Local Anesthetics Flashcards
What are the 3 structural moieties of local anesthetics?
Lipophilic aromatic moiety - allows penetration of the molecule across the cell membrane
Intermediate alkyl chian - ester or amide
Hydrophilic tertiary amine - undergoes protonation & deprotonation
How does the pK of local anesthetics affect their efficacy?
Local anesthetics are weak bases, pK ~ 7.7-9.0
The higher the pK of the agent (stronger base), the greater a proportion of molecules will be protonated at any given time; thus, stronger base molecules have a slower onset of action
How does pH affect anesthetic efficacy?
Changes in tissue pH (i.e. tissue acidity due to infection) decreases the amount of neutral (membrane-crossing) local anesthetic present, requiring use of an increased dose to achieve anesthesia
What percentage of lidocaine is in the neutral form at physiological pH?
20% neutral
80% cationic
What is the mechanism of action of local anesthetics?
Local anesthetics pass through the cell membrane in the neutral form; within the cell the molecule becomes protonated and binds to AA residues within the Na channel pore, thereby blocking inward Na current and AP propagation
Anesthetic can only block channels in their open state - this is “use dependence”
What is the secondary mechanism of local anesthetic action?
Local anesthetics increase the stability of the inactivated state of the Na channel, prolonging the refractory period of the nerve; this enhances AP blockade because fewer Na+ channels are available to open in response to membrane depolarization
Which neuronal properties correlate with increased sensitivity to local anesthetic?
Small diameter
Absence of myelin
Slow conduction velocity
i.e. local anesthetics preferentially effect pain C fibers
How do physiochemical properties of local anesthetics affect clinical properties?
Lower pKa –> Faster onset
Higher lipid solubility –> greater potency
Greater a1-acid glycoprotein binding in the serum –> longer duration (amides)
How are ester vs. amide LAs terminated?
Esters are hydrolyzed in the plasma by pseudocholinesterase and, to a lesser degree, in the liver
Amides are metabolized solely in the liver (and may be contraindicated in patients with hepatic failure)
Excretion occurs via the kidney
Topical use of LA
Application directly onto skin/cornea/mucous membranes; i.e. tetracaine, lidocaine, cocaine
EMLA Cream
Lidocaine + Prilocaine
Exists as an oil at room temperature; can penetrate intact skin, producing anesthesia up to a depth of 5mm
Infiltration anesthesia
Injection of LA into tissue without consideration of the location of cutaneous nerves
Large doses are needed; potential risk of systemic absorption
Nerve block anesthesia
Injection of LA near a peripheral nerve
Allows anesthesia of larger body regions vs. infiltration anesthesia; lidocaine most commonly used for 2-4 hours procedures and bupivacaine used for longer procedures
IV regional anesthesia
AKA Bier’s Block; blood is squeezed out of a limb and a tourniquet is placed proximally before LA (Lidocaine) is injected via a catheter; limb anesthesia develops within 5-10 minutes
Risk of tourniquet pain, ischemic injury; LA is injected into circulation and so cardiotoxic drugs (Bupivacaine) are contraindicated
Spinal anesthesia
LA injection into the lumbar spinal CSF; anesthesia with ester-linked LAs (i.e. tetracaine) is prolonged because there is little plasma esterase activity in the CSF
Only for surgical procedures of the lower abdomen, perineum, and lower extremities; allows anesthesia of large body regions with low drug plasma levels
