Pharmacology of Opioid Narcotic Analgesics and Related Drugs Flashcards
opioid narcotic mu R antagonists
- Nalozone
- Naltrexone
- Methyl naltrexone (GI specific)
opioid partial agonists or mixed agonists/antagonists
- Buprenorphine
- Buprenorphine–naloxone
- pentaxocine
insolube, poorly absorbed opioid R agonists used for diarrhea?
- loperamide
- diphenoxylate
common opioid related anti-tussive agents (cough suppression)
- codeine
- dextromethorphan
- hydrocodone
pain impulse pathway
-afferent signal pathway (opioid R unoccupied)
-increases Ca influx
increases glutamate discharge
-increases NMDA R NA influx
opioid agonist-mediated signaling pathway
- blunts signal (opioid agonist occupying opioid Rs)
- blunts Ca influx
- blunts glutamate discharge
- increases K efflux
full agonists to mu opioid receptors
- fentanyl (more potent)
- morphine
-partial agonist/mixed to mu opioid receptors
-Buprenorphine
Antagonists to mu opioid receptors
- Naloxone
- Naltrexone
mild pain–what treatment
- NSAID
- acetaminophen
moderate pain–or persisting or uncontrolled–what treatment?
- Codeine
- with/without acetaminophen, tramadol
severe oaub–or persisting or uncontrolled–what treatment
Morphine
fentanyl
acetaminophen, NSAIDS used for?
tissue injury
opioids (morphine) used for?
tissue injury=acute stimuli=nerve injury
anticonvulsants–used for?
nerve injury
what is the prototype mu agonist?
morphine
mu R clinical effect
- analgesia (supra-spinal)
- euphoria
- CNS and respiratory depression
- drug dependence
- miosis
- GI, uterine motility
Kappa R clinical effet
- analgesia (spinal)
- sedation
- miosis
- GI, uterine motility
tolerance to morphine (mu agonists)
-analgesia
-euphoria
-sedation
-nausea
-resp depression
(have to increase dose or rotate to diff opioid)
no tolerance to morphine (mu agonists)
- mioisis
- constipation
morphine side effect
- respiratory depression
- causes acidosis (high H), low HCO3, high PCO2
- along with hyperkalemia
morphine depresses what?
sensitivity to CO2! –respiration
contraindications to morphine
-brain injury
-emphysema
due to it depresses respiration
clinical indications for morphine
- post operative pain
- cancer pain
- other pain–sickle cell crisis, trauma
mu agonists–group 1
- full agonists, parenteral and oral
- morphine
- methodone
- meperidine
- hydromorphone
- oxymorphone
- levorphanol
mu agonists group 2
full agonists, short acting
- fentanyl
- sufentanil
- remifentanyl
mu agonists–group 3
- codeine–related
- hydrocodone
- oxycodone
group 1 what differs from morphine in efficacy
-morphine-10
-meperidine-60
hydromorphine-1.5
-oxymorphone-1.5
-levorphanol- 2-3
morphine has high first pass metabolism (low oral bioavailability)–what group has good oral bioavailbaility?
- methadone
- levorphanol
morphine metabolism–active metabolites
- via UGT 1A1 and 2B7
- M3 glucuronide
- M6 glucuronide
- hydromorphone (via dehydrogenase)
morphine metabolism–inactive metabolites
- via CYP 3A4
- normorpine
methadone
- full mu agonist
- longer t/12 (27 hours vs 2 for morphine)
- better bioavailability (90% vs 20% for morphine)
methadone useful for?
- withdrawl/maintenance
- detoxification
methadone side effect??
- QT interval prolongation (in acute overdose or long term treatment)
- unrelated to its interaction with mu Rs (blocks flow of K ions)
Meperidine–distinctions as mu agonist?
- pupil dilation (those who abuse this drug can escape detection)
- Normeperdine–toxic metabolites–accum and causes seizures
Group 2 short acting full agonists potency?
- fentanyl
- sufentanil
- remifentanil–very short acting
- 100% more potent than morphine
remifentanil used for?
- analgesia for childbirth
- metabolized by plasma and tissue esterases–rapid metabolism in fetus lowers risk for neonatal depression
- rapid onset
Fentanyl–characteristics
- rapid onset and distribution
- short duration of action
- tranmucosal (lollipop)
- transdermal patch delivery (slows onset, prolongs delivery)–caution-resp depression–abuse potential via heating patches
group 3 codeine and its relatives–characteristics
- partial agonists
- less potential for drug dependence and respiratory depression
- bioavailability–50% (vs 20% for morphine)
- moderate pain
- anti-tussive (mu-independent)
safer antitussive agent?
- dextromethophan–independent of opioid Rs
- not analgesic; not addictive
which does codeine cause death sometimes?
- active metabolite via CP2D6–morphine
- inactive–morcodiene
- some people are ultrafast metabolizers
codeine metabolism differs
- ultrafast-CYP2D6 duplication and ultrafast allele
- intermediate–CYP 2D6–heterozygous
- -poor metabolizers–CYP2D6–gene deltions, slow allele
morphine–active metabolite
- M6G, M3G
- hydromorphone
codeine–active metabolite
morphine
meperidine active metabolite
-normeperidine (toxic)
doesnt have active metabolites
hydromorphone
oxymorphone
opioids used as anti-diarrheals
- loperamide
- diphenoxylate
- mu opioid receptors in gut
- have poor solubility; poor penetration of BBB
Tramadol
- moderate mu agonist
- moderate pain
- inhibits catecholamine reuptake (caution in patients on SRI anti-depressants)
- associated with seizures
Pentazocine
- mixed-K agonist + mu partial agonist/delta antagonist
- supra-spinal analgesia
- can precipitate withdrawl in abusers
- SE–tachycardia, hallucinations
Buprenorphine
- mu partial agonist plus K an delta antagonist
- analgesia
- can precipitate withdrawl in abusers
- office-based detox/maintenance in combo with naloxone
heroin is what?
- di-acetylmorphine
- penetrates BBB rapidly–exaggerated euphoria–addiction liability
addiction program
- methadone
- buprenorphine
- naltrexone
opioid overdose symptoms
-respiratory rate
mu R antagonists
- Naloxone (iV)
- Naltrexone (po)
- occupy but dont activate mu receptors
- competitive
antidote for opioid overdose??
- Naloxone (IV
- Naltrexone (po)
major issue re post surgery and chronic use of opioids
- constipation
- opioids inhibit coordinated peristalsis–nausea, vomiting, costipation
treatment for opioid–induced constipation
- Methylnalrexone
- cant cross BBB
- peripheral acting opioid antagonist
