Local Anesthetics I (Exam IV) Andy's Cards Flashcards
What was the first local anesthetic?
Cocaine
Is cocaine an ester or amide?
Cocaine is an ester.
What was cocaine first used for and what was the effect?
Ophthalmology (1884)
Local vasoconstriction: shrink nasal mucosa.
What was the first synthetic ester developed in 1905?
Procaine
What was the first synthetic amide developed in 1943?
Lidocaine
Gold Standard
What are the 3 types of uses mentioned in ppt for Local Anesthetics (LAs)?
- Treat dysrhythmias
- Analgesia: Acute and chronic pain
- Anesthesia- ANS Blockade, Sensory Anesthesia, Skeletal Muscle Paralysis
What antiarrhythmic Drug Class is lidocaine in?
Class I: Sodium Channel Blockers
MAGA: What is the intra-op infusion dose of lidocaine?
1 mg/kg over an hour
What is the IV dose of Lidocaine?
- 1 to 2 mg/kg IV (initial bolus) over 2 - 4 min.
- 1 to 2 mg/kg/hour (drip)
When should lidocaine be terminated?
Terminate within 12 - 72 hours
Dose Dependent Effects of Lidocaine if plasma lidocaine concentration is 1-5 mcg/ml.
Analgesia
Dose Dependent Effects of Lidocaine if plasma lidocaine concentration is 5-10 mcg/ml.
- Circum-oral numbness
- Tinnitus
- Skeletal muscle twitching
- Systemic hypotension
- Myocardial depression
Dose Dependent Effects of Lidocaine if plasma lidocaine concentration is 10-15 mcg/ml.
- Seizures
- Unconsciousness
Dose Dependent Effects of Lidocaine if plasma lidocaine concentration is 15-25 mcg/ml.
- Apnea
- Coma
Dose Dependent Effects of Lidocaine if plasma lidocaine concentration is >25 mcg/ml.
- Cardiovascular Depression
Describe the components that make up the molecular structure of lidocaine.
Lipophilic Portion (Aromatic Section)
Hydrocarbon Chain
Hydrophilic (Amino Group)
Bond between the lipophilic portion and the hydrocarbon chain will determine if LA is an ester or an amide.
What structural component of a LA determines if it is an ester or an amide?
Bond between the lipophilic portion and the hydrocarbon chain will determine if LA is an ester or an amide.
What type of local anesthetic would you anticipate from the figure below?
Ester due to the ester bond between the aromatic and the intermediate chain
What type of local anesthetic would you anticipate from the figure below?
Amide due to the amide bond between the aromatic and the intermediate chain
Local anesthetics will typically have a pH of _____ and are weak _______. ?
pH of 6; weak bases
A majority of LA are weak bases
Increased potency generally correlates to increased __________.
duration
Which ester is the most potent?
Tetracaine
What 3 local anesthetics will exhibit the highest degree of protein binding?
- Bupivacaine
- Levobupivacaine
- Ropivacaine
Which two local anesthetics will have the most rapid onset?
Chloroprocaine
Lidocaine
Which 3 LA will have the highest protein binding?
Levobupivacaine (>97%)
Bupivacaine (95%)
Ropivacaine (94%)
Lipid solubility correlates to _______ of the drug.
Which LA has the highest lipid solubility?
Which has the lowest?
- potency
- Tetracaine
- Procaine
pK values closer to a pH of ___________ will have the fastest onset of action.
7.35 - 7.45
Which three local anesthetics have pK values closest to 7.35-7.45 ?
- Lidocaine (pK = 7.9)
- Prilocaine (pK = 7.9)
- Mepivacaine (pK = 7.6)
Which ester has the greatest degree of lipid solubility?
Tetracaine
Which amide has the greatest degree of lipid solubility?
Bupivacaine (28)
Ester:
Tetracaine (80)
How do liposomes and local anesthetics interact?
What is the result?
- Liposomes unload LA’s into tissue at a controlled rate.
- Prolonged duration of action & decreased toxicity
The FDA released this local anesthetic that contains liposomes and can last up to 96 hours.
Exparel - (Bupivacaine ER)
What is the mechanism of action of Local Anesthetics?
- Binds to voltage-gated Na+ channels
- Block/inhibit Na+ passage in nerve membranes
Slowed rate of depolarization - does not reach threshold potential, so no action potential
LA must be non-ionized and lipid-soluble to go through the cell membrane and block the Na+ gated channel from within the cell.
What two chemical things will cause a local anesthetic to not work anymore?
Becoming water-soluble and ionized.
What factors affect the degree of blockade seen from local anesthetics?
- Lipid solubility or non-ionized form
- Repetitively stimulated nerve (↑ sensitivity)
- Diameter of the nerve (↑ diameter, ↑ LA need)
What happens when you expose LA (a weak base) to an acidic environment?
LA becomes ionized.
When LA becomes ionized, it will not cross cell membrane to block Na+ gated channels.
What other receptors can be targeted by local anesthetics besides sodium channels?
- Potassium channels
- Calcium Ion Channels
- G protein-coupled receptors
Minimum Effective Concentration or Cm (LAs) = _________ (Volatile Agents)
MAC
What component of the local anesthetic is required for the conduction block?
Non-ionized form (equates with lipid solubility)
Larger fibers need _____ concentrations of LAs.
higher