Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
26 Cards in this Set
- Front
- Back
|
2. Identify the core chemical structural entities of most local anesthetics.
|
a. Local anesthetics are either amide-based or ester-based. They all have a common core structure of an aromatic right, a tertiary amine, and an alkyl chain. The difference is the linking bond of the alkyl chain, which can either be an ester linkage or an amide linkage.
|
|
|
3. Distinguish between ester and amide classes of local anesthetics.
|
ester based - rapidly metabolized
short half life amide based - longer half life |
|
|
what are the ester based local aneshetics?
|
i. Procaine, cocaine, tetracaine, chloroprocaine, benzocaine
|
|
|
what are the amide based local andesthetics
|
i. Lidocaine, mepivacaine, bupivacaine, etidocaine, prilocaine, dibucaine, ropivacaine
|
|
|
how are ester based metabolized
|
rapidly metabolized by plasma cholinesterase and thus have very short half-lives.
|
|
|
how are amide based metabolized
|
metabolized in the liver by N-dealkylation and hydrolysis and tend to have longer half-lives. Metabolism is decreased in patients with liver disease or decreased hepatic blood flow.
|
|
|
4. Identify the mechanism of action of all local anesthetics.
|
a. Local anesthetics interact with open sodium channels on the inner surface of the axonal membrane and inhibit neuron conduction.
|
|
|
what is the effect of pKa on local anesthetics
|
a. The pKa is a major determinate of local anesthetic onset. Since local anesthetics exert their effect on the inner surface of the nerve axonal membrane, they must be able to move from the extracellular space to the inside of the axon. Only the non-ionic form of the molecule is able to penetrate the lipid bilayer.
|
|
|
what is the pKa of most local anesthetics?
|
b. The pKa of most local anesthetic agents is usually 7.7-9.0, which is higher than physiologic pH. Based on the Henderson-Hasselbach equation, this means that most of the anesthetic will be in the ionized form at physiologic pH.
|
|
|
6. Determine the general sequence by which local anesthetics affect nerve fibers and modalitites that they conduct.
|
a. In general, smaller nerve fibers are more susceptible than larger, heavily myelinated fibers
|
|
|
7. Identify the effect of most local anesthetics on the vasculature.
|
a. All local anesthetics, with the exception of cocaine, are associated with vasodilation. Vasodilation decreases the duration of action of local anesthetic molecules and prolongs onset time.
|
|
|
8. Identify clinical side effects of local anesthetics.
|
a. Cardiac toxicity: all (except cocaine) are vasodilators and direct myocardial depressants.
c. Tissue toxicity: all local anesthetic molecules at sufficient concentration are directly cytotoxic to nerve cells. |
|
|
i. Bupivacaine and etidocaine are particularly cardiotoxic because
|
they have increased lipid solubility as well as specific binding to the cardiac conduction system.
|
|
|
b. Prilocane is associated with
|
methemoglobinemia. This occurs because prilocaine is associated with oxidation of the ferrous form of hemoglobin to the ferric form, which leads to a blue tinge of the skin. Most of the time this is benign, but it can be treated with methylene blue. The major importance is to correctly identify this when it occurs in infants, rather than attributing the blue color of the infant to hypoxia and treating with oxygen
|
|
|
which drug type is most prone to allergy?
|
d. Allergy: mostly occurs with ester agents; allergy is caused by the preservative methylparaben rather than the anesthetic itself.
|
|
|
what is the most cardiotoxic local anesthtic and thus wouldnt be used in heart disease
|
a. Bupivacaine is the most cardiotoxic, so you wouldn’t want to use this in someone with heart disease.
|
|
|
what is MOA of local anesthetics
|
block Na channels by binding to them only in their cationic form
|
|
|
what happens when these drugs are injected?
|
they ionize and form two forms teh ionised drug and the free base only the free base crosses the membrane and then it ionizes again and the cation is what actualy binds the sodium channel
|
|
|
what is the key structureal difference between the amide and ester based drugs?
|
amide bond= N bound to two C
ester bond = O bound to two C |
|
|
what is the most important property of potency?
|
lipid solubility
|
|
|
what affects duration of conduction block?
|
higher protein binding capcity associated with long duration of action
|
|
|
what are the causes of increases to protein binding capacity
|
major trauma
major surgery tobacco smoking chonic inflammation chronic pain uremia cancer solocal anesthetics last longer |
|
|
what are the causes of decreased protein binding capacity?
|
pregnancy
oral contraceptiv newborn status so local anesthtic last less time |
|
|
what sites would you have to worry about more chance of systemic toxicity?
|
high vascularity of the site
this is mediated by giving vasoconstricters (when possible) |
|
|
what is therapeutic safety index?
|
to little means no effect but to much will kill the nerve.
|
|
|
what is the effect of acitvity on local anesthtics?
|
degree of block preduced by given conc. of local anesthetic depends on how much and how recntly the never has been stimulated bc Na channels open more often and in higher amounts in nerves that are used often.
resting nerves are much less sesitive to affects of the lcoal anesthetics |
