Hydrocodone

Last updated

Hydrocodone
Hydrocodone skeletal.svg
Hydrocodone-Spartan-PM3-3D-balls.png
Clinical data
Trade names Hysingla ER, Zohydro ER
Other namesDihydrocodeinone, hydrocodone bitartrate
AHFS/Drugs.com Monograph
MedlinePlus a601006
License data
Dependence
liability 		High [1]
Addiction
liability 		High
Routes of
administration 		Clinical: By mouth [2]
Others: Intranasal, rectal
Drug class Opioid
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability Oral: 70% [4]
Protein binding Low [4] [5]
Metabolism Liver: CYP3A4 (major), CYP2D6 (minor) [6]
Metabolites • Norhydrocodone [6]
• Hydromorphone [6]
• Others [6]
Onset of action 10–20 minutes [2]
Elimination half-life Average: 3.8 hours [7]
Range: 3.3–4.4 hours [2]
Duration of action 4–8 hours [2]
Excretion Urine [8] [9]
Identifiers
  • 4,5α-epoxy-3-methoxy-17-methylmorphinan-6-one
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.004.304 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C18H21NO3
Molar mass 299.370 g·mol−1
3D model (JSmol)
  • O=C4[C@@H]5Oc1c2c(ccc1OC)C[C@H]3N(CC[C@]25[C@H]3CC4)C
  • InChI=1S/C18H21NO3/c1-19-8-7-18-11-4-5-13(20)17(18)22-16-14(21-2)6-3-10(15(16)18)9-12(11)19/h3,6,11-12,17H,4-5,7-9H2,1-2H3/t11-,12+,17-,18-/m0/s1 Yes check.svgY
  • Key:LLPOLZWFYMWNKH-CMKMFDCUSA-N Yes check.svgY
   (verify)

Hydrocodone, also known as dihydrocodeinone, is a semi-synthetic opioid used to treat pain and as a cough suppressant. [10] It is taken by mouth. [10] Typically, it is dispensed as the combination acetaminophen/hydrocodone or ibuprofen/hydrocodone for pain severe enough to require an opioid [11] [12] [13] and in combination with homatropine methylbromide to relieve cough. [10] It is also available by itself in a long-acting form sold under the brand name Zohydro ER, among others, to treat severe pain of a prolonged duration. [10] [14] Hydrocodone is a controlled drug: in the United States, it is classified as a Schedule II Controlled Substance.

Contents

Common side effects include dizziness, sleepiness, nausea, and constipation. [10] Serious side effects may include low blood pressure, seizures, QT prolongation, respiratory depression, and serotonin syndrome. [10] Rapidly decreasing the dose may result in opioid withdrawal. [10] Use during pregnancy or breastfeeding is generally not recommended. [15] Hydrocodone is believed to work by activating opioid receptors, mainly in the brain and spinal cord. [10] Hydrocodone 10 mg is equivalent to about 10 mg of morphine by mouth. [16]

Medical uses

Hydrocodone is used to treat moderate to severe pain. In liquid formulations, it is used to treat cough. [10] 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). [17] 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. [18] Some references state that the analgesic action of hydrocodone begins in 20–30 minutes and lasts about 4–8 hours. [19] The manufacturer's information says onset of action is about 10–30 minutes and duration is about 4–6 hours. [20] Recommended dosing interval is 4–6 hours. Hydrocodone reaches peak serum levels after 1.3 hours. [21]

Available forms

Hydrocodone is available in a variety of formulations for oral administration: [22] [23] [24]

Hydrocodone is not available in parenteral or any other non-oral forms. [5] [2]

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. [26]

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. [27] [28] Other researchers have suggested that paracetamol is the primary agent responsible for the ototoxicity. [29] [30]

The U.S. Food and Drug Administration (FDA) assigns the drug to pregnancy category C, meaning that 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. [31] [32] The baby may also exhibit respiratory depression if the opioid dose was high. [33] An epidemiological study indicated that opioid treatment during early pregnancy results in increased risk of various birth defects. [34]

