Local Anesthetics Flashcards
Rules of the Henderson-Hasselbalch equation (pertaining to this class)
Acid form has a proton that is lacking form the basic form
Either the basic form is negatively charged or the acid form is positively charged
Review how to calculate how much of the basic form there is…
Good job!
What are the 3 structural components of a local anesthetic?
Amine group
Ester or amide linkage
Aromatic group
What is the difference in ester or amide linkage?
Local anesthetics with an ester linkage are hydrolyzed by pseudocholinesterases and have a short plasma half life
Anesthetics with amide linkage are metabolized in the liver and have a longer half life
Esters are more allergenic
Amides have an ‘i’ somewhere in their name prior to “caine”
amides are favored in dentistry
What is the significance of the amine group of local anesthetics?
It will be a 1’, 2’, or 3’ amine (2’ and 3’ are favored in dentistry)
Uncharged form of the amine will help cross cell membranes where they can produce a block
Once inside the cell, the charged form will bind better to the Na channel to block it
So both acid and basic forms are important
T/F - S and R forms of chiral drugs act the same
False - they may have different or similar pharmacokinetic and/or pharmacodynamic properties
They act as different molecules with different receptors and different actions
What is the molecular mechanism of local anesthetics?
They cross the axon membrane and block Na channels in their open and inactive states
Why are both the ionized and nonionized forms of a local anesthetic important?
The form without the proton crosses the membrane
The form with the proton blocks the Na channel
What are the major structures of a peripheral nerve?
Fascicle
Connective tissue coverings
Fascicle
Organized bundle of nerve fibers
What are the connective tissue coverings of a peripheral nerve?
Epineurium
Perineurium
Endoneurium
Epineurium
Outermost layer
Perineurium
Surrounds fascicles
Endoneurium
Surrounds individual nerve fibers
What type of nerve fiber is the most important to local anesthetics?
D fibers
Deal with pain and temperature
Heavily myelinated
Which nerves do local anesthetics inactivate faster?
Nerves that fire APs more frequently
Are A, B, or C fibers more readily disrupted by local anesthetics?
B and C are more readily disrupted than A
What is the relationship between neuron diameter and sensitivity to local anesthetics?
Narrower fibers are more sensitive to local anesthetic than wide
What is the “first on, last off” principle?
The faster a fiber is blocked, the longer it takes to recover
Would etidocaine or bupivacaine be favored for an epidural?
Bupivacaine, because it produces sensory anesthesia at 1/3 the concentration required for motor blockage, but etidocaine shows no selectivity
It provides anesthetic, but maintains uterine muscle contractility
Why is inflammed tissue more difficult to anesthetize?
Products released by cells in inflammed tissue lowers pH, making it more difficult to get sufficient levels of anesthetic in the cell
Why must we balance lipophilicity and hydrophilicity with local anesthetics?
Anesthetic must be sufficiently hydrophilic to diffuse to its site of action
But once at the site, the more lipid-soluble local anesthetic have a longer duration of action
Why is the pKa important for local anesthetics?
The pKa can’t stray too far from the physiological pH, because we need ionized and unionized forms to bind the channel and enter the cell, respectively
What happens to the pH is we add epinephrine to a local anesthetic?
It is lowered to 4-5 to stabilize the epinephrine
The buffering capacity at the injection site should neutralize this
Some might add NaHCO3 to add free base, but this risks precipitating the local anesthetic
What pharmacology/toxicology effects can local anesthetics have on the CNS?
Local anesthetics readily pass from the periphery to the CNS
CNS is very sensitive to local anesthetics - bloodstream concentrations that don’t effect periphery can still effect CNS
What pharmacology/toxicology effects can local anesthetics have on the cardiovascular system?
Direct effects
- block Na channels
- block Ca channels at very high concentrations
- depress pacemaker activity, excitability, and conduction
Indirect effects
-inhibit sympathetic responses: depress contractility and produce hypotension
What local anesthetic can be especially cardiotoxic?
Bupivicaine - binds tighter to Na channels and leaves slower
Which type of local anesthetic are more significantly related to allergic reactions?
Esters (but amides are used in dentistry so who cares)
What pharmacology/toxicology effects can local anesthetics have on vasoconstriction?
Epinephrine can cause vasoconstriciton
What is the benefit of adding epinephrine to local anesthetics?
Better success rate and intensity of the anesthetic
Toxicity of anesthetic is reduced
Less blood loss
What are problems of adding epinephrine to local anesthetics?
Usually no problems unless there’s excess dosing or inadvertent intravascular injection, which lead to cardiovascular side effects
What is the limit for epinephrine injection in one session?
200 ug for a normal patient
40 ug for a compromised patient
T/F - all local anesthetic get absorbed
True
Why is it important to supply a vasoconstrictor (epinephrine) with lidocaine and procaine?
They produce potent vasodilation to be more readily absorbed
How do local anesthetics get distributed?
They bind to plasma proteins, and unbound drugs are free to diffuse into various tissues, including the CNS and placenta
Why is absorption in the liver of local anesthetic important?
Absorption (and metabolism) by the liver are important to keep systemic concentration of amide local anesthetics low
What is the plasma half life of ester local anesthetics?
less than a minute, because they are hydrolyzed by pseudocholinesterases in the plasma and tissues
What is the half life of amide local anesthetics?
1.5-3.5 hours - hydrolyzed in the liver
exceptions are prilocaine and articaine which are metabolized quickly
What are the guiding principles of administering local anesthetics to do so safely?
1) administer the smallest dose that’s effective
2) use proper injection technique
3) use a vasoconstrictor-containing solution unless contraindicated
What do you do if patient has convulsions due to local anesthetic administration?
Treat with benzodiazepine, barbituate, or succinylcholine
What do you do if a patient is in respiratory distress due to local anesthetic administration?
Ventilaiton and oxygen treatment
What do you do if a patient has hypotension due to local anesthetic administration?
Treat with sympathomimetic agents (epinephrine)
What do you do if patient has a dermatological allergic reaction to local anesthetics?
Treat with antihistamines
What do you do if patient goes into anaphylaxis do to local anesthetic allergic reaciton?
Epinephrine
What category of drug is lidocaine and prilocaine?
Category B - safe to use during pregnancy
What category of drug is articaine, mepivacaine, and bupivacaine?
Category C - weight the risks before use during pregnancy
Why are local anesthetics thought to be safe?
Low doses used in dentistry (1/10 dose to what is used in epidural)
Low fatalities
Adverse effects are around 3% - and the “symptoms might reflet anxiety
