Local Anesthetics Flashcards
Local anesthetics produce _____ of impulses along the central and peripheral nerve pathways
reversible conduction blockade
1st Local Anesthetic
1st Synthetic Local (Ester)
1st Amide Local
1st Local Anesthetic Cocaine 1884
1st Synthetic Local (Ester) Procaine 1905
1s Amide Local Lidocaine 1943
Chemical structure:
Lipophilic and hydrophilic portion separated by
hydrocarbon
In the chemical structure, the lipophilic portion is the….
What is it necessary for?
Benzene Ring
Necessary for activity
What is the chemical structure for esters and amides
ester C-O-C
amide NH-C
Where does ion trapping happen?
within the cell
What is the pH extracellulary?
What is the pH intercellular?
extracellular 7.4
intracellular 7.0
What are the S and R enantiomers?
S = LEFT (Sinister) R = RIGHT (Rectus)
Racemic mixtures have what type enantiomer?
BOTH
Pure Isomers only have 1 enantiomer, which enantiomer? and which LAs?
Ropivacaine and Levobupivacaine (ONLY 2!)
Both are S enantiomers
What is the benefit of S enantiomers?
Less cardio and neurotoxic
“this is why we give ropi in kids”
What is the MOA for LAs?
Inhibit Na+ ions passage through ion-selective Na+ channels
What does the inhibition of Na ions do?
Slows rate of depolarization
Threshold potential not reached
No action potential propogated
What does the inhibition of Na ions NOT alter
Resting membrane potential
Threshold potential
Local anesthetics bind to the (alpha or beta) subunits of the voltage gated sodium channel
Alpha (there are 2 alpha subunits in the Nm receptor)
When can LAs bind?
in the active and inactive states (CANNOT bind during the resting phase)
(the more frequently the nerve is depolarized, the voltage gated Na channel opens - the more time for LA binding to occur)
Nerves with more activity have faster blockade!
Where does the LA bind to on the alpha subunit?
internal (this is a weak binding)
What are other sites of action for LAs?
Voltage-dependent potassium ion channels
(Much lower affinity)
Calcium ion currents (L-type)
G protein-coupled receptors
What is minimum concentration (Cm)?
minimum concentration to produce conduction blockade
Analogous to MAC
What are factors that increase or decrease (Cm)
Increases: larger diameter
Decreases: higher frequency, higher pH
T/F: the Cm for motor is twice the amount for sensory
True (Possible explanation for sensory block with no motor)
How many Nodes of Ranvier must be blocked?
2, preferably 3
What is the order of blockade?
B Fibers (preganglionic sympathetic efferent) C Fibers A delta (post ganglionic, afferent) A gamma A beta A alpha
Which nerves are unmylinated?
C fibers
Which nerves travel faster?
mylinated
What is the function of A alpha fibers
motor, proprioception
What is the function of A beta fibers
touch, pressure
What is the function of A gamma fibers
muscle tone
What is the function of A delta fibers
Pain (fast), cold temp, touch
What is the function of B fibers
Preganglionic (efferent), autonomic
What is the function of C fibers
Postganglionic (afferent)
Pain (slow), warm temp, touch
What is the order of a differential blockade?
ATP-TP-MVP
Autonomic Temperature Pain Touch Pressure Motor Vibration Proprioception
What is a differential blockade?
Blockade of some fibers but not others
May block, B fibers, C fibers, and small and medium A fibers
May not block Large A fibers
You may have a sympathectomy from a differential block. What is a sympathectomy?
Loss of sensation for pain, and temp
May still have proprioception and motor
LAs are _____, with a pKa of ____, and pH values of ____
weak bases
- 6-8.9
- 9-6.5
Acid+base =
more ionized
What form does the LA need to be to in order to cross the lipid bylayer
un-ionized
Do LA with pka nearest to physiologic pH have a faster or slower onset?
FASTER
All LAs are weak bases with one exception, which is:
What is the pka?
Benzocaine
pKa – 3.5
Does not ionize based on pH
What is the MOA of benzocaine?
unknown
Lidocaine pka is 7.9, when placed in an environment with a pH of 7.9, what does this mean?
