Local Anesthetics Flashcards
When LA is injected around a nerve, which fibers are blocked first? How does this manifest clinically?
Fibers on outer surface are blocked first, before more central fibers. This means anesthesia generally occurs first in more proximal areas of an extremity.
With increasing concentration of LA, which types of nerve fibers are blocked? (what order?)
Autonomic > sensory > motor
What does the pKa of a LA say about the ionization of the LA in the body?
The lower the pKa, the more likely the LA exists in an uncharged state.
Why is bicarbonate added to LA solutions?
Bicarbonate increases the unionized fraction of LA and can hasten onset of anesthesia.
Why does LA cause a use-dependent/frequency dependent block?
LA binds better to sodium channels in the active or inactivated-closed state relative to the resting closed state. More depolarization of the nerve leads to better binding.
How do LA block conduction?
Binding to sodium channels and not allowing depolarization of nerves
What state must a LA be in to successfully reach its receptor?
Unionized (to cross lipid membrane)
However, it becomes charged in axoplasm after crossing and this form binds and blocks the ion channel
What are the three structural components of a LA?
Aromatic head (lipophilic)
Linking hydrocarbon chain
Terminal Amine
How are esters and amides structurally different?
In the hydrocarbon chain, ester LAs have ester linkages and amide LAs have amide linkages
What does lipid solubility of a LA correlate with?
More lipid soluble > more potent, longer duration of action, POSSIBLY shorter time to onset
LAs generally vaso_______
Dilate
How are ester LAs metabolized?
Plasma ester hydrolysis
How are amide LAs metabolized?
Liver (hepatic microsomal enzymes)
What does addition of a vasoconstrictor do to LAs?
Limits systemic absorption, prolongs duration of action. Alerts you to intravascular injection. NO effect on onset
What is the toxic dose of lidocaine?
5 mg/kg
7 mg/kg with epi
What is the toxic dose of bupivacaine?
2.5 mg/kg
What are warning signs of intra vascular LA injection?
Circumoral numbness, facial tingling, restlessness, vertigo, tinnitus, slurred speech, tonic-clinic seizures
What are first line /readily available drugs to use for LA induced seizures?
Benzos, propofol
Why do high plasma concentrations of LA cause hypotension?
Relaxation of arterial vascular smooth muscle + direct myocardial depression
How does cardiac toxicity from LA manifest on the EKG?
Prolonged PR interval and widened QRS
Why do LAs cause cardiovascular toxicity?
Binding to cardiac sodium channels
Are allergic reactions to LAs common?
No.
Most will be to esters rather than amide, due to reaction to PABA.
Tetracaine is commonly used for ______ anesthesia and not _______ anesthesia because _________
Used for spinal not epidural because of slow onset, profound motor blockade, and toxicity at high doses
Duration of action of chloroprocaine in epidurals is relatively _______
Short
Why is epidural use of chloroprocaine sometimes avoided? (hint: interferes with…)
Impairs the anesthetic/analgesic action of epidural bupivacaine or opioids used concurrently or sequentially
What is a concern with using lidocaine in a spinal?
Neurotoxicity (cauda equina syndrome)
-or-
Transient neurological symptoms in up to 1/3 of people getting spinal lidocaine - pain and dysethesia (onset 12-24 hours postop not associated with sensory loss, motor weakness, or bowel/bladder dysfunction)
How does mepivacaine compare to lidocaine? (duration, vasoactive property?)
Mepivacaine is similar to lidocaine but with less vasodilation and slightly longer duration of action. Ineffective as topical agent. Still has some risk of TNS in spinals.
Which LAs cause methemoglobinemia?
Prilocaine and benzocaine
Major features of bupivacaine (3)
Long duration of action, great sensory blockade relative to motor blockade, increased risk of cardiac toxicity compared to lidocaine.
Ropivacaine produces ______ vasoconstriction compared to bupivacaine
More
contributes to reduced cardiac toxicity
Why is Ropivacaine said to be safer and more efficacious than bupivacaine?
Less binding of cardiac sodium channels, and better differential blockade of sensory > motor (disputed)
What two LAs are found in EMLA?
Lidocaine and prilocaine
