Local Anesthesia Flashcards
What is the fundamental difference between local anesthetics and environmental toxins.?
environmental toxins have irreversible effects whereas local anesthetics produce only temporary, and fully reversible, blockade of neuronal activity.
What is the MOA of local anesthetics?
fully reversible neuronal blockade (thought to work on voltage-gated sodium channels involved in the process of neuronal conduction)
Where do local anesthetics function?
nerve axons only
A portion of local anesthetic action is thought to arise from what?
drug is “dissolved” in the neuronal membrane and modulates sodium channel funciton and has surface-charge disruption
Why are action potentials not propogated with administration of local anesthetics?
In the presence of local anesthetic, the critical threshold for spontaneous opening of sodium channels in the immediate vicinity is never reached
True or false: local anesthetics have no effect on the resting membrane potential.
TRUE
List the factors associated with differential blockade.
- Diameter of the nerve bundle (larger diameter nerves require more local anesthetic)
- Position in the nerve bundle (takes longer to impact fibers in the center of the bundle)
- Myelination (“zone of anesthetic” is longer for a myelinated nerve than for a non-myelinated nerve)
- Extent of spontaneous nerve activity (greater blockade in hyperkalemia; less blockade in hypercalcemia)
Which fibers are most affected by local anesthetics?
B- myelinated, larger diameter
C (symp)- nonmyelinated, smallest diameter
C (dorsal root)- nonmyelinated, small diameter
What signals do B and C (symp) fibers carry?
vasomotor, pilomotor, visceromotor
What signals do C (dorsal root) fibers carry?
protopathic
Which fibers are least affected by local anesthetics?
A-alpha
A-beta
myelinated, large
Which signals do A-alpha and A-beta carry?
motor and proprioception
In what states of the Na channel can local anesthetics bind?
activated
inactivated
Why can local anesthetics not bind to the sodium channel in its resting state?
too bulky
In what state of Na channel does the majority of local anesthetic drug binding take place?
inactivated
activated too transient
What is required for passage of a drug across a membrane?
neutral or uncharged state
At what pKa do most local anesthetics act?
8 (weak bases)
What is the pH within nerves?
approximately 7
What is the significance of a pH of 7 inside nerves?
local anesthetics (pKa of 8) get largely ionized and “stuck” within the nerve, which is necessary for sodium channel binding to take place
What happens if extraneural pH changes to 9?
10X more drug (pKa of 8) exists in the neutral state and passes easily across the nerve membrane
What happens if the extraneural pH changes to 7?
10X more drug (pKa of 8) exists in the ionized (charged) form and is trapped in the extraneural state (leads to a less durable nerve block).
What happens if extraneural pH changes to 6 (ex. infalmmation)?
only an extremely low proportion of applied drug can access the nerve and hence the blockade might fail, or at the very least, be extremely weak
Why should you not inject local anesthetic in an inflamed area?
blockade might fail and lead to repeated application until physician has surpassed the maximum recommended dose.
Fibers in the center of a nerve bundle serve what?
distant anatomic locations
Fibers in the outer layers of a nerve bundle serve what?
local anatomic locations
When a local anesthetic is applied, which fibers achieve the most rapid blocking?
fibers in outer layers (get loss of sensation to proximal areas before distal areas)
When a local anesthetic is wearing off, what affect does this have?
outer fibers (to proximal tissues) lose their blocking concentration most rapidly and fibers in the center of the bundle (distal tissues) retain their blocking concentration longest
List the amide type of local anesthetics.
Lidocaine Mepivacaine Prilocaine Bupivacaine Ropivacaine Articaine
(all have “i” before “caine”)
List the ester type of local anesthetics.
Procaine
Chloroprocaine
Tetracaine
Cocaine
(none have “i” before “caine”)
List the local anesthetics for topical use ONLY (too toxic for injection).
Benzocaine
Dibucaine
Dyclonine
Pramoxine
Which local anesthetics are neither amides or esters?
Dyclonine
Pramoxine
Which type of local anesthetic has a thiophene ring and amide located between aromatic and amine?
Amide type
Which type of local anesthetic has an ester group located between aromatic and amine?
Ester type
In which local anesthetic does loss of biological activity occur following ester cleavage (but also has amide bond)?
Articaine
What does a thiopentine ring do to local anesthetics?
gives it lipophilicity
Where does the metabolism of amide local anesthetics occur?
transformed in the liver (eliminated in the urine)
Where does the metabolism of ester local anesthetics occur?
Can be metabolized (hydrolyzed) into any tissue (except for the CSF) by cholinesterases→ urinary elimination
What is the implication for the different metabolisms of amide and ester type local anesthetics?
ester type have a shorter duration of effect
Which local anesthetic is rapidly metabolized to articainic acid (inactive product)?
articaine
Which type of local anesthetic’s metabolism is impacted by: liver disease, pregnancy, chemotherapy, atypical enzyme activity (high accumulation!)
ester type
Which type of local anesthetic’s metabolism is impacted by: CV status, liver disease, toxemia of pregnancy, cimetidine, volatile anesthetics, and Beta-blockers
amide type
Which local anesthetic is good for dental blocks (because it has good penetration into bone)?
articaine
Which topical local anesthetics are administered on mucous membranes (mouth, urethra, etc.)?
benzocaine
dyclonine
Which topical local anesthetics are administered to skin only?
pramoxine
dibucaine
How are systemic toxicities most easily avoided?
remaining below the maximum recommended dose, and by using every effort to avoid inadvertent intravascular injection
Which local anesthetic may lead to ringing in ears, metallic taste, numbness of lips and tongue?
lidocaine (need to stop injection IMMEDIATELY)
True or false: the majority of local anesthetic administered works to produce the neuronal blockade.
