Lecture 16: Pharmacology of LOCAL anesthetics Flashcards
What are local anesthetics?
Reversibly block nerve conduction
Act on every type of nerve fiber
Act on cardiac, skeletal muscle and brain
No structural damage to nerve cell
What is purpose of local anesthetic?
To operate on awake patient without pain
To suture without pain
To do painful procedures without pain
What is the “ideal” local anesthetic?
Nonirritating to the tissue to which it is applied
Short onset
Long enough duration, but not too long as to entail a prolonged recovery period
What is the general overall chemical structure of local anesthetics?
- Aromatic group
- Intermediate group
- Tertiary Amine
Weak base
How can you tell the difference between amides and ester anesthetics?
Use generic name
Two “I’s’ = amide
One “I” = ester
What enantiomer is the best therapeutically?
S for Sexy
Where does local anesthetic bind once it is in the blood stream?
Local anesthetics bind to the alpha subunit of SODIUM CHANNELS
What is the mechanism of local anesthetics?
Blocks membrane permeability to NA by crossing the membrane and
Binds to the INTERNAL membrane of the sodium channel
Binds only in the OPEN and INACTIVATED state
-so does not bind when in closed state (which makes sense)
-ionic gradient/resting membrane potential is unchanged
What happens when local anesthetic is injected into an acidic medium like an abscess?
Anesthetics are basic…so when coupled with acidic medium, it would not be able to cross the membrane
What effects do local anesthetics potentiate?
- Decreased the amplitude of the AP
- Slow the rate of depolarization
- Increase the firing threshold
- Slow impulse conduction
- Prolong the refractory period
What are the pharmokinetics of local anesthetics?
- local anesthetics bind in the blood of alpha 1-glycoprotein and albumin
- considerable first-pass uptake of local anesthetics by the lung
- local anesthetics enter the blood stream by
- direct injection
- absorption (epinephrine)
What is the significance of alpha 1-glycoprotein and albumin?
The proteins in blood that bind to local anesthetic
What is the distribution of local anesthetics
- Alpha phase = rapidly redistributed to well-perfused tissue
- primarily goes to alpha phase
- Beta phase = less perfused or slowly equilibrating tissue
- Gamma phase = clearance representing metabolism and excretion
Which of the following organs is at the greatest risk of toxicity from an overdose of local anesthetic?
Brain
Because it is a well perfused tissue
Where are esters metabolized?
Hydrolyzed in the plasma by pseudocholinesterase
-breakdown product = para-aminobenzoicacid
Risk of ester toxicity is much les
-can lead to PABA allergy
What is pseudocholinesterase?
The enzyme in the plasma that breaks down esters
What is para-aminobenzoic acid (PABA)?
The breakdown product of esters
Can lead to ALLERGIES
PABA is an allergen
Where are amides metabolized?
Occurs in the LIVER, specifically in the ER of the hepatocytes
-tertiary amines are metabolized into secondary amines that are then hydrolyzed by amidases
A patient with end-stage liver disease is most susceptible to local anesthetic toxicity from which local anesthetic?
bupivacaine (amides)
Because amides are broken down in liver
What is the lipid:water partition coefficient?
How much more soluble a local anesthetic is in fat vs. water
The higher the coefficient, the greater the potency
E.g. bupivacaine = 27.3 and lidocaine = 2.9…so bupivacaine is more potent but slower onset
What is the lipid:water partition coefficient?
How much more soluble a local anesthetic is in fat vs. water
The higher the coefficient, the greater the potency
E.g. bupivacaine = 27.3 and lidocaine = 2.9…so bupivacaine is more potent but slower onset
Why do you choose lidocaine vs. bupivacaine when applying a local anesthetic prior to suturing?
Because lidocaine has a faster onset
Why do you choose lidocaine vs. bupivacaine when applying a local anesthetic prior to suturing?
Because lidocaine has a faster onset
How do you know if something has a faster response?
The closer to the body pH of 7.4
We want more drugs to be in the UNIONIZED form (because basic vs. acidic)
How do you know if something has a faster response?
