Hydrocodone

The name of the pictureThe name of the pictureThe name of the pictureClash Royale CLAN TAG#URR8PPP




Not to be confused with Dihydrocodeine.


Hydrocodone
Hydrocodone skeletal.svgHydrocodone-Spartan-PM3-3D-balls.pngClinical dataTrade names
Vicodin, Norco, many others
Synonyms
Dihydrocodeinone

AHFS/Drugs.com

Micromedex Detailed Consumer Information
MedlinePlus
a601006
Pregnancy
category


  • US: C (Risk not ruled out)

Dependence
liability
Very high
Routes of
administration
Clinical: oral[1]
Others: intranasal, rectal

ATC code

  • R05DA03 (WHO)

Legal statusLegal status



  • AU: S8 (Controlled)


  • CA: Schedule I


  • DE: Anlage III (Special prescription form required)


  • UK: Class A


  • US: Schedule II




Pharmacokinetic dataBioavailability

Oral: 70%[3]
Protein binding
Low[3][4]
Metabolism

Liver: CYP3A4 (major), CYP2D6 (minor)[2]
Metabolites
• Norhydrocodone[2]
• Hydromorphone[2]
• Others[2]
Onset of action
10–20 minutes[1]
Elimination half-life

Average: 3.8 hours[5]
Range: 3.3–4.4 hours[1]
Duration of action
4–8 hours[1]
Excretion

Urine[6][7]
IdentifiersCAS Number

  • 125-29-1 ☑Y


PubChem CID

  • 5284569

IUPHAR/BPS
  • 7081

DrugBank

  • DB00956 ☑Y

ChemSpider

  • 4447623 ☑Y

UNII
  • 6YKS4Y3WQ7

KEGG

  • D08045 ☑Y

ChEBI

  • CHEBI:5779 ☑Y

ChEMBL

  • ChEMBL1457 ☑Y

ECHA InfoCard

100.004.304 Edit this at Wikidata
Chemical and physical dataFormula

C18H21NO3
Molar mass
299.368 g/mol g·mol−1
3D model (JSmol)
  • Interactive image


.mw-parser-output .noboldfont-weight:normal
  (verify)

Hydrocodone, sold under brand names such as Vicodin and Norco among many others, is a semisynthetic opioid derived from codeine, one of the opioid alkaloids found in the opium poppy.[8] It is a narcotic analgesic used orally for relief of moderate to severe pain, but also commonly taken in liquid form as an antitussive/cough suppressant.[9]


As with members of all categories of semi-synthetic opioids derived from morphine (and codeine is one of these, in fact) with the exception of the simple esters of morphine like heroin, nicomorphine, acetyldipropanoylmorphine etc., hydrocodone made commercially is manufactured in a much more efficient synthesis from thebaine, a close chemical relative of codeine found in fairly high concentrations in opium. Hydrocodone is two steps from codeine and therefore three from morphine, and in fact a number of syntheses were found, with others being from dihydrocodeine, dihydromorphine, tetrahydrothebaine and a large number of total syntheses from coal tar or petroleum through morphine, codeine, and thebaine. Hydrocodone's closest structural relatives are fellow 14-hydroxycodeineones such as oxycodone, oxymorphone, hydromorphinol, oxymorphol, and hydromorphone. Much of hydrocodone's activity is from the last of these produced in the liver from the hydrocodone, in the one step which activates similar drugs by turning them into stronger derivatives in the same fashion in which the liver turns codeine to morphine. However, hydrocodone is also turned into other active products by other metabolic pathways and hydrocodone does, like oxycodone, have intrinsic activity of its own to a greater extent than is the case for codeine.


Hydrocodone is an opioid, and acts as a selective agonist of the μ-opioid receptor, the main biological target of the endogenous neuropeptide β-endorphin.[10][11]


It was patented in 1923.[12] Hydrocodone is prescribed predominantly within the United States, with the International Narcotics Control Board reporting that 99% of the worldwide supply in 2007 was consumed in the United States. Several common imprints for hydrocodone are M365, M366, M367.[13] In 2016 it was the 113th most prescribed medication in the United States with more than 6 million prescriptions.[14]


.mw-parser-output .toclimit-2 .toclevel-1 ul,.mw-parser-output .toclimit-3 .toclevel-2 ul,.mw-parser-output .toclimit-4 .toclevel-3 ul,.mw-parser-output .toclimit-5 .toclevel-4 ul,.mw-parser-output .toclimit-6 .toclevel-5 ul,.mw-parser-output .toclimit-7 .toclevel-6 uldisplay:none



