Local Anesthetics

Question 1

definition of local anesthetic

Answer 1

an agent that reversibly prevents transmission of nerve impulse in the region to which it is applied, without affecting consciousness.

Question 2

what was the first local anesthetic?

Answer 2

cocaine

Question 3

ion levels in intra and extracellular fluid

Answer 3

intracellular fluid has an abundance of potassium ions, while extracellular has an abundance of sodium ions

Question 4

what is the charge of the interior of a neuron

Answer 4

negative

Question 5

how do nerves conduct?

Answer 5

opening of voltage gated Na channels transiently, Na rushes into cell and depolarizes. Na channels close, and then voltage gated K channels open resulting in repolarization. Both K and Na channels close resulting in resting state.

Question 6

preemptive analgesia

Answer 6

nerve block is performed prior to the incision

Question 7

where do local anesthetics bind?

Answer 7

reversibly bind to the intracellular portion of sodium channel and inactivate the channel. as more and more sodium channels are blocked, more action potential is needed to send a nerve impulse. eventually impulse is completely blocked

Question 8

resting state

Answer 8

during the resting nerve period, where there is an absence of stimulus. no sodium is moving

Question 9

active state

Answer 9

starts immediately on depolarization. sodium is moving and gates are open

Question 10

inactivated state

Answer 10

refractory to repeat stimulus. repolarizing is happening to bring you back to resting state.

Question 11

is blockade of sodium channels voltage dependent, time dependent, or both?

Answer 11

both! effects are more marked in an activated state rather than in a resting or inactivated state. therefore, the effect of drug is more marked in rapidly firing axons

Question 12

greater lipid solubility = ?

Answer 12

greater potency. need to be lipid soluble to pass through the nerve sheath!

Question 13

esters mechanism

Answer 13

hydrolyzed by enzyme in plasma, pseudocholinesterae. rapid metabolism to water soluble metabolites. genetically abnormal pseudocholinesterase exists, causing long lasting ester effects. CSF lacks the enzyme.

Question 14

amides mechanism

Answer 14

transformed by hepatic carboxyl esterases and CYP-450 enzymes. slow metabolism. liver disease may lead to accumulation and toxicity. low hepatic blood flow can lead to prolonged effects

Question 15

terminal amine

Answer 15

can be tertiary form (lipid soluble) or quaternary form (water soluble). acts as on-off switch allowing the local anesthetic to exist in either lipid soluble or water soluble conformations

Question 16

what does onset of action depend on?

Answer 16

depends on what percentage of the drug exists in the active ionized form

Question 17

how do you get drug to exist in ionized form?

Answer 17

the greater the difference between pKa of a drug and pH of the body fluid, the more the drug will exist as ionized form and will not be able to penetrate membranes. this makes it less potent

Question 18

pain is transmitted by what types of nerve fibers?

Answer 18

A delta and C. C is non-myelinated

Question 19

rank the types of nerve fibers from fast to slow and diameter

Answer 19

A alpha, A beta, A delta, C. works for speed and diameter

Question 20

are proximal or distal fibers blocked first

Answer 20

proximal

Question 21

what does absorption of local anesthetics depend on ?

Answer 21

site of injection (vascularity), dose of drug, drug’s intrinsic properties, addition of epinephrine (reduces blood flow around injection site)

Question 22

cauda equina syndrome

Answer 22

reported with continuous spinal catheters and high dose lidocaine usage. severe back pain in the setting of motor deficit, sensory deficit, and loss of bowel/bladder control

Question 23

transient neurologic symptoms

Answer 23

transient pain or dysesthesia linked to the use of lidocaine for spinal anesthesia. not related to dose. increased risk with certain positions. increased risk with ambulatory anesthesia. found with procaine and mepivacaine, bot not bupivacaine or chlorprocaine

Question 24

what drug has worst side effects

Answer 24

bupivocaine

Question 25

CNS toxicity

Answer 25

readily cross BBB producing dose dependent effects. factors increasing potential for CNS toxicity: low protein binding, decreased clearance, metabolic acidosis

Question 26

cardiac toxicity

Answer 26

much higher doses are needed for this than for CNS tox. correlates with potency. Cardiac Na channel blockade: depression of myocardial contractility and reduced refractory period. All local anesthetics are vasodilators except cocaine and ropivacaine = cardiac arrest

Question 27

allergy

Answer 27

high instance with esters due to PABA metabolites, a known allergen. amides have no such metabolites. methylparaben may be a preservative, and this metabolizes to PABA. no cross reaction between the two groups.