Local Anesthetics Flashcards
What is the resting potential of a neuron?
Negative 60-70
What does Na-K ATPase pump do?
Pumps 3 Na ions out for every 2 K, maintaining a negative intracellular environment
What ion are neurons leaky to?
Potassium
What ion does depolarization of a neuron ?
Voltage gated sodium channels
Where do local anesthetics bind?
The alpha subunit preventing activation and thus sodium influx
What happens as more local anesthetic is used?
The sodium channel becomes unable to conduct sodium ions and the threshold for propagation goes up
Why is a local anesthetic block termed “use dependent”?
Because the local anesthetics have a higher affinity for open or inactivated channels so the fraction of Na channels with bound local anesthetic increased with frequent depolarization
What other receptors may local anesthetics block?
Calcium
Potassium
Trpv
Which has a higher sensitivity to the local anesthetic- smaller or larger diameter axons?
Smaller
Which has a higher sensitivity to the local anesthetic- myelinated or unmyelinated axons?
Myelinated
What is the order of sensitivity of the neurons?
Autonomic > sensory > motor
Which neurons are unmyelinated?
C dorsal root (pain, temperature) and C sympathetic fibers
What is the structure of local anesthetics?
Aromatic benzene ring and a tertiary amine bound by an ester or amide
Are local anesthetics weak acids or weak bases?
Weak bases with a positive charge at the tertiary amine are physiologic ph
What does potency of a local anesthetic correlate with?
Octanol solubility
Increased by adding alkyl groups
What does acidity due to a block?
Antagonism
What does hypokalemia do to a block?
Antagonism
What does hypercalcemia due to a block?
Antagonism
What is pka?
The pKa is the ph at which the fraction of ionized and nonionized drug is equal
What form of local anesthetic will have a more rapid onset?
Nonionized because it permeates the epineurium more rapidly
Which form more avidly binds the Na channel?
The charged cation
What are the commercial forms of local anesthetics?
Hydrochloride salts with ph of 6-7
Why are solutions with epinephrine more acidic (ph 4-5)
Because epinephrine is unstable in alkaline environment
What does addition of sodium bicarbonate cause?
Speeds the onset of block and improves the quality due to more free base availability
What does duration of action depend on?
Lipid solubility and potency
What has a longer duration of action - lipid soluble or insoluble?
Soluble because they diffuse more slowly from the lipid rich environment to the aqueous bloodstream
What binds local anesthetics in the blood?
Alpha 1- acid glycoprotein
Which sites of injection absorb the fastest?
Tracheal > intercostal > paracervical> epidural > brachial plexus > sciatic > subcutaneous
Which organs are responsible for initial uptake of local anesthetic?
Brain, lung, liver, kidney, heart because these are the highly perfused organs
What is the alpha stage?
The initial uptake
What is the beta stage?
The slower redistribution to moderately perfused tissues (muscle, gut)
What tissue provides the greatest reservoir for distribution of local?
Muscle
How are esters metabolized?
By pseudocholinesterase then metabolites are excreted in the urine
What do procaine and benzocaine get metabolized to?
PABA - can cause anaphylaxis
What lacks esterases?
CSF
How do intrathecal blocks get terminated?
By redistribution into the bloodstream
What are the ester local anesthetics?
Cocaine
Procaine
Benzocaine
Tetracaine
How are amides metabolized?
By P459
Which amides are metabolized fastest?
Prilocaine > lidocaine> mepivacaine > ropivacaine > bupivacaine
What will decrease the metabolism of amides?
Cirrhosis
Decreased liver blood flow: CHF, H2 blockers, Bb
What does prilocaine cause?
Methemoglobinemia because it is metabolized to o-toluidine
What other local anesthetic causes methemoglobinemia
Benzocaine
How do you treat methemoglobinemia
1-2 mg/kg of methylene blue of 1% solution over 5 minutes
Are the toxic effects of local anesthetics additive or synergistic?
