Opiates/Opioids (Final Exam) Flashcards
What type of drugs are opioids?
analgesics and sedative-hypnotics
While they are the best pain killers known that cause euphoria, at high doses Opioids can lead to…
coma and death
What type of flower specifically is the source of “opiates”?
The opium poppy
Raw opium contains about 10% _______ or about 0.5% ______
morphine; codeine
What are the routes of administration for opium?
oral and smoking
True or false: Opium has been used for medical purposes since before recorded history?
True
A drug that used opium in the 1680s was called Laudanum which was weak due to tinctures of opium. What are tinctures?
Tinctures = medicine made by dissolving a drug in alcohol
What was Laudanum used for in the US until 1914?
primarily for pain; also diarrhea and coughing
Recreationally, raw opium is usually ________?
smoked
What are the principal active ingredients in opoim?
Morphine and codeine (natural source)
What is morphine used for medically?
Medical use as an analgesic (schedule 2)
What is codeine used for medically?
some analgesic effects, really good for cough (schedule 2 or 3 based on dose)
What form of opioid is heroin?
semi-synthetic
What is heroin derived from and what is it formed by?
Heroin is derived from morphine, and it is a semi-synthetic opioid formed from adding two acetyl groups to morphine
What did bayer first advertise heroin as?
A less addictive replacement for morphine
Facts about Heroin:
- Heroin is illegal in the US (schedule 1)
-Heroin can be smoked, snorted, or taken IV (fastest)
-The purity of street heroin varies because it may include adulterants to enhance the effects (ex: fentanyl)
What do the two acetyl groups added to morphine do?
increases lipid solubility and speed to the brain
Which is more potent? Heroin or morphine?
Heroine is 2-4x more potent than morphine when taken IV
What is desomorphine? Potency in relation to morphine?
It is Krokodil aka “flesh-eating drug” and it is 8-10 times more potent than morphine
Is desomorphine natural, synthetic, or semi-synthetic?
semi-synthetic
Fentanyl is a synthetic opioid used to treat pain that has a high potency. It is ____x more potent than morphine and ___ more potent than heroin
100; 50
illicit fentanyl and opioids are laced with what drug?
xylazine aka “tranq”
What could happen as a result of xylazine intake?
increased risk of respiratory depression and overdose
Prescription opioids are used for what two purposes?
analgesic and antitussive (cough)
What three things does chronic use of opioids increase potential for?
abuse, addicion, and overdose
What has there been a large increase in over the past 20 years?
opioid overdose deaths
What is one factor that contributed to the prescription opioid and heroin epidemic?
Purdue aggressively marketed OxyContin (controlled release oxycodone)
True or False: A large percentage of people with opioid prescriptions become addicted
False! Only about 3% of people that have a prescription for pain have an addiction
Factors leading to opioid crisis:
-Chronic use of Rx opioids
-Lacing of heroin with fentanyl
Recreational routes of administration for opioids
-IV injection
-SC injection
-smoking/inhalation
-snorting
IV heroin reaches the brain much faster than morphine due to _____ ________
lipid solubility
difference in half-life between morphine and methadone
Morphine and most oral Rx: 2-4 hours
Methadone (oral (drank)): 24 hours due to depot binding
Effects of low doses of opioids
-analgesia
-suppression of cough reflex
-reduced GI motility (constipation)
-euphoria
-some dysphoria (unpleasant feelings)
-Nausea/vomiting
also: slowed respiration, pupil constriction, drowsiness, decreased concentration
Effects of high doses of opioids
-unconsciousness
-pinpoint pupils
-reduced temperature and blood pressure
-respiratory depression
-reversed rapidly by naloxone (antagonist for opioid receptors)
Withdrawal are (similar or opposite) to acute effects?
Opposite
(Rebound hyperactivity in GI tract, autonomic nervous system, brain, and spinal cord)
Is opioid withdrawal deadly?
it is not life threatening
True or False: there is cross-dependence and cross tolerance for all opioids
True
______ duration opioid causes longer withdrawal with ______ intensity
lower; lower
Factors driving tolerance
-metabolic tolerance
-pharmacodynamic tolerance
-psychological tolerance
Treatment options for opioids
-detoxification
-pharmacological support (opioid agonists and antagonists)
-group/individual counseling
-harmful reduction programs
What is the pharmacodynamic action for all opioid drugs?
