m and m 16 - local anes Flashcards
(72 cards)
What is the ratio of the sodium potassium ATPase
3 Na out for 2 K+ in
What is the composition of the sodium channel?
1 large alpha, 1 or 2 smaller beta
What subunit of the sodium channel do LA’s bind to?
The alpha subunit, prevent sodium influx
LAs have the least affinity for the sodium channel in which of the 3 possible state?
During resting phase. More affinity during the open or inactivated state
What is use-dependent block?
The concept that LA has more affinity for sodium channels that are more frequently depolarized
LAs bind to the sodium channel on the intracellular or extracellular surface?
Intracellular
What are 3 other types of channels that local anesthetics can also bind to?
Calcium channels, K+ channels and TRPV1
Name 5 agents that can non-specifically bind to sodium channels
TCAs (Amytriptyline) Meperidine Volatile anesthetics Calcium channel blockers Ketamine
What agent is able to bind and block the action of sodium channels from the extracellular surface?
tetrodotoxin
When discusses purely A type fibers, what characteristics increase sensitivity to LAs? Larger or smaller diameter?
The smaller the diameter of the A fiber, the more sensitive it is to LA e.g. A-delta is more sensitive than A-alpha
Which is more sensitive to LAs - Small unmyelinated C fibers or large myelinated A fibers?
Large myelinated A fibers are more sensitive, Small unmyelinated C fibers are relatively resistant
In what order does inhibition of nerve function by LA occur i,e. what goes first? Motor, autonomic, sensory
Autonomic -> Sensory -> Motor
What are the functional groups on a typical local anesthetic?
Lipophilic group (Benzene ring) + Hydrophilic group (tertiary amine) separated by ester or amide linkage
At physiological pH, local anesthetic is [weak/strong] [acid/base] with [+ or -] charge on the tertiary amine
Weak base with + charge on amine
What is an easy trick to separate amide vs ester local anesthetics (what letter?)
Amides all have “I” before the “caine”
How does octanol solubility affect LA function? How can you alter octanol solubility of an LA?
The more octanol soluble, the more permeable to lipid membrane an LA is
Increase octanol solubility (an potency) by increasing size of the alkyl group
[Acidic/Basic] conditions antagonize local anesthetic
[hypo/hyper]-kalemia antagonizes local anesthetic
[hyper/hypo] -calcemia antagonizes local anesthetic
Acidic conditions antagonize
Hypokalemia and Hypercalcemia antagonize block
What is pKa?
The pH where the fraction of ionized and non-ionized are equal
Generally speaking - which have faster onset - more potent or less potent LA?
Less potent (and less lipid soluble) will have faster onset of action
Majority of local anesthetics have pKa greater than 7.9. At pH 7.4 are most of the molecules in the ionized or non-ionized form?
Majority in the ionized form
What form of the LA [ionized/non-ionized] binds the sodium channel more avidly? Remember it is the non-ionized that crosses the epineurium
The ionized binds better. The non-ionized crosses then becomes ionized
True / False - onset of action is directly correlated with pKa?
False. This would mean that as pKa increases, onset of action should decrease. The agent with the fastest onset of action - chloroprocaine - has the highest pka of clinically used agents
Epinephrine is unstable In alkaline environments. How does this affect “packaging” of local anesthetics?
LAs that are prepared epinephrine free have higher pH (6-7) vs those that have epinephrine (4-5). Epi free will have faster onset of action (more of the non-ionized form available)
How does infection (in tissues) alter the effectiveness of local anesthetics?
Infected tissues more acidic, slower onset of action of LA in infected tissues
