Local Anesthetics (Exam #1) Flashcards
In what two ways do Esters differ from Amides?
ESTERS have…
- Shorter DOA
- MORE systemic toxicity
How are local anesthetics transported across cell membranes?
- Non-ionized form to cross
- Ionized form to bind intracellularly
What type of base are most local anesthetics, and at physiological pH, what form dominates?
How would this change their activity if the extracellular pH is more acidic? More basic?
LAs = weak bases
- At pH of 7.4, ionized form dominates
- If more ACIDIC environment = ionized dominates, so LESS activity because can’t cross membrane
- If more BASIC environment = non-ionized dominates, so MORE activity because more crosses and then becomes ionized → can bind
What is the exception to the pKa/pH rule for local anesthetics, and what does this mean for its use?
Benzocaine has pKa of 3.5 and NON-ionized dominates
- Topical use only because unable to bind within cell
What is the MOA for all local anesthetics?
Block Na channels
What type of axon are blocks more effective in? How do elevated Ca vs. elevated K affect the block?
Block MORE effective in rapidly firing axons (NOT resting)
- High Ca = block diminished (channels in resting state)
- High K = block enhanced (channels in open/firing state)
How is duration of action determined for local anesthetics?
DOA = time at site of action
Which local anesthetic is SHORT duration of action? Which is INTERMEDIATE? Which three are LONG?
- Short: Procaine
- Intermediate: Lidocaine
- Long: TBR (Tetracaine, Bupivicaine, Ropivicaine)
How are amides metabolized? How are esters metabolized?
- Amides = CYP450s (liver)
- Esters = butyrylchlolinesterases
What is a differential block, and what are two examples of different blocks? What is the order of sensitivity from most to least sensitive?
Differential block: different degrees of sensory and motor blocks
- Bupivacaine = sensory before motor (epidural)
- Etidocaine = motor before sensory (inverse diff. block)
Sympathetic > Sensory > Touch > Motor
What characteristic of fibers makes them MORE sensitive? Which two characteristics make them LESS sensitive?
- More sensitive: smaller diameter
- Less sensitive: myelinated, faster conduction velocity
What AE differs between esters and amides?
Esters are MORE likely to cause hypersensitivity
What local anesthetic has an AE of increased CV toxicity?
Bupivacaine (amide)
What local anesthetic has an AE of methemoglobinemia, and how might this present?
Prilocaine (amide)
- Chocolate colored skin
Is Procaine an ester or amide? What is its DOA, and what is its primary use?
ESTER
- SHORTEST duration of action
Used for diagnostic blocks
Is Tetracaine an ester or amide? What is its DOA, and what does this mean for its use?
What is its primary use?
ESTER
- LONG duration of action = more potent and more AEs
Used for ophthalmology
Is Benzocaine an ester or amide? What is its primary use, and why is this important?
ESTER
Used topically ONLY bc exception to pH rule
Is Cocaine an ester or amide? What is its MOA, and in what two ways might it be used?
ESTER
- Increase DA → block Na channels
Can be used as topical anesthesia or for dental procedures to reduce bleeding
Is Lidocaine an ester or amide? What is its DOA, and what are its two primary uses? What is it NOT used for?
AMIDE
- INTERMEDIATE duration of action
GO-TO: used for infiltration blocks and epidural anesthesia
- NOT spinal blocks
Is Prilocaine an ester or amide?
AMIDE
What is an important note about Prilocaine compared to other amides?
Prilocaine has the highest rate of clearance of all amides = SAFER
Is Bupivacaine an ester or amide? What is its DOA? What is its primary use, and why is this?
AMIDE
- LONG duration of action
Used for epidural blocks in labor/childbirth because more potent SENSORY block than motor
What is the primary AE associated with Bupivacaine? What similar drug can be used as an alternative, and why?
Cardiac toxicity
- Ropivacaine is the enantiomer of Bupivacaine and is LESS lipid soluble/cleared more rapidly than Bupivacaine
What two reasons might Ropivacaine be used?
- Vasoconstriction effects (most other LAs are vasodilating)
- Less cardiac toxicity than Bupivacaine
What drug is associated with an inverse differential block, and what does this mean?
Etidocaine
- Motor nerves acted on before sensory nerves
Which drug is both an amide AND an ester, and what is its primary use?
Articaine
- Used in dental medicine (allows for multiple injections throughout procedure if needed)
What drug can be used to evaluate for butyrylchlinesterase mutations?
Dibucaine
Is Dibucaine an ester or amide? What is its primary use?
AMIDE
- Dibucaine Number Test = butyrylchlinesterase mutations
What is the MOA of Diazepam, and what does this mean? What type of a muscle relaxant is it?
Acts on GABA A rec. → inhibits Cl channels
- Centrally-acting
What is the MOA of Baclofen, and what does this mean? What type of a muscle relaxant is it?
Acts on GABA B rec. → inhibits Ca influx via Gi proteins
- Centrally-acting
What is the MOA of Tizanidine? What type of a muscle relaxant is it?
a2 receptor agonist
- Centrally-acting
What is the MOA of Dantrolene, and what does this mean? What type of a muscle relaxant is it?
Inhibits Ca release → interferes with excitation-contraction coupling (actin/myosin)
- Direct-acting
What is the MOA of Botulinum Toxin? What type of a muscle relaxant is it?
Inhibits ACh release
- Direct-acting
What PK property regulates AEs/toxicity?
Half life
