Local Anesthetics Trulearn Flashcards
The …. metabolized by plasma cholinesterase, where … metabolized by liver and eliminated by kidneys
Esters (one i) by plasma
Amids (2 ii) by liver
is it the low pKa or high faster onset of action?
A local anesthetic with a lower pKa will have a greater unionized fraction (and generally faster onset) at physiologic pH (7.4) than a local anesthetic with a higher pKa (greater ionized fraction at physiologic pH and generally slower onset).
Whats the effect on onset when adding bicarbonate to a local anesthetic mixture ?
The addition of bicarbonate to a local anesthetic mixture speeds the onset of action by raising the pH of the anesthetic solution so that more of the unionized fraction is available. Note that bicarbonate should only be mixed just prior to injection as the mixture becomes less stable for storage.
Whats the effect on onset when adding Epinephine to a local anesthetic mixture ?
Epinephrine causes local vasoconstriction, which prolongs the duration of effect of local anesthetics. By decreasing local blood flow, local anesthetic is maintained in the area of injection. Epinephrine solutions must be acidic (pH 2-5) to preserve the epinephrine. The addition of typical amounts of fresh epinephrine to plain local anesthetics (pH ~6) has little effect on the speed of onset of local anesthetics. However, premixed local anesthetic solutions with epinephrine are significantly more acidic (pH 3-4); this drives the local anesthetic to its ionized form, thus potentially slowing speed of onset.
Whats the effect on onset when increasing the concentration of a local anesthetic mixture ?
Local anesthetic concentration also affects the speed of onset. The greater the concentration, the faster the speed of onset since there is a steeper concentration gradient to drive local anesthetics intracellularly. This is how chloroprocaine (pKa 9, which would predict a slow onset) has such a rapid onset: a 3% solution is highly concentrated compared to, for example, 0.25% bupivacaine (pKa 8.1).
What is the effect on local anesthetic when injected into inflamed tissue?
Tissue inflammation slows the onset of effect of local anesthetics. Inflammation leads to a localized acidic environment. This drives more local anesthetic into its ionized form (local pH is farther from local anesthetic pKa), thus decreasing the speed of onset. Additionally, increased blood flow associated with inflammation washes local anesthetics away from their site of action.
The onset of effect of a local anesthetic is affected by ..
- its concentration (higher is faster).
- lipid solubility (higher is faster).
- pKa (lower is faster).
- environment pH (higher is faster).
Anything that increases the concentration or proportion of local anesthetic in its unionized form will speed the onset of analgesia.
While pKa is generally closely related to the onset time of local anesthetics, why 2-chloroprocaine has a very rapid onset despite a high pKa?
This is due to the high concentration of 2-chloroprocaine that can be safely given secondary to its rapid metabolism and low systemic toxicity
lipid solubility determines …
protein binding determines …
pKa determines …
Potency of local anesthetics. (more soluble, higher)
Duration of local anesthetics. (less binding, shorter )
Onset of of local anesthetics. (low pKa, faster onset)
2-chloroprocaine has an onset time of … and duration of action is …
6-12 minutes.
Duration of action is 45-60 minutes plain and 60-90 minutes when mixed with epinephrine (1:200,000 dilution).
Chloroprocaine is hydrolyzed rapidly by plasma cholinesterases (half-life elimination of 21 seconds). However, metabolism is decreased in patients with a pseudocholinesterase deficiency.
What are the first signs of CNS induced lidocaine toxicity
Numbness around the lips and tongue are the first signs/symptoms.
Visual and auditory disturbances (tinnitus) then follow. The clinical scenario then progresses to dizziness/lightheadedness, muscular twitching, unconsciousness, and seizure activity. These clinical signs may then be followed by cerebral edema, increased intracranial pressure, coma, respiratory arrest, and ultimately cardiovascular depression and death. Patients who are premedicated with anticonvulsants, such as benzodiazepines or barbiturates, may have masked CNS symptoms and develop cardiovascular depression before other signs are apparent.
The rate of systemic absorption of local anesthetics is dependent on the blood supply at the site of injection. Areas of regional anesthesia from highest to lowest vascularity include:
intravenous > tracheal > intercostal > caudal/paracervical > epidural > brachial plexus > sciatic/femoral > spinal > subcutaneous.