Bind to opioid receptors in the central nervous system and periphery
The first endogenous opioid discovered was…?
beta-endorphin
what type of neurotransmitters are all endogenous opioids?
peptide neurotransmitters
What are the types of endogenous opioids that act as NT and hormones?
endorphins, enkephalins, and dynorphins
How many gene families (that encode long propeptides) are all opioid peptides products of?
4 families
Endogenous peptide synthesis
peptides are made in the soma, cleaved and packaged into vesicles in the Golgi, and then transported into terminals
Release of peptide transmitters (aka endogenous opioids)
Neuropeptides are not typically the only transmitter at a synapse. Instead, they are co-released together with a classical neurotransmitter
inactivation of peptide transmitters
after release, peptides are degraded together with a classical neurotransmitter
Where are opioid receptors located?
in both the CNS and periphery
Bioassay for opioids
ability of opioids to influence contractions of guinea pig intestine (ileum) strongly predicts human analgesic properties
the 4 major types of opioid receptors
mu, delta, kappa, nociceptin/orphanin FQ
What receptor do abused opioids bind to?
the mu-opioid receptor
Are opioid receptors ionotropic or metabotropic?
all are metabotropic receptors and all are Gi coupled
opioid binding causes inhibition of AC and actions at G-protein-gated ion channels (opening K+ and closing Ca2+ channels)
Opioid _______ can be presynaptic or postsynaptic
receptors
What occurs in the brain regions where endogenous opioids are found?
pain and emotion signaling
Locations of opioid receptors
CNS, PNS, Periphery
Opioid Agonists and Antagonists
Agonists: many Rx and abused opioid drugs
Competitive Antagonists: naloxone, naltrexone (SHIFTS CURVE RIGHT)
Partial agonists: buprenorphine
Genetic knockout of mu receptor that leads to loss of morphine effects:
-spinal analgesia
-supraspinal analgesia
-reward
-withdrawal
-respiratory depression
-inhibition of GI motility
-psychomotor activation
Analgesia effects of opioids due to actions at:
- Spinal Cord: opioids inhibit incoming pain signal
- Periaqueductal gray
- Forebrain: sensory and emotional response to pain
Reward associated with Mu receptors
-strongly implicated in reward and euphoria
-strong self-administration and CPP for selective mu receptor agonists
Evidence that DA does mediate opioid reward
-mu agonists: increase VTA DA cell firing and DA release in striatum (NAc)
-DA antagonists: sometimes reduce opioid CPP and self-administration
Evidence that DA does not mediate opioid reward
-DA receptor antagonists and 6-OHDA lesions do not have large effects of heroin self-administration
-DA-deficient mice still show morphine CPP
Respiratory control levles
- fundamental drive generated by brainstem
2.conscious modulations from cortex
3.subconscious modulations from blood chemoreceptors
What is considered the “gold standard” in antitussive therapy (cough suppression)
Codeine
What was developed as a non-addictive substitute for codeine that does not act at opioid receptors?
Dextromethorphan (DM)
Mechanisms of opioid-induced nausea
- trigger zone is area postrema (has weak BBB)
- increased vestibular sensitivity
- Delayed gastric emptying
What causes pupil constriction?
opioid disinhibition of brainstem nuclei
Where do opioid drugs act to produce their major effects? Analgesia
spinal cord, periaqueductal gray, forebrain
Where do opioid drugs act to produce their major effects? Reward
Brain- dopamine neurons
Where do opioid drugs act to produce their major effects? Gastrointestinal
stomach, small/large intestine
Where do opioid drugs act to produce their major effects? Respiratory Depression
brainstem, cortex, blood chemoreceptors
Where do opioid drugs act to produce their major effects? Cough suppression
brainstem and sensory nerves
Where do opioid drugs act to produce their major effects? Nausea and Vomiting
area postrema, vestibular system, and GI
Where do opioid drugs act to produce their major effects? Pupil constriction
brainstem
