What are examples of phenanthrene opioids?
codeine, hydrocodone, morphine, oxycodone, hydromorphone, oxymorphone
What are examples of non-phenanthrene opioids?
methadone and fentanyl
Where are Mu receptors located?
along nerve tissue and in the GI tract
What is the general MOA of the opioids?
Mu receptor agonist - increases the signal threshold of the spinal neuron, making it unable to transmit pain signals (basically turning the nerve off)
Where will the periphery sensory nerve make a synapse with another neuron to pass along pain sensation?
in the dorsal root ganglion (a joining b/t a 1st and 2nd order neurons)
After periphery sensory nerve synapses and passes along pain sensation, where does the signal go?
up the spinal neuron to the thalamus
What is Morphine effective for?
nociceptive pain, dyspnea and congestive heart failure
What type of pain is morphine and other phenanthrenes not effective for?
neuropathic pain (burning, itching, etc)
What is dyspnea?
trouble breathing, shortness of breath, feelings of being unable to breath
With regard to morphine treatment of dyspnea, what is the goal?
relieve the patient of feeling unable to breath, not to actually slow respirations - just make the patient feel comfortable
What membranes will morphine not cross?
oral mucuous membranes or alveoli - b/c it is water soluble
Where is morphine absorbed?
in the second portion of the duodenum (takes about 20-30 minutes to be absorbed)
How much morphine is metabolized/removed on first pass?
2/3 of the morphine (so PO is only 1/3 as potent as IV)
What are the sources of toxicity in morphine?
metabolites (morph-3-glucuronide and morph-6-glucuronide)
What increases the level of morphine metabolites?
renal impairment, so don't use morphine in patients with renal failure
How long does it take for peak effect of morphine?
What should be done to the dosing of morphine if there is no effect in 1 hour?
double it up
What is duration of action of morphine dependent on?
the level of analgesia needed (lower level = longer duration of action / higher level = shorter duration of action)
What agent is equipotent to morphine?
hydrocodone / 0.25 mL of morphine (5 mg) = 1 Vicodin (5/500)
How fast will SQ morphine peak?
How fast will IV morphine peak?
What are some common side effects of morphine?
sedation, N, dry month, constipation, urinary retention, hypotension, respiratory depression, syndrome of opioid toxicity
Which side effect will patients develop a tolerance to with morphine use?
Which side effects of morphine are associated with Mu receptors in the GI?
nausea, dry mouth and constipation
What part of the GI tract specifically holds the Mu receptors?
myenteric plexus - hit the receptors there and you stop muscle contraction
What agents will help constipation due to morphine use?
stimulants only (such as Bisacodyl)
How much urine will morphine cause the bladder to retain?
1 - 1.5 L
What causes syndrome of opioid toxicity?
build up of the morphine metabolites (higher the dose, the more rapid the accumulation)
What are symptoms of opioid toxicity/
confusion and restlessness, myoclonic jerking/twitching, worsening of pain/development of neuropathic pain, and seizures (rare)
What should be done to help patients suffering from opioid toxicity?
Switch to another agent besides morphine
What should be considered first-line therapy with regards to morphine?
start with short-acting morphine (Roxanol or MS IR) - that way if you give too much, it won't take long for it to get cleared
What agent is a competitive antagonist for the Mu receptor with stronger affinity than morphine?
How do you determine the dose for long-acting morphine?
use the total daily dose of short-acting morphine after titration
What should NOT be done to long-acting morphine (like MS Contin)?
do NOT crush
What should be done to short-acting morphine when administering long-acting?
continue availability of short-acting for breakthrough pain
What should be done if your patient is on long-acting morphine but requires short-acting often for BTP?
increase the dose of long-acting morphine
What is a drawback to rectal morphine?
absorption is erratic and has to be administered Q2H
What are differences in respiratory failure due to morphine and due to other forms of respiratory distress?
pupils will be constricted and breathing is way low (only 4-5 breaths a minute)
What is notable about the therapeutic index for morphine?
there is a wide window b/t symptom relief and respiratory depression (this window is the sedation window) so it is actually kinda tough to kill someone with morphine
What is the relative potency of Oxycodone to Morphine?
1.5 times more potent than morphine so 20 mg = 30 mg of morphine
What is the only dosage form available for oxycodone?
oral - and only comes in brand
What is the name of the new long-acting formulation for Hydromorphone?
What is the relative potency of hydromorphone to morphine?
5 times more potent so 1 mg Dilaudid = 5 mg morphine
What should be noted about metabolism of hydromorphone?
first pass metabolism removes 75-80% of oral dose (so IV to oral is now 4:1 instead of 3:1 with morphine)
When would you typically switch a patient from oral morphine to parenteral dilaudid?
during opioid syndrome
What is the conversion of oral morphine to parenteral dilaudid?
Divide dose by 4 to convert from oral to parenteral and then divide dose by 5 to convert morphine to dilaudid (20:1 ratio)
What is the name of the opioid medication that typically comes in a patch?
Fentanyl - fat soluble drug so it can transit mucous membranes and skin
What is the dosing for Fentanyl?
all forms done in mcg instead of mg: patch is 12, 25, 50, 75 or 100 mcg/hr and lozenge is 200, 400, 800 or 1600 mcg
What is the onset and offset times for fentanyl infusion?
onset less than 30 seconds / offset about 1 minute
What should be noted about equilibrium/delivery of fentanyl in patch form?
as it crosses the skin it deposits in the fat so even after you remove the patch, the drug is still there
How long will a Fentanyl patch last and how much of that will be due to fat stores?
72 hours (the last 12 due to SQ stores)
What is the onset/offset for fentanyl patch?
onset 12-18 hours / offset 72 hours
What is a benefit of Actiq?
basically fentanyl on a stick - rapid absorption bucally of about 90% of dose (not through swallowing) so good for breakthrough pain, but the effect wanes quickly
What is important to note about fentanyl elimination?
not dialyzable so once it is in, it is in until it is gone
What patient population should NOT use fentanyl?
opioid naive patients, as well as the frail and elderly
What is the relative potency of Fentanyl to Morphine?
25 mcg/hr patch is equivalent to oral morphine b/t 45 and 150 mg (so not a reliable conversion)
What is a major difference of Methadone versus other opioids?
works at the Mu receptor, but also the delta and NMDA inhibition (the latter may be why it helps with neuropathic pain)
What types of pain will Methadone help and not help with?
helps with nociceptive and neuropathic pain, but not so much with dyspnea
Why is Methadone a good drug to use for addicts?
doesn't have a euphoric effect
What should be noted about Methadone absorption?
fat soluble so it can be given in a variety of dosage forms with about 80-90% of oral dose being available systemically
How long will it take to achieve steady state with Methadone/
2-10 days due to a half-life of about 90 hours
How is Methadone eliminated?
both in the urine and in bile
What is the dosing for Methadone after achieving steady state?
What dose of Methadone will the chance of QTc prolongation increase and what will that lead to?
300 mg - increases chance by about 17% and leads to torsade de pointes
What is the relative potency of Methadone to morphine?
widely variable patient to patient, but typically 1 mg = 20 mg of morphine
Which of the opioids is typically the cheapest?
What are the three opioid drugs to avoid?
Demerol, Darvocet and Lortab/Norco/Percocet/Vicodin
What is the relative potency of Demerol to morphine?
50 mg = 10 mg morphine
Why is demerol not used?
metabolites accumulate quickly and produce seizure as part of opioid toxicity
Why is darvocet not used?
similar metabolite/problem to demerol and no more potent than tylenol alone
Why is lortab,etc not used?
sufficient enough opioid level will carry with it significant toxic doses of acetaminophen