Local Anesthetics Flashcards
Which drug is the prototype for esters?
Procaine with a potency ratio of 1
What is the potency of Chloroprocaine?
4
What is the onset of Chloroprocaine?
Rapid
What is the duration of action of Chloroprocaine?
30-45 minutes
What is the max safe dose without epi for Chloroprocaine?
11 mg/kg
What is the max safe dose with epi for Chloroprocaine?
14 mg/kg
What is the potency ratio for Tetracaine?
16
What is the onset of Tetracaine?
Slow
What is the duration of action for Tetracaine?
60-180 minutes
What is the max safe dose without epi for Tetracaine?
1-2 mg/kg
What is the max safe dose with epi for Tetracaine?
3 mg/kg
What is the potency ratio of Lidocaine?
1
What is the onset of Lidocaine?
Rapid
What is the duration of action of Lidocaine?
60-120 minutes
What is the max safe dose of Lidocaine without epi?
5 mg/kg
What is the max safe dose of Lidocaine with epi?
7 mg/kg
What is the potency ratio of Ropivacaine?
4
What is the onset of Ropivacaine?
Slow
What is the duration of action of ropivacaine?
240-480 minutes
What is the max safe dose without epi for ropivacaine?
2-3 mg/kg
What is the max safe dose with epi for ropivacaine?
3 mg/kg
What is the potency ratio of bupivacaine?
4
What is the onset of bupivacaine?
slow
What is the duration of action of bupivacaine?
240-480 minutes
What is the max safe dose without epi for bupivacaine?
2-3 mg/kg
What is the max safe dose with epi for bupivacaine?
3 mg/kg
How does lipid solubility affect LA?
Determines their onset of action, more lipid soluble LA will have greater potency and duration of action; there is greater affinity of drug to lipid membranes and therefore greater proximity to sites of action
What characteristics of LA affect their duration of action?
protein binding
How are esters metabolized?
hydrolyzed by plasma esterases
How are amides metabolized?
Primarily hepatic with CYP450
How can you tell if a LA is an amide or ester?
Esters have 1 i and amides have 2 i’s
What is the MOA of LA?
bind to voltage gated Na channels in interior of cell and block depolarizing Na current
Will you need more or less LA for a highly stimulated nerve?
Less because more Na channels will be in ready conformation
Does more lipid solubility increase or decrease risk for toxicity?
Increases, decreases therapeutic index for hydrophobic drugs
Are LA more susceptible to small or large nerve fibers?
Small
Are myelinated or unmyelinated fibers easier to block?
Myelinated because the drug pools near axonal membrane
In what order to LA inhibit different sensations?
- pain
- temperature
- pressure
- motor function
If you only want to block pain and temperature with a LA, what would you do to achieve that?
Smaller volume or less concentrated
What factors determine the plasma concentration of LAs?
- dose of the drug administered
- rate of absorption of the drug
- site injected, vasoactivity of the drug, use of vasoconstrictors
- biotransformation and elimination of the drug from the circulation
- amount bound to protein
Where is the primary site of action of LA in the cardiovascular system?
myocardium, LA decrease electrical excitability, conduction rate, and the force of myocardial contraction
What other effect do LA cause in the cardiovascular system?
arteriolar dilatation & hypotension
What is the relationship between cardiac depressant effects and anesthetic potency in LA?
They parallel each other, bupivacaine which is 4 times more potent than lidocaine is also 4 times more potent in depressing cardiac contractility
Can cardiac collapse occur with no warning signs or symptoms of CNS toxicity?
Yes
What causes an increased free fraction of bupivacaine in the plasma in pregnant women and newborns?
lower circulating alpha1-acid glycoprotein (AAG)
What LAs are preferred in pregnancy and have less risk of cardiac toxicity?
Intermediate duration LAs such as lidocaine and nepivacaine
What is the only naturally occurring LA?
cocaine
What are the clinically desired actions of cocaine?
Blockade of nerve impulses and local vasoconstriction secondary to inhibition of local NE reuptake
Why is cocaine not in popular use now?
High risk for abuse and toxicity
What causes the euphoric effects of cocaine?
inhibition of catecholamine uptake, particularly dopamine at CNS synapses
What is cocaine currently used for?
Provides topical anesthesia of the upper respiratory tract, where its combined vasoconstrictor and LA properties provide anesthesia and shrinking of mucosa with a single agent
Which LA has the most rapid onset and is also metabolized the quickest?
chloroprocaine
Is there no placental transfer with chloroprocaine?
no, limited transfer and very useful for emergency c-sections
Which ester LA is more slowly metabolized and is considerably more toxic?
Tetracaine
How is tetracaine currently used?
for spinal anesthesia when a drug of long duration is needed as well as in various topical anesthetic preparations
What is the most widely used and versatile LA?
Lidocaine
What are the common concentrations of lidocaine?
1% and 2%
What percent lidocaine would you use for IV regional anesthesia?
0.5%
What is the other amide LA with pharmologic properties similar to lidocaine?
Mepivacaine
What population would you not want to give mepivacaine?
neonates, higher risk for toxicity, so not used in obstetric anesthesia
How are the structures of bupivacaine and lidocaine different?
bupivacaine has butylpiperidine
Which LA is substantially more cardiotoxic than the others?
bupivacaine
Can you ever give bupivacaine IV?
