local anesthesia

Question 1

physical properties of local anesthetics

Answer 1

• weak bases
• lipophilic group (usually a benzene ring)
• hydrophilic group (usualy a tertiary amine)
• these groupas are connected by a ester or amide (this is the classifying factor)

Question 2

differentiating amides and ester LA’s

Answer 2

• amides have 2 “i” in there generic name

- esters have 1

Question 3

metabolism of esters

Answer 3

• metabolized by plasma/pseudocholinesterase which is found in the blood
• short systemic half life of about 1 minutes
• degraded into p-aminobenzoic acid

Question 4

metabolism of amides

Answer 4

• metabolized by the CYP450 enzyme in the liver
• elimination half life is 2-3 hours
• N-dealkylation of amide link via hydrolysis

Question 5

LA effect on action potential

Answer 5

• impairs the porpogation of action potential
• rate of rise of action potential is decreased, the threshold is not reached
• no effect on the resting or threshold potential

Question 6

LA cellular effect

Answer 6

• when in an uncharged state (unbound from a H+), the LA will move into the neuron by crossing the lipid bilayer
• once in the neuron, it binds a H+ and becomes charged again
• this allows the anesthetic to block the Na+ channel thereby blocking the propogation of action potential

Question 7

local anesthetics work better in a “blank” environment

Answer 7

-basic

Question 8

the pka of the acid to closely associated with

Answer 8

• the onset of action
• the closer the LA’s pka is to physiological pH, the faster the LA will act
• however, a higher pH of LA solution, the faster the onset as well

Question 9

lipid solubility of the LA is associated with

Answer 9

• LA potency

- this is related to their abiility to cross nerve membranes easily

Question 10

LA protein binding is most closely associated with

Answer 10

• duration of action
• higher protein binding increases duration of action
• they say that this is due to the binding reducing the ability of the blood to wash away the anesthetic but the prof said that this is probably wrong

Question 11

lidocaine duration of action

Answer 11

-short acting

Question 12

etidocaine duration of action

Answer 12

-long acting

Question 13

blocking unmyelinated verus myelinated nerve fibers

Answer 13

myelinated are easier to block

-LA gets concentrated at a node and stops the action potential right there

Question 14

clinical effects of LA’s

Answer 14

• sympathetic block (vasodilation, skin temp)
• loss of pain and temperature sensation
• loss of proprioception
• loss of touch and pressure
• loss of motor function

Question 15

order of clinical effects when giving LA

Answer 15

1. sympathetic blockade
2. sensori blockade
3. motor blockade
   - this have to do with how deep the nerves are within the nerve bundle

Question 16

Neuro (tissue) toxicity of LA’s

Answer 16

• rare but can occur if the concentration rises too high in a muscle
• in high concentrations, these are directly neurotoxic and inhibit nerve growth
• TRI or TNS are clinical syndromes of local toxicity following intrathecal injection of LA in clinical doses

Question 17

systemic toxicity of LA

Answer 17

• presence of toxic LA levels in the blood either due to IV injection or massive absorption
• CNS toxicity occurs before respiratory arrest and cardio tox

Question 18

symptoms of CNS tox

Answer 18

• metallic taste in mouth
• tinnitus
• light-headedness
• numbness of lips and tongue
• muscle fasciculations
• LOC
• seizures
• coma

Question 19

CVS symptoms of tox

Answer 19

• negative inotropy
• refractory cardiac arrhythmias
• loss of vasomotor tone
• CV collapse: often difficult to treat
• exacerbated by acidosis, hypercarbia, hypoxia
• narrow therapeutic margin for bupivaccaine

Question 20

fact about bupivicaine

Answer 20

• narrow therapeutic margin

- we do not give 0.75% solutions to pregnant women becasue of the increased risk for maternal cardiac arrest

Question 21

LA tox and pregnancy

Answer 21

• more sensitive to bupivicaine

- less LA produces hypotension, resp arrest, and circulatory collapse

Question 22

treatment of systemic LA tox

Answer 22

• apply oxygen: low oxygen worsens the effects
• hyperventalate (make blood more basic): acidosis and hypercarbia worsen effects of LA tox
• intrralipid 20% IV solution: seperats the LA from the sodium channel and binds it, works as a lipid sink and facilitates cario pulmonary resuscitation

Question 23

benzocaine

Answer 23

• topical agent only

- oxidizer that can induce methemoglobin if it is used systemically

Question 24

prilocaine

Answer 24

• metabolized to ortho-toludine
• ortho-toludine can oxidize hemoglobin to methemoglobin
• may occur in prilocaine doses greater than 600mg

Question 25

metabolism of licocaine

Answer 25

-first to monoethylglycinexylidide then to xylidide

Question 26

cocaine as a LA

Answer 26

• ester LA
• blocks NE reuptake
• sympathomimetic (this is why it is used in surgery around the nose so it stops bleeding)
• vasoconstrictor
• CNS stimulant
• coronary vasoconstriction
• hyperthermia

Question 27

allergies to LA

Answer 27

• extremely rare to have true allergic reaction
• usually a reaction to a intravascular injection or to epinephrine admixture
• esters may cause allergic reaction due to the metabolits PABA
• amides may cause an allergic reaction when methylparaben is used as a preservative

Question 28

commercial prep of LA

Answer 28

• usually in an acidic environment which does not help with absorption
• antimicrobial prep contains paraben derivatives (PABA)
• antioxidants: sodium metabisulfite (allergy in sulfa sensitivity) and EDTA which may cause muscle pain by Ca binding in large doses