Full agonists (8)
Partial agonists (1)
Agonist - Antagonist (2)
mu-agonist 5-HT NE reuptake inhibitor (1)
Drugs that inhibit preception (5)
Drugs that inhibit transmission (2)
Drugs that inhibit peripheral sensitazation of nociceptors (transduction) (4)
Drugs that modulate the spinal pathway (7)
What are the opioid receptors linked to?
What does Gi protein stimulus cause?
What effects does opioids have on ion channels?
Close - Presynaptic Ca2+ channels (u + d + K)
Open - postsynaptic K+ channels (u)
What effects does closing the Ca2+ channels have?
Decrease NT release
What is the effect of opening post-synaptic K+ channels?
What are the major overall effects of opioids?
INhibition of pain transmitting ascending systems
Stimulating descending pain transmission inhibiting neurons
What are the actions of opioids at the presynaptic terminal?
decrease NT release
What effects does opioids have post-synaptically?
Increase gK+ - IPSP
Where in the body are mu receptors found?
Dorsal horn of spinal cord
What are the effects of mu receptor activation?
Supraspinal + Spinal analgesia
Decrease GI motility (ACh effect)
What NT are effected by mu receptors?
Where in the body are kappa receptors found?
What is the result of kappa receptor activation?
Spinal + Supraspinal analgesia
What NT is affected by kappa? What is the result?
Stops release to induce diuresis
Where are the delta receptors found?
What occurs with delta receptor activation?
Spinal + Supraspinal analgesia
What NT is affected by delta receptors?
What are the three endogenous opioids?
What levels of analgesia occur with opioid administration?
What receptor has the largest analgesic effects?
What is the relationship between duration of action and 1/2 life with opioids? Why?
Duration of action normally shorted then 1/2 life
Desensitization + Down regulation of receptors
What CNS occur with opioids at high and low concentrations?
Low - Depression
High - Excitation
What respiratory effects are seen with opioids?
mu receptors = depressants
will see panting due to change in thermoregulatory set point
What is the effect of the respiratory depression seen with opioids?
Increase in arterial CO2 tension
Decreate in arterial O2 tension
Decrease in pH
What are the cardiovascular effects of opiods?
For the most part spare the CV system
Hypotension can occur
What can be seen in dogs with opioid administration that effects heart rate?
Induce barorecptor response
Why do you see vasodilation with opioid administration?
What are the GI effects of opioid administration?
IM - vomiting dogs
IV decreases this effect
Constipation + decrease gastric emptying
What are the pupilary effects of opioids?
Mydriasis - Cats + Horses
Morphine - Vomit induction in Dogs
Stimulate chemoreceptor trigger zone
Morphine - Uses
Acute pain - dogs, cats, horses
Sedative to reduce pacing + standing procedures - horse
Antitussive - Dogs
Morphine - BA
<20 % - dogs given PO
Due to first pass effect
Morphine - Excretion
Morphine - Metabolism
Morphine - Adverse effects
Abnormal body temp
What animals see hyperthermia with morphine?
Why is cerebral hemorrhage + edema a concern with morphine?
Arterial CO2 increase
INcrease cerebral blood flow - increased pressure
What animals see hypothermia with morphine?
Tramadol - Mechanism
inhibits reuptake of serotonin + NE
What contributes to tramadols analgesic effects?
Inhibition of serotonin + NE
Tramadol - use
Anlagesic + Antitussive
Tramadol - Admin
Tramadol - BA
Tramadol - Metabolism
Tramadol - 1/2 life
Dogs = 0.8 to 1.7 hours
Cats - 3 to 5 hours
Horses = 1.5 to 4 hours
Methadone - Mechanism
May have NMDA receptor antagonist activity
Methadone - Admin
IV + IM + SC
Methadone - Use
Pre-med or Analgesic alternative in dogs/cats
Methadone - BA
very low with PO
Methadone - Protein binding
Albulmin - 60 yo 90%
Methadone - Metabolism
Liver - Cytochrome P450
Methadone - Adverse side effects
Less sedation + vomiting compared to morphine
Oxymorphone/Hydromorphone - Potency
ten times that of morphine
Oxymorphone/Hydromorphone - Uses
Oxymorphone/Hydromorphone - Admin
IV + IM + SC + Rectal
Fentanyl - Mechanism
Fentanyl - Admin
IV + Patch
Fentanyl - Duration of Action
Patch - 72 hours
Fentanyl - Use
Fentanyl - Pain control
Fentanyl - Onset
More rapid then morphine due to increase lipid solubility
Fentanyl - Metabolism
Fentanyl - Excretion
Fentanyl - Adverse effects
Sensitive to noise
Panting + defecation + flatulence
How can bradycardia + hypersalivation due to fentanyl be treated?