Contents





  • 1 Medical uses

    • 1.1 Available forms



  • 2 Side effects


  • 3 Interactions


  • 4 Pharmacology

    • 4.1 Pharmacodynamics


    • 4.2 Pharmacokinetics

      • 4.2.1 Absorption


      • 4.2.2 Distribution


      • 4.2.3 Metabolism


      • 4.2.4 Elimination




  • 5 Chemistry

    • 5.1 Detection in body fluids



  • 6 History


  • 7 Society and culture

    • 7.1 Formulations

      • 7.1.1 Combination products


      • 7.1.2 Zohydro ER



    • 7.2 Legal status

      • 7.2.1 United States




  • 8 See also


  • 9 References


  • 10 External links




Medical uses


Hydrocodone is used to treat moderate to severe pain, although it is often prescribed to treat mild pain as well.
In liquid formulations, it is used as an antitussive to treat cough.[9] In one study comparing the potency of hydrocodone to that of oxycodone, it was found that it took 50% more hydrocodone to achieve the same degree of miosis (pupillary contraction).[15] The investigators interpreted this to mean that oxycodone is about 50% more potent than hydrocodone.


However, in a study of emergency department patients with fractures, it was found that an equal amount of either drug provided about the same degree of pain relief, indicating that there is little practical difference between them when used for that purpose.[16] Some references state that the analgesic action of hydrocodone begins in 20–30 minutes and lasts about 4–8 hours.[17] The manufacturer's information says onset of action is about 10–30 minutes and duration is about 4–6 hours.[18] Recommended dosing interval is 4–6 hours.



Available forms


See also: Hydrocodone/paracetamol, Hydrocodone/ibuprofen, and Hydrocodone/aspirin

Hydrocodone is available in a variety of formulations for oral administration:[19][20][21]


  • The original oral form of hydrocodone alone, Dicodid, as immediate-release 5 and 10 mg tablets of the hydrochloride (by analogy to Dilaudid, the original hydromorphone product invented around the same time, both in Germany) is available for prescription in Continental Europe per national drug control and prescription laws and Title 76 of the Schengen Treaty, but dihydrocodeine has been much more widely used for the same indications since the beginning in the early 1920s, with hydrocodone being regulated the same way as morphine in the German Betäubungsmittelgesetz, the similarly named law in Switzerland and the Austrian Suchtmittelgesetz, whereas dihydrocodeine is regulated like codeine. For a number of decades, the liquid hydrocodone products available are cough medicines.

  • Hydrocodone plus homatropine (Hycodan) in the form of small tablets for coughing and especially neuropathic moderate pain (the homatropine, an anticholinergic, is useful in both of those cases and is a deterrent to intentional overdose) was more widely used than Dicodid and was labelled as a cough medicine in the United States whilst Vicodin and similar drugs were the choices for analgesia.

  • Extended-release hydrocodone in a time-release syrup also containing chlorphenamine/chlorpheniramine is a cough medicine called Tussionex in North America. In Europe, similar time-release syrups containing codeine (numerous), dihydrocodeine (Paracodin Retard Hustensaft), nicocodeine (Tusscodin), thebacon, acetyldihydrocodeine, dionine, and nicodicodeine are used instead.

  • Immediate-release hydrocodone with paracetamol (acetaminophen) (Vicodin, Lortab, Lorcet, Maxidone, Norco, Zydone)

  • Immediate-release hydrocodone with ibuprofen (Vicoprofen, Ibudone, Reprexain)

  • Immediate-release hydrocodone with aspirin (Alor 5/500, Azdone, Damason-P, Lortab ASA, Panasal 5/500)

  • Controlled-release hydrocodone (Hysingla ER, Zohydro ER)[22]

Hydrocodone is not available in parenteral or any other non-oral forms.[4][1]



Side effects


Common side effects of hydrocodone are nausea, vomiting, constipation, drowsiness, dizziness, lightheadedness, anxiety, abnormally happy or sad mood, dry throat, difficulty urinating, rash, itching, and contraction of the pupils. Serious side effects include slowed or irregular breathing and chest tightness.[23]


Several cases of progressive bilateral hearing loss unresponsive to steroid therapy have been described as an infrequent adverse reaction to hydrocodone/paracetamol misuse. This adverse effect has been considered by some to be due to the ototoxicity of hydrocodone.[24][25] Other researchers have suggested that paracetamol is the primary agent responsible for the ototoxicity.[26][27]


Hydrocodone is in U.S. Food and Drug Administration (FDA) pregnancy category C. No adequate and well-controlled studies in humans have been conducted. A newborn of a mother taking opioid medications regularly prior to the birth will be physically dependent. The baby may also exhibit respiratory depression if the opioid dose was high.[28] An epidemiological study indicated that opioid treatment during early pregnancy results in increased risk of various birth defects.[29]