What happens in a ph of 7.6, 7.4, 7.2
50% ionized, 50% unionized
As you decrease pH, it becomes more and more ionized (REMEMBER, its the un-ionized portion that crosses lipid bilayer)
What happenes when you inject lidocaine into a septic patient?
there will be more ionized portion of the drug and be less effective
What does adding bicarb to LA do?
Higher pH is closer to pKa of about 8
More un-ionized to cross
Faster onset by 3-5 minutes
Also higher pH thought to lessen sting of local infiltration
How are LA’s distributed?
1st large uptake to lungs 2nd distribution to high perfused tissue (heart, brain, kidneys) 3rd distribution to low perfused tissue (muscle and fat)
Are esters or amides are widely distributed?
Amides
What is placental transfer influenced by?
Which drugs are highly protein bound?
Influenced by protein binding
(proteins too large to cross)
Bupivacaine and Ropivacaine highly bound
Lidocaine not as much
Explain fetal ion trapping
Once un-ionized local crosses placenta and hits low fetal pH more drug is ionized and can’t cross back
Build up of trapped local in fetal circulation leads to toxicity in fetus
What is potency related to?
Lipid solubility
More lipid soluble means easier to cross lipid by-layer
What is onset related to?
State of Ionization – most important
Lipid Solubility
What is duration of action related to?
Protein Binding
Lipid Solubility
How are amides metabolized?
Mainly HEPATIC metabolism
Minimal renal excretion of unchanged drug
What are the fast, intermediate, slow amides with regard to metabolism and clearance
Fastest
- Prilocaine
Intermediate
- Lidocaine and Mepivicaine
Slow
- Etidocaine, Bupivacaine, Ropivacaine
How are esters metabolized?
Rapid hydrolysis
- Cholinesterases (pseudocholinesterase)
- Mostly plasma, lesser liver
What are the rapid, intermediate, slow esters with regards to metabolism and clearance?
Rapid
- Chloroprocaine
Intermediate
- Procaine
Slow
- Tetracaine (tetracaine is longest acting ester)
For esters, what is the one exception to hydrolysis?
Cocaine - significant metabolism by the liver
What is PABA and what can happen?
Metabolites of esters mostly inactive Paraaminobenzoic acid (PABA)
PABA - allergic
What common local injection site contains little to no cholinesterase enzyme?
CSF
Must wait until drug goes into systemic circulation for hydrolysis
In what states are plasma cholinesterase (pseudocholinesterase) inhibited in?
Deficiency Liver disease Increased BUN Parturients Chemotherapy patients
What can be added to LAs for vasoconstriction?
Epinephrine, phenylephrine, norepinephrine
epi superior
What is the epi dose?
1:200,000
or 5mcg/ml
What do the vasoconstrictions do?
Limits systemic absorption Maintains drug concentration around nerves Can prolong Lidocaine by 1/3 No effect to onset Helps to decrease toxicity
Which 2 local anesthetics have no vasodilator activity?
Cocaine
Ropivacaine
(also Lidocaine according to Nagelhout)
(Chloroprocaine according to APEX)
What is the risk of adding opioids to spinals and epidural LAs
Risk for respiratory depression and oxygen desaturation
Clonidine: Is a preservative free \_\_\_\_\_ Enhances \_\_\_\_\_\_ anesthesia When used in combination with opioids is \_\_\_ Epidural dose: Spinal dose:
alpha 2 agonist Neuraxial Additive Epidural 150 mcg or 2mcg/kg Spinal 15-45 mcg (PROLONGS block)
(APEX - increases analgesia properties via alpha 2 agonism)
What is the pH of 2% lido?
What is the pH of 2% lido with epi?
- 5
4. 5 with epi
What benefit does mixing locals have?
Combos
Faster onset
Longer Duration
Lido/Bupivicaine
Cholorprocaine/Bupivicaine
Mixing locals has what type of effect?
additive and not synergistic!!
T/F: allergic reactions to LAs are common?
FALSE
Rare - <1% allergic reaction
Most are adverse responses to excess plasma concentration
Allergic reaction to preservative free amides is so low its not even reportable
Esters are more likely to cause allergic reaction d/t?
PABA
What is the other thing that make people allergic to LAs
the preservative (Methylparaben)
Is there a cross sensitivity to LAs?
NOOO
After LA injection you notice hypotension with syncope or tachycardia, what probably happened?