FALSE: Only a small portion of applied drug produces neuronal blockade. Some undergoes non-specific binding to non-neuronal tissue, whereas the remainder accesses the vasculature and hence systemic circulation.
What are the systemic toxicities of lidocaine?
CNS excitation (twitching) followed by unconsciousness, coma, respiratory and cardiovascular arrest.
How do you treat local anesthetic-induced seizures?
protect airway
give diazepam
give succinylcholamine if reaction is severe
True or false: true allergic reactions to local anesthetics are rare.
TRUE
Which local anesthetic is broken down to an allergenic product?
procaine (broken down into PABA)
True or false: if a patient is allergic to an amide anesthetic, you should try another amide.
FALSE: you should try an ester
What can be used in patients with allergies to both esters and amides.
Diphenhydramine
What is the most serious consequence in inadvertent systemization of long-acting local anesthetics like bupivacaine?
if they get into the systemic circulation, they will bind to binding to sodium channels in the heart as long as they would those in neuronal sodium channels (and lengthen the CV support necessary to sustain life). Why second generations like ropivacine have been produced.
What local anesthetics produces producing paresthesias at a higher rate than with other local anesthetics?
articaine
What drug can be co-administered with local anesthetics to allow a larger portion of drug to pass down the gradient into the adjacent nerve bundle?
vasoconstricotrs
List the vasoconstrictors used with local anesthetics.
epinephrine, phenylephrine, oxymetazoline, and levonordefrin.
Who gets adverse effects to vasoconstrictors?
young childrenw ith large doses
Epinephrine has DDIs with what drugs?
beta-blockers
TCAs
Halothane
Epinephrine is contraindicated with what conditions?
closed angle glaucome heart failure CHF HTN CV disorders Hyperthyroidism Diabetes
What are the toxicities of vasoconstrictors?
pallor, unrest, sweating, fatigue, palpitations (seem injection anxiety related)
What drug is an alpha adrenergic blocker used as a reversal agent in local anesthesia to facilitate bloodflow in the anesthetized area (produce localized vascular dilation, which increases blood supply, and hastens the removal of local anesthetic), thereby shortening recovery time for neuronal function?
Phentolamine
How many mg/cc is 1% solution?
10 mg/cc
How many ug/cc is 1:100,000 solution?
10 ug/cc
How many ug/cc is 1:10,000 solution?
100 ug/cc
List the short acting local anesthetics.
Procaine (slow onset)
Chloroprocaine (rapid onet)
List the most potent local anestehtics.
Procaine
Mepivacine
List the long acting local anesthetics.
Bupivacine
Ropivacine
Tetracaine
What characteristic of local anesthetics determines potency?
lipid solubility (increased lipid solubility means more potent)
What characteristic of local anesthetics determines speed of onset?
pKa and pH
agents with lower pKa have quicker onset–greater proportion in diffusible state
What characteristic of local anesthetics determines the site and rate of metabolism?
chemical linkage
What characteristic of local anesthetics determines the duration of drug association with the sodium channel receptor?
strength of protein binding
What drugs produce methemoglobinemia?
Prilocaine
Benzocaine (less likely)
What are symptoms of methemoglobinemia?
bluish skin discoloration, headache fatigue, SOB and lack of energy
What is methemoglobinemia?
unusual and unhealthy accumulation of excessive levels (>25%) of the ferric form of hemoglobin that cannot release oxygen to the tissues
What is the antidote for methemoglobinemia?
IV methylene blue
What is EMLA?
eutectic mixture of local anesthetics) is a topical product comprised of lidocaine and prilocaine
What is EMLA used for?
applied and covered with an occlusive dressing for a hour or more to permit anesthetization of surface tissues in advance of cannulation, or skin graft harvesting, etc
HOw long does dermal anesthesia from EMLA last?
Occurs at 1 hr
Reaches max at 2-3 hours
Persists for 1-2 hours after removed
What is LET?
lidocaine, epinephrine, tetracaine OR tetracaine phenylephrine
What is LET used for?
provides analgesia and vasoconstriction (Pediatric emergency rooms to apply to lacerations requiring stitches)
What is lidocaine-oxymetazoline used for?
reduces vascular engorgement while providing analgesia (can be used by otolaryngologists to aid in visualization of engorged nasal passages)
What type of drug administration diffuses across the dura to act on nerve roots and spinal cord and also diffuses to the paravertebral area via the intervertebral foramina to produce multiple paravertebral blocks (fibers exiting cord at that level, NOT on the spinal cord itself)?
epidural drug (or subarachnoid injection)
What is the term for the density of solution when compared with cerebrospinal fluid?
baricity
What characteristic of an in injection lead to higher block?
larger dose
Higher concentration
What characteristics of an increased spead?
Higher volume
Increased solution temperature
When an isobaric solution (mixing local anesthetic with CSF) is injected, where does it go?
stays at the level of the injection
When a hyperbaric solution (mix local anesthetic with dextrose) is injected, where does it go?
migration of the solution downwards relative to gravity (depends upon the positioning of the patient; the solution would try to find its lowest point).
When a hypobaric solution (mix local anesthetic with sterile water) is injected, where does it go?
drug finds the highest point relative to patient orientation
Why are local anesthetics formulated to be acidic?
to aid in pharmaceutical stability
How do you fix the fact that acidic solutions are not as well taken up neuronal membranes?
neutralize or alkalinize with sodium bicarbonate immediately before use
