Opioids Flashcards
Final Exam
Analgesics
Analgesics are drugs that relieve pain without causing loss of consciousness.
opioid
An opioid is any drug, natural or synthetic, that has actions similar to those of morphine.
opiate
The term opiate is more specific and applies only to compounds present in opium (e.g., morphine, codeine).
There are three main classes of opioid receptors
- mu,
- kappa
- delta.
What are the most important receptors from a pharmacologic perspective?
Mu receptors
Why are Mu receptors the most important?
are the most important because opioid analgesics act primarily by activating mu receptors (although they also produce weak activation of kappa receptors).
Responses to Mu receptor activation include:
analgesia,
respiratory depression,
euphoria,
sedation
Physical dependence
What is Mu receptors related to?
Physical dependence
Activation of Kappa receptors causes what?
activation of kappa receptors can produce analgesia and sedation.
kappa activation may underlie psychotomimetic effects seen with certain opioids.
Kappa activation may underlie what?
kappa activation may underlie psychotomimetic effects seen with certain opioids.
At each receptor, a drug can act in three ways:
- Agonist
- Partial agonist
- Antagonist
Partial agonist
A drug that produces low to moderate receptor activation when administered alone but will block the actions of a full agonist if the two are given together.
What happens if a partial agonist is given with an agonist?
Partial agonists will block the actions of a full agonist if the two are given together.
Drugs that bind opioids receptors fall into three major categories:
- pure opioid agonists
- agonist-antagonist opioids
- pure opioid antagonists.
What do pure opioid receptors activate?
The pure opioid agonists activate mu receptors and kappa receptors.
By activating mu and kappa receptors, what do pure agonist produce?
The pure agonists can produce analgesia, euphoria, sedation, respiratory depression, physical dependence, constipation, and other effects.
What are the two groups that pure opioid agonists can be subdivided into:
- moderate to strong opioid agonists
- strong opioid agonist
What is the prototype drug for strong opioid agonists
Morphine
Four agonist-antagonist opioids are available: and what is the prototype?
- pentazocine
- nalbuphine
- butorphanol
- buprenorphine
When administered alone, what do agonist-antagonists do?
When administered alone, the agonist-antagonist opioids produce analgesia.
What happens if Agonist Antagonist is given to a patient taking a pure opioid agonist?
Giving an agonist antagonist will block Mu receptors and will stimulate withdrawal symptoms because we block mu receptors that have grown tolerant to the drug.
If given to a patient who is taking a pure opioid agonist, however, these drugs can antagonize analgesia caused by the pure agonist.
What do pure opioid antagonists do?
The pure opioid antagonists act as antagonists at mu and kappa receptors.
What kind of effect do pure opioid antagonists have?
These drugs do not produce analgesia or any of the other effects caused by opioid agonists.
The principal use of pure opioid antagonists?
Their principal use is reversal of respiratory and CNS depression caused by overdose with opioid agonists.
What drug is used to treat opioid induced constipation? What class is it?
methylnaltrexone—is used to treat opioid-induced constipation.
It is a pure opioid antagonist
What is the prototype of the pure opioid antagonists?
Naloxone
What is the prototype drug of the strong opioid analgesics?
Morphine
Pharmacological effects of morphine?
including analgesia
sedation
euphoria
respiratory depression
cough suppression
suppression of bowel motility
Overview of Pharmacologic Actions of Morphine:
relieving pain,
the drug causes drowsiness and mental clouding, reduces anxiety,
and creates a sense of well-being.
Through actions in the CNS and periphery, morphine can cause respiratory depression, constipation, urinary retention, orthostatic hypotension, emesis, miosis, cough suppression, and biliary colic.
Through actions in the CNS and periphery, morphine can cause:
morphine can cause:
respiratory depression,
constipation,
urinary retention,
orthostatic hypotension,
emesis,
miosis,
cough suppression,
and biliary colic.
With prolonged use of morphine, what does the drug produce?
With prolonged use, the drug produces tolerance and physical dependence.
What is the principle indication for morphine?
The principal indication for morphine is relief of moderate to severe pain. `
What type of pain is morphine best for?
The drug is more effective against dull, constant pain than against sharp, intermittent pain.
What is the most serious adverse effect of morphine?
Respiratory depression is the most serious adverse effect.
Time course of respiratory depression with morphine use varies with what?
route of administration.
