Opioids Flashcards
What is the metabolism of fentanyl, oxycodone, buprenorphine, and tramadol?
- CYP3A4
What is the metabolism of codeine and hydrocodone?
- CYP2D6
What is the metabolism of morphine, hydromorphone, and oxymorphone?
- Glucuronidation
What are the three major classes of opioid receptors?
- Mu
- Kappa
- Delta
How does morphine and other pure opioid agonists relieve pain?
- Mimicking the action of endogenous opioid peptides, primarily at mu receptors but partly at kappa receptors
What can complement pain relief with opioid use?
- Opioid-induced sedation and euphoria
What is the most serious adverse effect of opioids?
- Respiratory depression
What are some other important adverse effects of opioids?
- Constipation
- Urinary retention
- Orthostatic hypotension
- Emesis
- Birth defects
- Elevation of intracranial pressure
What are the important responses to activation of Mu receptors?
- Analgesia
- Respiratory depression
- Sedation
- Euphoria
- Physical dependence
- Decreased GI motility
What are important responses to activation of Kappa receptors?
- Analgesia
- Sedation
- Decreased GI motility
What are the actions at Mu and Kappa receptors of morphine, codeine, hydrocodone, meperidine, and other morphine-like drugs?
- Mu: agonist
- Kappa: agonist
What are the actions at Mu and Kappa receptors of pentazocine?
- Mu: Antagonist
- Kappa: Agonist
What are the actions at Mu and Kappa receptors of butorphanol?
- Mu: partial agonist
- Kappa: agonist
What are the actions at Mu and Kappa receptors of buprenorphine?
- Mu: Partial agonist
- Kappa: antagonist
What are the actions at Mu and Kappa receptors of naloxone, naltrexone, and others?
- Mu: antagonist
- Kappa: antagonists
What are some examples of pure opioid agonists?
- Morphine
- Codeine
- Hydrocodone
- Meperidine
- And other morphine-like drugs
What are some examples of agonist-antagonist opioids?
- Pentazocine
- Butorphanol
- Buprenorphine
What are some examples of pure opioid antagonists?
- Naloxone
- Naltrexone
What does sudden opioid withdrawal cause?
- Abstinence syndrome that is unpleasant but not dangerous
How should opioids be withdrawn?
- Gradually to minimize symptoms of abstinence
What occurs with prolonged use of opioids?
- Tolerance develops to analgesia, euphoria, sedation, and respiratory distress
Which effect of opioids does tolerance not affect?
- Constipation and miosis
Where are larger doses of opioids generally given?
- Parentally
What are some precautions of opioid use?
- Pregnancy
- Labor and delivery
- Head injury
- Decreased respiratory reserve
What happens when opioids and alcohol or other CNS depressants are mixed?
- Intensify the opioid-induced sedation and respiratory depression
What is a class of drugs that needs to be avoided in people taking opioids?
- Anticholinergic because these drugs can exacerbate opioid induced constipation and urinary retention
What is the triad of symptoms of an opioid overdose?
- Coma
- Respiratory depression
- Pinpoint pupils
How does fentanyl compare to morphine?
- 100x more potent
- Same adverse effects
- CYP3A4 substrate
What are some notable formulations of fentanyl?
- IM
- IV
- Transderm
- Transmucosal
- Nasal spray
- Lozenge on stick
- Buccal tabs
How do the potencies of alfentanil, remifentanil, and sufentanil compare to morphine?
- Alfentanil: 10x
- Remifentanil: 100x
- Sufentanil: 1000x
What are alfentanil, remifentanil, and sufentanil used for?
- Induction of anesthesia
- Maintenance of anesthesia in combo with other drugs
- Sole anesthetic agents
What is meperidine?
- Shares major properties of morphine
- Was considered first line drug for moderate to severe pain but use has declined
Why is meperidine not used now?
- Short half life
- Adverse interactions with other drugs since it interacts with MAO inhibitors leading to coma or death
- Continuous use leads to build up of a toxic metabolite
How was it abused by healthcare workers?
- Lacks anticholinergic effects so there is no pinpoint pupils in patients
What is methadone?
- Shares major properties of morphine
- Has long duration of action
- Used to treat pain increased 7x from 1997-2004
Who is best to use/administer methadone? Why?
- Professionals
- Prolongs QT interval –> torsades de pointes
- Need to be careful if given with other drugs that prolong the QT interval
What is heroin?
