Local Anesthetics Flashcards
Who utilized cocaine as a local anesthetic?
Carl Koller and Sigmund Freud
They used it for tongue numbing and corneal anesthesia.
What are the drawbacks of cocaine as a local anesthetic?
Significant toxicity, short duration, high cost, and addiction.
Who synthesized procaine?
Alfred Einhorn
Procaine is a degradation product of cocaine.
What is differential nerve block?
Blockade of sensory information via sodium channels with limited blockade at potassium and calcium channels.
What is the general structure of local anesthetics?
A lipophilic substituted benzene ring linked to a hydrophilic amine group (teritiary or quaternary) through either an ester or amide linkage.
Name some examples of amide local anesthetics.
- Lidocaine
- Prilocaine
- Mepivicaine
- Ropivicaine
- Bupivicaine
- Levobupivicaine
- etidocaine
What are structure activity relationships of local anesthetics about?
Its an ester
weak bases
Lipid soluble neutral form in equilibrium with hydrophilic charged form
pKa
protein binding
racemic mixture
R-enantiomers
tachyphylaxis
What are the types of esters in local anesthetics?
- Cocaine
- Procaine
- 2-chloroprocaine
- Tetracaine
- Benzocaine
What is the nature of local anesthetics? strong or weak base?
They are weak bases.
What is the equilibrium state of local anesthetics?
Lipid soluble neutral form in equilibrium with hydrophilic charged form.
What does pKa represent in local anesthetics?
pKa (dissociation constants) is the pH at which the two forms occur equally.
How does lower pKa affect local anesthetics?
Lower pKa agents have more rapid onset.
What effect does increased lipophilicity have on local anesthetics?
It slows the rate of onset and prolongs the duration of action.
What is the effect of increased portein binding?
It increases the duration of action
How does increased protein binding affect local anesthetics?
Increased protein binding increases the duration of action.
What are racemic mixtures?
They are anything except lidocaine, ropivicaine, and levobupivicaine.
What are racemic mixtures in the context of local anesthetics?
They are mixtures that include various enantiomers, except for lidocaine, ropivicaine, and levobupivicaine.
What is the efficacy and toxicity of R-enantiomers in local anesthetics?
R-enantiomers have greater efficacy but greater systemic toxicity.
What is tachyphylaxis in the context of local anesthetics?
Tachyphylaxis (tolerance) does not occur if re-dosing occurs before pain occurs.
What are the techniques used to increase local anesthetic activity?
- Use epi
- alkalinization
- opioid
- alpha 2 agonists
How does epinephrine affect local anesthetic activity?
Epinephrine prolongs local anesthetic block and decreases systemic absorption through vasoconstriction, which slows clearance from the injection site.
Typically used at a ratio of 1:200,000.
What is the effect of alkalinization on local anesthetic onset?
Alkalinization shortens the onset to blockade.
–pH of commercial solutions is 3.9-6.47 (lower with epi); pKa of agents is 7.6-8.9 (<3% is in lipid soluble, neutral form)
–1 ml of sodium bicarbonate per 10 ml of lidocaine will hasten blockade by 3-5 minutes
What is the pH range of commercial local anesthetic solutions?
The pH of commercial solutions is 3.9-6.47 (lower with epinephrine).
What is the pKa range of local anesthetic agents?
The pKa of agents is 7.6-8.9, with less than 3% in lipid soluble, neutral form.
How can sodium bicarbonate affect lidocaine blockade?
1 ml of sodium bicarbonate per 10 ml of lidocaine will hasten blockade by 3-5 minutes.
What is the effect of opioids when used with local anesthetics?
Opioids provide synergistic analgesia with local anesthetics when given neuraxially, except for 2-chlorprocaine.
What are the administration methods for local anesthetic/opioid combinations?
Local anesthetic/opioid combinations can be administered intra-articularly and through infiltration.
What role do alpha2 agonists play in local anesthesia?
Alpha2 agonists are techniques to increase local anesthetic activity.
