06b: Opioids Flashcards
(Opium/opiate/opioid) is naturally occurring alkaloid.
Opiate
(Opium/opiate/opioid) is mixture of alkaloids from Papaver somniferum.
Opium
(Opium/opiate/opioid) is any natural or synthetic compound with morphine-like properties.
Opioid
Morphine falls into the category of (opium/opiate/opioid).
Opiate
Morphine is opioid receptor (agonist/antagonist). Give another example in this category.
Agonist;
Fentanyl
Buprenorphine is opioid receptor (agonist/antagonist).
Agonist-antagonist (binds multiple receptors)
Naloxone is opioid receptor (agonist/antagonist).
Antagonist
Morphine is (natural/synthetic), as is (heroin/codeine/fentanyl).
Natural; codeine
Methadone is (natural/synthetic), as is (heroin/codeine/fentanyl).
Synthetic;
Fentanyl
Most clinically important opioid analgesics are (selective/non-selective) (agonists/antagonists) to (X) receptor class. Give an example.
Selective; agonists;
X = mu (MOP)
Sufentanil
T/F: All opioid receptors are RTKs.
False - all GPCRs
Opioids generally work through which second-messenger pathway?
Go/Gi (inhibit AC, decrease cAMP)
Opioid effects: (vasoconstriction/vasodilation), (brady/tachy)-cardia, (miosis/mydriasis).
Vasodilation, bradychardia, miosis
Opioid effects: smooth muscle (X) and skeletal muscle (Y).
X = spasm Y = hypertonus (stiffness)
Opioid (mu) receptor class impacts (pre/post)-synaptic (afferent/efferent) neuron by (increasing/decreasing) Ca (uptake/release). What does this do?
Pre-synaptic; (primary) afferent
Decreasing uptake;
Decrease neurotransmitter release
Opioids decrease release of which NT from primary afferents?
Substance P, ACh, NE, SA
Opioid (mu) receptor class impacts (pre/post)-synaptic neuron by (increasing/decreasing) K (uptake/release). What does this do?
Post-synaptic;
Increasing
Release (outward K current);
Hyperpolarize (IPSP)
List the three locations in CNS where opioids play a role.
- Limbic system (impact affect to pain)
- PAG (descending pain modulation)
- Dorsal horn (primary afferent pain fibers)
Clinical selection of an opioid is usually based on (X) considerations.
X = pharmacokinetic
T/F: Pts, after opioid administration, typically report pain has vanished.
False - pain still present, but dulled and no longer bothers them as much
T/F: Opioids can vary drastically in lipophilicity.
True - partition coeff of morphine 1.4 and fentanyl is 860
Morphine: (slow/rapid) absorption and clearance. Relatively (hydrophobic/hydrophilic), so CNS penetration/exit are (slow/fast). This accounts for morphine’s (slow/fast) onset and (short/long) duration.
Rapid absorption/clearance;
Hydrophilic;
Slow;
Slow onset, long duration
(Fentanyl/Codeine/Morphine) cleared by hepatic biotransformation.
All three (almost all opioids cleared by liver)
Fentanyl: (slow/rapid) absorption and clearance. Relatively (hydrophobic/hydrophilic), so CNS penetration/exit are (slow/fast).
Rapid absorption/clearance;
Hydrophobic (extremely lipophilic!!)
Fast (effects rapidly parallel changes in plasma conc)
Which property of (fentanyl/morphine) allows its administration via multiple routes?
Fentanyl; lipophilicity
transdermal patch, intranasal spray, buccal tablet, lollipop
Conjugation, specifically (X), of morphine can result in (Y) product 15% of the time. This is problematic, especially in which patient population?
X = glucuronidation Y = morphine-6-glucuronide
Active metabolite, slow to clear, builds up in brain; renal failure patients
Codeine undergoes (methylation/de-methylation) to become (X). This is a (minor/major) pathway of codeine metabolism.
O-Demethylation
X = morphine
Minor (10% of codeine)
BUT accounts for nearly all opioid activity
T/F: Most codeine metabolism (80%) results in inactive metabolites.
True - only morphine product active
T/F: Opioids most likely to cause problems in hepatic failure, since most cleared by liver.
False - renal failure because many opioids have polar active metabolites (buildup if clearance is slow)
Opioids: polymorphisms in clearance may be good or bad, depending on which two things?
- Effect of metabolite
2. Activity of parent drug
T/F: Analgesia from opioids is always accompanied by some respiratory depression/effect.
True
Opioids: depression of ventilatory response to (high/low) (CO2/O2) levels. The extent of this resp depression is dose-(dependent/independent).
High CO2, low O2
Dose-dependent
(X) is the major toxicity of opioids and nearly always cause of death from overdose. Treatment is (Y).
X = respiratory depression Y = naloxone
T/F: Tolerant individuals requiring large amounts of opioids for analgesia are at proportionately increased risk for resp depression.
False
N-Methylnaltrexone is (centrally/peripherally)-acting (agonist/antagonist) of mu opioid receptors. What’s it used for?
Peripherally;
Antagonist
Treats opioid-induced constipation/urinary retention without antagonizing analgesia (can’t enter CNS)
Opioids cause nausea/vomiting via which mechanism?
Direct stimulation of CTZ (chemoreceptor zone) in area postrema (floor of fourth ventricle); this activates vomiting center in medulla
Opioid-induced hives by (X) release (is/isn’t) indicative of (Y) reaction. What’s the mechanism?
X = His;
Isn’t (no IgE);
Y = Anaphylactoid
Competitive displacement of His from tissue mast cells
T/F: Opioid physical dependence is the same as opioid addiction.
False
Opioid withdrawal is treated with:
small dose of opioid
List some symptoms of opioid withdrawal.
- Rhinorrhea
- Vomit/diarrhea
- Gooseflesh/shaking
- Mydriasis
- Sweating (diaphoresis)
Opioid addiction: agonist maintenance utilizes which drugs? What’s the method of administration?
Methadone or Buprenorphine;
Orally (decrease HIV/hepatitis seroconversion)
Methadone maintenance to treat opioid addiction has which disadvantages?
- Special license required
- Separate from med care
- Limited availability
- Stable/unstable pts mixed
- No privacy (social stigma)
- Can’t “graduate” from program
