Opioid InfoDataDose MegaTable v. 1
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KLEINERkIFFER'S ANTI-OBFUSCATIONIST ODE TO OBDURANTOPIOIDS
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Disclaimer:Nobody here is licensed to even drive, do not use this as medicaladvice[/FONT]
Opioids are a wide range of substancesthat act on opioid receptors (mu, delta, kappa, nociceptin). They canbe categorized into opiates (natural alkaloids found in the resin ofPapaver somniferum), semisynthetic (compounds of the poppy plant areused to synthesize new substances)and synthetic opioids (fullysynthetically produced). So all opiates are opioids, but not allopioids are opiates. Papaver somniferum has been used for hundreds,if not thousands of years, while moprhine was first isolated in the19th century and synthetic opioids were invented in the 20th century.Medical uses include pain, diarrhea and cough.
How do they work?
There are three main opioid receptors(mu (1-3), delta and kappa)
The mu receptor is responsible foranalgesia, physical dependence, respiratory depression, euphoria, andpossible vasodilation. Mu1 seems to be implicated in analgesia andmu2 in respiratory depression and physical dependence
The delta receptor is responsible forthe analgesia, antidepressant and convulsant effects as well asphysical dependence.
The kappa receptor is responsible forthe analgesia, anticonvulsant, dissociative and deliriant effects aswell as dysphoria, neuroprotection and sedation.
Opioids mimic the actions of endogenousopioid peptides by interacting with mu, delta or kappa opioidreceptors. The opioid receptors are coupled to G1 proteins and theactions of the opioids are mainly inhibitory. They close N-typevoltage-operated calcium channels and open calcium-dependentinwardly-rectifying potassium channels. This results inhyperpolarization and a reduction in neuronal excitability. They alsodecrease intracellular cAMP which modulates the release ofnociceptive neurotransmitters (e.g. substance P).
(
https://www.ncbi.nlm.nih.gov/pubmed/9202932)
Dangerousinteractions
Don't combine with other depressants(like alcohol, benzos etc.) as they'll potentiate each other,increasing respiratory depression etc.
Adding stimulants can result inaccidental excessive intoxication
Don't combine with dissociatives
Some opioids shouldn't be combined withMAOIs/antidepressants
Good to know
Hormone imbalance
Opioid-induced hypogonadism seems to bea common complication of therapeutic or illicit opioid use.
(
https://www.ncbi.nlm.nih.gov/pubmed/19333165)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4590093/
http://jaoa.org/article.aspx?articleid=2093682
Constipation
Constipation megathread
Attenuating tolerance withNMDA-antagonists
Oxycodone
Morphine equivalency: Oral 1.5 to 2 IV1
Full/partial agonist: Full MOR agonist
Onset of action: 10-30 minutes IR, 60minutes CR
Half life: 2 to 3 hours IR, 4 to 5hours CR
Duration of action: 3 to 6 hours IR, 8to 12 hours CR
Bioavailability of different ROAs: Oral60 to 87% Intranasal 45 to 77% IV 100%
Mode of action: MOR agonist. Talk ofKOR agonism is likely unfounded
Dosage: varies based on tolerance
Dangerous dosage: varies based ontolerance
Good to know: Metabolized primarily byCYP 3A4 to noroxycodone and CYP 2D6 to oxymorphone. Despite bothmetabolites being active, analgesia is produced mainly by oxycodoneitself due to poor CNS penetration of noroxycodone and only 10%converted to oxymorphone. Studies with poor 2D6 metabolizers haveshown little difference in pain relief compared to normalmetabolizers insinuating oxycodone and not oxymorpone produces theanalgesic effect.
Available in many dosage forms with orwithout acetaminophen (paracetamol) or NSAIDs. Most common would bePercocet (oxycodone + APAP, IR) 2.5, 5, 7.5, and 10mg/ 325 oxy/apap,IR oxycodone (various forms Roxicodone, Oxynorm) 5 to 30mg, andoxycodone ER/CR (Oxycontin 10 to 80mg) Available IV in some countries(UK) but not in US
Diacetylmorphine (Heroin)
Morphine equivalency: 2.5
Full/partial agonist: Full MOR agonist
Onset of action: Depending on ROA,within minutes
Half life: 2-3 min, morphine around 3h,6-MAM around 20 min
Duration of action: 4-5 h
Bioavailability of different ROAs: 5%oral, 44–61% smoked
Mode of action: Prodrug (lowµ-affinity), but mostly metabolism into 6-MAM and morphine
Dosage: 2.5-10 mg IV
Dangerous dosage. 20-25 mg IV
Good to know: Metabolized to morphinevia first-pass metabolism, via I.V. rapid crossing of BBB andmetabolized into 3-MAM (inactive) and 6-MAM (active) in the brain
Forms -> Black tar, ......
