Wednesday, 8-24-Narcotics And Analgesics-Fitzpatrick Flashcards
How does an opioid agonist affect the pain impulse pre and post synaptically?
When opioid agonist occupies its receptor, blunts Ca influx and blunts Glu discharge pre-synapse, and increases K efflux post-synapse
In terms of drugs that bind to mu opioid receptors:
___ are full agonists
___ are partial agonist/mixed
___ are antagonists
Fentanyl and morphine=full
Buprenorphine=partial/mixed
Naloxone and naltrexone=antagonist
Which full agonist is more potent: fentanyl or morphine?
Fentanyl –> but both are equally efficacious
In terms of the pain treatment ladder:
___ are used for mild pain
___ are used for moderate or persisting or uncontrolled pain
___ are used for severe or persisting or uncontrolled pain
NSAID and acetaminophen
Codeine, codeine-related +/- Acetaminophen, Tramadol
Morphine, fentanyl
What is the opioid prototype?
What is the MOA of opioids?
What is the clinical utility of opioids?
Morphine
Mu receptor agonists
Tissue injury=acute stimuli > or equal to nerve injury
What are the clinical effects of agonists acting at opioid receptors?
- analgesia (supra-spinal)
- euphoria
- CNS and resp depression
- drug dependence
- miosis
- GI, uterine motility
What clinical effects can a person build up tolerance for morphine?
There is no tolerance to ___ with morphine
Analgesia, euphoria, sedation, nausea, resp depression
Miosis and constipation
What are contra-indications for morphine regarding respiration?
Brain injury, emphysema
What are some clinical indications for morphine?
Post-operative pain –> procedures and surgery
Cancer pain –> primary and metastatic malignancy
Other pain –> sickle cell crisis, trauma, severe diarrhea, dyspnea caused by pulmonary edema from LV failure
Group 1 opioids are full agonists that can be given IV or PO. List the drugs:
Morphine
Methadone
Meperidine
Hydromorphone
Oxymorphone
Levorphanol
Group 2 opioids are full agonists and short acting. List the drugs:
Fentanyl
Sufentanil
Remifentanyl
Group 3 opioids are codein-related. List the drugs:
Hydrocodone
Oxycodone
Which group 1 full agonists have high (good) oral bioavailability?
Methadone and Leveorphanol
Oral/parenteral potency ratio
Describe the bioavailability of oral morphine:
POOR bioavailability –> 1st pass metabolism effect
The pharmacokinetic properties of this opioid agonist drug are useful for withdrawal/maintenance and detoxification
Methadone
Compare the half life and oral bioavailability of methadone vs morphine:
Methadone has higher t1/2 (27 hrs vs 2 hrs for morphine)
Methadone has better oral bioavailability (90% vs 20% for morphine)
Methadone can affect cardiac electrical conduction, producing __ prolongation in acute overdose or during long-term methadone tx
QT-interval
This mu agonist causes mydriasis. Abuse is difficult to detect via pinpoint pupils. Accordingly, those who abuse this drug can escape detection
Meperidine
__ is a toxic metabolite of meperidine which accumulates and causes seizures
Normeperidine
Which of the group 2 opioid agonists has affects as a kappa, delta, and mu agonist?
Sufentanil
Compare the potency of Group 2 opioid agonists vs morphine and methadone (group 1 opioid agonists)
100x more potent than morphine and methadone
___ is gaining popularity for providing analgesia for childbirth if regional anesthesia is either contraindicated or not desired. It is metabolized by plasma and tissue esterases. Although it transfers across the placenta, its rapid metabolism in the fetus lowers the risk for neonatal depression. Its rapid onset of action, within 1 minute following IV injection, is another advantage
Remifentanil
___ is a strong mu agonist (meperidine analog), used in anesthesia, has a rapid onset and distribution (lipophilic), short DOA (procedures), transmucosal (lollipop), and can be given via transdermal patch delivery. There is high abuse potential via heating patches
Fentanyl
__ is a group 3 mu partial agonist for moderate pain and cough. It has less potential for drug dependence and respiratory depression
Codeine
Compare the oral bioavailability of codeine compared to morphine:
Reliable oral absorption–> 50% versus 20% for morphine
Is the anti-tussive effect for cough relief with codeine mu dependent?
No, it is u-independent
This a safer antitussive agent that relieves cough independently of opioid receptor. It is not an analgesic and not addictive
Dextromethophan
Formulation of hydrocodone and oxycodone with acetaminophen complicates __ management
Overdose
What phase 1 enzyme is responsible for converting codeine to the active metabolite morphine?
CYP2D6
These opioids have a special use for anti-diarrhea with limited abuse potential:
Loperamide and diphenoxylate
These interact with mu opioid receptor in the gut, have low solubility, and poor penetration of BBB
__ is a moderate mu agonist, its active metabolite is N-desmethyl, has reliable oral absorption/bioavailability (70% vs 20% for morphine), analgesia for moderate pain, inhibits catecholamine reuptake (associated with seizures) and should be cautious with patients on tricyclic or SSRIs
Tramadol
__ is a mixed kappa agonist plus mu partial agonist/ delta antagonist. Used for supra-spinal analgesia, can precipitate withdrawal (in abusers), and side effects include tachycardia, hallucinations
Pentazocine
___ is a mu partial agonist plus kappa and delta antagonist used for analgesia. It can precipitate withdrawal in abusers. It is also used in office-based detox/maintenance in combo with naloxone
Buprenorphine
__ is an illegal substance that penetrates the BBB rapidly –> exaggerated euphoria –> addiction liability
Heroin (Di-acetylmorphine)
Maintenance with this drug in addition programs has the highest compliance (50-80%):
Methadone
What are signs/symptoms of opioid analgesic overdose?
RR
These mu receptor antagonists occupy, but do not activate mu receptors. They competitively inhibt (displace) heroin, morphine, fentanyl from mu receptors.
Naloxone (IV) and Naltrexone (PO)
What is the antidote for opioid overdose?
Naloxone (IV) and Naltrexone (PO)
In emergency setting, use Naloxone since it is parenteral. Naltrexone can be given after pt is revived in the ED setting since it is PO
This mu receptor antagonist can reverse coma and respiratory depression ~1 minute after IV bolus. It has a short DOA of about 1-2 hrs and can lead to apparent “relapse” of overdose symptoms
Naloxone
This mu receptor antagonist has a long DOA (48 hrs for single dose orally) in overdose
Naltrexone
What strategies might work for opioid-induced side effects such as constipation?
Methylnaltrexone: a quaternary derivative of naltrexone with restricted ability to cross the BBB. Functions as a peripheral acting opioid antagonist, including actions on the GI tract to inhibit opioid-induced decrease GI motility and delay in GI transit time, thereby decreasing opioid-induced constipation. Does not affect opioid analgesic effects or induce opioid withdrawal symptoms
Describe the pre- and post-synaptic pain impulse:
Afferent sensory signal –> opioid receptor unoccupied and an increasing influx of Ca in the pre-synaptic nerve increases glutamate discharge from pre-synaptic –> increase in NMDA-receptor Na influx on Post-synaptic side –> pain impulse