Likely IV injection
What is LA toxicity dependent on?
Dependent of total amount of drug
NOT volume or Concentration
Ex.
40mL of 1% or 80mL of 0.5%
Both 400 mg
Lidocaine Max dose: Max dose with epi: Plain mg/kg: With epi mg/kg:
Max dose: 300
Max dose with epi: 500
Plain mg/kg: 4.5
With epi mg/kg: 7
Ropiviciaine: Max dose: Max dose with epi: Plain mg/kg: With epi mg/kg:
Max dose: 200
Max dose with epi: (not listed)
Plain mg/kg: 2.5
With epi mg/kg: 2.5
Bupiviaine: Max dose: Max dose with epi: Plain mg/kg: With epi mg/kg:
Max dose: 175
Max dose with epi: 225
Plain mg/kg: 2.5
With epi mg/kg: 3
What is the progression of plasma levels and CNS effects?
Vertigo Tinnitus Ominous feelings Circumoral numbness Garrulousness Tremors Myoclonic jerks Convulsions Coma Cardiovascular collapse
What is the blood flow of LA to tissues (fastest to slowest)
IV Tracheal Intercostal Caudal Paracervical Epidural Brachial Plexus Subarachnoid Subcutaneous (In time I can please everyone but Suzi and Sally)
What is transient neurologic symptoms (TNS)?
Moderate to severe pain
Lower back, buttocks, and posterior thighs
What is TNS most common with?
Highest risk after intrathecal lidocaine
What is cuada equine syndrome
Diffuse injury across lumbosacral plexus
- Various degrees of sensory anesthesia
- Bowel and bladder sphincter dysfunction
- Paraplegia
What are big red flags to doing a caudal block?
Sacral dimple and hairy nevi
What is anterior spinal artery syndrome
Lower extremity paresis and variable sensory deficit
Cardiotoxicity is more or less resistant than CNS
more
Why can you see profound hypotension with cardiotoxicity?
Relaxation of arteriolar vascular smooth muscle
Direct myocardial Depression
In what anesthetic might you see cardiotoxicity BEFORE CNS effects?
Bupivacaine
Order of CV toxicity according to APEX
Bupi > Levobupiva > Ropiva > Lidocaine
What is the initial treatment of LAST?
Airway management
- 100% O2
Seizure suppression
- Benzodiazepines
- AVOID propofol if cardiovascular instability
- Alert for possible cardiopulmonary bypass
What is the next treatment for LAST?
Management of arrhythmias
- BLS and ACLS
- AVOID vasopressin, calcium channel blockers, betablockers, or local anesthetic
- REDUCE epi to <1 mcg/kg
Explain Lipid Emulsion Therapy (20%) for LAST
- 5 mL/kg (lean body mass) IV over 1 minute
- 25 mL/kg/min
Repeat Bolus once or twice for persistant cardiovascular collapse
Double infusion rate to 0.5 mL/kg/min if BP remains low
Continue infusion for at least 10 min after circulatory stability
Upper limit: Approximately 10 mL/kg lipid emulsion over first 30 minutes
Methamoglobinemia is related to which LAs?
Prilocaine >8 mg/kg, Benzocaine, Cetacaine, Lidocaine
Also Nitroglycerin, Phenytoin, and Sulfonamides
What is the treatment of methamoglobinemia?
Methylene Blue 1-2mg/kg IV over 5 minutes
Do not exceed 7.8 mg/kg
What are the low potency/short duration LAs?
Procaine
Chloroprocaine
What are the intermediate potency/duration LAs?
Lidocaine
What are the long acting/long duration LAs?
Bupivacaine, Ropivacaine, Tetracaine
What are the Fast Onset LAs?
Cloroprocaine & Lidocaine
What are the slow onset LAs?
Bupicacaine, Ropivacaine, Tetracaine, Procaine
- the further away the pKa from physiologic (pH 7.4) the slower the onset
Bupivacaine 8.1
Ropivacaine 8.1
Tetracaine 8.5
Procaine 8.9
Factors that increase neurotoxicity
Hypercarbia, Hyperkalemia, Hypoxemia, Acidosis
Factors that decrease neurotoxicity
Hypocarbia, hypokalemia, CNS depressants
