Analgesic Agents- Opioids Flashcards
Define ‘Pain’
An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.
Define Nociception
Perception of pain or injurious stimuli
-Nociception is the sensory nervous system’s process of encoding noxious stimuli. In nociception, intense chemical (e.g., cayenne powder), mechanical (e.g., cutting, crushing), or thermal (heat and cold) stimulation of sensory nerve cells called nociceptors produces a signal that travels along a chain of nerve fibers via the spinal cord to the brain. Nociception triggers a variety of physiological and behavioral responses and usually results in a subjective experience, or perception, of pain in sentient beings.
Define Allodynia
a condition where pain is caused by a stimulus that does not normally elicit pain. For example, bad sunburn can cause temporary allodynia, and touching sunburned skin, or running cold or warm water over sunburned skin can be very painful.
Define Hyperalgesia
Increased sensitivity to pain
Define Neuropathic Pain
Neuropathic pain is pain caused by damage or disease affecting the somatosensory nervous system
Define Central Sensitization
Central sensitization is a condition of the nervous system that is associated with the development and maintenance of chronic pain.
When an animal is repeatedly exposed to a painful stimulus, the animal’s pain threshold will change and result in a stronger pain RESPONSE
Define Analgesia
The reduction in the intensity of pain perceived
What are the 4 compartments of the pain pathway that can be targeted for pain management?
Transduction (PNS)
Transmission (PNS)
Modulation (CNS)
Perception (CNS)
Define an Opiate and an Opioid
Opioids refer to all natural, semisynthetic, and synthetic opioids
Opiates refer to only natural opioids such as heroin, morphine and codeine
What is the mechanism of action of opioids?
- Bind to opioid recepters (OP mu, Kappa, delta)
- Opioid receptors are G-protein coupled receptors and lead to inhibition of adenylate cyclase and reduction in cAMP
- Leads to K+ channels opening and an efflux of K+, leading to hyperpolarization
- Ca+ channels are inhibited, causing reduced transmitter release
- Ultimately this leads to a decrease of nociceptive impulses
Where in the body are opioids metabolized and excreted?
Metabolized: Liver
Excreted: Urine and Bile
Where in the nervous system are the opioid receptors found?
- Brain and CTZ
- Dorsal horn (sensory)
- Peripheral terminals of nociceptive afferent neurons
With regards to the pupils, what happens in our domestic species upon administration of opioids?
Dogs get pupil constriction
Cats, horses and ruminants get pupil dilation
With regards to thermoregulation, what happens in our domestic species upon administration of opioids?
Dogs get a hypothermia
Cats, horses and ruminants get a hyperthermia
What are the effects of certain opioids on the CVS?
- Pethidine/ Morphine: can cause a severe histamine release, which can cause severe vasodilation and death if untreated
- All opioids (except Pethidine) can cause Bradycardia
What are the clinical signs associated with an overdose of opioids in animals?
- Severe respiratory depression
- Bradycardia and hypotension
- Altered mental state: depressed and coma-like
- Hypothermia
- Mioisis
- Death
What is the reversal agent to opioids?
Naloxone
How are opioids classified?
Based on the opioid receptor they bind to
Mu, Delta and Kappa
List the 4 or 5 Mu receptor agonists
- Morphine
- Methadone
- Pethidine
- Fentanyl
- Tramadol or Tapentadol: has mild Mu receptor activity
All are, except Ketamine, which is a mu antagonist but kappa agonist
What are the actions of Tramadol?
- Mild Mu receptor activity
- Serotonin reuptake inhibitor
- Noradrenaline reuptake inhibitor: increases activation of descending inhibitory control pathways in the spinal cord
- Alpha2 receptor agonist
- Antagonist of muscarinic receptors
Is tramadol an appropriate analgesic in the dog?
No, the dog doesnt seem to be able to produce high enough quantities of the active metabolite of Tramadol to receive appropriate pain control
Where in the body is Tramadol metabolized and excreted?
Metabolized: liver- to the active form (M1)
Excreted: urine
What are the side effects that can occur with Tramadol administration?
CNS
GI
CVS
- CNS: Sedation, trembling, ataxia, seizures
- GI: nausea, vomiting and anorexia
- CVS: Bradycardia
- Serotonin Syndrome: IF given with tricyclic antidepressants, serotonin reuptake inhibitors or MAO inhibitors
Is Tramadol an appropriate analgesic in cats?
Yes, for acute pain
What are the actions of Tapentadol?
- Mild Mu receptor activity
- Noradrenaline reuptake inhibitor: increases activation of descending inhibitory control pathways in the spinal cord
What are the benefits of using Tapentadol over Tramadol in dogs?
- an appropriate analgesic for acute and neuropathic pain
- No nausea or vomiting reported
- Less risk of Serotonin Syndrome
Tapentadol is considered an appropriate analgesic in dogs, meanwhile Tramadol is NOT
What drug preparation is available and suitable for wild/zoo species for restraint and surgery?
Immobilon: a preparation of etorphine (an opioid) and Acepromazine
What is the reversal agent to Immobilon?
Animals: Diprenorphine aka Revivon
Humans (in case of accidental exposure): Naloxone
Where in the body is Immobilon metabolized and excreted?
Metabolized: liver
Excretion: Urine and bile
What drug is available and suitable for large game species (elephants and rhinos etc.) for sedation?
Carfentanil
