Local Anesthetics Flashcards
What does the aromatic ring portion of agent determine?
lipophilic portion–> determines potency
What does the terminal amine portion of agent determine?
hydrophilic portion–> determines onset of action (depends on pKa of agent and tissue pH)
What are the 4 amino ester anesthetic agents?
cocaine, procaine, benzocaine, tetracaine [no ‘i’ before ‘caine’]
What are the 6 amino amide anesthetic agents?
lidocaine, mepivicaine, bupivicaine, prilocaine, ropivicaine, dibucaine [all have >1 ‘i’]
what does a high pKa of agent mean? What can be done to correct?
-high pKa –> lower concentration of unionized (diffusible) form at physiologic pH –> slower onset
alkalinization (i.e. adding bicarb) of infusion to raise tissue pH favors unionized (diffusible) form –> speeds onset
What is the mechanism of action of local anesthetics?
Nonionized form crosses axonal membrane; ionized form (active form) blocks intracellular portion of inactive (refractory) voltage-gated sodium channel –> slows repolarization –> prevents propagation of further APs
What 3 things effect onset of block?
- size of nerve fiber (smaller blocked more quickly)
- degree of myelination (myelinated is quicker since only needs to be blocked at nodes of Ranvier)
- firing frequency (more firing = more inactive channels to block = quicker onset)
How are the 2 subclasses metabolized?
Amino esters –> plasma esterases (widespread and rapid- shorter half life); excreted in urine
Amino amides –> hepatic amidases (need functioning liver); metabolites dependent on renal clearance
Which subclass is more likely to cause allergic reactions? why?
amino esters –> derivatives of para-aminobenzoic acid (PABA)- a known allergen
what is systemic toxicity most likely due to?
accidental intravascular injection (rarely absorption from tissue)
What are some local toxicity side effects of these agents?
Local: transient neurologic symptoms (basically, really bad pain), neuronal injury.
What are some systemic toxicity side effects?
Systemic (more common with long-acting local anesthetics): CNS (early excitation: decreased inhibition, sensory disturbances, restlessness, tremor, tinnitus; later depression: lethargy, hypotension, seizures), cardiovascular (reduced conductivity, excitability, and contractility; arrhythmias (QRS widening an early sign); indirect vasodilation and bradycardia.