Symptoms of hydrocodone overdose include narrowed or widened pupils; slow, shallow, or stopped breathing; slowed or stopped heartbeat; cold, clammy, or blue skin; excessive sleepiness; loss of consciousness; seizures; or death.[23]


Hydrocodone can be habit forming, causing physical and psychological dependence. Its abuse liability is similar to morphine and less than oxycodone.[30]



Interactions


Patients consuming alcohol, other opioids, anticholinergic antihistamines, anti-psychotics, anti-anxiety agents, or other central nervous system (CNS) depressants together with hydrocodone may exhibit an additive CNS depression.[28] Hydrocodone may interact with serotonergic medications.[31]



Pharmacology



Pharmacodynamics























Hydrocodone (and metabolite) at opioid receptors
Compound
Affinities (Ki)		RatioRef
MORDORKORMOR:DOR:KOR
Hydrocodone11.1 nM962 nM501 nM1:87:45[10]
Hydromorphone0.47 nM18.5 nM24.9 nM1:39:53[32]




































Equianalgesic doses[33][34][35]
CompoundRoute
Dose
CodeinePO200 mg
HydrocodonePO20–30 mg
HydromorphonePO7.5 mg
HydromorphoneIV1.5 mg
MorphinePO30 mg
MorphineIV10 mg
OxycodonePO20 mg
OxycodoneIV10 mg
OxymorphonePO10 mg
OxymorphoneIV1 mg

Hydrocodone is a highly selective full agonist of the μ-opioid receptor (MOR).[17][36][10] This is the main biological target of the endogenous opioid neuropeptide β-endorphin.[11] Hydrocodone has low affinity for the δ-opioid receptor (DOR) and the κ-opioid receptor (KOR), where it is an agonist similarly.[10]


Studies have shown hydrocodone is stronger than codeine but only one-tenth as potent as morphine at binding to receptors and reported to be only 59% as potent as morphine in analgesic properties. However, in tests conducted on rhesus monkeys, the analgesic potency of hydrocodone was actually higher than morphine.[5]Oral hydrocodone has a mean equivalent daily dosage (MEDD) factor of 0.4, meaning that 1 mg of hydrocodone is equivalent to 0.4 mg of intravenous morphine. However, because of morphine's low oral bioavailability, there is a 1:1 correspondence between orally administered morphine and orally administered hydrocodone.[37] The relative milligram strength of hydrocodone to codeine is given as 6 fold, that is 5 mg has the effect of 30 mg of codeine; by way of the Roman numeral VI this is said to have given rise to the trade name Vicodin.[citation needed]



Pharmacokinetics



Absorption


Hydrocodone is only pharmaceutically available as an oral medication.[1] It is well-absorbed, but the oral bioavailability of hydrocodone is only approximately 25%.[3][4] The onset of action of hydrocodone via this route is 10 to 20 minutes, with a peak effect (Tmax) occurring at 30 to 60 minutes,[38] and it has a duration of 4 to 8 hours.[1]



Distribution


The volume of distribution of hydrocodone is 3.3 to 4.7 L/kg.[4] The plasma protein binding of hydrocodone is 20 to 50%.[17]



Metabolism


In the liver, hydrocodone is transformed into several metabolites, including norhydrocodone, hydromorphone, 6α-hydrocodol (dihydrocodeine), and 6β-hydrocodol.[2] 6α- and 6β-hydromorphol are also formed, and the metabolites of hydrocodone are conjugated (via glucuronidation).[39][40] Hydrocodone has a terminal half-life that averages 3.8 hours (range 3.3–4.4 hours).[5][1] The hepatic cytochrome P450 enzyme CYP2D6 converts hydrocodone into hydromorphone, a more potent opioid (5-fold higher binding affinity to the MOR).[2][41] However, extensive and poor cytochrome 450 CYP2D6 metabolizers had similar physiological and subjective responses to hydrocodone, and CYP2D6 inhibitor quinidine did not change the responses of extensive metabolizers, suggesting that inhibition of CYP2D6 metabolism of hydrocodone has no practical importance.[42][43] Ultra-rapid CYP2D6 metabolizers (1–2% of the population) may have an increased response to hydrocodone; however, hydrocodone metabolism in this population has not been studied.[44]


Norhydrocodone, the major metabolite of hydrocodone, is predominantly formed by CYP3A4-catalyzed oxidation.[2] In contrast to hydromorphone, it is described as inactive.[41] However, norhydrocodone is actually a MOR agonist with similar potency to hydrocodone, but has been found to produce only minimal analgesia when administered peripherally to animals (likely due to poor blood–brain barrier and thus central nervous system penetration).[45] Inhibition of CYP3A4 in a child who was, in addition, a poor CYP2D6 metabolizer, resulted in a fatal overdose of hydrocodone.[46] Approximately 40% of hydrocodone metabolism is attributed to non-cytochrome P450-catalyzed reactions.[47]



