Local Anesthetics Flashcards
What are local anesthetics (LA)?
Drugs that reversibly block conduction of electrical impulse along nerve fibers
- removal of drug is followed by spontaneous and complete return of nerve conduction, without evidence of structural damage to nerve fibers
What is the ability of LA to produce reversible blockade of impulses along pathways dependent on?
- physiochemical properties of LA
- anatomy of nerves being blocked
What is the difference in myelinated vs unmyelinated nerves?
- Unmyelinated: lacks fatty myelin sheath, charge can leak, impulse can slow down as it goes
- myelinated: impulse can jump, no electrolyte leaking, IMPULSE SPEEDS UP
- Na+ propagates action potential
How does an action potential work along axons?
Exactly the same way as a muscle cell action potential, with Na+ and Ca++ moving into the cell and K+ moving out, only the resting membrane is -70mv
What factors of nerve fibers influence sensitivity to LA?
Diameter and myelination
SIZE effects susceptibility more than myelination
- smaller= more susceptible than myelin
Do different types of fibers (myellin/demyelinated) send a different type of pain impulse?
Yes
In spinal nerves, sensitivity to LA is:
1st: autonomic nerve fibers
2nd: sensory nerve fibers
3rd: motor nerve fibers
LA mechanism of action?
- reversibly block Na+ Chanel’s
- receptors, located on inside of cell have a greater affinity for charged from of LA
- BUT first must penetrate cell membrane, much easier in uncharged state
How does LA get into cell to work on the receptors?
- LA is given as a weak base
- when injected into the body will stay in same form (body is a weak base too) and diffuse into cell
- once inside the neuron- acidic environment separates LA into ionized and unionized forms
- cation (ionized form) binds with receptor on inside of neuron
All LA have a similar structure of an aromatic ring with an amine group at the very end? What splits LA into 2 groups?
The intermediate group:
- can either be an ester linkage or an amide linkage
- clinically important as it affects metabolism and allergy potential
Which LA are esters?
Procaine
Chloroprocaine
Tetracaine
Cocaine
Which LA are amides?
* If you remove the “caine” their is an “i” in all Am”i”des** Lidocaine Prilociane Levobupivicaine Mepivacaine Bupivacaine Ropivacaine Etidocaine
The onset of action depends on:
- lipid solubility* —> main determinant in amount of LA that is in non-ionized form
- pka is the pH of LA where amount of ionized and non-ionized form of drug are equal
- LA with pka closes to physiologic pH will have HIGHER CONCENTRATIONS of non-ionized form that can readily pass through nerve cell membrane
What is ion trapping and what is it caused by?
Loss of penetration into nerve
- occurs when injecting into an acidic area (ischemia)
- a weak base injected into an acidic environment converts to ionized form and cannot enter cell*
- will not work to control pain
Duration of action:
- correlates with lipid solubility
- higher lipid solubility = longer duration —> less likely to be cleared by blood flow (stored in lipid depot)
- higher lipid soluble are typically highly protein bound
—> adding large chemical radicals to amide results in greater protein binding
Which LA have a duration of 200 + minutes?
Robivicane and bupivicine
- tetracaine duration is 200 minutes
Which LA have a duration of 30-60 or 30-90 minutes?
Lidocaine: 30-60 minutes
Prilocaine: 30-90 minutes
Which LA have duration in the 40 minutes range?
Mepicacaine: 45-90 minutes
Procaine: 40 minutes
Chlorpromazine: 45 minutes
How long until the onset of action in most LA?
5-15 minutes
If you have a 1% solution of lidocaine, what does that mean?
1G/100mL
How are LA distributed?
Unlike most meds, LA are meant to remain in area of injection/application
- the HIGHER the CONCENTRATION of drug that REMAINS AT THE AREA of the nerve, the FASTER the ONSET OF ACTION
- Systemic absorption = offset and termination of drug effect
How do LA leave the area of injection?
If close to blood vessels —> swept away more quickly
Sits in fatty tissue longer
- does not get metabolized in place-needs to dissipate away to be metabolized
What does systemic absorption depend on?
- Blood flow
- specific agent
- highly lipid soluble
- intrinsic vasodilation properties
What does adding vasoconstrictors (epi) to the mix do?
- decreases vascular absorption
- increases nerve cell uptake
- enhances quality of anesthesia
- prolongs duration of action
- limits toxic effects *
Why do you add epi to LA?
All LA, except cocaine, relax vascular smooth muscle—> vasodilation—> systemic absorption
- epi counters the vasodilation - cocaine is the only one that doesn’t dilate—> strong vasoconstrictor (alpha and beta adrenergic stimulator)
Once LA is absorbed systemically, how is it distributed?
Initially to highly perfused organs-> brain, lungs, liver, kidneys, heart
- slower distribution to moderately perfused organs
- muscles and gut (muscles d/t large mass)
How are LAs with ester linkages metabolized?
Mainly by pseudocholinESTERase
- targets “Ester” linkage
- ester hydrolysis is a rapid process
- H2O soluble metabolites are excreted in the urine
- pts with genetically abnormal pseudocholinesterase are at risk for toxic side effects (you won’t know until you give the med)
What enters have metabolites that can cause allergic reactions?
Procaine and Benzocaine
Metabolized to PABA, which causes an allergic reaction
How are amides metabolized?
By CYP 450- liver takes longer than breaking ester linkages
- decreased liver function decreases metabolism—>increases toxicity
- metabolism depends on renal clearance
Which LAs create metabolites that convert to methemoglobin?
Prilocaine and benzocaine
What does methemoglobin do to the body?
Produces a left shift
- brownish gray cyanosis
- tachypnea
- met. Acidosis
- Severs s/s: tissue hypoxia, HA, irritability, LOC *
What is the treatment for methemaglobinemia?
Methylene blue: immediate reversal
Is methemoglobinemia an issue in healthy patients?
No, becomes a problem with anemia or CHF- pts that can’t tolerate decrease in O2 carrying capacity
What does adding opioids, NaHCO3,and epi to LA do?
added to increase safety, quality, intensity, duration, and rate of anesthesia
Toxicity of LA occurs when:
- accidental IV administration
- excessive dose
What will you see in toxicity?
Cardiac and cerebral effects
- famous lidocaine side effects with systemic absorption—> gibberish, tinnitus, confusion, seizures, metallic Tate
- will see HR and BP increase then both will drop
- high death rate if significant toxicity
- combo of bradycardia, heart block, and low BP cause cardiac arrest
What is the treatment for systemic LA toxicity?
Lipid infusion: binds lipophillic med
If you need to give LA and you pt has had an allergic reaction in the past what do you do?
Find out which one and if it’s an amide or ester-> then use one from the other class
What is EMLA?
Mix of lido and prilocaine
Dermal pain receptors, lipophillic
- about 1 hours to onset of analgesia
Can topical anesthetic absorb systemically?
Yes: avoid high blood flow membranes
What is topical cocaine used for?
ENT- excellent in nasal surgery—> Shrinks nasal mucosa
- produces vasoconstriction by blocking norepinephrine and epinephrine uptake int adrenergic nerve endings
What can happen if epinephrine is injected into nasal mucosa prior to cocaine admin?
Toxic effect of epi may occur since cocaine blocks epi reuptake
—>life threatening arrhythmias
