Opioids Flashcards
why might a patient start to wake up under general anesthetic alone? How can we prevent this?
-General anesthetics produce unconsciousness but do not inhibit pain signal generation or propagation
-Patients do not feel mildly painful surgical manipulations because the small numbers of pain signals, which are transmitted to the Reticular Activating System (RAS) in the medulla, are insufficient to awaken the patient
-If surgical manipulations produce large numbers of pain signals, the RAS may be stimulated to the point where the anesthetized patient begins to awaken
-We can prevent this by administering an analgesic beforehand
Opioid drugs are used for:
1) Analgesia
2) Sedation
3) Cough suppression (Antitussive)
4) Treatment of diarrhea (Constipation is a major side effect of the opioids)
3 opioid receptor families that mediate analgesia:
- Mu (μ; MOR)
- Delta (δ; DOR)
- Kappa (κ; KOR)
opioid receptor type that produces dysphoria
Sigma (σ)
Opioid mechanism of action: mechanism of analgesic effects
Opioids stimulate opioid receptors in pain pathways
Pain afferent (from periphery)
-Pre-synaptic Mu, Delta, Kappa opioid receptors inhibit Ca2+ entry, which inhibits NT release
Spinal pain neuron
-Post-synaptic Mu opioid receptors open K+ channels, which causes hyperpolarization > inhibits action potentials
Effects of opioid receptor stimulation: MOR, DOR, KOR
MOR:
* Analgesia
-Full stimulation causes intense analgesic effect
* Euphoria (> dependence)
* Miosis or mydriasis
* Resp. depression (> less sensitive to CO2)
DOR:
-analgesia, similar to MOR
KOR:
* Analgesia (moderate effect, and primarily visceral)
Sigma R stimulation effects:
- Dysphoria: intense feeling of unease or even terror
- Resp. & vasomotor stimulation
- Stimulated by opioids in some patients, and by some non-opioids (e.g., ketamine)
full agonist vs partial agonist opioid
Opioids can stimulate opioid receptors:
maximally > called a “full agonist” or
weakly > called a “partial agonist”
what is a mixed agonist/antagonist opioid
Some opioids are agonists at some opioid receptors and antagonists at others
why are partial agonist opioids sometimes called “partial agonist/antagonists”
Because they can competitively block the action of full agonists
Describe the mechanistic interaction of fentanyl (full mu agonist) with butorphanol (kappa agonist which also weakly stimulates mu receptors)
Fentanyl alone: intense analgesic effect, binds to MOR
Butorphanol alone: binds to KOR for a moderate analgesic effect, and binds to MOR for a weak analgesic effect
Together: butorphanol binds KOR for a moderate analgesic effect. Some MOR are weakly stimulated by butorphanol, and others are maximally stimulated by fentanyl.
=> Overall analgesic effect will be less than fentanyl alone
Morphine works on what receptor, with what interaction? Primary effect?
Mu agonist, analgesia
Codeine works on what receptor, with what interaction? Primary effect?
Mu agonist, analgesia (poor)
Hydromorphone works on what receptor, with what interaction? Primary effect?
Mu agonist, analgesia
Meperidine works on what receptor, with what interaction? Primary effect?
Mu agonist, analgesia
Fentanyl works on what receptor, with what interaction? Primary effect?
Mu agonist, analgesia
Buprenorphine works on what receptor, with what interaction? Primary effect?
Mu partial agonist > Analgesia (counters the effects of full mu agonists)
Kappa antagonist
Butorphanol works on what receptor, with what interaction? Primary effect?
Kappa agonist > analgesia (main mechanism)
Mu partial agonist > analgesia (counters the effects of full mu agonists)
opioid that can be used for cough suppression
butorphanol
opioid that can induce vomiting in dogs
apomorphine
opioid that causes contipation the most
loperamide
hydromorphone duration of analgesia
3-6 h
buprenorphine duration of analgesia
4-8 h
pharmacokinetics of opioids
- Weak bases
- Phase I & Phase II metabolism with high first-pass effect
> most opioids are therefore administered parenterally
difference between codeine metabolism in dogs vs humans
In humans, ~10% of codeine is metabolized into morphine
> main source of codeine’s analgesic effect
This occurs to a low or negligible extent in dogs
what body systems do full mu agonists effect?
- CNS
- Cardiovascular
- Respiratory
- GI
- Urinary
CNS effects of full mu agonists (eg. morphine)
- 3-6 hours of analgesia + sedation (not sleep)
-Sedation is most likely in dogs & primates
Excitement is likely in most other species - High doses of morphine cause excitement
cardiovascular effects of full mu agonists (eg. morphine)
- Usually little effect on CVS at the dosages normally administered
- Morphine may trigger histamine release > vasodilation > hypotension
respiratory effects of full mu agonists (eg. morphine)
- Dose-dependent depression
- Death from overdose is due to respiratory arrest – a Mu effect
GI effects of full mu agonists (eg. morphine)
- Increase segmentation but reduce propulsion in large bowel > stool becomes dehydrated > constipation
- Bile duct sphincter constriction > increase in gall bladder pressure > biliary colic
- Nausea & vomiting (chemoreceptor trigger zone MOR stimulation)
Urinary system effects of full mu agonists (eg. morphine)
Urinary bladder sphincter tone increased & detrusor muscle tone increased > urgency to urinate but difficult
fentanyl main uses? How is it commonly administered?
- For profound pain relief in small animals
- Also commonly used as an analgesic + sedative
prior to induction - Commonly administered as a transdermal patch
Etorphine (“M-99”) use and effects? Similar drug? what other drug should be used with this?
-wildlife restraint
Carfentanyl is similar
* Renders large animals ataxic within seconds
(e.g., ~5 mg immobilizes an elephant or rhino)
- Reversal agent required for recovery
>Keep M99 and M5050 together
>Load the M5050 syringe first
butorphanol mechanism and main uses:
- Commonly used for post-op analgesia
- Kappa agonist/partial Mu agonist*
> for clinical purposes it is usually considered a Kappa agonist and Mu antagonist - Used for mild/moderate pain; ineffective for severe pain
buprenorphine mechanism and main uses:
- Analgesia lasts ~4-6 h
- Partial Mu agonist/Kappa antagonist
- Main advantage is for home (oral transmucosal) administration for animals with chronic pain (long duration)
apomorphine main use
- Used to cause dogs to vomit
- Vomit reflex is triggered through dopamine receptors; cannot be stopped with naloxone
alternative to apomorphine to induce vomiting
Ropinirole - not an opioid, stimulates dopamine receptors
main opioid antgonist - how does it work
naloxone
Bind & block Mu opioid receptors (competitive inhibition)