Elimination


Hydrocodone is excreted in urine, mainly in the form of conjugates.[6][7]



Chemistry



Detection in body fluids


Hydrocodone concentrations are measured in blood, plasma, and urine to seek evidence of misuse, to confirm diagnoses of poisoning, and to assist in investigations into deaths. Many commercial opiate screening tests react indiscriminately with hydrocodone, other opiates, and their metabolites, but chromatographic techniques can easily distinguish hydrocodone uniquely. Blood and plasma hydrocodone concentrations typically fall into the 5–30 µg/L range among people taking the drug therapeutically, 100–200 µg/L among recreational users, and 100–1,600 µg/L in cases of acute, fatal overdosage. Co-administration of the drug with food or alcohol can very significantly increase the resulting plasma hydrocodone concentrations that are subsequently achieved.[48][49]



History


Hydrocodone was first synthesized in Germany in 1920 by Carl Mannich and Helene Löwenheim.[50] It was approved by the Food and Drug Administration on 23 March 1943 for sale in the United States and approved by Health Canada for sale in Canada under the brand name Hycodan.[51][52]


Hydrocodone was first marketed by Knoll as Dicodid, starting in February 1924 in Germany. This name is analogous to other products the company introduced or otherwise marketed: Dilaudid (hydromorphone, 1926), Dinarkon (oxycodone, 1917), Dihydrin (dihydrocodeine, 1911), and Dimorphan (dihydromorphine). Paramorfan is the trade name of dihydromorphine from another manufacturer, as is Paracodin, for dihydrocodeine.[citation needed]


The name Dicodid was registered in the United States and appears without a monograph as late as 1978 in the Physicians' Desk Reference; Dicodid may have been marketed to one extent or another in North America in the 1920s and early 1930s. The drug was pure hydrocodone in small 5 and 10 mg tablets, physically similar to the Dilaudid tablets. It is no longer manufactured by Knoll in Germany, nor is a generic available. Hydrocodone was never as common in Europe as it is in North America—dihydrocodeine is used for its spectrum of indications. Germany was the number two consumer of hydrocodone until the manufacture of the drug was discontinued there. Now,[when?] the world outside the United States accounts for less than 1% of annual consumption. It was listed as a Suchtgift under the German Betäubungsmittelgesetz and regulated like morphine. It became available in the Schengen Area of the European Union as of 1 January 2002 under Title 76 of the Schengen Treaty.[citation needed]



Society and culture



Formulations



Combination products


Main articles: Hydrocodone/paracetamol and Hydrocodone/ibuprofen



Hydrocodone and paracetamol (acetaminophen) 5-500 tablets (Mallinckrodt)


Most hydrocodone is formulated in combination with a second analgesic, such as paracetamol (acetaminophen) or ibuprofen. Examples of hydrocodone combinations include Norco, Vicodin, Lortab, Vicoprofen and Riboxen.[53]



Zohydro ER



Zohydro ER
What is this drug for?
treatment of severe, chronic pain that requires around-the-clock opioid treatment[54]
Who might consider taking it?
Adults who need opioid treatment but who find alternative treatments to be inadequate[54]
Who should not take it?

  • People with severe asthma, advanced chronic lung problems, or chronic obstructive pulmonary disease[54]

  • people with a bowel obstruction or ileus[54]

  • very frail people[54]

  • people with brain pressure[54]

  • people with a history of substance abuse should be cautious[54]

What other choices are there?

  • Non-drug options include exercise, weight loss if necessary, physical therapy, cognitive behavioral therapy, or alternative medicine[54]

  • drug options include other pain medication[54]

In 2014, the FDA approved a formulation of hydrocodone called Zohydro ER made by Zogenix Pharmaceuticals. The approval of Zohydro ER was controversial, due to concerns over its potential for substance abuse. The FDA approved Zohydro ER over the objections of its own review panel, which voted 12 to 2 against approval. The panel stated that if approved, Zohydro ER would likely "be abused, possibly at a rate greater than that of currently available hydrocodone combination products". Thirty U.S. states asked the FDA not to approve Zohydro ER in capsule form due to its potency and the ease with which it could be abused, by being crushed and then snorted or injected.[55][medical citation needed] Zohydro ER was briefly prohibited in Massachusetts before a federal judge ruled that the state's ban was preempted by the earlier federal approval.[56][57]



Legal status



United States


The US government imposed tougher prescribing rules for hydrocodone in 2014, changing the drug from Schedule III to Schedule II.[58][59][60][61] In 2011, hydrocodone products were involved in around 100,000 abuse-related emergency department visits in the United States, more than double the number in 2004.[62]



