What is the difference between an opiate and an opioid?
an opiate is a drug derived from the opium poppy
an opioid encompasses the opiates, but includes any substance that acts on the opioid receptors (can be man-made or endogenous)
What are the 3 receptors opioids bind?
Mu (analgesia, respiratory depression, decreased GI motility, dependence)
kappa (analgesia, sedation, decreased GI motility)
delta (modules mu activity)
What are the encogenous opioids that act on the mu receptors? keppa? delta?
mu - endorphins and endomorphines
kappa = dynorphins
delta = enkephalins
What sort of receptor is the Mu receptor?
What does the mu receptor do when activated? On the presynaptic terminal!
It inhibits a Ca2+ channel and adenylyl cyclase (less cAMP)
Because the Ca2+ channel is inhibited, you have reduced release of glutamate and substance P
thus, the signal isn't transmitted
In addition to blocking Ca2+ on the presynaptic terminal, what happens in the post synaptic terminal?
the receptor activation opens K+ channel, allowing K+ to flow out, causing hyperpolarizaiton and decreased excitability
makes the postsynaptic neuron even less likely to fire
The inhibition of the ascending pain transmission pathway occurs mostly where?
in the dorsal horn, but also in the spinal cord, thalamus and maybe the periphery
What are opioids effect on the descending inhibitory pathway?
It enhances the descending inhibitory pathway, thus further inhibiting the ascending pain pathway
Under normal conditions, an inhibitory interneuron is constitutively releasng GABA onto the efferent presynaptic neuron, thus inhibitin the descending pathway
Opioid receptor activation blocks release of GABA from the inhigitory interneuron, so you get activation of the inhibiting descending pathway
thus, greater inhibition of nociceptive processing in dorsal horn of the spinal cord (Gate theory)
What are some examples of opioid agonists?
they bind the receptor and produce an effect:
morphine, methadone, oxycodone, heroin
How does an antagonist work and what are two examples?
it binds to the receptor but doesn't have an effect, so it's usually used to compete for the receptor in opiate addiction
examples include Nalozone and Naltrexone
Why would you maybe want to prescribe a partial agonist and what is an example of one?
It's less efficacious than a full agonist, but it has lower abuse potential
Buprenorphine is one
It's often used in tandem with nalozone (combo is subozone)
What is an example of a mixed agonist/antagonist? What is the clinical relevance?
it's an agonist at kappa and antagonist at Mu
this means if you change someone who is opiate dependant to this, they will enter withdrawal
What are the pros and cons of using opioids orally?
Pro: convenient, longer duration than parenteral routs, better for chronic treatment
Con: high first pass metabolism is limiting, slowe ronset, delayed peak effect
What are the pros and cons of giving opioids IV?
pro: precide and accurate dosin, rapid onset, you can do bolus or continuous and patient can control dose with button
con: increased risk of adverse effects
What are some of the benefits of giving opioids intra-thecally?
longer duration at lower doses than systemic
can avoid some of the brain-mediated adverse effects like respiratory depression
What is nice about recetal suppositories for opioids
administration can be discontinued easily
What is first pass metabolism and what does it mean for dosing?
a drug that is absorbed from the GI tract has to go to the liver first and opioids are rapidly and efficiently metabolized
oral morphine has to require 3-6x higher the dose you'd give parenterally
which opioid drug is less impacted by first pass metabolism?
What will make an opioid more addictive than another opioid?
how fast it crosses the BBB = more lipid solubility (heroin is more lipid solubel than mophine)
What is a pharmacologically active metabolite of morphie? Why is renal function a concern with this?
it's active, but it's excreted int he urine so if renal function is compromised, this can build up and cause opioid overdose
What is a toxic metabolite of an opioid? What does it cause and what does that mean for this drug's use?
normeperidine is a metabolite of meperidine
it is excitotoxic, causing tremor, twitching and convulsing
this means meperidine should only be used acutely
Why is miosis (pinpoint pupils) a very good indicator of opioid use?
it doesn't develop tolerance, so a person who is chronically abusing opioids will still have pinpoint pupils
What effect do opioids have on the GI tract? Respiratory system? Uterus? Ureters? Skin?
GI = decreased motility, constipation, cramping
Repiratory = bronchilar construction at high doses
Uterus = prolongs labor
Ureters = difficulty urinating
Skin = itching and flushing due to histamine release
Although opioids are sometimes used to slow progress of obstetric labor, what is the concern?
it can cross the placental barrier and caus eneonatal respiratory depression
What opioids are given for diarrhea?
loperamide (imodium) doesn't cross the BBB so it's not addictive
Diphenoxylate and Atropine (Lotomil) the atropine is put in for its negative seide effects to discourage abuse
What antagonist do you use to treate acute overdose? Which do you use to treat addiction?
OD = naloxone; injected - extremely rapid effect and short duration of action
Addiction = naltrexone - given orally and a single dose on alternate days can block heroin effects
Which effects of opioid reach tolerance first, which never do?
most rapid: analgesia, euphoria, sedation, respiratory depression, cough suppression, nausea, and vomiting
Never: miosis and constipation
What are some symptoms of opioid withdrawl?Is it life threatening?
rhinorrhea, lacrimation, yawning, chills, gooseflesh, hyperventilation, hyperthermia, mydriasis, muscular aches, vomiting, diarrhea, anxiety and hostility
not life threatening
What does the word "narcotic" really mean
it means something that puts you to sleep, but now it's taken on more of a legal term for controlled substances