The closer to the body pH of 7.4
We want more drugs to be in the UNIONIZED form (because basic vs. acidic)
A newly discovered local anesthetic was found to have a pKa of 7.4. What percent of anesthetic will be unionized in the plasma?
50% (because 50/50 = log 1 = 0)
A newly discovered local anesthetic was found to have a pKa of 7.4. What percent of anesthetic will be unionized in the plasma?
50% (because 50/50 = log 1 = 0)
A 22 yo sexually active man presented with recurrent erythmatoous-edamotous dermatitis of shaft of penis. He uses condoms for birth control. What is diagnosis?
PABA allergy
Condoms have benzocaine
A 22 yo sexually active man presented with recurrent erythmatoous-edamotous dermatitis of shaft of penis. He uses condoms for birth control. What is diagnosis?
PABA allergy
Condoms have benzocaine
Where are local anesthetics?
EVERYWHERE from first aid liquids, ointments, condoms
-mostly esters because ester is much easier to metabolize (avoiding toxicity)
Where are local anesthetics?
EVERYWHERE from first aid liquids, ointments, condoms
-mostly esters because ester is much easier to metabolize (avoiding toxicity)
What are the toxic effects of local anesthetics?
Starts with numbness, lightheadedness, and
Visual disturbance
Evolves into
Muscular twitching, unconsciousness, coma, respiratory arrest, CVS depression
Cardiotoxicity includes
-interference with contractility and automaticity
-ventricular arrhythmias
What are the toxic effects of local anesthetics?
Starts with numbness, lightheadedness, and
Visual disturbance
Evolves into
Muscular twitching, unconsciousness, coma, respiratory arrest, CVS depression
Cardiotoxicity includes
-interference with contractility and automaticity
-ventricular arrhythmias
What are the primary side effects of local toxicity?
Seizures
-induced because the inhibitory neurons are much more sensitive to local anesthetics than excitatory neurons
Cardiovascular toxicity (more prolonged)
What are the primary side effects of local toxicity?
Seizures
-induced because the inhibitory neurons are much more sensitive to local anesthetics than excitatory neurons
Cardiovascular toxicity (more prolonged)
What is the only exception to toxicity?
Bupivicaine
-cardiac dysarrhythmias are seen at subconvulsant levels
What is the only exception to toxicity?
Bupivicaine
-cardiac dysarrhythmias are seen at subconvulsant levels
How do you treat lidocaine toxicity?
Halt injection
If seizures occur, hyperventilate with 100% oxygen
Use benzos or thipental
Interlipids
How do you treat lidocaine toxicity?
Halt injection
If seizures occur, hyperventilate with 100% oxygen
Use benzos or thipental
Interlipids
A 38 yo woman underwent liposuction of abdmen and hips. 30 minutes following local anesthetic administration, she seized. What was the diagnosis?
Lidocaine toxicity
REMEMBER THE local anesthetics can be toxic
A 38 yo woman underwent liposuction of abdmen and hips. 30 minutes following local anesthetic administration, she seized. What was the diagnosis?
Lidocaine toxicity
REMEMBER THE local anesthetics can be toxic
How do you treat cardiac toxicity? Why does this make sense?
Add lipids into the blood
Because anesthetics are much more soluble in lipids
Lipids will take those local anesthetics out of blood and will be instead carried in the lipids
How do you treat cardiac toxicity? Why does this make sense?
Add lipids into the blood
Because anesthetics are much more soluble in lipids
Lipids will take those local anesthetics out of blood and will be instead carried in the lipids
What is intralipid? Significance?
It is something that increases lipid plasma concentration
Reverses local anesthesia toxicity
What is intralipid? Significance?
It is something that increases lipid plasma concentration
Reverses local anesthesia toxicity
91-year old man received a block for arm surgery. Following injection of 30 ml mepivicaine, he became unresponsive and developed bigeminy. Which medication should he receive?
Intralipid
91-year old man received a block for arm surgery. Following injection of 30 ml mepivicaine, he became unresponsive and developed bigeminy. Which medication should he receive?