Sorted by potency from low to high
Tramadol
Morphine equivalency 0.1
Full/partial agonist: Fullµ-opioid-receptor agonist, low affinity
Onset of action: Orally IR 30-60min;Injected 20-45min; Orally XR 60-90min
Half life: around 6h, Metabolitesaround 9-10 hours
Duration of action: IR 6-10h; Injected6-9h
Bioavailability of different ROAs: Oral70–75%; Rectal 77%; IM/IV 100%
Mode of action: low affinity forµ-opioid receptor, SRI&SRA, Metabolite O-Desmethyltramadol hasa higher affinity for the µ-opioid receptor and NRI
Dosage: 25-100mg IR
Dangerous dosage: anything above 300mgcan lead to seizures, risk of respiratory depression is rather low
Good to know: Acts as SRI (primarymetabolite is a NRI) so combining it with SSRIs, MAOIs etc. canresult in Serotonin Syndrome; Lowers the seizure threshold, sodon’t go over 300mg; Main metabolite O-Desmethyltramadol hashigher affinity for the µ-opioid receptor and adds a lot to theeffects, so people with a CYP2D6 mutation making them poormetabolizers won't feel as much
those with decreased CYP2D6 activityrequire a dose increase of 30% in order to achieve the same degree ofpain relief as those with a normal level of CYP2D6 activity.(Wikipedia)
Codeine
Morphine equivalency: 0.1
Full/partial agonist: barely active onit's own
Onset of action: 15-60min
Half life: 2.5-6h
Duration of action: 4-6h
Bioavailability of different ROAs: Oralaround 50-90%; no other ROAs as it's a prodrug and IV can be lethal
Mode of action: barely active on it'sown, Metabolite Morphine full µ-opioid receptor agonist
Dosage: single dosage 0,5-1mg/kg BW;daily dosage 2-4mg/kg BW
Dangerous dosage: around 250-500mg, forfast metabolizers less
Good to know: Prodrug -> needs to bemetabolized into morphine; thus people people with a CYP2D6 mutationmaking them poor metabolizers won't feel as much/anything; InjectingCodeine can result in pulmonary edema (fluid in lungs), facialswelling and other life threatening complications as it provokes astrong histamine reaction, don't do it!; If you have acodeine-apap/ibuprofen/something else combo do a CWE
Tilidine
Morphine equivalency: 0.1-0.2
Full/partial agonist: Full agonist, butlow potency
Onset of action: 10-30min
Half life: 3-5h; Metabolites 3,5-5h
Duration of action: IR 4-6h; XR up to11-13h
Bioavailability of different ROAs: Oralaround 6-7%, IV 100%
Mode of action: only a really weakopioid on it's own, the active metabolites are mostly responsibly forthe effects (tilidine-> nortilidine-> bisnortilidine.Dextilidine seems to responsible for the analgesic activity
Dosage: single dosage 25-100mg; dailydosage 100-400mg
Dangerous dosage: 5-8mg/kg BW; above400mg
Good to know: Needs to be metabilizedvia the enzymes CYP3A4 and CYP2C19, thus people people with a CYP2D6mutation making them poor metabolizers won't feel as much/anything
Pethidine aka Meperidine
Morphine equivalency: 0,1-0.2
Full/partial agonist: Full MOR agonist
Onset of action:
Half life: 0,1-0.2
Duration of action: 2-5 h
Bioavailability of different ROAs:50–60% oral
Mode of action: MOR agonist, NET andDAT inhibition, interaction with sodium ion channels, muscarinicacetylcholine receptor antagonist , ?-opioid agonism
Dosage: 50 - 200 mg (other sourcestates 30-70 mg)
Dangerous dosage: > 210 mg ?
