Pain Pathway & Opioids (Dr. Garcia)

Question 1

Opioids method of action

Answer 1

Hyperpolarizes cells by potassium channels

Question 2

Pain

1.

2.

3.

4.

5.

Answer 2

1. From Latin meaning punishment
2. Sensory and emotional experience assoc. with actual or potential tissue damage
3. Subjective and genetic
4. Requires functional CNS
5. Multiple brain areas

Question 3

Pain pathway

1.

2.

3.

4.

5.

Answer 3

1. Transduction
2. Transmission
3. Modulation
4. Projection
5. Perception

Question 4

Classifications of Pain

Acute vs Chronic

Answer 4

1. Acute: Physiologic purpose
   - short term with easy identifiable cause
   - bodies warning of tissue damage or disease
2. Chronic pain
   - Persistant pain
   - May be constant or intermittent
   - Outlived usefulness, more difficult to treat

Question 5

1. Neuropathic pain
2. Visceral pain
3. Somatic pain

Answer 5

1. Generated by the nervous system
2. Organs…
3. Skin and muscle

Question 6

1. Nociception
2. Analgesia
3. Hyperalgesia
4. Allodynia

Answer 6

1. Nociception

• ability to perceive/sense pain
• opiates produce ‘anti-nociception’

2. Analgesia

• Loss of sensitivity to pain WITHOUT loss of consciousness
  
  • opiates => ‘narcotic analgesics’
  • NSAIDs => non-narcotics

3. Hyperalgesia
   * Inc response to painful stimuli
4. Allodynia
   * Pain caused by a stimulus that would not normally provoke pain

Question 7

SIgns of pain

Behavioral Signs

Answer 7

Behavioral Signs

• Vocalization
• Protective postures
• Mood changes: aggression
• Self-mutilation
• Loss of appetite
• Shallow/rapid breathing

Question 8

Signs of Pain

Physiological Changes

Answer 8

Physiological Changes

• General CV activation (inc sympathetic activity)
• inc stress response (activation of HPA axis)
• hyperglycemia (inc glycogenolysis & inc lipolysis)
• reduced GI activity (ileus)
• reduced immune function (diminished wound healing)

Question 9

Therapeutic uses of Opioid drugs

Answer 9

1. Anti-Tussive: Codeine and derivatives
   * Butorphanol…?
2. Emetic: Apomorphine

• Morphine
• hydromorphone

*opioids also an anti-emetic…? after repeat doses

Question 10

Problems

Answer 10

1. Difficulty to assess pain in animals
2. Specific behavior for each species
3. Training personell and use validated scales
4. Time and efficiency
5. Subjective assessment

Question 11

Multidimensional scales

Answer 11

Scales

• Glasgow composite

Categories

• physiologic parameters
• behavioral responses

Question 12

Approaches to Alleviate Pain

Answer 12

1. Prevention
2. Acupuncture

• May activate endogenous pathways for pain suppression
  
  • opioid peptides: endorphins, enkephalins

3. Analgesics

• drugs that block stimulation of sensory nerve endings (transduction)
  
  • NSAIDS, Glucocorticoids
• drugs that block impulse transmission in sensory nerves
  
  • Local Anesthetics
• Drugs that block or modulate transmission in spinal / supraspinal pathways or alter the central perception of pain
  
  • Opioids
  • Alpha-2 Agonists
  • Dissociative Anesthetics (NMDA Antagonists)
  • NSAIDS
  • Local anesthetics

Question 13

Analgesic Drug Action

CNS Action

Answer 13

1. Alpha-2 agonists
2. NMDA Antagonists
3. Opioids
4. Cannabinoids

Question 14

Analgesic Drug Action

Epidural Injection

Answer 14

1. Opioids
2. Local Anesthetics
3. NMDA Antagonists
4. Alpha-2 Agonists
5. NSAIDS

Question 15

Analgesic Drug Action

Nerve Block

Answer 15

1. Local Anesthetics

Question 16

Analgesic Drug Action

Peripheral

Answer 16

1. NSAIDs
2. Corticosteroids

Question 17

DEA-Regulated Opioids

C1-CIV

Answer 17

Class 1:

• heroin
• bufotenine

Class 2

• morphine
• fetanyl
• opium

Class 3

• buprenorphine

Class 4

• butorphanol

Question 18

Opioid Receptors

Answer 18

mu

kappa

delta

Question 19

Required Drugs

Morphine =>

Butorphanol =>

Buprenorphine =>

Naloxone =>

Answer 19

Morphine => full agonist

-limiting factor is side-effects

Butorphanol => agonist-antagonist

• will eventually reach full analgesia
• ceiling effect (and will reverse itself at high doses I think)

Buprenorphine => partial agonist

-ceiling effect (and will reverse itself at high doses I think)

Naloxone => antagonist

Question 20

mu receptor

Answer 20

Most effective opioid recepter (most potent analgesic)

Has the most side effects

Question 21

Pharmacological Actions of Opioids

Answer 21

Depresses

• CNS
  
  • analgesia
  • mood alteration
  • sedation
  • nausea/vomiting (dogs)
  • depressed breathing (change)
• GI
  
  • contipation (dec propulsive activity)
• CV
  
  • bradycardia hypotension (histamine release)

Question 22

Opioid Analgesia

Effect and levels of action

Answer 22

Effect involves at least two levels of action

Spinal Cord (modulation)

• dec substance P release from sensory afferents
• dec postsynaptic actions of substance P

Supraspinal Level (perception)

• dec affective response to pain
• dec fear / anxiety associated with pain

Question 23

Opioid Sedation

Answer 23

1. Variable degree of sedation depending on species, age and demeanor
2. Additive depression with other CNS depressants
   * reduces overall anesthetic requirement in most animals
3. Dopinergic decrease
4. Opioids can cause excitement as a premed

Question 24

Ventilatory Depression in opioid

Answer 24

1. Depresses PCO2 sensitivity of brainstem repiratory center neurons

• reversible with naloxone
• most common cause of death in humans in opioid overdose

Question 25

Opioid Nausea & Emesis

Answer 25

1. Caused by stimulation of brainstem chemoreceptor trigger zone (CTZ) * apomorphine is extremely effective * reduced by phenothiazines and other dopamine antagonists * Anti-emetic after first dose * Effect of Vomiting Center

Question 26

Opioid cough suppression

Answer 26

Butorphanol

Question 27

Opioid pupillary Effect

Answer 27

Species specific

Question 28

GI Actions of Opioids

Answer 28

1. Inhibit most indices of GI activity 2. GI effects **local** and **CNS** actions * dec propulsive movements (peristalsis) * dec secretion * inc segmental contractions (tone, intragastric pressure)

Question 29

Cardiovascular actions of Opioids

Answer 29

Cause * dec heart rate * dec blood pressure if: **histamine release** Reversed by **anti-cholinergic** agents

Question 30

Morphine

Answer 30

1. Moderate lipid solubility, mod ability to penetrate blood-brain barrier * ideal for epidural administration 2. High first pass metabolism 3. **Metabolized via glucuronic conjugation** 4. Active metabolites * morphine-6-glucuronide (M6G) * morphine-3-glucoronide (M3G) 5. Potency 1 (related to dose, 1 not very potent)

Question 31

Fentanyl

Answer 31

1. Potent synthetic opioid agonist * 100X more potent than morphine for most indications 2. Good analgesic in dogs, cats and horses 3. Less cardiovascular impact than morphine * **less histamine release** 4. fairly short half life (rapid liver metabolism

Question 32

Meperidine

Answer 32

1. Good sedative in young / geriatric patients 2. Structure similar to atropine * only opioid to cause inc in heart rate 3. Give IM because of histamine release

Question 33

Buprenorphine

Answer 33

1. Mild-moderate analgesic 2. given SC, IM, IV, * sublingual in cats

Question 34

Butorphanol

Answer 34

1. **Mu antagonist /** **kappa agonist** * Can use to reverse some of effects of Mu agonists while providing analgesia via kappa 2. Minimal side effects 3. Mild analgesic in dogs, cats * less CV and respiratory depression * effective anti-tussive in dogs and cats 4. Good analgesia in Horses and ruminants

Question 35

Naloxone

Answer 35

1. Full antagonist 2. Shorter half-life than most opioids 3. opioid intoxication reverseral

Question 36

Neuroleptanalgesia

Answer 36

1. animal unresponsive to sensory stimuli and no response to pain **but not completely unconscious** 2. Combination of an analgesic with a sedative * penothiazines * alpha-2 agonists