Intralipid
What are the effects of local anesthetics?
High concentrations: Vasodilation
All local anesthetics EXCEPT for cocaine (horners)
What are the effects of local anesthetics?
High concentrations: Vasodilation
All local anesthetics EXCEPT for cocaine (horners)
An ENT surgeon would like to do a nasal endoscopy. Which local anesthetic should she use to tropicalize the nasopharynx prior to surgery?
A: Cocaine
Because cocaine is a vasoconstrictor, it is used when you want to limit bleeding
An ENT surgeon would like to do a nasal endoscopy. Which local anesthetic should she use to tropicalize the nasopharynx prior to surgery?
A: Cocaine
Because cocaine is a vasoconstrictor, it is used when you want to limit bleeding
What is significance of cocaine?
Only local anesthetic that is NOT a vasodilator
Because cocaine is a vasoconstrictor, it is used when you want to limit bleeding
What is significance of cocaine?
Only local anesthetic that is NOT a vasodilator
Because cocaine is a vasoconstrictor, it is used when you want to limit bleeding
Why are esters used for local anesthesia?
Because it has a smaller risk of SYSTEMIC toxicity when compared to amides
Why are esters used for local anesthesia?
Because it has a smaller risk of SYSTEMIC toxicity when compared to amides
What isomer is most effective?
S isomer is better
Example: Levobupivacaine
What isomer is most effective?
S isomer is better
Example: Levobupivacaine
What is the significance of prilocaine?
Can cause to methemoglobinemia
Because prilocaine is metabolized to alpha-orthotoludine
What is the significance of prilocaine?
Can cause to methemoglobinemia
Because prilocaine is metabolized to alpha-orthotoludine
What is Eutectic Mixture of Local Anesthetic (EMLA)?
A cream (used in pediatrics)
Contains lidocaine, prilocaine, emulsifier, thickener, distilled water
-must be applied one hour prior to procedure
PRILOCAINE cane lead to METHEMOGLOBINEMIA
What is Eutectic Mixture of Local Anesthetic (EMLA)?
A cream (used in pediatrics)
Contains lidocaine, prilocaine, emulsifier, thickener, distilled water
-must be applied one hour prior to procedure
PRILOCAINE cane lead to METHEMOGLOBINEMIA
What causes methemoglobinemia?
Prilocaine
-disease is characterized by iron isomer that has less affinity for oxygen, leading to probable hypoxia
What causes methemoglobinemia?
Prilocaine
-disease is characterized by iron isomer that has less affinity for oxygen, leading to probable hypoxia
A 30 yo woman applies EMLA cream to both legs but developed tongue numbness and cyanosis afterwards. What is diagnosis?
Methemoglobinemia
A 30 yo woman applies EMLA cream to both legs but developed tongue numbness and cyanosis afterwards. What is diagnosis?
Methemoglobinemia
lipid partition coefficient of lidocaine is 3 and bupivacaine is 27
Which is most potent? Shortest duration?
Bupivicaine because highest lipid partition coefficient
Lidocaine = shortest duration
lipid partition coefficient of lidocaine is 3 and bupivacaine is 27
Which is most potent? Shortest duration?
Bupivicaine because highest lipid partition coefficient
Lidocaine = shortest duration
What are the two key features of new class of local anesthetics?
- lipid partition coefficient (to know potency/duration)
2. pKa (so that you know how fast it brings about effect)
What are the two key features of new class of local anesthetics?
- lipid partition coefficient (to know potency/duration)
2. pKa (so that you know how fast it brings about effect)
During the injection of bobacaine, the patient complains of a metallic taste in the mouth. The most likely explanation is
Central nervous system toxicity
During the injection of bobacaine, the patient complains of a metallic taste in the mouth. The most likely explanation is
Central nervous system toxicity
If you have a metallic taste in mouth after local anesthetics
You have CNS Toxicity
If you have a metallic taste in mouth after local anesthetics
You have CNS Toxicity