Good to know:Don't combine with MAOIsand antidepressants; Toxic metabolite, norpethidine, with an halflife of 8-12 (regular administration can lead to accumulation), hasconvulsant and hallucinogenic effects (probaply due toanticholinergic activity) and SRI effects
Dihydrocodeine
Morphine equivalency: 0.2
Full/partial agonist: Full MOR agonist
Onset of action: 0.3-1 h
Half life: 3-4 h
Duration of action: 3-5 h
Bioavailability of different ROAs:10-40 %
Mode of action: MOR agonist
Dosage: 50-250 mg
Dangerous dosage: >250 mg
Good to know: IV can lead toanaphylaxis and pulmonary edema, metabolites dihydromorphine (viaCYP2D6) and dihydromorphine-6-glucuronide have higher affinityes forMOR, but most likely only produced in small amounts
Hydrocodone
Morphine equivalency: 0.6 (in rhesusmonkeys higher than morphine; 1:1 with oral administered morphine)
Full/partial agonist: Full MOR agonist
Onset of action: 10-20 min
Half life: 3-5 h
Duration of action: 4-8 h
Bioavailability of different ROAs:60-70 % oral, 75 % rectal
Mode of action: MOR agonist, six timesless affinity for DOR
Dosage: 5-25 mg oral
Dangerous dosage: 50 mg oral
Good to know: Metabolized tonorhydrocodone (CYP3A4, but poor BBB-penetration) and hydromorphone(CYP2D6), around 40 % are metabolized via non,cytochrome-catalyzedreactions
Pentazocine
Morphine equivalency: 0.3
Full/partial agonist:agonist/antagonist maybe KOR agonist and MOR antagonist
Onset of action: 15-30 min
Half life: 2-5 h
Duration of action: 3-5 h
Bioavailability of different ROAs: highfirst pass metabolsim, so only 20 % oral
Mode of action: high first pass, soonly 20 % oral
Dosage: 20-50 mg
Dangerous dosage: 150 mg
Good to know: IV of pentazocine lactatemay lead to necrosis and sepsis, can be plugged (decrease dosage, asBA is higher), can increase BP and HR, may cause hallucinations anddelusions due to KOR agonism, has ceiling
Tapentadol
Morphine equivalency: 0.3 -0.6
Full/partial agonist: Full mOR agonist
Onset of action: 15-45 min
Half life: 4 h
Duration of action: 4-6 h
Bioavailability of different ROAs: 30%oral
Mode of action: MOR agonist and NRI
Dosage: 25-75 mg
Dangerous dosage:
Good to know: Don't combine with MAOIsand antidepressants, may lower seizure treshold, may causehypotension
Morphine
Morphine equivalency: 1
Full/partial agonist: Full MOR agonist
Onset of action: 10 s - 5 min (IV), 15min (IM), 20 min (PO)
Half life: 2-3 h
Duration of action: 3-7 h
Bioavailability of different ROAs: 20%to 40% oral, 36% to 71% rectal, 100% IV/IM
Mode of action: MOR agonist
Dosage: 10-20 mg oral, 2.5-5 mg IV
Dangerous dosage: 50 mg oral, 25 mg IV
Good to know: May lower seizuretreshold, high histamine release, may influence the production ofneutrophiles and cytokines (important for the immune system),endogenous opioid
Methadone (racemate)
Morphine equivalency: 2
Full/partial agonist: Full MOR agonist
Onset of action: 0.5 - 4 h oral, 0.3 -3 h rectal
Half life: 10-60 h
Duration of action: 4-12 h
Bioavailability of different ROAs:40-99 % oral
Mode of action: MOR agonist, weak NMDAantagonist, weak SRI, nicotinic acetylcholine receptor antagonist
Dosage: 3-15 mg oral
Dangerous dosage: 15 mg I.V., 20 mgoral
Good to know: Levo-methadone is twiceas potent; binds to and blocks hERG (alpha subunit of potassium ionchannel in the heart) thus can lead to Long-QT-syndrome, metabolsimvia CYP3A4 -> CYP3A4 can be inhibited by WGJ, don't combine withMAOIs and antidepressants
Hydromorphone
Morphine equivalency: 7.5
Full/partial agonist: Full MOR agonist
Onset of action: 20-60 min oral, 20 s -10 min IV
Half life: 2-3 h
Duration of action: 3-5 h
Bioavailability of different ROAs:30-50 % oral, 50-60 % intranasal
Mode of action: MOR agonist, may beweak kappa-agonist
Dosage: 1-4 mg oral
Dangerous dosage: 6-12 mg oral
Good to know: /
Oxymorphone
Morphine equivalency: 10-12
Full/partial agonist: Full MOR agonist
Onset of action: 10 s -10 min IV
Half life: 7-9 h
Duration of action: 3-6 h
Bioavailability of different ROAs: 10 %oral, 40 % intranasal
Mode of action: MOR agonist, may be DORagonist
Dosage:
Dangerous dosage:
Good to know: /
Buprenorphine
Morphine equivalency: 30-40
Full/partial agonist: Partial
Onset of action: 30 min
Half life: 20-70 h
Duration of action: up to 24 hours
Bioavailability of different ROAs: 30 %sublingual, 50 % intranasal
Mode of action: partial MOR agonist,DOR and KOR antagonist
Dosage: 0.2-0.8 mg
Dangerous dosage: ?
