Lecture 2 & 3 - Local Anesthetics

Question 1

Discus pain and the what happens if it is ‘long term’

Answer 1

Pain: protective mechanism to make an anaimal withdrawla from a potentially damaging situation
untreated and needless pain can:
- lead to behavioral distress and withdraw from the enviornemnt
- it cna also lead to chronic activation of the stress axis, both HPA axis and SNS
-

Question 2

nocicpetion

Answer 2

neural response to painful stimulus

Question 3

Nociceptors

Answer 3

Nociceptors: nerve endings that detetc pain via specific recpetors (lkowcated on sensory fibers):
- heat, touch, pH, chemicals, or
- paarcrine substnces releassed during trauma (prostaglandins, kinins, substance P)
-

Question 4

A __ fibers

Answer 4

fast conducting –> first pain that is sharp and acute. They have discretereceptive fields making localizinng pain eaiser

Question 5

C fibers:

Answer 5

C fibers:
- slow conducting –> ‘second’ pain that is dull, ahcing, burning, or throbbing pain that is hard to localize

Question 6

Hyperalgesia

Answer 6

Hyperalgesia –> exagerrated repsonse to painful stimuli (asa. response to therapy or infectioon)

Question 7

Allodynia

Answer 7

Pain due a stimulus which does not nornmally provoke pain (touch, light pressure, cold felt as pain)

Question 8

discusss signs of pain (feline specific)

Answer 8

• hunched posture
• head held low
• swuinted eyes
• sitting quiety or hiding
• ## resent handling

Question 9

discuss signs of pain for equine

Answer 9

Question 10

Discuss the mechanism of action for local anesthetic drugs

Answer 10

Mechanism of action: reversioble block of nerve impulse conduction by blocking volatge depednent sodium channels that are required fpr action potentials

NOTE: the block is in the open channel
- bloclk is use depednent
- the more a nerve fires, thew more its blocked
-

Question 11

when considerign the different types of nerve fibers, which one is most sensitive? ALso discuss the ‘order of loss’

Answer 11

small unmyelinated fibers are most sensitiv

Order of loss: - pain sensation is lost first, then temperature, touch, joint, deep pressure

Question 12

Discuss the ‘make up’ of local anesthetic drugs

Answer 12

Local anesthetic drugs are weak bases generally consisting of:
- lipophilic group
- an intermediate chain: either an ester or amide link
- hydrophilic group capable of iuonization (usually a tertiary amine)

Question 13

For local anesthetics, discuss bioavailability

Answer 13

Bioavailaibility - gettoing to the site of action:
- Local anesthetics (LAs) are 1) weak bases 2) generally available as salts 3) in tissue, LA siaaociate to free base 4) LAs approach their bidning site on the Na channel from the intracellular side 5) LAs must be uncharged to cross the cell membrane and gain access to inside of the cell

ALSO: inflamed tissue is more acidic than normal tissue –> thus LAs are less effective in inflamed tissue (trapped in the extracellular space)

Question 14

Discuss the breakdown categories of local anesthetics

Answer 14

So basically, LAs are broken down into 2 categories: 1) amino esters (cocaine, benzocaine, procaine, proparacaine,) and 2) amino amides (lidocaine, mepivacaine, bupivacaine)

Question 15

Discuss teh metbaolism of amino esters

Answer 15

AMino esters are hydrdrolyzed by plasma esterase enzymes (non specific pseudocholinesterases) ….. can lead to:
- can lead to formation of par aminobenzoix acid (PABA)
- potential allergen - can lead to allergic reactions
- plasma pseduocholinesterases are reduced during pregnancy prolongin the actions of ester local anesthetics

Question 17

Discuss the metabolism of amino amides

Answer 17

AMino amides are biotrandofmed by liver enzymes:
- rarely evokes allergic reaction
- chnages in heoatic function will impact metabolism:
- age, disease, species
- if conjugation with glucouronide is necesarty before excretion (i.e bupivacaine) cats have alimited ability to do this and so toxicity could occur
- changes in heoatic blood flow during regional or general anesthesia
- matbvolism of some amino amides which can cause methemoglobinemia

Question 18

Discuss the routes of administration for surface anesthesia

Answer 18

• sprayed on the mouth, nose, larynx
• dropped in the eye
• pacthes

Question 19

discuss

discuss the routes of administratio for conduction anesthesia and spinal anesthesia

Answer 19

Conduction anesthesia:
- nerve block: injection in nueroplexus, ganglia, nerve trunks

SPiunal anesthesia:
- injection in subarachnoid space
- epidural block

Question 20

Discuss the adverse effects

Answer 20

Dose related drug toxicity:
- **CNS excitation: **
- seizures, twitching, seemes paradoxical but it is bnecause LAs affects inhibitory CNS neurons first …… but very high levels get CNS depression

- Cardiovascular:
- can cause dysarrtythmias, including ventricular fibrilation
- hypotension –> due to decreased myocardial contraction leading to decreased cardiac output as well as relaxation of vascular smooth muscle

Methemoglobinemia: remmeber, methemoglobin is a form of hemoglobin that does not bind oxygen

Can get respiratory depression if gets to C5 - C7 or CNS regulation of respiration

Question 21

Discuss the order of effects for local anesthetics

Answer 21

1) analgesia
2) altered consciousness
3) ,uscle twitching and hypotension
4) myocardial depression
5) unconscioussness and apnea
6) cardiovascular collapse and death
7)

Question 22

Discuss the unusual reactions when considering the adverse effects of local anesthetics

Answer 22

1) hypersensitivity (allergic) reactions: esters > amids (this is normally due to formation of PABA)
2) Drug idosyncrasy: atypical pseducoholinestrrases (esters)

Question 23

Discuss the interactactions local anesthetics have with vasocnstrictors

Answer 23

A) sympathomimetic amines: epinephrine, norpeinephrine, phenyleprine
B) Objectives: 1) increase durationnof local anesthesia 2) decrease systemic toxicity
C) can cause. aproblem with circulation –> caution with use near digits, tails, ears, and penis
D) can increase risk of arrythmias and ventricular fibrillation