NO, high risk for cardiac toxicity
What is generally the treatment for cardiac toxicity caused from bupivacaine?
cardiopulmonary bypass until bupivacaine metabolized out of system
What long-acting LA is slightly less potent than bupivacaine and has less risk for cardiac toxicity?
ropivacaine
What is the purpose of adding epinephrine to your LA?
decreases blood flow and increases length of block and marker for intravascular injection (if inadvertently inject into vasculature, will see dramatic increase in HR)
What are some reasons to add opioids to your LA?
useful for injection in spinal cord because there are opioid receptors present in the substantia gelatinosa, not much clinical use in using opioids peripherally since opioid receptors are absent or weak
What is the purpose of using clonidine with your LA?
when administered into the epidural or subarachnoid space, produces dose-dependent analgesia and does not produce depression of ventilation, pruritis, nausea, or vomiting
What is the MOA of clonidine?
produces analgesia by activating postsynaptic alpha2 receptors in the substantia gelatinosa of the spinal cord
What guides your decision in determining correct LA for your case?
- length of surgery
- speed of onset necessary
- need for post-op pain control
- patient-related factors
Your surgeon asks you what would be the max dose of lidocaine with epi for a 50 kg patient?
350 mg
The surgeon administers some lidocaine with epi and you see the patient’s HR jump from 80 to 120. Would you be concerned about this, and if so what would be your next action?
Not a significant increase in HR so not concerning, the systemic absorption of epi causes a transient increase in HR, if epi injected in vasculature you would a much more dramatic increase in HR
Do LA alter the resting membrane potential?
No, they solely prevent the action potential from occurring
Which type of LA are more likely to cause allergic reactions?
Esters
What causes allergic reactions in certain LA?
PABA (p-aminobenzoic acid-related compounds –>metabolite of ester LA) which is common in many skin products, make-up, lotions, etc.
If someone has an allergy to ester LA, can they get amide LA?
YES, no cross-reactivity between esters and amids
What factors enhance bupivacaine toxicity?
pregnancy presence of calcium channel blockers arterial hypoxemia acidosis hypercarbia
What factors influence lidocaine metabolism?
pregnancy-induced hypertension
hepatic disease
reduced liver blood flow
volatile anesthetics
What is lidocaine’s effect on ventilation response to hypoxia?
Depressed response
What are clinical uses of EMLA applications?
Arterial cannulation
Venipuncture
Myringotomy (ear tubes)
Lumbar puncture
Which LA produce localized vasoconstriction and anesthesia?
cocaine and lidocaine
Which is more cardiotoxic, ropivacaine or bupivacaine?
bupivacaine
What are electrophysiological characteristics of lidocaine toxicity?
ECG-PR interval prolongation
Does more lipophilic LA benefit from using epi?
no
What is EMLA cream composed of?
2.5% lidocaine and 2.5% prilocaine
Which LA tend to have a shorter duration of action?
esters
The magnitude of systemic absorption of LA is dependent upon:
presence of epi in solution
physiochemical properties of the LA
dose administered into the tissues
vascularity of injection site
What does the addition of sodium bicarbonate do to LA?
Speeds onset
LA are chemically classified as:
weak bases
What effect does fetal acidosis have on local anesthetic accumulation in the body?
Increases anesthetic accumulation
The lower the pKa of a LA…
the shorter the onset of action
What 3 layers of connective tissue do LA have to diffuse across to affect the nerve?
Endoneurium (surrounds nerve fibers)
Perineurium (surrounds nerve fascicle)
Epineurium (surrounds peripheral nerve)
Typically how much of a LA dose will actually hit the nerve?
1-2%
Which type of nerves are generally blocked first?
smaller myelinated nerves such as B fibers or A delta fibers (sharp pain and temperature)
Which type of nerves are generally blocked last?
small unmyelinated nerves such as C fibers that transmit dull pain
Describe detailed MOA of LA
LAs are weak bases that are unionized (lipophilic) and able to cross cell membrane, once they cross cell membrane they pick up H+ to become charged (hydrophilic) and are able to block Na channel from inside of cell
What is tonic block?
dose-dependent block of Na channels
What is use-dependent block?
relies on the fact that open Na channels are bound more tightly by local anesthetic, so if repeatedly stimulate Na channel it will be in the open conformation more often and LA will be able to better bind to channel
What chemical structure gives LA its lipophilic nature?
benzene ring
What is the importance of the intermediate chain in LAs?
determines if LA is ester or amide
What chemical structure gives LAs its hydrophilic property?
amine group
Do acidic environments make LA more or less effective?
Less effective, tissue pH is decreased so when LA is injected into the tissue, more LA is going to become protonated and charged and less will be available to enter cells
Which LAs have a metabolite that can cause met Hgb?
Prilocaine with large doses in epidurals and benzocaine in sprays (treated with methylene blue)
What are the 8 progressive signs of systemic toxicity?
- drowsiness
- paresthesias in the mouth and tongue
- tinnitus, auditory hallucinations
- muscular spasm
- seizures
- coma
- respiratory arrest
- cardiac arrest
What are mechanisms of cardiac toxicity in the CNS?
acts at level of medulla to cause hypotension
What are mechanisms of cardiac toxicity in the PNS?
Autonomic effects that block sympathetic effects
Vasomotor effects which lead to vasodilation
What are mechanisms of cardiac toxicity in the cardiovascular system?
blocks sodium channels
Bupivacaine blocks calcium release and reduces mitochondrial activity
What is transient neurological syndrome?
pain in the lower extremities that begins within a few hours to 24 hours after spinal anesthesia, resolves by 2-7 days
What are some mechanisms to prevent systemic toxicity?
syringe aspiration (when giving a peripheral nerve block or spinal, epidural - make sure not in vein)
test dose
monitors
pre-treat with benzos - helps threshold for seizures
ultrasound
What are some treatments for systemic toxicity?
NO MORE LA ABCs Benzos for seizures ACLS for cardiac instability IV lipids Cardiopulmonary bypass for patients not responding to lipid emulsion or ACLS
Explain what makes the pharmacokinetics of LA different than most drugs.
LA are injected into tissue and work at injection site and when they are absorbed they are no longer effective, most drugs get injected and have to be absorbed to be effective
