Chemistry and Pharmacodynamics
- Weak bases available as salts
- Basic components of most agents:
- Lipophilic group (e.g., an aromatic ring)
- An intermediate chain
- An ionizable group (e.g., tertiary amines)
- Cocaine: a naturally occurring tropane alkaloid
- Benzocaine: the benzoate ester of para-aminobenzoic acid
Mechanism of action
- Polar compounds are held together by covalent bonds and have distinct regions of positive and negative charges that result from bonding with atoms including nitrogen, oxygen, and sulfur.
- Polar compounds are water soluble.
- Local anesthetics are polar compounds that can acquire nonpolar properties and cross cell membranes.
- Once the nonpolar molecule crosses the cell membrane, it reverts to its polar form and binds to the receptor in the sodium channels.
- Local anesthetics bind to sodium channels and block sodium influx.
- Blocking sodium influx into the cell prevents membrane depolarization and the conduction of painful stimuli.
- Interruption of sodium influx into neuronal membranes prevents the sudden change in membrane voltage that is necessary for signaling.
- Rapid-firing autonomic nerve fibers are most susceptible to local anesthetics.
- Reduction in the sensation of pain without causing a loss of consciousness
- Paralysis (local nerve block)
- Nerve fibers transmitting pain are more sensitive than other fibers that carry sensations such as pressure and proprioception, which may remain partially intact.
- Most local anesthetics are rapidly absorbed into the blood (e.g., lidocaine):
- Often administered with a vasoconstrictor (e.g., epinephrine) to retard the rate of absorption
- Longer-acting agents are less dependent on vasoconstrictors.
- Cocaine is a potent vasoconstrictor owing to its intrinsic sympathomimetic effects:
- Vasoconstriction results in decreased local blood flow.
- Decreased blood flow prolongs the local concentration and effect of the anesthetic.
- Phases of absorption and distribution of local anesthetics are the highest in highly vascularized tissues followed by less vascularized tissues and fat.
- Esters are protein bound to a lesser extent than amides.
- Renal failure increases the accumulation of local anesthetics.
- Esters are rapidly hydrolyzed by pseudocholinesterase to para-aminobenzoic acid.
- Half-life is between 1 and 8 minutes.
- Amide anesthetics undergo a metabolic pathway that involves aromatic hydroxylation, hydrolysis, and dealkylation.
- The half-life of amides is longer than that of esters.
- Excreted by the kidneys
- Amide excretion relies on hepatic metabolism:
- Reduced hepatic blood flow results in the accumulation of metabolites.
- Critical illnesses may reduce blood flow to the liver and result in the accumulation of metabolites.
- Metabolites accumulate in individuals with renal dysfunction.
Pharmacokinetics of commonly used local anesthetics
|Agent||Half-life (adults)||Onset of action||Metabolism||Excretion|
|Cocaine||30 minutes to 1.5 hours||15–30 seconds||Hydrolysis: spontaneous and by plasma pseudocholinesterase; hepatic||Renal|
|Benzocaine||11 h||15–30 seconds||Hydrolysis by plasma cholinesterase; hepatic||Renal|
|Procaine||7–8 minutes||5–10 minutes||Hydrolysis by plasma cholinesterase||Renal|
|Lidocaine||2 hours||45–90 seconds||Hepatic (CYP1A2 and CYP3A4)||Renal|
Classification by structural group
Local anesthetics can be classified into 2 structural groups:
- Aminoamides (amides):
- Metabolized in the liver
- Should be used judiciously in individuals with liver failure
- Aminoesters (esters):
- Often cause allergic reactions
- Metabolized by pseudocholinesterase
Classification by route of administration
Local anesthetics can be classified on the basis of how they are administered.
- Subcutaneous infiltration:
- Ophthalmologic: tetracaine
|Topical agents||Parenteral agents||Intermediate acting||Long acting|
Local anesthetics are chosen because of their onset of action, potency, and duration of action. The choice of a local anesthetic depends on the clinical needs, tolerance of the individual, and physician preference. Local anesthetics are often used in combination with nonsteroidal anti-inflammatory drugs, opioids, and anticonvulsants.
- Used to manage acute pain during or after surgery, trauma, and labor
- Used in the management of chronic pain resulting from medical conditions
- Surgery: Anesthesia is necessary during surgery. Local anesthetics play an important role during surgery and may be used in combination with general anesthetics:
- Dental procedures
- Eye surgery
- Rectal surgery
- Orthopedic surgery
- Dermatologic surgery
- Painful medical procedures that may require the use of local anesthetics:
- Lumbar puncture
- Bone marrow aspiration and biopsy
- Intravenous device placement
Adverse Effects and Contraindications
- Local side effects include edema and skin blanching.
- Nervous system:
- Nerve damage: Temporary or permanent nerve damage is possible.
- Vasovagal episode due to overactivity of the parasympathetic nervous system
- Metallic taste in the mouth
- Changes in sensation: tingling, numbness
- Seizures: mostly associated with the use of bupivacaine
- Respiratory depression
- Hematologic: hematoma
- Atrioventricular (AV) conduction delay
- History of allergies
- Arrhythmia (e.g., Wolff-Parkinson-White syndrome)
- Glucose-6-phosphate-dehydrogenase (G6PD) deficiency
- Septicemia and cerebrospinal disease
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