Local Anesthetics

Question 0

Local anesthetics have a lipophillic aromatic ring connected to an ionizable group (usually a tertiary amine) by either an ester or an amide linkage. Which linkage is more stable? What does this say about duration of action?

Answer 0

Amide linkages are stronger so ester links have a shorter duration of action

Question 1

pK of local anesthetics (weak bases) is 8.0-9.0. What form predominates at physiological pH? Which form is most active? Which form crosses membranes easier?

Answer 1

Cationic predominates and also most active. Uncharged penetrates membranes better

Question 2

What physiological action is important in local anesthetics to prolong their action?

Answer 2

Vasoconstriction - keeps drug at the area

Question 3

Local anesthetics are usually combined with what drug to potentiate their actions?

Answer 3

Epinephrine

Question 4

Which local anesthetic can prevent its own absorption by vasoconstriction effects?

Answer 4

Cocaine

Question 5

What additional effect does epinephrine have as an additive to local spinal anesthesia?

Answer 5

Acts on alpha 2 receptors to prevent release of substance P (pain mediator)

Question 6

How does metabolism of local anesthics differ between the two different types of structural linkages?

Answer 6

Ester-linked degraded by tissue and plasma esterases (pseudocholinesterases)

Amide-linked are degraded by P450 in liver

Question 7

Local anesthetics stop action potentials through blockage of what channels?

Answer 7

Voltage gated sodium channels

Question 8

What is the most important factor that determines the potency of a local anesthetic?

Answer 8

Lipophilicity

Question 9

Which three local anesthetics are the most potent and longest acting? Why?

Answer 9

Tetracaine
Ropivacaine
Bupivacaine

More liposoluble thus more potent

Question 10

Name the two intermediate acting local anesthetics

Answer 10

Lidocaine and prilocaine

Question 11

Name the short acting local anesthetic

Answer 11

Procaine

Question 12

If blood levels of local anesthetics get too high, what two important effects on CNS can be seen? What can be given as prophylaxis against these effects if large amounts of local anesthetic must be used?

Answer 12

CNS simulation (tremors and convulsions) followed by CNS depression (death by respiratory failure)

Benzos protect against the seizures

Question 13

Give the major adverse effects of local anesthetics if given in large doses to the: PNS, cardiovascular, and blood

Answer 13

PNS: direct nerve toxicity
CV: dec contractility leading to hypotension
Blood: can convert Hb to methemoglobin

Question 14

Which local anesthetic is MOST cardio toxic?

Answer 14

Bupivacaine

Question 15

What is the only local anesthetic that can cause hypertension instead of hypotension?

Answer 15

Cocaine - vasoconstrictor

Question 16

Which local anesthetic is responsible for the adverse effect of methemoglobinemia?

Answer 16

Prilocaine

Question 17

Name the ester local anesthetics

Answer 17

Cocaine
Procaine
Tetracaine
Benzocaine

Question 18

Which linkage subtype of local anesthetics is more likely to cause allergic reactions? Why?

Answer 18

Ester linkage subtype - metabolized to PABA and many people have allergies to it (amide linkage allergies are very rare)

Note: the amide linkage local anesthetics have an additional “i” in their name outside of the -caine ending

Question 19

Name the amide local anesthetics

Answer 19

Lidocaine
Bupivacaine
Prilocaine
Ropivacaine

All the amides have an additional i outside the ending

Question 20

Name the drugs that treat allergies to local anesthetics if the reaction is mild? Severe?

Answer 20

Mild: diphenhydramine (Benadryl)
Severe: SC epi

Question 21

Procaine is metabolized to PABA. Which class of drugs should not be used with procaine? Why?

Answer 21

Sulfonamide antibiotics - they act by blocking PABA synthesis, giving procaine would render them ineffective