Local Anesthetics Flashcards
How can you tell amides and esters apart by their names?
Amides: 2 i’s
Esters: 1 i
What is a local anesthetic?
drug that reversibly blocks impulse conduction along nerve axons and other excitable membranes.
Use voltage-gated Na+ channels
What else do local anesthetic bind to, and what is the significance?
Other receptors: Ca, K, AC, NMDA
Not well understood, may be important
What is the perfect anesthetic?
1 Non irritating 2 Transient effect 3 low systemic toxicity 4 quick onset 5 action to span duration of surgery
What is the acid/base character of a local anesthetic?
Weak bases
What forms are needed for the 2 functions of a LA?
- Neutral form to diffuse to site of action
2. Charged form required for activity
What is the ideal pKa for a LA and why?
As close to physiological pH as possible so that ionized is roughly equal to non-ionized
What is the basic structure of a LA?
- Aromatic ring (lipophilic)
- Intermediate chain (ester or amide)
- Ionizable group (often 3 amine)
What is the mechanism of a local anesthetic?
Block Na+ channels in excitable membranes without changing resting potential
Reduce aggregate inward Na+ current
What is the modulated receptor hypothesis?
LA binding is a function of conformational state of the channel:
- higher affinity for activated/inactivated states
- less affinity for receptor in the resting state
What is frequency dependent block?
Fibers that fire at a faster rate are most susceptible to effects of local anesthetics
Repeated depol produces more effective LA binding
What are the 3 important properties of local anesthetics?
- Lipophilicity
- pKa
- Protein binding
How does lipophilicity affect LA action?
Increase lipophilicity: increase potency and duration
Decrease onset of action
How does pKa affect LA action?
Increase pKa, slower onset of action
How does protein binding affect LA action?
Increase protein binding, increase duration
What type of drugs tend to be bound to proteins?
High potency, highly hydrophobic drugs
What are the 3 main uses of local anesthetics?
1 Topical
2 infiltration (subQ)
3 Regional anesthesia and analgesia
How do we use peripheral nerve blocks?
Plexus anesthesia
Individual nerve blocks
IV regional (Bier block)
How do we use neuraxial blocks?
Spinal (low volume): single injection
Epidural/caudal (high volume): single injection or continuous infusion
What is the concept of differential blockade?
Different nerve fibers (A, B, C) vary in their sensitivity to LAs
What studies do we use to look at for differential blockade?
In vivo
What is the order of loss in neuraxial blockade?
- Autonomic/pain fibers
- sensory fibers
- motor fibers
What causes the difference between nerve fiber sensitivities? (2 reasons)
1 Geographic arrangement of nerve fibers
2 Intrinsic sensitivity of nerve fiber types
What is important about PK and LA?
Absorption, distribution and elimination all serve to terminate the clinical effect