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. [26]

Hydrocodone can be habit forming, causing physical and psychological dependence. Its abuse liability is similar to morphine and less than oxycodone. [35]

Interactions

Hydrocodone is metabolized by the cytochrome P450 enzymes CYP2D6 and CYP3A4, and inhibitors and inducers of these enzymes can modify hydrocodone exposure. [36] One study found that combination of paroxetine, a selective serotonin reuptake inhibitor (SSRI) and strong CYP2D6 inhibitor, with once-daily extended-release hydrocodone, did not modify exposure to hydrocodone or the incidence of adverse effects. [36] [37] These findings suggest that hydrocodone can be coadministered with CYP2D6 inhibitors without dosage modification. [36] [37] Conversely, combination of hydrocodone/acetaminophen with the antiviral regimen of ombitasvir, paritaprevir, ritonavir, and dasabuvir for treatment of hepatitis C increased peak concentrations of hydrocodone by 27%, total exposure by 90%, and elimination half-life from 5.1 hours to 8.0 hours. [38] Ritonavir is a strong CYP3A4 inhibitor as well as inducer of CYP3A and other enzymes, and the other antivirals are known to inhibit drug transporters like organic anion transporting polypeptide (OATP) 1B1 and 1B3, P-glycoprotein, and breast cancer resistance protein (BCRP). [38] The changes in hydrocodone levels are consistent with CYP3A4 inhibition by ritonavir. [38] Based on these findings, a 50% lower dose of hydrocodone and closer clinical monitoring was recommended when hydrocodone is used in combination with this antiviral regimen. [38]

People consuming alcohol, other opioids, anticholinergic antihistamines, antipsychotics, anxiolytics, or other central nervous system (CNS) depressants together with hydrocodone may exhibit an additive CNS depression. [33] Hydrocodone taken concomitantly with serotonergic medications like SSRI antidepressants may increase the risk of serotonin syndrome. [39]

Pharmacology

Pharmacodynamics

Hydrocodone (and metabolite) at opioid receptors
Compound Affinities (Ki Tooltip Inhibitor constant)RatioRef
MOR Tooltip μ-Opioid receptor DOR Tooltip δ-Opioid receptor KOR Tooltip κ-Opioid receptorMOR:DOR:KOR
Hydrocodone11.1 nM962 nM501 nM1:87:45 [40]
Hydromorphone 0.47 nM18.5 nM24.9 nM1:39:53 [41]

Equivalent analgesia doses [42] [43] [44]
Compound Route Dose
Codeine PO200 mg
HydrocodonePO30 mg
Hydromorphone PO7.5 mg
Hydromorphone IV1.5 mg
Morphine PO30 mg
Morphine IV10 mg
Oxycodone PO20 mg
Oxycodone IV10 mg
Oxymorphone PO10 mg
Oxymorphone IV1 mg

Hydrocodone is a highly selective full agonist of the μ-opioid receptor (MOR). [19] [45] [40] This is the main biological target of the endogenous opioid neuropeptide β-endorphin. [46] Hydrocodone has low affinity for the δ-opioid receptor (DOR) and the κ-opioid receptor (KOR), where it is an agonist similarly. [40]

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. [7] 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. [47]

Pharmacokinetics

Absorption

Hydrocodone is only pharmaceutically available as an oral medication. [2] It is well-absorbed, but the oral bioavailability of hydrocodone is only approximately 25%. [4] [5] 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, [42] and it has a duration of 4 to 8 hours. [2] The FDA label for immediate-release hydrocodone with acetaminophen does not include any information on the influence of food on its absorption or other pharmacokinetics. [48] Conversely, coadministration with a high-fat meal increases peak concentrations of different formulations of extended-release hydrocodone by 14 to 54%, whereas area-under-the-curve levels are not notably affected. [49] [50] [51] [52]

