Local anesthestics Chapter 14 Flashcards
Describe the how the resting membrane potential is made in a neuron.
The Na+-K+ ATPase couples the transport of 3 Na+ ions out of the cell for every 2 K+ ions into the cell. Because of variation of permeability of K and Na, a relative excess of negatively charged ions accumulates intracellularly and creates a negative resting potential (-70 mV)
Describe the mechanism of how an action potential occurs in a neuron.
There are voltage-gated N and K channels in neurons that depolarize after chemical, mechanical and electrical stimuli. Once the threshold level is reached, voltage-gated Na challenes are activated allowing an influx of Na ions into the cell which results in a reversal of membrane potential to +35 mV (resting is -70 mV).
What are the three states that voltage-gated Na channels exist on a neuron?
Resting, open, inactivated
What is the main mechanism of action of most local anesthestics?
There are 2 subunits of the voltage-gated Na channel on the neurons
1) Alpha- where the Na ions pass
2) Beta- other
The LA bind to the alpha subunit and block it from within and prevent channel activation and depolarization
In addition to blocking Na channels, what are other mechanism of action of local anesthetics?
Block calcium and NMDA receptors to varying degrees
Rank the following in order of greatest to least sensitivity to LA: sensoray, motor, autonomic
Small diameter fibers and lack of myelin enhance sensitivy to LA. Autonomic> sensory> motor
Potency of a local anesthestic is determine by its….?
lipid solubility; higher the solubility the greater the potency
Onset of action of local anesthetics is determined by its…?
pKA- the relative concentration of the nonionzied lipid-soluble form and ionized water soluble form
–less lipid soluble agents have faster onset times
What are the 2 types of local anesthetics? Name a few in each category
Aminoesters- prcaine, chloroprocaine, tetracaine
Aminoamides- lidocaine, bupivacaine, ropivacaine
How are the 2 types of local anesthetics metabolized?
Aminoesters- hydrolysis by pseudocholinesterases in the blood
Aminoamides- biotransformation in the liver
In terms of the ionized and unionized forms of local anesthetics, describe their mechanism of action.
1) The unionized base (B) diffused across the nerve membrane
2) reequilibration of the base (B) and cation form (BH+) in the axoplasm
3) binding of the cation (BH+) to the alpha subunit on the interior side of the Na channel
If a patient has an allergy to “local anesthetics”, which type is it most likely and why?
Most likely ester local anesthetics because procaine and benzocaine are metabolized to PABA
Local anesthetics WITH epi are typically alkaline/acidic?
Without- typically alkaline (pH 6-7), but because epi is unstable in an alkaline environment, with the addition of epi the solutions are made more acidic (pH 4-5) which increases the amount of BH+ form and slows the onset
What factors influence the duration of action of local anesthetics?
The greater the protein binding, the longer the duration of action. Additionally, the duration of action is influenced by the peripheral vascular effects- i.e. lidocaine causes vasodilation which causes increases metabolism and asorption which decreases the duration of action.
Which sites are associated with the greatest degree of systemic vascular absoption of local anesthetics?
IT ICE!
intravenous> tracheal >intercostal> caudal > epidural > brachial plexus > sciatic/femoral
What are 2 syndromes of neurotoxicity that have been described after spinal and epidural anesthesia?
1) transient neurologic symptoms- pain in the lower back, butt, thighs that start 24 hours after spinal and generally resolve within 7 days. Common after lidocaine, very rare with bupivacaine. Lithotomy position is also a risk.
2) Cauda equina syndrome- continuous spinal anesthesia with 5% lidocaine and microcatheter. MOA thought to be high concentration of lidocaine directed towards sacral nerve roots with subsequent toxicity.
Which local anesthetics are associated with methemogloinemia?
1) Prilocaine- metabolized to O-toluidine that can oxidize hemoglobin to methemoglobin
2) Benzocaine
***Treatment: IV methalene blue 1-2 mg/kg
What is EMLA cream?
eutetic (easily melted) mixture of local anesthetics- including 1:1 lidocaine 5% and prilocaine 5%
What effect do local anesthetics have on bronchial smooth muscle?
relaxation
What effect do local anesthetics have on cardiovascular system?
depress myocardial automaticity (spontaneous phase IV depolarization) and decrease the duration of the refractory period
- at high doses it decreases the conduction velocity
- -can result in heart block
What are risk factors for bupivcaine toxicity?
1) pregnancy
2) hypoxemia
3) respiratory acidosis
4) children
Why is bupivicaine more cardiotoxic than lidocaine?
the R (+) isomer of bupivicaine avidly blocks the sodium channels and dissociates very slowly, and because of the high degree of protein binding it makes the resuscitation very difficult
