Opioids Flashcards
Natural opiates
Morphine and Codine
How do opioids work?
They act on GABA neurotransmission by disinhibiting presynaptic release of GABA.
Types of opioid receptors
Mu (endorphins, morphine)
Delta (enkephalins)
Kappa (Dynorphins)
Distribution of opioids
Distribute to highly perfused tissues (lungs, brain, kidneys, spleen, liver)
Is there a first pass effect?
yes, big one.
Metabolism/excretion
Converted to polar metabolites and excreted through the kidney.
Morphine
Mu receptor agonist, causes analgesia, euphoria, vasodilation, decreased GI motility, decreased urination
How to opioids effect pupils?
Cause pupillary constriction because parasympathetic inputs are indirectly stimulated.
Metabolism of Morphine
90% to morphine-3-glucuronide, 10% to morphine-6-glucuronide (which is an active analgesic). Happens in liver
Excretion of morphine
90% excreted as M3G in the urine
Codeine
Another opiate, binds to mu receptor as an opiate receptor agonist, gets converted to morphine. Used as a cough suppressant, and a weaker analgesic than morphine
Side effects of codeine
Increased nausea/vomiting, worstening pruritis
Diacetylmorphine
Heroin, converted to morphine and 6-acetylmorphine (also active) in blood.
Activity at all opioid receptors.
Half-life of diacetylmorphine
3 minutes before conversion to constituent drugs.
Oxycodone
Semi-synthetic opioid, acts similarly to morphine. Used for analgesia (moderate to severe), not great in liver/kidney.
Hydrocodone
Semisynthetic, chemically related to codeine. Used for analgesia (mild-moderate) and as a potent anti-tussive. With acetaminophen as vicodin.
Hydromorphone
The powerful. Morphine derivative that is 7-8x times more potent. Used for moderate to severe pain, safer in patients with liver/kidney disease. Better for kidney disease.
Meperidine
First synthetic opioid. Mu and kappa receptor agonist. Some anticholinergic properties (like atropine). High first pass metabolism.
Fentanyl
Strong, safe, portable.
Mu receptor agonist. Doesn’t cause histamine release. For severe pain and dyspnea. Great transdermal bioavailablilty.
Methadone
Opioid with extra powers. Mu receptor agonist, but also NMDA receptor ANTAGONIST. Analgesia and neuropathic pain (as NMDA receptor). Safe in liver/kidney patients. Can have cardiac side effects.
Loperamide
Doesn’t cross BBB, slows intestinal contractions and stops diarrhea.
Dextromethorphan
The psychedelic cough suppressant. Mu receptor agonist (little analgesia) NMDA receptor antagonist.
Tramadol
The opioid thats not an opioid. Serotonin releasing agent, NMDA receptor antagonist, NE reuptake inhibitor. Used for moderate analgesia. Lowers seizure threshold. Side effects are not like other opioids.
Naloxone
Mu, kappa delta competitive ANTAGONIST. Used for opioid intoxication.
Naltrexone
Twice as potent as naloxone, lasts twice as long. Use with opioid overtose, alcohol intoxication, or opioid abuse.
Methylnaltrexone
Peripherally acting antagonist. Relieves constipation related to opioids.
Hypothesis for development of tolerance
Hypothesized to be due to upregulation of cAMP, failure of receptor recycling, receptor and G-protein uncoupling.
Tolerance for sedation/respiratory depression vs tolerance for nausea/vomiting/constipation
Tolerance for sedation develops first (days), nvd takes weeks.
Three step ladder for pain relief prescribing
Step one: NSAIDs/acetominophen
Step two: Hydrocodone, codeine, oxycodone, oral morphine, tramadol.
Step three: morphine IV, hydromorphone, fentanyl, methadone
Rotating from one opioid to another requires 2 steps:
1) calculate equianalgesic dose 2)reduce for incomplete cross tolerance – reduce by half. Don’t need to do this if switching from PO to IV though.
Dependence
The development of a withdrawal syndrome following dose reduction or administration of an antagonist
Tolerance
Change in dose-response relationship induced by exposure
OUD
Opioid use disorder: a problematic pattern of use leading to impairment or distress
Addiction
Compulsive use despite harm
Pseudo-addiction
Behaviors that are reminiscent of addiction, but are driven by pain
How do opioids lead to addiction?
Inhibition of GABAergic neurons in VTA, leading to disinhibition of DA neurons
Buprenorphine
Partial mu agonist, good for treating opioid dependence. Antagonist of delta and kappa. High affinity for mu so can replace morphine etc.
Suboxone
Buprenorphine/Naloxone. Used so that injection doesnt work.