Additive
Why is local anesthetic toxicity of the CNS excitatory?
Because they preferentially block inhibitory pathways
What does hyperventilating do to the seizure threshold?
Raises it
How much Propofol is needed to break a seizure?
0.5-2 mg/ kg
How much does infused lidocaine decrease the MAC by?
40%
What do IV lidocaine due to the cerebral blood flow?
Decreases it
Why don’t we use lidocaine in spinal anesthesia?
Side effects of dysesthesia, burning pain and aching in butt and LE
Direct neurotoxicity
What is the max dose of lidocaine?
4.5 mg/kg
7 mg/kg with Epi
What is this max dose of mepivacaine?
4.5 mg/kg
7 mg/kg with Epi
What is the max dose of ropivacaine
3 mg/kg
What is the max dose of bupivacaine
3 mg/kg
What does lidocaine due to hypoxemic drive?
Depresses it through the medullary respiratory center
What is apnea due to in a high spinal?
Hypotension
What does lidocaine due bronchial smooth muscle?
Relaxes it
What do local anesthetics do to the heart?
Depresses automaticity Depresses contractility and conduction Arterial vasodilation (high doses) Inhibit nitric oxide causing vasoconstriction (low doses)
What happens first CNS or cardiac signs of toxicity
CNS
At low doses, what is th effect of local anesthetics on the CV system?
Inhibition of nitric oxide and therefore vasoconstriction
What does IV administration off bupivacaine produce?
Severe left ventricular depression, Vt, AV block, VF
What are the CV effects of cocaine?
Decreases uptake or norepinephrine so HTN, ventricular ectopic, vasoconstriction
What can bupivacaine intoxication be treated with?
1.5 ml/kg lipid solution
Which you of locals are more likely to illicit an allergic response?
Esters
What are the heme effects of local?
Decreases platelet aggregation and thrombosis
Increases fibrinolysis
What are the musculoskeletal effects of locals?
Myotoxic
Worse with steroids or Epi
What do local anesthetics due to nondepolarizing blocks.
Potentiation them
What kind of local is dibucaine?
Amide
What drugs prolong local anesthetics?
Clonidine
Opioid
Organophosphates
Anti-acetylcholinesterase
How does an action potential in a neuron get terminated?
Inactivation of voltage gated sodium channels
Potassium efflux
What is EMLA cream?
Local anesthetic applied transdermally to provide anesthesia for the skin
What does EMLA cause?
Methemoglobinemia secondary to prilocaine in the formulation
What deficiency should EMLA cream not be used in?
G6PD deficiency
What other drugs cause methemoglobinemia
Benzocaine Prilocaine Quinine Sulfa Dapsone Choral hydrate
How long should EMLA cream be applied for to get the desired effect?
1 hour under an occlusive dressing
How long does anesthesia from EMLA cream last after removal?
1-2 hours
What is 20% benzocaine used for?
Mucosa
What is 4% cocaine used for?
Awake intubation so
Sinus surgery
What is 11.8% TAC used for?
Wound repair
What is LET and what is it used for?
Lidocaine + Epi + tetracaine
Laceration repair
Which local anesthetic cross the placenta the least?
Chloroprocaine because it is rapidly metabolized by plasma cholinesterase
How does fetal ph affect local anesthetic concentration
Fetal ph is lower than mom’s so you will get ion trapping and more concentration of local anesthetic in the fetus
What is the plasma half life of chloroprocaine?
12 seconds
What is the onset of action of chloroprocaine
6-10 minutes
What is the duration of action of chloroprocaine
30-60 minutes
What is the disadvantage of chloroprocaine?
Antagonistic effects on opioids and other locals
Neurotoxicity
What are the first signs of lidocaine toxicity?
Numbness/tingling of lips
What are the second set of signs of lidocaine toxicity?
Tinnitus
What are the third set of signs?
Dizziness, lightheadedness, twitching,seizure
What is intrathecal lidocaine known to cause?
