Opioids Flashcards
What are endorphins?
Polypeptides that come from poropiomelanocortin and prodynorphin in the pituitary and hypothalamus that are potent analgesics
What do endorphins work?
Hyperpolarization of nerves by opening K and Ca channels in 1st and 2nd order neurons
Inhibition of ascending pathways in the CNS
Excitation of descending adrenergic and seratonerigic pathways
What is the mu receptor?
An opioid receptor that modulates most of the effects of opioids
What would happen if you got rid of the mu receptor?
You would be more sensitive to pain and less responsive to morphine
What group of people are less responsive to opioids?
Red heads
Which opioids are phenanthrene derivatives?
Morphine, codeine, hydrocodone, hydromorphone, oxycodone
Which opioids are phenylpiperidine derivatives?
Meperidine, fentanyl, sudenatil
Which opioid is a diphenylheptane derivative?
Methadone
What opioids are naturally derived from poppy seeds?
Morphine and codeine
What was the first semi synthetic opioid?
Diacetyl morphine (heroin) gets into brain faster than regular morphine
What are the pharmacological effects of opioids?
Inhibition of pain and pain perception, sedation and anxiolysis (drowsiness, cognitive impairment), depression of respiration, cough suppression, reduction of intestinal motility, pupil constriction, nausea and vomiting (stimulates then inhibits)e
When would depression of respiration from opioids be clinically useful?
People with respiratory failure who are close to dying and gasping for air
Scuba divers use to make oxygen tanks last longer (stupid)
What is the main cause of death from opioid overdose?
Depression of respiration
What is the saying for opioids?
By the mouth by the clock by the ladder
Why are opioids usually given by mouth?
Less effective than IV but has longer effect requiring less doses
Avoids the “highs” and is thus less addictive
Safer in terms of overdose
What does it mean to give opioid ‘by the clock’?
Give the opioid based on time rather than pain so there won’t be a time between where you’re in pain and have to get out of it
What are the benefits of giving opioids ‘by the clock’?
Uses less drug to maintain rather bring out of pain
Avoids euphoria associated with release of pain
Avoids development of chronic pain syndromes from pathway rewiring
How does dosing opioids ‘by the ladder’ work?
Assures the safest and least potent drug is used
Avoids addictive potential because opioids are not used until required
What is the WHO Pain Ladder?
Mild: NSAIDs
Moderate: NSAIDs + codeine
Severe: Morphine + NSAIDS + codeine
What is codeine?
The weakest, most commonly used opioid (little addiction risk) with 10% the potency of morphine
What is codeine used for?
Pain, diarrhea, coughing and to inhibit breathing
What drugs shares a step in the pain ladder with codeine?
Tramadol
What makes tramadol unique from other opioid agonists?
Has 2 complementary mechanisms:
Activates mu opioid receptor (like other opioids)
Weak inhibitor of norepinephrine and serotonin reuptake
Less potential for addiction, greater pain control (better against joint pain)
What are the pharmacokinetics of morphine?
Oral: Poor availability 15-60 minutes before onset Lasts 3-6 hours IV: Twice as potent as oral Duration can either be immediate or about 2 hours
What makes oxycodone different from morphine?
Equal or slightly higher potency (up to double)
Greater oral availability
Slightly greater half life
Dosed at half morphine dose
What are the different forms of oxycodone?
Slow release form is OxyContin
With tylenol is Percocet
What are the pharmacokinetics for hydromorphone?
Oral: Take 15-30 minutes to begin working
IV: Lasts 3-4 hours and will take 30-60 minutes to peak
5 times more potent than morphine
What is hydromorphone used for?
Surgical setting for moderate to severe pain (cancer, bone trauma, burns)
What are the pharmacokinetics of fentanyl?
Highly lipophilic and very potent
Given sublingually and transdermally
What is sublingual fentanyl used for?
Acute but temporary pain
Debriding wounds and breakthrough pain in pallative care
7-12 minutes to work, lasts 1-2 hours
What is transdermal fentanyl used for?
More severe pain (cancer, palliative)
12-17 hours to work, lasts 72-96 hours
Safer, less chance of addiction
What is sufentanyl?
A form of fentanyl that is 10 times more potent
What is naltrexone? What is it used for?
An oral opioid inhibitor that used to treat alcohol addiciton
What does naltrexone do?
Reverses the psychomimetic effects of opiate agonists, reverses hypotension and cardiovascular instability
What is naloxone? What is it used for?
A potent antagonist that is used in emergency situations (respiratory depression, heroin overdose)
What does naloxone do?
Very quickly blocks opioid binding
Blocks all major effects of opioids, including pain control
Patients will be in pain during use
What is methadone used for?
Addiction medicine and palliative care where the patient has developed resistance or toxicity to other opioids
What are the pharmacokinetics of methadone?
More potent then morphine but highly variable by patient
Very long but variable half-life (up to 5 days) but effective for 6-12 hours
What is the drawback of methadone?
Though it is less addictive, there is a greater risk of accidental overdose (accumulation) even in medical settings
How do you titrate the dose of an opioid?
Titrate based on response and side effects until maximum analgesia and function are attained with tolerable side effects
What should we try to switch our opioids to?
Try to switch the short acting opioid to a long acting opioid at equianalgesic doses (reduce peaks and valleys of pain control)
What should be done when a patient shows tolerance to an opioid?
Opioid rotation to improve analgesia (use with caution) 30% of equianalgesic form
Typically used in cancer treatment
Why may we discontinue an opioid therapy?
Intolerable side effects (myoclonus, respiratory depression, level of consciousness) with little evidence of analgesia
High doses without analgesia
Evidence of addiction
No evidence of any effort to increase function (may need a cognitive behavioural program)
What is tolerance?
Reduced potency of analgesic effects of opioids following repeated administration
Related to opioid receptor regulation
“save” opioids for terminal phase in cancer
What is physical dependence?
The normal response to chronic opioid administration. Evident with opioid withdrawal
How can we avoid opioid withdrawal?
Decreasing the dose by 20-30% everyday
What are some symptoms of opioid withdrawal?
Yawning, sweating, tremor, fever, increased heart rate, muscle cramps, dilated pupils
What is addiction?
A psychological dependence
Characterized by a craving for opioids that manifests by compulsive drug seeking behaviour leading to overwhelming involvement in use an procurement of the drugs
Will stick to 1 drug, not switch
How do you deal with opioid tolerance?
Prevent dose escalation
Use a medication holiday following slow withdrawal
Plan for this at the beginning of treatement
What are some other effects of opioids on the body?
Causes vomiting then depresses it
Pinpoint pupils (sign of tolerance)
Vasodilation (flushing of skin, decrease in blood pressure)
Constipation (big problem)
Decreases sex hormones in males and females (decreases libido and fertility)
