sensation without loss of consciousness in a localized area
• Tetracaine


  A potent and long-acting ester
• Benzocaine


  • The first synthetic local anesthetic is an amino-ester
  • It has been supplanted by newer agents, and its use now is confined to infiltration anesthesia and occasionally for diagnostic nerve blocks due to its low potency, slow onset, and short duration of action
  • It is hydrolyzed in vivo to produce para-aminobenzoic acid or PABA, which inhibits the actions of sulfonamides
• Cocaine


  • An ester LA capable of blocking nerve impulses and also the only LA capable of local vasoconstriction due to inhibition of norepinephrine uptake
  • It is NOT used clinically because of its known toxicities and potential for abuse
• Local Anesthetics


  • Loss of sensation without loss of consciousness
  • Avoids physiologic perturbation associated with general anesthesia
  • Neurophysiological response to pain and stress can be modified beneficially
• Applications of Local Anesthetics


  • Topical Anesthesia
  • Infiltration Anesthesia
  • Field Block Anesthesia
  • Nerve Block Anesthesia
  • Spinal or Epidural Anesthesia
• Local Anesthetic Systemic Toxicity (LAST)

  • Cardiovascular toxicity with hypotension mostly except for cocaine, arrhythmias to cardiovascular collapse
  • CNS toxicity with changes in sensorium, diplopia, metallic taste in the mouth, circumpolar numbness, nystagmus, tinnitus, tonic-cloning seizures
  • Hematologic as methemoglobinemia
  • Allergic reaction
• Direct Neurotoxicity


  When the drugs is injected directly or in very close proximity to the spinal cord or neural trunks leading to acute pain, paresthesia, or prolonged sensory and motor block
• Prevention of Toxicity


  1. Use the smallest effective dose required for adequate surgical procedure

  2. Avoid inadvertent intravascular injection or injection in highly perfused highly vascular areas

  3. Premedication with benzodiazepine
• Management of Toxicity


  1. Give oxygen and ventilate the patient

  2. Tracheal intubation may be warranted to facilitate ventilation and prevent pulmonary aspiration

  3. Give anticonvulsant medications such as Thiopental, Midazolam, or Diazepam if convulsion occurs

  4. Lipid emulsion 20%: Definitive treatment for local anesthetic systemic toxicity for both Central Nervous System (CNS) and Cardiovascular System (CVS) toxicity
• Methemoglobinemia


  • O-toluidine (metabolite of prilocaine) converts hemoglobin to methemoglobin
  • Patient is cyanotic with chocolate-colored blood
  • Treatment: Methylene blue OR Ascorbic acid
• Allergic Reaction


  • Rare, but maybe seen with Ester-type LA because some are metabolized to P-amino benzoic acid (PABA: e.g. Procaine or Benzocaine)
  • Amide-type LA are not metabolized to PABA. Allergic reactions are rare.
• Direct Neurotoxicity


  • Manifested as Transient radicular irritation with transient neuropathic symptoms due to pooling of high concentrations of local anesthetic in the cauda equina leading to interference with axonal transport
  • Chloroprocaine and Lidocaine appear to be more neurotoxic than other LA
• LA reversible block voltage-gated Na channels, interrupting propagation of impulse in axons
• LA are of 2 classes: esters and amides

  
• Toxicities involve CNS, CVS, blood. Therefore, prevention and knowledge of resuscitation are imperative