Medical Pharmacology Topics   

Preliminary Outline

Local Anesthetics   Ester          Procaine          Tetracaine          Benzocaine          Cocaine   Amide          Lidocaine          Mepivacaine          Prilocaine          Bupivacaine          Etidocaine

Local Anesthetics

The chemical structure of local anesthetics have three domains: an hydrophobic domain, and intermediate linkage and a hydrophilic domain. The hydrophobic domain is aromatic, and it increases the partition into hydrophobic sodium channels, increasing the potency and duration of action. The intermediate domain can be either and amide or ester linkage. Ester linkages are hydrolyze by plasma esterases and may lead to hypersensitivity reactions. The hydrophilic domain is a tertiary or secondary amine.

Commonly used amide local anesthetics are: lidocaine, mepivacaine, prilocaine, bupivacaine and etidocaine. The latter two have a longer duration of action. An eutectic (?) mixture of lidocaine and prilocaine is available that produce anesthetic action 5 mm into the tissue after topical application.

Commonly used ester local anesthetics are: procaine, tetracaine, benzocaine and cocaine. Procaine has a short duration of action. Cocaine is used topically in eyes, nose and throat procedures because of its vasoconstrictive properties.

Many amide local anesthetics have a high affinity for plasma proteins. They are metabolized by hepatic enzymes, therefore patients with impaired hepatic function may be more susceptible to toxicity. A metabolite of prilocaine can cause methemoglobinemia.

Ester local anesthetics are hydrolyzed by plasma esterase (problems may arise with poor metabolizers). There is little esterase activity in the cerebral spinal fluid, so there is little metabolism after a spinal injection.

Redistribution occurs from site of injection into the systemic circulation. Local aesthetics are often given with the vasoconstrictor epinephrine to decrease the rate of absorption and redistribution, resulting in a prolonged duration of anesthesia and decreased systemic toxicity. Epinephrine should not be used near end arteries to avoid gangrene.

Local anesthetics are more effective in pregnant women. They should not be used in patients with spinal cord injury.

Adverse effects of local anesthetics include:

• CNS
  • stimulation, restlessness, tremor, clonic convulsions
  • stimulation followed by depression, drowsiness, sedation, and eventually respiratory failure
  • euphoria or dysphoria
    
    
• Cardiovascular:
  • decreased electrical excitability, conduction rate and force of contraction
  • vasodilation and decreased vascular tone
  • rarely, low concentrations cause vascular collapse
  • lidocaine used as an antiarrythmic
    
    
• Smooth muscle
  • decreased bowel contraction
  • decreased uterine tone and contractions
    
    
• Neuromuscular junction and autonomic ganglia
  • high concentrations decrease muscle activation
  • central administration decreases sympathetic activity
  • high concentrations block K+ channels
    
    
• Hypersensitivity reactions
  • rare but possible with ester anesthetics
  • dermatitis, asthma attacks, etc.
    

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