Local Anesthetics Flashcards
What is the mechanism of action of local anesthetics?
LAs are hydrophilic tertiary animes that function as weak bases. They bind to sodium channels, blocking depolarization-induced influx of Na, thereby blocking propagation of nerve impulses.
What are the two classes of LAs? What drugs are in each class?
LAs have a lipophilic benzene ring linked to an amine group by a hydrocarbon chain of ester or amide linkage.
- Esters: procaine, benzocaine, tetracaine
- Amides: lidocaine, bupivacaine
What are the differences between esters and amide LAs?
Esters:
- are more likely to cause allergic reactions b/c of their cross-reactivity with PABA
- shorter duration of action (typically)
- metabolized by plasma pseudocholinesterases (avoid in pts with deficiency)
Amides:
- allergies rare
- longer duration of action
- metabolized by hepatic microsomal p450 enzymes (via N-dealkylation followed by hydrolysis)
How are LAs prepared?
Formulations as percent solutions, or grams per 100mL of solution, e.g. a 1% lidocaine solution contains 1g of lidocaine in 100mL of solution, or 10mg per mL.
What is the order of nerve fiber blockage by LAs?
Small, unmyelinated are blocked before larger, myelinated fibers:
Sympathetic -> pain and temp -> proprioception -> touch and pressure -> motor
*Block resolution occurs in the reverse order
How do pKa and lipid solubility affect chemical properties of LAs?
pKa determines onset of action. pKa is the pH at which the drug is present in both charged and uncharged forms. Only the uncharged (anionic) form can access the intracellular binding site. LAs with pKa closer to 7.4 will have a higher % of active, anionic molecules and will thus have a quicker onset of action. Exceptions are procaine and chloroprocaine which both have a high pKa but rapid onset of action.
Lipid solubility is directly related to potency.
How do protein binding and dose injected affect chemical properties of LAs?
The higher the degree of protein binding, the longer the LA engages the sodium channel, and thus the longer duration of action.
The higher the dose, the faster the onset of action and the longer the duration of blockade.
How does the site of injection affect the chemical properties of LAs?
The more vascular the site, the higher the peak plasma level of the LA, the higher the potential for toxicity, and the shorter the duration of blockade.
Peak plasma levels from highest to lowest:
- Intravenous -> intercostal -> caudal -> epidural -> UE (brachial plexus) -> LE (sciatic/femoral)
How does addition of sodium bicarbonate affect LAs?
Bicarbonate increases the pH which increases the onset of action by increasing the % of anionic molecules. It may also decrease the pain of injection.
How does addition of epinephrine affect LAs? What other benefit does it have?
Epinephrine causes local vasoconstriction -> less systemic uptake. This leads to:
- Decreased risk of toxicity
- Increased duration of action (for infiltration or peripheral blockade, this is only true for shorter acting LAs like lidocaine and chloroprocaine)
- Analgesic affect by a2-agonism
Epinephrine is useful in test doses b/c gives one the ability to detect intravascular (specifically intraarterial) injection by increasing HR and/or blood pressure by 10-20%. This would mean the needle/catheter would have to be repositioned before injecting the LA.
Is there a downside to using epi in LA solutions?
Epi-containing solutions can NOT be injected into ears, fingers, toes or the penis because of risk of infarction due to the arterial vessels being too constricted.
What are the factors that affect LA onset of action?
Shorter onset of action with:
- higher dose
- lower pKa
- bicarbonate addition
- shorter distance of diffusion to target nerve
What factors affect duration of action of an LA?
Longer duration of action with:
- higher dose
- increased protein binding
- less vascular site of injection (b/c of less systemic uptake)
- higher lipid solubility
- epinephrine (for peripheral blockade and infiltration, epi only increases duration of short-acting LAs)
- pseudocholinesterase deficiency (for esters)
- liver disease (for amides)
Why are opioids, clonidine, and dexmedetomidine used in conjunction with LAs?
All of these increase duration of neuraxial blockade.
Clonidine and Precedex are used in peripheral blocks for the same purpose.
Describe local anesthetic toxicity syndrome (LATS)
Toxicity mainly affects the CNS then the CV system. Progressive signs of LATS are:
- Lightheadedness -> circumoral numbness -> facial tingling -> tinnitus -> slurred speech -> seizures -> unconsciousness -> respiratory arrest -> cardiovascular depression -> cardiac arrest