Alfentanil - Potency
4x's less potent then fentanyl
Alfentanil - Mechanism
Alfentanil - Admi
IV + IM + SC
Alfentanil - Metabolism
Liver - P450
Alfentanil - Use
Analgesic + Sedative
Adjunctive anesthesia (cats)
Sufentanil - Potency
5 to 10x's more potent then fentanyl
Sufentanil - Admin
IV + IM + SC + Epidural
Sufentanil - Use
Sufentanil - Metabolism
Small Intestine via O-demethylation
Sufentanil - Adverse effect
CNS + respiratory depression
Carfentanil - Potency
10,000 x's more then morphine
Carfentanil - Admin
Carfentanil - 1/2 life
2 to 24 hours
needs a reversal due to this
Carfentanil - Adeverse effects
Disruption of body temp
CNS + respiratory depression
Carfentanil - Reversal Agent
Longer duration of action
Butorphanol - Mechanism
Parital agonist for mu-receptor
Full Agonist for kappa-receptor
Butorphanol - Use
Not a great alnalgesic
Opioid reversal - reverses mu-receptor effects
(sedation + respiratory depression)
Antitussive - Dogs with chronic cough
Analgesia in cats + cattle
Anti-emetic for chemotherapy
Chemical resitrant in cattle
Butorphanol - Withdrawl
5 days meat withdrwal
Butorphanol - BA
Horses - 37% via IM in adults
67% in Foals
Butorphanol - 1/2 life
6 hours - adults
2 hours - foals
Butorphanol - Adverse effects in horses
Startle to loud Noises
Butorphanol - Dogs elimination
P-glycoprotein mediates elimination from CNS
Butorphanol - Adverse effects in Dogs
hets - 25% reduction in dose
homos - 50% reduction in dose
What are the subtypes of the opioid agonist/antagonists?
1 - antagonize mu + activate kappa
2 -partial agonist for mu + antagonist for kappa
Buprenorphine - Potency
30x's the analgesic effect compared to morphine
Buprenorphine - Mechanism
Partial Agonist for mu
Antagonist for kappa
Very strong affinitiy for mu
Buprenorphine - Reversals
Resistant to Naloxone due to strong mu affinity
Buprenorphine - Admin
IV + IM + SC + Transmucosal + Topical
Buprenorphine - Use
Analgesic/Premed in Small Animals
Analgesic in horses
Buprenorphine - Protein binding
Buprenorphine - 1/2 life
5 to 6 hours
Buprenorphine - Metabolism
Buprenorphine - Adverse effects
respiratory depression + sedation
Nalbuphine - Mechanism
Antagonist for mu-receptor
Agonist for kappa-receptor
Nalbuphine - Potency
equal to morphine
Nalbuphine - Admin
Nalbuphine - Use
Mild to moderate pain
Nalbuphine - Duration of action
Dogs = 45 minutes
Cats = 2 to 3 hours
Nalbuphine - Protein binding
does not bind
Nalbuphine - Metabolism
Liver - Glucoronidation
Nalbuphine - Excretion
Nalbuphine - 1/2 life
Dogs = 1.2 hours
Naloxone - Mechanism
High affinity for mu-receptor
Low affinity for kappa + delta
Naloxone - Use
Naloxone - Metabolism
Liver - CYP450
Naloxone - Excretion
Naltrexone - Mechanism
Long- acting antagonist
Naltrexone - use
Naltrexone - Admin
IV + IM
When is naltrexone given orally to dogs? How?
To treat behavioral problems in dogs
Reduced endorphine binding