Local Anesthetics

Question 1

nociception

Answer 1

pain awareness

Question 2

how can drugs block pain perception?

Answer 2

in the periphery or CNS through the inhibition of Na channels in neurons (axons) in the spinal cord

Question 3

where/how do local anesthetics work?

Answer 3

they block the transmission of pain signals to the CNS for processing - prevents the signal from reaching the brain

Question 4

what do all local anesthetics end in?

Answer 4

-aine

Question 5

Amides

Answer 5

have 2 "i"s 
lidocaine
	lidocaine + hydrocortisone (patch)
	bupivacaine
	prilocaine
	mepivacaine
	ropivacaine
	levobupivacaine
	articaine
	dibucaine (local)

Question 6

Esters

Answer 6

has one “i” - destroyed by esterase enzymes - these are short acting- not widely used

chloroprocaine
cocaine (local)
procaine
tetracaine
benzocaine
proparacaine (ophthalmic)

Question 7

how are amides destroyed?

Answer 7

by amidase- found only in the liver –longer acting

Question 8

Procaine (Novocaine©)
- rapid acting - short duration

What is the half life?

Answer 8

• ester local anesthetic
• contains similar aromatic
  lipophilic group, central group is an ester (CO) and similar terminal tertiary amine
  group.

< 1 minute

Question 9

what is the half life of lidocaine?

Answer 9

1.6 hrs - cam increase to 6hrs with liver Dz

Question 10

What is the MOA of local anesthetics?

Answer 10

(a) block voltage-gated sodium channels
(b) during action potential,
(1) sodium channel opens, sodium flows in,
(2) neuron depolarizes to + 40 mV
(3) sodium channel closes
(4) potassium channel opens
(5) potassium flows out
(6) neuron repolarizes
(7) sodium channel returns to resting state
(c) other ways to disrupt sodium channels
(1) toxins block sodium channels (batrachotoxin, aconitine, veratridine, scorpion venoms)
(2) these toxins bind to receptor and prolong inward flow of sodium
(d) local anesthetic block of sodium channels is voltage and time- dependent

Question 11

What is the problem with local anesthetics?

exam Q - blow CO2 to enhance the analgesia

Answer 11

1) water soluble - most active at the receptor
2) you must alter the pH - relying on the interstitial fluid 7.45 pH - to help buffer the lidocaine at an appropriate pH

Infected sites have low pH (from bacterial
growth, lactic acid), low pH promotes
ionization of the drugs which makes them
poorly lipid soluble.

Question 12

Pharmacokinetics A

Answer 12

A) Absorption from the site of injection controlled
by:
1. Dosage
2. Site of injection (further from central compartment)
3. Drug-tissue binding
4. Local tissue blood flow
5. Use of vasoconstrictors (epinephrine)
6. Physiochemical properties of the drug

Question 13

Pharmacokinetics B

Answer 13

vasoconstrictors (epinephrine) co-administered will reduce blood flow and prolong actions of the local anesthetic

Question 14

Pharmacokinetics C

Answer 14

epinephrine, clonidine and dexmedetomidine are agonists at alpha 2 receptors in the spinal cord, when co-administered with local
anesthetics they prolong the actions by blocking the release of
- Substance P which reduces sensory neuron firing

Question 15

what is the pka of most local anesthetics?

Answer 15

8-9

Question 16

what is the pH of normal tissue?

Answer 16

7.4

Question 17

what is the pH of infected tissues?

Answer 17

6.4

Question 18

Why doesn’t the 2nd injection work as well as the first?

Answer 18

Becuase you have depleted the buffering capacity at the injection site - must buffer it yourself so that it can be effective - pt won’t be able to buffer as well

Question 19

what do all local anesthetics cause? except for cocaine

Answer 19

vasodilation

Question 20

what is epinephrine used for?

Answer 20

it is a vasoconstrictor to induce blood flow- and prolong the duration of the drug of action

Question 21

How does the MOA of local anesthetics work?

Answer 21

Local anesthetics abolish ability to generate an action potential

Question 22

what drug crosses the lipid membrane?

Answer 22

nonionized drug

Question 23

Usual routes of administration

Answer 23

1) topical (nasal mucosa, wound [incision site] margins)
(2) injection into vicinity of peripheral nerve endings (peri-neural infiltration) <45 min
(3) injection into major nerve trunks (blocks)
(4) injection into the epidural or subarachnoid spaces surrounding the spinal cord

Question 24

What are the major ADRs of local anesthetics?

KEEP IT OUT OF BLOOD STREAM

Answer 24

(a) systemic effects following absorption of the local anesthetic for the site of administration (injection not being restricted)
(b) direct neurotoxicity from the local effects of these drugs when high concentrations are administered in close proximity to the spinal cord and other major nerve trunks.
(c) elevated blood levels can induce a variety of toxic actions

Question 25

CNS toxicity: sedation, light-headedness,
visual and auditory disturbances. Early
signs of CNS toxicity metallic taste and
tongue numbness.

Answer 25

a) inadvertent intravascular administration induces local anesthetic
toxicity
(1) circumoral and tongue numbness
(2) metallic taste
(3) nystagmus and muscular twitiching
(4) tonic-clonic convulsions
(5) generalized CNS depression follows seizure activity
(b) midazolam raises seizure threshold and prevents seizure activity from larger doses

Question 26

What is the reversal of bupivacaine toxicity?

EXAM Q

Answer 26

Intralipid® a parenteral lipid emulsion used
for nutrition, supplementation acts as a “lipid
sink” that appears to pull the lipid soluble
bupivacaine from peripheral plasma.
Appears to work with many another lipid
soluble drugs ( administered to pts who can’t eat)

Question 27

Which is most likely to cause an allergic reaction? *Exam Q

Answer 27

ESTERS - people allergic to PABA - Lidocaine
- same ones that cause an allergic response to sulfa drugs

amide local anesthetics not biotransformed to PABA, allergic reactions
extremely rare

Question 28

Why do you want to treat an infection site prior to local anesthetic (lidocaine)?

Answer 28

To improve the pH otherwise the anesthetic will not be effective.

Blockade of the inactivated
sodium channel on the axon membrane.
The threshold for sensory nerve excitation is
increased (block sodium channels)
• Infections lower tissue fluid pH, drug
transport into neuron is reduced, drug is less
effective.

Question 29

what would happen if you accidentally injected a local anesthetic intravenously?

Answer 29

causes CNS ADR - tonic-clonic seizures, respiratory depression and death

Question 30

Articaine

Answer 30

Amid group - lipid solubility

approved for dental anesthesia, unique amide drug with an ester group.

Question 31

Benzocaine

Answer 31

ester

topical (high lipid solubility),
may induce methemoglobin (Hb that can not transport oxygen)

Question 32

Bupivacaine

Answer 32

amide

0.25% for spinal or epidural,
long duration of action making use in
ambulatory surgery centers limited

Question 33

Chloroprocaine

Answer 33

ester

epidural in obstetrics, rapid hydrolysis minimizes exposure to the fetus.

Question 34

cocaine

Answer 34

ester

ENT topical use only, intense
vasoconstriction limits bleeding. Reduce
usage due to controlled substance handling

Question 35

Lidocaine exam q

Answer 35

Reference standard against

which all other local anesthetics are judged.

Question 36

Levobupivacaine

Answer 36

enatomer of bupivacaine
with less cardio-toxicity, can also be
reversed with lipid emulsion.