Module 9: Opiates & Opioids Flashcards
opium poppy
Papaver Somniferum
Miosis
Pinpoint pupils (constricted)
Follows 1st-pass metabolism when taken orally
Low oral bioavailability (more potent when taken other ways)
Slow to cross blood-brain barrier
Metabolite of codeine and heroin
Duration of action: 4-5 hours
Morphine
Endogenous Opioid Peptide that bind to mu opioid receptors.
Endorphins
Endogenous Opioid Peptide that bind to delta opioid receptors primarily.
Enkephalins
Endogenous Opioid Peptide that bind to kappa opioid receptors primarily.
Dynorphins
3 types of Opioid receptors
Mu, Kappa, Delta
Peak of Opioid Abstinence Syndrome
36-72 hours
Duration of Opioid Abstinence Syndrome
7-10 days
Beginning of Opioid Abstinence Syndrome
6-8 hours
Category of Opioids including morphine, codeine, hydromorphone, etc.
Phenanthrenes
Category of Opioids including Fentanyl, sufentanil, furanryl fentanyl, etc.
Phenylpiperidines
Opioid Classifications (mode of action)
Agonist, Antagonist, Mixed Agonist/Antagonist
Agonist
Highest oral bioavailability
10-15% metabolized to morphine
Duration of analgesia: 3-4 hours
Codeine
Agonist
2-3 times more potent than morphine (penetrates BBB)
poor oral biovavailbility
rapid metabolism to 6MAM (half life = 2-6 min) then to morphine
Heroin
Agonist Derivative of Codeine
metabolized to hydromorphone and dihydrocodeine
Duration of analgesia: 3-5 hours
Hydrocodone
Agonist
metabolite of hydrocodone and morphine (minor)
More potent than morphine
Duration of analgesia: 4-5 hours
Hydromorphone
Agonist
Derived from thebaine
15% metabolized to oxymorphone
Duration of analgesia: 3-4 hours
Oxycodone
Agonist
Metabolite of Oxycodone
Duration of analgesia: 3-4 hours
Oxymorphone
Agonist
Most potent and fast-acting opioid
50-200x more potent than Morphine
Transdermal patches can give delayed concentrations for 12-24 hrs
Duration of analgesia: 1-15. hours
Fentanyl
Agonist
Long elimination half life
Metabolizes to EDDP and EDMP
Duration of analgesia: 4-6 hours
Methadone
Atypical opioid agonist
Metabolite (o-dm-) is 2x more potent (contributes to toxicity)
Duration of analgesia: 4-6 hours
Tramadol
Agonist used to decrease diarrhea
Doesn’t have effects like morphine except in high doses (do to opioid receptor activities)
“poor man’s methadone”
Loperamide
Antagonist
Narcan
Rapid action (minutes)
Short duration of action (2 hours)
Naloxone
Antagonist
Used to treat addition after withdrawal complete
Used for chronic alcoholics
Naltrexone
Mixed Agonist/Antagonist
Produces withdrawal if an opioid agonist is also taken
Partial agonist at mu receptor and kappa antagonist
Available in preparation w/ naloxone (Suboxone) or by itself (Buprenex)
Inactive metabolite (nor-)
Buprenorphine
Location of opioid metabolism in body.
Liver
Metabolized to more polar compounds
Primary mechanisms of metabolism of opiods.
N-dealkylation, conjugation of hydroxyl groups, hydrolysis
3 Opioids where the metabolites account for most of the desired effects
Codeine, Heroin, Tramadol
Isozyme largely responsible for first-pass metabolism of Opiods
CYP2D6
Morphine is primarily excreted as:
Morphine-3-glucuronide (inactive)
*Morphine-6-glucuronide (more potent than morphine)
**Think about how codeine is less potent and that differs from morphine at 3 group also
Opioid effects on:
Pupils
Eye Reaction to Light
Pulse
Blood Pressure
Body Temperature
Pupils - constricted
Eye Reaction to Light - little to none
Pulse - down
Blood Pressure - down
Body Temperature - down
3 main signs of opioid ODs
CNS depression (respiratory depression)
Coma
Pinpoint Pupils
Compound present indicates ingestion of poppy seeds
Thebaine
The opioid receptor that produces central depression, analgesia, miosis, reduced gastrointestinal motility
Mu
Opioid used clinically since 1957, but recommended for removal from the U.S. drug market in 2010.
Propoxyphene
When codeine is taken as a parent drug, approximately _______ is metabolized to morphine.
10%
Semisynthetic analgesic agonist derived from codeine that is used in cough syrups:
Hydrocodone
In the hair matrix, 6-MAM has been detected in hair of heroin users at typically _______ concentrations than for morphine.
The same
smaller
greater
6-MAM not present in hair
Greater
Opioids are _______ in nature.
Basic, Neutral, or Acidic
Basic
Organic solvents are often used to extract opioids from aqueous mixtures in the pH range of:
8-10
True or False: Opiates cause pupil dilation.
False
They cause constriction.
Has less potency relative to morphine:
Hydrocodone, Oxycodone, Fentanyl, Codeine, Methadone
Codeine
_______ is the major metabolic route for opioids that contain available hydroxyl (OH) groups.
Sulfation, Demethylation, Glucuronidation, Dealkylation, Methylation
Glucuronidation
True or False: Only the levorotatory isomer of morphine is a potent analgesic.
True
Successfully used for the treatment of respiratory depression after postsurgical opioid administration:
Buprenorphine, Levorphanol, Methadone, Nalbuphine, Fentanyl
Nalbuphine
This metabolite is more potent than morphine:
Morphine-6-glucuronide, Codeine, Tramadol,
Morphine-3-glucuronide, Morphine
Morphine-6-glucuronide
Acidic hydrolysis of conjugated metabolites should be done with caution as this analyte may be degraded.
Dihydrocodeine, Oxymorphone, Hydromorphone, 6-MAM, Codeine
6-MAM
Opioid Metabolism takes place primarily in the _______.
Liver, Brain, Kidney, Urine, Spinal Fluid
Liver
This drug the longest half-life out of the listed choices.
Morphine, Tramadol, Methadone, Hydrocodone, Fentanyl
Methadone
This opioid has approximately 100-200x the analgesic potency of morphine.
Fentanyl
True or False: Rapid deaths are often characterized by a higher ratio of the concentrations of free morphine to total morphine.
True
Total morphine includes conjugated morphine - body has had time to process and metabolize morphine. Free morphine has not been conjugated for excretion.
Typical pKa values for Opioids are:
1.2-3.4
3.2-4.6
7.6-8.9
9.2-10.6
>10
7.6-8.9
Used to manage intestinal upset and has been used to lessen withdrawal or produce euphoric effects:
Alfentanil, Loperamide, Difenoxin, Hydromorphone, Diphenoxylate
Loperamide
The presence of a low concentration of codeine relative to morphine may indicate the use of _______.
Codeine only
Morphine only
Codeine and morphine
Heroin
A, C and D
A, C and D
*Think: morphine does not metabolize to codeine so it can’t be only morphine. Codeine metabolizes to Morphine.
True or False: All opioids are highly protein bound.
False