- Has higher lipid solubility than morphine, giving a greater high when injected by facilitating access of morphine to brain
What is the use of hydromorphone?
- Moderate to severe pain
What are the adverse effects of hydromorphone?
- Similar to morphine
- Reversed by naloxone
What is special about hydromorphone?
- Water soluble so it can be diluted in a smaller volume for ingection
What is codeine?
- Prototype for moderate to strong opioid agonists
How is codeine usually given?
- PO
What is special about the metabolism of codeine?
- Metabolized to morphine by CYP2D6 which is required for analgesia
- If a person lacks this gene, codeine is ineffective
How is codeine formulated?
- Alone and with nonopioid analgesics
What is an effective use of codeine?
- Cough suppressant
What is oxycodone?
- Moderate to strong opioid agonist similar to codeine
How is oxycodone metabolized?
- By CYP3A4 making it susceptible to induces or inhibitors
What was one way that people abused oxycodone? How is this prevented now?
- Used to crush and snort
- Prevented now by the powder turning into gel when mixed with water or alcohol
What are some adverse effects of oxycodone?
- Drowsiness
- Dizziness
- Pruritus
- Constipation
- Nausea
- Vomiting
What is hydrocodone?
- Moderate to strong opioid agonist similar to codeine
What is the most prescribed form of hydrocodone?
- Acet + hydro
What is pentazocine?
- Prototype for the agonist-antagonist opioids used to treat mild to moderate pain (not used in US anymore)
How does pentazocine and butorphanol affect the perception of pain?
- Causes inhibition of ascending pain pathways, altering the perception of and response to pain
What effects do pentazocine and butorphanol cause?
- Analgesia
- Sedation
- Respiratory depression
Why is the abuse potential low with pentazocine?
- Due to unpleasant reactions (anxiety, strange thoughts, nightmares)
What does pentazocine and butorphanol do in someone physically dependent on mu agonists?
- Precipitates withdrawal
How is pentazocine and butorphanol toxicity reversed?
- Higher levels of naloxone
What is butorphanol?
- Prototype for the agonist-antagonist opioids used to treat mild to moderate pain
What is the nasal spray formulation of butorphanol used for?
- Migraines
What situation is butorphanol contraindicated in? Why?
- MI
- Increases cardiac work
What is buprenorphine?
- A kappa opioid receptor antagonist and partial agonist at mu receptors
What is buprenorphine primarily used for?
- Treat addicts (suboxone)
- Treat acute mild to moderate pain, not recommended for long term use
What effects does buprenorphine cause?
- Analgesia
- Sedation
- Respiratory depression (less than full mu agonists)
Does naloxone work against buprenorphine?
- No because it binds very tightly
What adverse effects can buprenorphine cause?
- Prolongs QT interval
- Spasm of sphincter of Oddi which poses risk for patients with pancreatitis or biliary disease
What is naloxone?
- Pure opioid antagonist
What is naloxone used for?
- Can reverse most effects of opioid agonists including respiratory depression, coma, and anlagesia
What happens when naloxone is administered in the absence of opioids?
- No significant effects
What happens in people are physically dependent on opioids?
- Precipitates immediate withdrawal reaction
What are some opioid withdrawal symptoms?
- Pain in muscles/joints
- Fast HR
- Restlessness or sweating
- General discomfort or anxiety
- Dilated pupils, watery eyes
- Diarrhea, vomiting, or nausea
- Excessive yawning
- Goose bumps
- Insomnia
- Tremor
What is naltrexone?
- Pure opioid antagonist used for alcohol and opioid abuse
- Prevents euphoria from opioids but does not prevent craving
How does naltrexone work in alcoholics?
- Reduces the “high” alcoholics get when consuming alcohol
When can’t naltrexone be used?
- When a patient is taking opioids for pain
What is methylnaltrexone?
- Mu-opioid antagonist that cannot readily cross blood-brain barrier
What is methylnaltrexone indicated for?
- For opioid-induced constipation in patients with end stage disease taking opioids continuously for pain
What is loperamide?
- Mu-opioid agonist that cannot readily cross blood brain barrier
What is loperamide indicated for?
- Acute and chronic diarrhea
What is pain?
- Subjective experience so you have to go based off the patient’s description
What could lead to addictive behavior for opioids?
- High doses to treat pain for > 20 days
What are some indications for opioids?
- Postoperative pain
- Obstetric analgesia
- Myocardial infarction
- Dyspnea
Why are opioids not used in head injuries?
- They cause ICP which will worsen head injury