See also


  • Equianalgesic


References




  1. ^ abcdefgh Jennifer A. Elliott; Howard S. Smith (19 April 2016). Handbook of Acute Pain Management. CRC Press. pp. 79–. ISBN 978-1-4665-9635-1..mw-parser-output cite.citationfont-style:inherit.mw-parser-output .citation qquotes:"""""""'""'".mw-parser-output .citation .cs1-lock-free abackground:url("//upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center.mw-parser-output .citation .cs1-lock-limited a,.mw-parser-output .citation .cs1-lock-registration abackground:url("//upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center.mw-parser-output .citation .cs1-lock-subscription abackground:url("//upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registrationcolor:#555.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration spanborder-bottom:1px dotted;cursor:help.mw-parser-output .cs1-ws-icon abackground:url("//upload.wikimedia.org/wikipedia/commons/thumb/4/4c/Wikisource-logo.svg/12px-Wikisource-logo.svg.png")no-repeat;background-position:right .1em center.mw-parser-output code.cs1-codecolor:inherit;background:inherit;border:inherit;padding:inherit.mw-parser-output .cs1-hidden-errordisplay:none;font-size:100%.mw-parser-output .cs1-visible-errorfont-size:100%.mw-parser-output .cs1-maintdisplay:none;color:#33aa33;margin-left:0.3em.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-formatfont-size:95%.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-leftpadding-left:0.2em.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-rightpadding-right:0.2em


  2. ^ abcdefg Shufeng Zhou (6 April 2016). Cytochrome P450 2D6: Structure, Function, Regulation and Polymorphism. CRC Press. pp. 164–. ISBN 978-1-4665-9788-4.


  3. ^ abc Gary S. Firestein; Ralph Budd; Sherine E. Gabriel; Iain B. McInnes; James R. O'Dell (21 June 2016). Kelley and Firestein's Textbook of Rheumatology. Elsevier Health Sciences. pp. 1081–. ISBN 978-0-323-41494-4.


  4. ^ abcd Bruce A. Chabner; Dan L. Longo (8 November 2010). Cancer Chemotherapy and Biotherapy: Principles and Practice. Lippincott Williams & Wilkins. pp. 700–. ISBN 978-1-60547-431-1.


  5. ^ abc Mellar P. Davis; Paul Glare; Janet Hardy (2005). Opioids in Cancer Pain. Oxford University Press. pp. 59–68. ISBN 978-0-19-852943-9.


  6. ^ ab Martin H. Bluth (16 November 2016). Toxicology and Drug Testing, An Issue of Clinics in Laboratory Medicine, E-Book. Elsevier Health Sciences. pp. 85–. ISBN 978-0-323-47795-6.


  7. ^ ab Howard S. Smith (21 February 2013). Opioid Therapy in the 21st Century. OUP USA. pp. 68–. ISBN 978-0-19-984497-5.


  8. ^ J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 639–. ISBN 978-1-4757-2085-3.


  9. ^ ab Karch, Steven B. (2008). Pharmacokinetics and pharmacodynamics of abused drugs. Boca Raton: CRC Press. pp. 55–56. ISBN 978-1-4200-5458-3.


  10. ^ abcd Codd EE, Shank RP, Schupsky JJ, Raffa RB (September 1995). "Serotonin and norepinephrine uptake inhibiting activity of centrally acting analgesics: structural determinants and role in antinociception". J. Pharmacol. Exp. Ther. 274 (3): 1263–70. PMID 7562497.


  11. ^ ab Nicholas J Talley; Brad Frankum; David Currow (10 February 2015). Essentials of Internal Medicine 3e. Elsevier Health Sciences. pp. 491–. ISBN 978-0-7295-8081-6.


  12. ^ Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 526. ISBN 9783527607495.


  13. ^ International Narcotics Control Board Report 2008. United Nations Pubns. 2009. p. 20. ISBN 978-9211482324.


  14. ^ "The Top 300 of 2019". clincalc.com. Retrieved 22 December 2018.


  15. ^ Zacny JP, Gutierrez S (April 2009). "Within-subject comparison of the psychopharmacological profiles of oral hydrocodone and oxycodone combination products in non-drug-abusing volunteers". Drug Alcohol Depend. 101 (1–2): 107–14. doi:10.1016/j.drugalcdep.2008.11.013. PMID 19118954.


  16. ^ Marco CA, Plewa MC, Buderer N, Black C, Roberts A (April 2005). "Comparison of oxycodone and hydrocodone for the treatment of acute pain associated with fractures: a double-blind, randomized, controlled trial". Acad Emerg Med. 12 (4): 282–8. doi:10.1197/j.aem.2004.12.005. PMID 15805317.