Good to know: high first-passmetabolism, ceiling and blocking effect, partial agonism -> highaffinity for receptor but low intrinsic activity
Fentanyl
Morphine equivalency: 120
Full/partial agonist: Full MOR agonist
Onset of action: 10 s - 5 min
Half life: depends on ROA, 3-12 h,longer with transdermal application, shorter with IV
Duration of action: depends on ROA
Bioavailability of different ROAs: 92%transdermal, 89% intranasal, 50% buccal, 3% oral
Mode of action: MOR agonist
Dosage: 12-50 µg ?
Dangerous dosage: ?
Good to know: metabolized by CYP3A4,little histamine release, high therapeutic index, half life mayincrease with repeated administration due to accumulation in muscleand fat-tissue due to high lipophilicity
Levorphanol*
Ketobemidone
Dipipanone
Propoxyphene*
Diphenoxylate*
Loperamide
Butorphanol*
Nalbuphaine
Dezocine
Remifentanil
Sufentanil
Carfentanil* (topical, was recentlyfound in heroin over here)
Etorphine
Antagonists
Naloxone
It's not a substitute for professionalmedical care, always call an abulance when someone overdoses!
Bioavailability: 2% oral due to highfirst-pass metabolism
Onset of action: 2-5 min
Half life: 1-1.5 h
Duration of action: 30-60 min
Mechanism of action: Non-selective andcompetetive opioid receptor antagonist, affinities mu(Ki 0.56nM)>delta(4.9 nM)>kappa (36.5 nM), (-)naloxone is active,(+)naloxone is pretty much inactive
Dosage: for IV/IM 0.4-2 mg, intranasal1-4 mg, maximum dosage 10 mg (if no response occurs at this time,alternative diagnosis and treatment should be pursued)
Good to know: In the United States,naloxone is classified as a prescription medication, though it is nota controlled substance. While it is legal to prescribe naloxone inevery state, dispensing the drug by medical professionals (includingphysicians or other licensed prescribers) at the point of service issubject to rules that vary by jurisdiction. In the following states,you can purchase naloxone from a pharmacist directly without gettinga prescription from a doctor: Alabama, Alaska, Arizona, Arkansas,California, Colorado, Connecticut, Florida, Georgia, Idaho, Illinois,Indiana, Iowa, Kentucky, Maine, Maryland, Massachusetts, Minnesota,Nevada, New Hampshire, New Jersey, New Mexico, New York, NorthCarolina, Ohio, Oregon, Pennsylvania, Rhode Island, South Carolina,Tennessee, Texas, Utah, Vermont, Washington, West Virginia andWisconsin.
USA
UK
Naltrexone
Primarily used to manage alcohol/opioiddependence. For opioid dependence should only be taken afterdetoxification as it can cause precipitated withdrawal. Can be takenorally or IM. Competetive antagonist at the mu-opioid receptor (Ki0.0825 nM) > kappa (Ki 0.509 nM) > delta(Ki 8.02 nM). Half lifeof 4 h, active metabolite, 6ß-naltrexol, half life of around 13hours, depot injections/SC implants have considerably longer durationof action.
