Pain Pathway & Opioids (Dr. Garcia) Flashcards
Opioids method of action
Hyperpolarizes cells by potassium channels
Pain
1.
2.
3.
4.
5.
- From Latin meaning punishment
- Sensory and emotional experience assoc. with actual or potential tissue damage
- Subjective and genetic
- Requires functional CNS
- Multiple brain areas
Pain pathway
1.
2.
3.
4.
5.
- Transduction
- Transmission
- Modulation
- Projection
- Perception
Classifications of Pain
Acute vs Chronic
- Acute: Physiologic purpose
- short term with easy identifiable cause
- bodies warning of tissue damage or disease - Chronic pain
- Persistant pain
- May be constant or intermittent
- Outlived usefulness, more difficult to treat
- Neuropathic pain
- Visceral pain
- Somatic pain
- Generated by the nervous system
- Organs…
- Skin and muscle
- Nociception
- Analgesia
- Hyperalgesia
- Allodynia
- Nociception
- ability to perceive/sense pain
- opiates produce ‘anti-nociception’
- Analgesia
- Loss of sensitivity to pain WITHOUT loss of consciousness
- opiates => ‘narcotic analgesics’
- NSAIDs => non-narcotics
- Hyperalgesia
* Inc response to painful stimuli - Allodynia
* Pain caused by a stimulus that would not normally provoke pain
SIgns of pain
Behavioral Signs
Behavioral Signs
- Vocalization
- Protective postures
- Mood changes: aggression
- Self-mutilation
- Loss of appetite
- Shallow/rapid breathing
Signs of Pain
Physiological Changes
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)
Therapeutic uses of Opioid drugs
- Anti-Tussive: Codeine and derivatives
* Butorphanol…? - Emetic: Apomorphine
- Morphine
- hydromorphone
*opioids also an anti-emetic…? after repeat doses
Problems
- Difficulty to assess pain in animals
- Specific behavior for each species
- Training personell and use validated scales
- Time and efficiency
- Subjective assessment
Multidimensional scales
Scales
- Glasgow composite
Categories
- physiologic parameters
- behavioral responses
Approaches to Alleviate Pain
- Prevention
- Acupuncture
- May activate endogenous pathways for pain suppression
- opioid peptides: endorphins, enkephalins
- 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
Analgesic Drug Action
CNS Action
- Alpha-2 agonists
- NMDA Antagonists
- Opioids
- Cannabinoids
Analgesic Drug Action
Epidural Injection
- Opioids
- Local Anesthetics
- NMDA Antagonists
- Alpha-2 Agonists
- NSAIDS
Analgesic Drug Action
Nerve Block
- Local Anesthetics
Analgesic Drug Action
Peripheral
- NSAIDs
- Corticosteroids
DEA-Regulated Opioids
C1-CIV
Class 1:
- heroin
- bufotenine
Class 2
- morphine
- fetanyl
- opium
Class 3
- buprenorphine
Class 4
- butorphanol
Opioid Receptors
mu
kappa
delta
Required Drugs
Morphine =>
Butorphanol =>
Buprenorphine =>
Naloxone =>
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
mu receptor
Most effective opioid recepter (most potent analgesic)
Has the most side effects
Pharmacological Actions of Opioids
Depresses
- CNS
- analgesia
- mood alteration
- sedation
- nausea/vomiting (dogs)
- depressed breathing (change)
- GI
- contipation (dec propulsive activity)
- CV
- bradycardia hypotension (histamine release)
Opioid Analgesia
Effect and levels of action
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
Opioid Sedation
- Variable degree of sedation depending on species, age and demeanor
- Additive depression with other CNS depressants
* reduces overall anesthetic requirement in most animals - Dopinergic decrease
- Opioids can cause excitement as a premed
Ventilatory Depression in opioid
- Depresses PCO2 sensitivity of brainstem repiratory center neurons
- reversible with naloxone
- most common cause of death in humans in opioid overdose
Opioid Nausea & Emesis
- 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
Opioid cough suppression
Butorphanol
Opioid pupillary Effect
Species specific
GI Actions of Opioids
- Inhibit most indices of GI activity
- GI effects local and CNS actions
- dec propulsive movements (peristalsis)
- dec secretion
- inc segmental contractions (tone, intragastric pressure)
Cardiovascular actions of Opioids
Cause
- dec heart rate
- dec blood pressure if: histamine release
Reversed by anti-cholinergic agents
Morphine
- Moderate lipid solubility, mod ability to penetrate blood-brain barrier
* ideal for epidural administration - High first pass metabolism
- Metabolized via glucuronic conjugation
- Active metabolites
- morphine-6-glucuronide (M6G)
- morphine-3-glucoronide (M3G)
- Potency 1 (related to dose, 1 not very potent)
Fentanyl
- Potent synthetic opioid agonist
* 100X more potent than morphine for most indications - Good analgesic in dogs, cats and horses
- Less cardiovascular impact than morphine
* less histamine release - fairly short half life (rapid liver metabolism
Meperidine
- Good sedative in young / geriatric patients
- Structure similar to atropine
* only opioid to cause inc in heart rate - Give IM because of histamine release
Buprenorphine
- Mild-moderate analgesic
- given SC, IM, IV,
* sublingual in cats
Butorphanol
-
Mu antagonist / kappa agonist
* Can use to reverse some of effects of Mu agonists while providing analgesia via kappa - Minimal side effects
- Mild analgesic in dogs, cats
- less CV and respiratory depression
- effective anti-tussive in dogs and cats
- Good analgesia in Horses and ruminants
Naloxone
- Full antagonist
- Shorter half-life than most opioids
- opioid intoxication reverseral
Neuroleptanalgesia
- animal unresponsive to sensory stimuli and no response to pain but not completely unconscious
- Combination of an analgesic with a sedative
- penothiazines
- alpha-2 agonists