  17. ^ abc Vallejo R, Barkin RL, Wang VC (2011). "Pharmacology of opioids in the treatment of chronic pain syndromes". Pain Physician. 14 (4): E343–60. PMID 21785485.


  18. ^ "Opioid (Narcotic Analgesics and Acetaminophen Systemic )". Retrieved 22 March 2014.


  19. ^ Mary Lynn McPherson (24 August 2009). Demystifying Opioid Conversion Calculations: A Guide for Effective Dosing. ASHP. pp. 187–188. ISBN 978-1-58528-297-5.


  20. ^ Jan Odom-Forren; Cecil Drain (11 February 2008). PeriAnesthesia Nursing: A Critical Care Approach. Elsevier Health Sciences. pp. 751–. ISBN 978-1-4377-2610-7.


  21. ^ Linda Skidmore-Roth (27 June 2013). Mosby's Drug Guide for Nursing Students, with 2014 Update. Elsevier Health Sciences. pp. 524–. ISBN 978-0-323-22268-6.


  22. ^ Vadivelu, Nalini; Schermer, Erika; Kodumudi, Gopal; Berger, Jack M. (2016). "The Clinical Applications of Extended-Release Abuse-Deterrent Opioids". CNS Drugs. 30 (7): 637–646. doi:10.1007/s40263-016-0357-0. ISSN 1172-7047. PMID 27290716.


  23. ^ ab MedlinePlus; Drug Information: Hydrocodone. Last Revised—1 October 2008. Retrieved on 20 April 2013.


  24. ^ Friedman RA, House JW, Luxford WM, Gherini S, Mills D; House; Luxford; Gherini; Mills (Mar 2000). "Profound hearing loss associated with hydrocodone/acetaminophen abuse". Am J Otol. 21 (2): 188–91. doi:10.1016/S0196-0709(00)80007-1. PMID 10733182.CS1 maint: Multiple names: authors list (link)


  25. ^ Ho T, Vrabec JT, Burton AW; Vrabec; Burton (May 2007). "Hydrocodone use and sensorineural hearing loss". Pain Physician. 10 (3): 467–72. PMID 17525781. Archived from the original on 23 July 2011.CS1 maint: Multiple names: authors list (link)


  26. ^ Yorgason JG, Kalinec GM, Luxford WM, Warren FM, Kalinec F (June 2010). "Acetaminophen ototoxicity after acetaminophen/hydrocodone abuse: evidence from two parallel in vitro mouse models". Otolaryngol Head Neck Surg. 142 (6): 814–9, 819.e1–2. doi:10.1016/j.otohns.2010.01.010. PMID 20493351.


  27. ^ Curhan SG, Eavey R, Shargorodsky J, Curhan GC (March 2010). "Analgesic use and the risk of hearing loss in men". Am. J. Med. 123 (3): 231–7. doi:10.1016/j.amjmed.2009.08.006. PMC 2831770. PMID 20193831.


  28. ^ ab "REPREXAIN (hydrocodone bitartrate, ibuprofen) tablet, film coated". dailymed.nlm.nih.gov. NIH. Retrieved 27 April 2013.


  29. ^ Broussard CS, Rasmussen SA, Reefhuis J, Friedman JM, Jann MW, Riehle-Colarusso T, Honein MA (April 2011). "Maternal treatment with opioid analgesics and risk for birth defects". Am. J. Obstet. Gynecol. 204 (4): 314.e1–11. doi:10.1016/j.ajog.2010.12.039. PMID 21345403.


  30. ^ Wightman R, Perrone J, Portelli I, Nelson L (December 2012). "Likeability and abuse liability of commonly prescribed opioids". J Med Toxicol. 8 (4): 335–40. doi:10.1007/s13181-012-0263-x. PMC 3550270. PMID 22992943.


  31. ^ Gnanadesigan N, Espinoza RT, Smith RL (June 2005). "The serotonin syndrome". N. Engl. J. Med. 352 (23): 2454–6, author reply 2454–6. doi:10.1056/NEJM200506093522320. PMID 15948273.


  32. ^ Filizola M, Villar HO, Loew GH (January 2001). "Molecular determinants of non-specific recognition of delta, mu, and kappa opioid receptors". Bioorg. Med. Chem. 9 (1): 69–76. doi:10.1016/S0968-0896(00)00223-6. PMID 11197347.


  33. ^ King (25 October 2010). Pharmacology for Women's Health. Jones & Bartlett Publishers. pp. 332–. ISBN 978-1-4496-1073-9.


