Local Anesthetic pharmacology

Question 1

local anesthetics are derived from what?

Answer 1

cocaine, but do not produce euphoria

Question 2

general effect of a local anesthetic

Answer 2

Inhibit pain without causing unconsciousness

Question 3

ester vs amide local anesthetics: difference in effects?

Answer 3

Esters (R-O-R): short duration because metabolized locally by plasma & tissue esterases (e.g., procaine)
Amides (R-N-R): all newer drugs; longer duration (also easier to overdose)

Question 4

should we inject local anesthetics quickly or slowly?

Answer 4

Rapid injection is painful (any drug)

Question 5

local anesthetic mechanism of action? How do they work? on what receptors? what is the drug’s chemical properties and why does this matter?

Answer 5

Block voltage-gated Na+ channels > inhibits action potentials
* Small fibres (e.g., pain) are blocked at lower concentration, larger motor fibres blocked last
* APs in myocytes are also blocked > blood vessel dilation
Receptor is on cytoplasmic surface of channel > must diffuse into cell to produce effect
Local anesthetics are weak bases (B + H+ -> BH+) > become protonated and therefore ionized in acidic tissue
> slower to produce effect in inflamed or infected tissues (more acidic)

Question 6

why might we combine a local anesthetic with a vasoconstrictor? what effects can this have?

Answer 6

LAs block channels until they diffuse away
* Can be combined with a vasoconstrictor (usually epinephrine)
* Slows removal of drug > prolongs action
* Can delay healing (reduces blood flow)
* Do not use where end-artery supplies organ
o Digits, teats, ears, nose, penis, etc. > necrosis
Skin necrosis can occur when lidocaine plus epinephrine is used SC

Question 7

systemic cardiovascular effects of local anesthetics?

Answer 7

• Decreased excitability of myocardium (SA node, Purkinje system less sensitive) > A-V block, arrhythmias possible
• Cardiac arrest requires very high plasma drug concentration (e.g., accidental bolus to heart)

Question 8

signs of a local anesthetic overdose?

Answer 8

First we see: drowsiness & muscle twitching
Next: unconsciousness, convulsions

Question 9

most widely used local anesthetic

Answer 9

Lidocaine is still the most widely used local
* Brand names: Xylocaine, etc.

Question 10

what species should we be cautious when using lidocaine with? why?

Answer 10

Use with caution in cats > sensitive to CNS
effects, seizures more likely

Question 11

what is mepivacaine used for? what is an advantage it has over other locals?

Answer 11

Used mainly for equine nerve blocks
* Appears to diffuse better in tissues than other local anesthetics
(due to pKa? > has a lower pKa (7.6) than other locals)

Question 11

what is mepivacaine used for? what is an advantage it has over other locals?

Answer 11

Used mainly for equine nerve blocks
* Appears to diffuse better in tissues than other local anesthetics
(due to pKa? > has a lower pKa (7.6) than other locals)

Question 12

bupivicaine difference in properties and uses vs lidocaine

Answer 12

• Slower onset because of pKa (more highly ionized) but longer duration vs. lidocaine

Question 13

what is Levobupivacaine? what is its advantage?

Answer 13

The s(-)-enantiomer of bupivacaine
* Does not distribute well to CNS, heart > safer

Question 14

use of proparacaine?

Answer 14

The least irritating anesthetic for the eye

Question 15

advantage/general uses of local anesthetic vs general anesthetic?

Answer 15

Cause local loss of sensation rather than unconsciousness > safer than general anesthesia

Question 16

general clinical uses of local anesthetics; what ways can we use it?

Answer 16

-surface anesthesia (topical)
-Infiltration anesthesia (SC)
-Field block
-Nerve block
-Intravenous Regional
-Epidural
-Paravertebral
-Systemic IV lidocaine

Question 17

use of local anesthetic for surface anesthesia? what does it do?

Answer 17

• Topical gel lasts <1h
• Without epinephrine, local anesthetics increase blood flow
• e.g., sometimes used to improve perfusion of burned skin – better healing

Question 18

how do we use local anesthetics for infiltration anesthesia? how can we increase duration?

Answer 18

• InjectSC
• Epinephrine doubles duration
• Large doses may be toxic (uncommon)

Question 19

goal of a field block with local anesthetic

Answer 19

• Like infiltration anesthesia, but goal is to prevent pain signals coming from “upstream” sites
• E.g.,“L”block
  Anesthetic placed sub-Q

Question 20

clinical use of local anesthetic as a nerve block. How do we use it? Advantage over field block?

Answer 20

-inject drug in vicinity of nerve (may be superficial or deep)
-less drug needed than field block
-eg. localizing pain in equine limb
-requires good anatomical knowledge

Question 21

how do we apply local anesthetic in an intravenous regional manner?

Answer 21

• Tourniquet confines drug to limb
• Diffuses from blood vessels into surrounding tissue, including the major nerves of the limb (recall from anatomy that major nerves are located in proximity to major vessels)
• Most of the dose has diffused out of the bloodstream by the time surgery has ended and tourniquet is removed
• E.g.,bovine digit surgery

Question 22

how do we we apply a local anesthetic epidural? what is it for?

Answer 22

• Inject into epidural space
• Lidocaine, mepivacaine, bupivacaine
  (or other drugs, e.g., an opioid)
• Diffuses across dura into subarachnoid space
• Management of pain in caudal body structures

Question 23

how do we perform a paravertebral nerve block? advantage over L block?

Answer 23

-inject drug where nerve leaves vertebral foramen
-eg. bovine standing surgery
-advantage over L-block: blocks peritoneum as well as abdominal wall

Question 24

what is the main use of systemic IV lidocaine? How does it work? What should be sure to avoid when using this method?

Answer 24

• Resting (closed) sodium channels have low affinity for lidocaine, whereas open sodium channels have high affinity; therefore highly active channels are most likely to be blocked while resting channels are likely to be unaffected (called ‘use-dependent block’)
• Arrhythmias are often caused by aberrant, frequent depolarizations of sodium channels in damaged cardiac muscle > inhibited at low concentration, while less frequent, normal signals in healthy cardiac tissue are relatively unaffected > antiarrhythmic effect
• Excessively high dose may cause heart block/arrhythmias (cardiac arrest at highest dosages)
  *** Do not use epinephrine-containing products
• Cats are especially sensitive to lidocaine
  o Seizures more likely in this species - avoid?