How long does depressant effects of morphine occur with IV injection?
Depressant effects begin about 7minutes after IV injection
How long does depressant effects of morphine occur with IM injection?
30minutes after intramuscular (IM) injection,
How long does depressant effects of morphine occur with SubQ injection?
up to 90minutes after subcutaneous (subQ)
With all three routes of administration for morphine, how long does significant depression persist?
With all three routes, significant depression may persist for 4 to 5hours.
Spinal injection of morphine- when does respiratory depression occur?
When morphine is administered by spinal injection, onset of respiratory depression may be delayed for hours;
What occurs with prolonged use of opioids like Morphine?
With prolonged use of opioids, tolerance develops to respiratory depression.
Huge doses that would be lethal to a nontolerant individual have been taken by opioid addicts without noticeable effect.
How does respiratory depression occur opioids addicts who have prolonged use of opioids like morphine?
Huge doses that would be lethal to a nontolerant individual have been taken by opioid addicts without noticeable effect.
What should be determined first before administering opioid?
Respiratory rate should be determined before opioid administration.
When should the opioid be held (having to do with respiratory rate) and what should you do?
If the rate is less than 12 breaths per minute, the opioid should be withheld and the prescriber notified.
Who are at greatest risk of respiratory depression with opioid use?
the very young
older adults
those with respiratory disease (e.g., asthma, emphysema),
are especially sensitive to respiratory depression, and hence must be monitored closely.
What increases respiratory depression with opioid use?
Concurrent use of other drugs with CNS-depressant actions (e.g., alcohol, barbiturates, benzodiazepines).
What can reverse pronounced respiratory depression?
Pronounced respiratory depression can be reversed with naloxone [Narcan], an opioid antagonist.
What class is naloxone?
An opioid antagonist
What should you monitor in patients taking opioid medications?
Monitor:
- level of consciousness
- respiratory rate
- oxygen saturation in patients receiving opioid medications.
Three issues in Opioid use? (From ppt)
- Constipation
- Biliary colic
- Emesis
How do opioids promote constipation? What do they activate?
Opioids promote constipation through actions in the CNS and gastrointestinal (GI) tract.
Specifically by activating mu receptors in the gut.
How can opioid induced constipation be managed?
Opioid-induced constipation can be managed with a combination of pharmacologic and nonpharmacologic measures.
How is opioid induced constipation managed? Non drug
Principal nondrug measures are physical activity and increased intake of fiber and fluids (for prevention) and enemas (for treatment).
Drug measures to reduce opioid induced constipation?
a stool softener, such as docusate [Colace] plus polyethylene glycol (an osmotic laxative) can provide additional benefit.
What is a last resort for handling opioid induced constipation?
As a last resort, patients may be given methylnaltrexone
Simple definition of methylnaltrexone
an oral drug that blocks mu receptors in the intestine.
methylnaltrexone cannot cross the blood-brain barrier, and hence does not reverse opioid-induced analgesia.
How does morphine promote nausea and vomitting?
Morphine promotes nausea and vomiting through direct stimulation of the chemoreceptor trigger zone of the medulla.
How to manage opioid induced Emesis:
Nausea and vomiting can be reduced by pretreatment with an antiemetic (e.g., prochlorperazine) and by having the patient remain still.
When are Emetic reactions to opioid use greatest? When does it diminish?
Emetic reactions are greatest with the initial dose and then diminish with subsequent doses.
What inactivates morphine?
Morphine is inactivated by hepatic metabolism.
Why would oral doses of morphine and other opioids need to be larger doses than parentaral?
Morphine is inactivated by hepatic metabolism. When taken by mouth, the drug must pass through the liver on its way to the systemic circulation. Much of an oral dose is inactivated during this first pass through the liver.
Tolerance
Defined as a state in which a larger dose is required to produce the same response that could formerly be produced with a smaller dose.
With prolonged treatment, what does tolerance develop to?
tolerance develops to
analgesia,
euphoria, and
sedation.
respiratory depression
As tolerance increases to opioid what does NOT increase in tolerance?
Very little tolerance develops to constipation and miosis.
What kind of tolerance exists between opioid and general CNS depressants?
No cross-tolerance exists between opioids and general CNS depressants (e.g., barbiturates, ethanol, benzodiazepines, general anesthetics).
