Drugs
Opioids
Mechanisms of Action
Potpourri
Attending Trivia
100
This drug is named after the God of Dreams.
What is Morphine?
PEARL: Morphine is the equianalgesic reference standard and is cleared by glucuronidation (UGT), not CYP. Its active metabolite M6G accumulates in renal failure, so avoid morphine in ESRD.
100
Classifications include Naturally Occurring, Synthetic and this
What is Semi Synthetic?
PEARL: Semi-synthetics (oxycodone, hydromorphone, hydrocodone, buprenorphine, heroin) are chemically modified natural alkaloids; fully synthetic agents (fentanyl, methadone, meperidine, tramadol) share no morphine backbone and are built de novo.
100
Opiates work by blocking this.
What are Voltage Gated Calcium Channels?
PEARL: This is only part of the mechanism. Opioid GPCRs (Gi/Go) also OPEN potassium channels (hyperpolarizing the neuron) and inhibit adenylyl cyclase (lowering cAMP), in addition to closing presynaptic voltage-gated calcium channels. Net effect: less neurotransmitter release and reduced excitability.
100
What does REMS stand for?
What is "Risk Evaluation and Mitigation Strategies"
PEARL: FDA’s official term is singular - "Risk Evaluation and Mitigation Strategy." The opioid analgesic REMS requires prescriber education for ER/LA and IR opioids; TIRF (transmucosal immediate-release fentanyl) products have their own dedicated REMS.
100
This Attending was almost rejected from the Fellowship.
Who is Dr. Gulati?
200
Take two morphines and pop them together
What is Heroin?
PEARL: Heroin is a prodrug - diacetylmorphine (morphine plus two acetyl groups, NOT two morphine molecules). Its high lipophilicity speeds brain entry; it is metabolized to 6-MAM and then to morphine.
200
Of Pure Agonists, Partial Agonists and this.
What are Antagonist-Agonists?
PEARL: Mixed agonist-antagonists (nalbuphine, butorphanol, pentazocine) and the partial agonist buprenorphine have an analgesic ceiling and can precipitate acute withdrawal in patients on full mu agonists - always screen the opioid history before dosing.
200
Name a Agonist-Antagonist
What are nalbuphine, butorphanol, pentazocine?
°Mu receptor antagonists
± May cause acute withdrawal in patients on
pure opioids
°Exert analgesic actions primarily as kappa
receptor agonists
± Has ceiling effect of analgesia
± May produce kappa-mediated psychotomimetic effects
PEARL: Because these agents antagonize the mu receptor, giving them to a patient on chronic full agonists can trigger acute withdrawal; their kappa activity accounts for the analgesic ceiling and the dysphoric/psychotomimetic effects.
200
How many DEA Drug classes are there?
What is 5?
±They are grouped according to:
°the drug's or substance's potential for being harmful
°the drug's value for medical purposes
°the potential for abuse, physical dependence, or addiction
±Schedule I drugs have no accepted medical use and are considered the most dangerous. Schedule V drugs are the least dangerous.
PEARL: Schedule I = no accepted medical use (heroin, LSD); Schedule II = high abuse, no refills allowed (most pain opioids - morphine, oxycodone, fentanyl, hydromorphone); III-V have decreasing abuse potential. Hydrocodone combination products were rescheduled from III to II in 2014.
200
This was the first Pain Fellowship Director?
Who was Howard Rosner?
300
Purdue Pharma got int trouble for this drug.
What is Oxycontin?
PEARL: Original OxyContin (controlled-release oxycodone) was reformulated in 2010 as abuse-deterrent (harder to crush or dissolve). Oxycodone is metabolized by CYP3A4 to noroxycodone and by CYP2D6 to the active metabolite oxymorphone.
300
The term used to describe Alkaloids derived from opium
What is Opiate?
PEARL: "Opiate" means naturally derived from opium (morphine, codeine, thebaine); "opioid" is the umbrella term for anything acting at opioid receptors - including semi-synthetics, synthetics, and endogenous peptides (endorphins, enkephalins, dynorphins).
300
This works on the MU and NMDA receptor
What is Methadone?
PEARL: Methadone's NMDA antagonism may help neuropathic pain and opioid-induced hyperalgesia, but its long, variable half-life (8-59h) risks delayed toxicity and it prolongs the QTc - get a baseline ECG and convert conservatively (the conversion ratio is nonlinear and rises at higher morphine doses).
300
If you practice in NJ, you need one of these
What is a CDS and NJ DEA?
PEARL: To prescribe controlled substances in NJ (and many states), you need a state Controlled Dangerous Substances (CDS) registration IN ADDITION to your federal DEA registration - both must be active and tied to the practice site.
300
This Attending is Tolkien fan.
Who is Seth Waldman?
400
Codones become these
What are Morphones?
PEARL: Hydrocodone is metabolized to hydromorphone and oxycodone to oxymorphone via CYP2D6. These -morphone metabolites are more potent than morphine (oral hydromorphone is roughly 4x oral morphine).
400
This is the plant from which Opioids arise.
What is Papaver Somniferum plant?
PEARL: The three principal alkaloids of opium are morphine, codeine, and thebaine. Thebaine itself is not analgesic but is the semi-synthetic precursor for oxycodone, oxymorphone, buprenorphine, and naloxone.
400
If I go through Withdrawal, I am addicted? True/False?
What is False?
PEARL: Key distinction - physical dependence (withdrawal on cessation) and tolerance are expected physiologic adaptations, NOT addiction. Addiction is compulsive use despite harm (loss of control, craving, continued use despite consequences). Pseudoaddiction is drug-seeking that resolves once pain is treated adequately.
400
It is called i-STOP in NY, but this in NJ
What is PMPAWARE?
PEARL: The NJ program is the New Jersey Prescription Monitoring Program (NJPMP), on the PMP AWARxE platform (spelled "AWARxE," not "AWARE"). NJ requires querying the PMP before an initial controlled-substance prescription and periodically thereafter.
400
The name of Dr. Rakesh's Podcast.
Who is the Ouchcast?
500
This is one of the most abused drugs.
What is Fentanyl?
PEARL: Fentanyl is highly lipophilic; a single IV dose is short-acting due to redistribution, but the transdermal patch has a 12-24h onset and a subcutaneous depot that persists after removal. No active metabolites makes it useful in renal failure.
500
Mu, Delta Receptors- What Else?
What is Kappa?
PEARL: Kappa agonism gives analgesia but also dysphoria, diuresis, and psychotomimetic effects. A fourth opioid receptor, nociceptin/orphanin-FQ (NOP/ORL-1), is now recognized; the sigma receptor is no longer classified as a true opioid receptor.
500
Escalating doses of opioids lead to increased sensitivity of pain
What is hyperalgesia?
PEARL: This is opioid-induced hyperalgesia (OIH) - diffuse, worsening pain despite dose escalation. Distinguish from tolerance (pain improves with more drug); OIH worsens with more drug. Manage by lowering or rotating the opioid or adding an NMDA antagonist (ketamine, methadone), not by escalating.
500
This how you decide to add a Long Acting Agent?
When the Frequency of the Short Acting is > 5 times/day.
PEARL: The '>5 short-acting doses/day' cutoff is a heuristic, not a mandate. Current CDC guidance (2016, updated 2022) cautions against routinely starting ER/LA opioids, avoids them for acute pain, and favors the lowest effective dose of immediate-release opioid with a clear reassessment plan.
500
This Attending's risked anaphylaxis to join the Fellowship
Who is Dr. Kramskiy?