  34. ^ David H. Chestnut; Cynthia A Wong; Lawrence C Tsen; Warwick D Ngan Kee, Yaakov Beilin, Jill Mhyre (28 February 2014). Chestnut's Obstetric Anesthesia: Principles and Practice E-Book. Elsevier Health Sciences. pp. 611–. ISBN 978-0-323-11374-8.CS1 maint: Multiple names: authors list (link)


  35. ^ Adriana P. Tiziani (1 June 2013). Havard's Nursing Guide to Drugs. Elsevier Health Sciences. pp. 933–. ISBN 978-0-7295-8162-2.


  36. ^ Thompson CM, Wojno H, Greiner E, May EL, Rice KC, Selley DE (February 2004). "Activation of G-proteins by morphine and codeine congeners: insights to the relevance of O- and N-demethylated metabolites at mu- and delta-opioid receptors". J. Pharmacol. Exp. Ther. 308 (2): 547–54. doi:10.1124/jpet.103.058602. PMID 14600248.


  37. ^ "Instructions for Mean Equivalent Daily Dose (MEDD)" (PDF). Archived from the original (PDF) on 27 July 2011. Retrieved 22 August 2010.


  38. ^ Mary C. Brucker; Tekoa L. King (8 September 2015). Pharmacology for Women's Health. Jones & Bartlett Publishers. pp. 322–. ISBN 978-1-284-05748-5.


  39. ^ Steven B. Karch, MD, FFFLM (9 October 2007). Pharmacokinetics and Pharmacodynamics of Abused Drugs. CRC Press. pp. 56–. ISBN 978-1-4200-5460-6.CS1 maint: Multiple names: authors list (link)


  40. ^ Amitava Dasgupta; Jorge L. Sepulveda (22 January 2013). Accurate Results in the Clinical Laboratory: A Guide to Error Detection and Correction. Newnes. pp. 239–. ISBN 978-0-12-415858-0.


  41. ^ ab Amitava Dasgupta; Loralie J. Langman (23 April 2012). Pharmacogenomics of Alcohol and Drugs of Abuse. CRC Press. pp. 175–. ISBN 978-1-4398-5611-6.


  42. ^ Kaplan HL, Busto UE, Baylon GJ, Cheung SW, Otton SV, Somer G, Sellers EM (April 1997). "Inhibition of cytochrome P450 2D6 metabolism of hydrocodone to hydromorphone does not importantly affect abuse liability". J. Pharmacol. Exp. Ther. 281 (1): 103–8. PMID 9103485.


  43. ^ Gardiner SJ, Begg EJ (September 2006). "Pharmacogenetics, drug-metabolizing enzymes, and clinical practice". Pharmacol. Rev. 58 (3): 521–90. doi:10.1124/pr.58.3.6. PMID 16968950.


  44. ^ Crews KR, Gaedigk A, Dunnenberger HM, Klein TE, Shen DD, Callaghan JT, Kharasch ED, Skaar TC (February 2012). "Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for codeine therapy in the context of cytochrome P450 2D6 (CYP2D6) genotype". Clin. Pharmacol. Ther. 91 (2): 321–6. doi:10.1038/clpt.2011.287. PMC 3289963. PMID 22205192.


  45. ^ Navani, D. M.; Yoburn, B. C. (2013). "In Vivo Activity of Norhydrocodone: An Active Metabolite of Hydrocodone". Journal of Pharmacology and Experimental Therapeutics. 347 (2): 497–505. doi:10.1124/jpet.113.207548. ISSN 1521-0103. PMID 23995596.


  46. ^ Madadi P, Hildebrandt D, Gong IY, Schwarz UI, Ciszkowski C, Ross CJ, Sistonen J, Carleton BC, Hayden MR, Lauwers AE, Koren G (October 2010). "Fatal hydrocodone overdose in a child: pharmacogenetics and drug interactions". Pediatrics. 126 (4): e986–9. doi:10.1542/peds.2009-1907. PMID 20837591.


  47. ^ Vuilleumier PH, Stamer UM, Landau R (2012). "Pharmacogenomic considerations in opioid analgesia". Pharmgenomics Pers Med. 5: 73–87. doi:10.2147/PGPM.S23422. PMC 3513230. PMID 23226064.


  48. ^ Spiller HA (March 2003). "Postmortem oxycodone and hydrocodone blood concentrations". J. Forensic Sci. 48 (2): 429–31. PMID 12665006.


  49. ^ Randall C. Baselt (2017). Disposition of Toxic Drugs and Chemicals in Man. Biomedical Publications. pp. 1050–1052. ISBN 978-0-692-77499-1.


  50. ^ Mannich, C.; Löwenheim, Helene (1920). "Ueber zwei neue Reduktionsprodukte des Kodeins". Archiv der Pharmazie. 258 (2–4): 295–316. doi:10.1002/ardp.19202580218. ISSN 0365-6233.


  51. ^ "Drugs@FDA—Approval History: Hycodan". FDA. Retrieved 7 January 2006.


