LOCAL ANESTHETICS

Question 1

what are the goals for local anesthetic use? (4)

Answer 1

1. minimize local irritation
2. minimize systemic toxicity
3. rapid onset: high concentration needed (0.5-4%)
4. sufficient duration

Question 2

what are the two alternative linking groups in local anesthetics?

Answer 2

amides (lidocaine)

esters (tetracaine)

Question 3

which local anesthetic group binds to plasma proteins? undergoes hydrolysis by plasma esterases?

Answer 3

amides bind to plasma proteins

esters are hydrolyzed by plama esterases

Question 4

what is the mechanism of action of local anesthetics?

Answer 4

1. block Na channels from the cytoplasmic mouth
2. stabilize inactivated state of channel

*voltage-dependent transitions of Na channel to open and inactivated states

Question 5

definition:

diameter of nerve fiber and its myelination state

firing rate, action potential duration (use-dependent block)

position of fiber in nerve bundle

local blood flow

drug size and hydrophobicity

liver function (for amides)

tissue pH (consequence of inflammation)

Answer 5

factors that influence effectiveness of local anesthetics

Question 6

place in order sensations and motor function in terms of decreasing sensitivity to blockade

Answer 6

pain>cold>touch>deep pressure>motor function

Question 7

what is the pKa of lidocaine?

Answer 7

7.9

Question 8

how does inflammation affect effectiveness of local anesthetics?

Answer 8

increase inflammation reduces effectiveness of local anesthetics

(at acidic pH, less drug is uncharged, therefore less drug crosses never membranes, therefore less nerve block)

Question 9

how does systemic toxicity of amides affect the CNS?

Answer 9

initially drowsiness and excitatin (up to seizures), followed by general depression, coma

Question 10

what are the cardiac effects of systemic toxicity of amides?

(especially bupivacaine)

Answer 10

depressed pacemaker activity, decreased conduction, arrhythmias,

cardiac toxicity is potentiated by hyperkalemia,

amides can synergize with anti-arrhythmic drugs to induce arrhythmias

Question 11

what are the effects of systemic toxicity of amides on peripheral blood vessels?

Answer 11

vasodilation leading to hypotension

(except cocaine – hypertension caused by block of NE reuptake)

Question 12

ester allergies are caused by ______________?

Answer 12

PABA derivatives

Question 13

amide allergies are caused by _______________?

Answer 13

preservatives