Physical dependence
Physical dependence is defined as a state in which an abstinence syndrome will occur if drug use is abruptly stopped.
The intensity and duration of the opioid abstinence syndrome depends on two factors:
- the half-life of the drug being used
- the degree of physical dependence.
Initial reactions of abstinence syndrome?
yawning,
rhinorrhea, and sweating.
When does onset of abstinence syndrome occur?
Onset occurs about 10hours after the final dose.
At peak of withdrawal syndrome, what occurs?
At its peak, the syndrome manifests as violent sneezing, weakness, nausea, vomiting, diarrhea, abdominal cramps, bone and muscle pain, muscle spasm, and kicking movements, which is where the phrase “kicking the habit” comes from.
What would stop withdrawal symptoms?
Giving an opioid at any time during withdrawal rapidly reverses all signs and symptoms.
Left untreated, how long would abstinence syndrome occur?
Left untreated, the morphine withdrawal syndrome runs its course in 7 to 10 days.
How do you minimize abstinence syndrome?
To minimize abstinence syndrome, opioids should be withdrawn gradually.
Morphine and all other strong opioids are classified under what schedule
morphine and all other strong opioid agonists are classified under Schedule II
Reflects a moderate to high abuse liability
What happens if agonist antagonist opioids are given to an individual physically dependent on a pure opioid agonist?
Agonist-antagonist opioids (e.g., pentazocine, buprenorphine) can precipitate a withdrawal syndrome if given to an individual physically dependent on a pure opioid agonist.
When are opioid antagonists mainly employed?
Opioid antagonists are employed primarily to treat opioid overdose.
What is a strong opioid analgesic that has a higher potency than morphine?
Fentanyl
high milligram potency (about 100 times that of morphine).
Four different routes of administration for fentanyl?
- parenteral
- transdermal
- transmucosal
- intranasal
What kind of adverse effects does fentanyl have?
Fentanyl, regardless of route, has the same adverse effects as other opioids:
respiratory depression, sedation, constipation, urinary retention, and nausea. Of these, respiratory depression is the greatest concern
Why don’t we use Merperidine as much now?
- First, the drug has a short half-life, so dosing must be repeated at short intervals.
- Second, meperidine interacts adversely with a number of drugs.
- Third, with continuous use, there is a risk for harm because of the accumulation of a toxic metabolite.
When should Meperidine be used?
Meperidine is better for gallbladder problems because its less likely to cause spasms
What is used to relieve pain and treat opioid addiction?
Methadone is used to relieve pain and to treat opioid addiction
What would be used instead of morphine because of morphine’s nausea effects?
hydromorphone may cause less nausea than morphine.
What is codeine used for?
Codeine is indicated for relief of mild to moderate pain.
What happens to codeine in the liver?
In the liver, about 10% of each dose of codeine undergoes conversion to morphine, the active form of codeine
What is the enzyme responsible for codeine’s conversion to morphine in the liver?
The enzyme responsible is CYP2D6 (the 2D6 isoenzyme of cytochrome P450).
Four agonist-antagonist opioids available?
- pentazocine,
- nalbuphine,
- butorphanol
- buprenorphine.
pentazocine, nalbuphine, butorphanol act as what?
these drugs act as antagonists at mu receptors and agonists at kappa receptors
Two reasons why codeine is ineffective in some individuals:
- Among people who lack an effective gene for CYP2D6, codeine cannot be converted to morphine,
- among ultrarapid metabolizers, who carry multiple copies of the CYP2D6 gene, codeine is unusually effective.
What happens if someone lacks the effective gene for CYP2D6? (having to do with codeine)
Among people who lack an effective gene for CYP2D6, codeine cannot be converted to morphine, and hence codeine cannot produce analgesia.
How does pentazocine act on receptors?
Pentazocine acts as an agonist at kappa receptors and as an antagonist at mu receptors.
How do pure opioid agonists compare with agonist-antagonist?
Compared with pure opioid agonists, the agonist-antagonists have a low potential for abuse, produce less respiratory depression, and generally have less powerful analgesic effects.
How does Buprenorphine differ from other agonist antagonists?
The drug is a partial agonist at mu receptors and an antagonist at kappa receptors.
Three main pure antagonists
- naloxone [Narcan],
- methylnaltrexone [Relistor],
- naltrexone [Vivitrol].