  52. ^ "FDA Docket No. 2007N-0353, Drug Products Containing Hydrocodone; Enforcement Action Dates". FDA. Retrieved 7 January 2006. See section I. B., DESI Review of Hydrocodone Products


  53. ^ "Hydrocodone Combination Products". MedlinePlus. The American Society of Health-System Pharmacists, Inc. Retrieved 14 July 2018.


  54. ^ abcdefghi Informulary (February 2015). "Drug Facts Box: ZOHYDRO ER (hydrocodone bitartrate)" (PDF). Consumer Reports. Consumer Reports. Retrieved 5 November 2015.


  55. ^ Rubin, Rita (27 February 2014). "Critics Oppose FDA Approval of Painkiller Zohydro". WebMD. Retrieved 14 May 2014.


  56. ^ Heger, Monica (7 May 2014). "State challenges to painkiller could threaten FDA authority". Nature Medicine. Retrieved 14 May 2014.


  57. ^ Valencia, Milton (23 April 2014). "Mass. limits use of the potent painkiller Zohydro". Boston Globe. Retrieved 14 May 2014.


  58. ^ McCarthy, Michael (2016). "Prescriptions for hydrocodone plummet after US tightens prescribing rules". BMJ. 352: i549. doi:10.1136/bmj.i549. ISSN 1756-1833. PMID 26819247.


  59. ^ Jones, Christopher M.; Lurie, Peter G.; Throckmorton, Douglas C. (2016). "Effect of US Drug Enforcement Administration's Rescheduling of Hydrocodone Combination Analgesic Products on Opioid Analgesic Prescribing". JAMA Internal Medicine. 176 (3): 399–402. doi:10.1001/jamainternmed.2015.7799. ISSN 2168-6106. PMID 26809459.


  60. ^ Chambers, Jan; Gleason, Rae M.; Kirsh, Kenneth L.; Twillman, Robert; Webster, Lynn; Berner, Jon; Fudin, Jeff; Passik, Steven D. (2016). "An Online Survey of Patients' Experiences Since the Rescheduling of Hydrocodone: The First 100 Days". Pain Medicine. 17 (9): 1686–1693. doi:10.1093/pm/pnv064. ISSN 1526-2375. PMID 26814291.


  61. ^ "Schedules of Controlled Substances: Rescheduling of Hydrocodone Combination Products From Schedule III to Schedule II". Federal Register. 2014-08-22. Retrieved 2017-08-11.


  62. ^ Abuse, National Institute on Drug. "Drug-Related Hospital Emergency Room Visits". Retrieved 2017-08-11.




External links



  • Hydrocodone at U.S. National Library of Medicine: Drug Information Portal


  • "DEA Schedules of Controlled Substances: Rescheduling of Hydrocodone Combination Products From Schedule III to Schedule II". Federal Register. Oct 6, 2014.








-

Popular posts from this blog

用户:Ww71338ww/绘画

Image
Clash Royale CLAN TAG #URR8PPP 你好～！欢迎来到萌娘百科！ 如果您是第一次来到这里，点这里加入萌娘百科! 欢迎具有翻译能力的同学～有意者请点→Category:需要翻译的条目← 如果您在萌娘百科上发现某些内容 错误/空缺 ，请 勇于 修正/添加！ 编辑萌娘百科其实很容易！ 觉得萌娘百科有趣的话，请推荐给朋友哦...
Read more

自由群

Image
Clash Royale CLAN TAG #URR8PPP 由兩個元素a, b 生成的自由群的凱萊圖 在數學中，一個群 Gdisplaystyle G 被稱作 自由群 ，如果存在 Gdisplaystyle G 的子集 Sdisplaystyle S 使得 Gdisplaystyle G 的任何元素都能唯一地表成由 Sdisplaystyle S 中元素及其逆元組成之乘積（在此不論平庸的表法，例如 st−1=su−1ut−1displaystyle st^-1=su^-1ut^-1 之類）；此時也稱 Gdisplaystyle G 為集合 Sdisplaystyle S 上的 自由群 ，其群...
Read more

卑爾根

Image
Clash Royale CLAN TAG #URR8PPP 卑尔根 Bergen 城市 Kommune av Bergen 旗幟 徽章 卑爾根在霍达兰郡的位置 卑尔根 卑爾根在挪威的位置 坐标： 60°22′N 05°24′E  /  60.367°N 5.400°E  / 60.367; 5.400 坐标： 60°22′N 05°24′E  /  60.367°N 5.400°E  / 60.367; 5.400 國家   挪威 郡 霍达兰郡 建立 1070年之前 政府  • 市長 Marita Moltu （KrF） 面积  • 城市 464.71 平方公里（179.43 平方英里）  • 陸地...
Read more