Cauda equina syndrome due to demyelination from pooling in this area
What are the risk factors of transient neurologic syndrome?
Lidocaine use Lithotomy position Early ambulation after surgery Needle trauma Same day surgery
What is transient neurologic syndrome?
Pain in legs, butt that develops within 24 hours of lidocaine spinal. Resolves spontaneously in 1-3 days
What is a Bier block?
It is IV local anesthetic used with 2 tourniquettes: a distal and proximal. The extremity is exsanguinated with an Esmarch bandage and then proximal cuff inflated. If the patient experience pain, the distal cuff is inflated and proximal deflated.
It lasts up to 90 minutes
How does a Bier block work?
Tourniquettes cause ischemia which provides some anesthesia and analgesia
Local diffuses into the vaso nervora and extravascularly to cutaneous branches in the skin
What determines the spread of spinal anesthesia?
Baricity of the drug, drug concentration, patient position
What does not determine the spread of spinal anesthesia?
Drug volume
What is baricity?
The density of a drug compared to the specific gravity of CSF
How is a solution made hyperbaric?
Adding glucose
How is a solution made hypobaric?
By adding water
How is a solution made isobaric?
By mixing 1:1 with CSF
What does drug volume affect in spinal anesthesia?
The level of blockade
When can a neuraxial catheter be removed with BID dosing of heparin?
Anytime
When can a neuraxial catheter be removed if a patient is on a heparin drip?
2-4 hours after the drip is stopped
When can an epidural be placed in someone taking Lovenox (1 mg/kg bid), Dalteparin, or Tinzaparin?
24 hours later
When can you restart lovenox after placing a catheter?
2 hours after
What happens when you mix sodium bicarb with ropivacaine or bupivacaine?
Precipitation and therefore decreased effectiveness and drug availability
Why is sodium bicarb added to local anesthetics?
It increases the ph of the solution to increase the amount of nonionized drug thereby increasing the onset time.
It also decreases pain on injection
What is post spinal back ache?
Happens within 7 days of spinal. Will go away on its own.
Treated conservatively with APAP
Which regional block has the highest blood levels of local after blocking?
Intercostal
Then caudal, epidural, brachial, IV, lower extremity
What is the adductor canal block?
Block of the femoral nerve under the sartorius to provide anesthesia to medial aspect of lower leg and distal femur
How much bupivacaine can you give with Epi?
2.5 mg/kg, not to exceed 225 mg
How much chloroprocaine can you give?
11 mg/kg
How much chloroprocaine with Epi can you give?
14 mg/kg
What’s the duration of action of lidocaine?
30-60 minutes
What’s the duration of action of lidocaine with Epi?
120-360 minutes
What’s the duration of bupivacaine?
120-140 minutes
What’s the duration of mepivacaine?
45-90 minutes
What’s the max dose of mepivacaine?
7 mg/kg
What determines potency?
Lipid solubility
What determines onset?
Pka/ph
What determines duration of action?
Protein binding (Highly - remain bound for longer so last longer)
What does BICEPSS stand for?
The order of site that absorbs the most local anesthetic b- blood (IV) I- intercostal c- caudal E- epidural P- plexus (brachial) S- sciatic S- subq
Which nerves are affected first?
Small, myelinated fibers (B fibers)
Autonomic> sensory> motor
What do A-delta and C fibers feel?
Pain and temperature
What do A-beta fibers feel?
Touch
What are B fibers?
Preganglionic sympathetic nerve fibers
What are the most resistant fibers to local?
C fibers
Why is bupivacaine more cardio toxic?
It has higher affinity for resting and inactivated sodium channels in the myocardium
How do you treat LAST?
Intra lipid bolus of 1.5 mg/kg
Then infusion of 0.25 ml/kg/min (increase to 0.5 if persistent hypotension)
Get CPB team, avoid vasopressin CCBs and BBs, lower Epi dosing
What is the preferred treatment for ventricular arrhythmias in the setting of LAST?
Amiodarone