Distribution

The volume of distribution of hydrocodone is 3.3 to 4.7 L/kg. [5] The plasma protein binding of hydrocodone is 20 to 50%. [19]

Metabolism

In the liver, hydrocodone is transformed into several metabolites, including norhydrocodone, hydromorphone, 6α-hydrocodol (dihydrocodeine), and 6β-hydrocodol. [6] 6α- and 6β-hydromorphol are also formed, and the metabolites of hydrocodone are conjugated (via glucuronidation). [53] [54] Hydrocodone has a terminal half-life that averages 3.8 hours (range 3.3–4.4 hours). [7] [2] The hepatic cytochrome P450 enzyme CYP2D6 converts hydrocodone into hydromorphone, a more potent opioid (5-fold higher binding affinity to the MOR). [6] [55] 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. [56] [57] 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. [58]

Norhydrocodone, the major metabolite of hydrocodone, is predominantly formed by CYP3A4-catalyzed oxidation. [6] In contrast to hydromorphone, it is described as inactive. [55] 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). [59] Inhibition of CYP3A4 in a child who was, in addition, a poor CYP2D6 metabolizer, resulted in a fatal overdose of hydrocodone. [60] Approximately 40% of hydrocodone metabolism is attributed to non-cytochrome P450-catalyzed reactions. [61]

Elimination

Hydrocodone is excreted in urine, mainly in the form of conjugates. [8] [9]

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. [62] [63]

Synthesis

Hydrocodone is most commonly synthesized from thebaine, a constituent of opium latex from the dried poppy plant. Once thebaine is obtained, the reaction undergoes hydrogenation using a palladium catalyst. [64]

Structure

There are three important structures in hydrocodone: the amine group, which binds to the tertiary nitrogen binding site in the central nervous system's opioid receptor, the hydroxy group that binds to the anionic binding site, and the phenyl group which binds to the phenolic binding site. [65] This triggers a G protein activation and subsequent release of dopamine. [66]

History

Hydrocodone was first synthesized in Germany in 1920 by Carl Mannich and Helene Löwenheim. [67] 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. [68] [69]

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. [70] [71]

Hydrocodone was patented in 1923, while the long-acting formulation was approved for medical use in the United States in 2013. [10] [72] It is most commonly prescribed in the United States, which consumed 99% of the worldwide supply as of 2010. [73] In 2018, it was the 402nd most commonly prescribed medication in the United States, with more than 400,000 prescriptions. [74]

Society and culture

Formulations

Several common imprints for hydrocodone are M365, M366, M367. [75]

Combination products

Hydrocodone and paracetamol (acetaminophen) 10-325 tablets (Mallinckrodt) Hydrocodone-paracetamol-5-500.jpg
Hydrocodone and paracetamol (acetaminophen) 10-325 tablets (Mallinckrodt)

Most hydrocodone formulations include a second analgesic, such as paracetamol (acetaminophen) or ibuprofen. Examples of hydrocodone combinations include Norco, Vicodin, Vicoprofen and Riboxen. [76]

The US government imposed tougher prescribing rules for hydrocodone in 2014, changing the drug from Schedule III to Schedule II. [77] [78] [79] [80] 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. [81]

Related Research Articles

<span class="mw-page-title-main">Analgesic</span> Drugs used to achieve relief from pain

An analgesic drug, also called simply an analgesic, antalgic, pain reliever, or painkiller, is any member of the group of drugs used for pain management. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in some instances eliminate, sensation, although analgesia and anesthesia are neurophysiologically overlapping and thus various drugs have both analgesic and anesthetic effects.

<span class="mw-page-title-main">Morphine</span> Pain medication of the opiate family

Morphine, formerly also called morphia, is an opiate that is found naturally in opium, a dark brown resin produced by drying the latex of opium poppies. It is mainly used as an analgesic. There are numerous methods used to administer morphine: orally; administered under the tongue; via inhalation; injection into a vein, injection into a muscle, injection under the skin, or injection into the spinal cord area; transdermal; or via administered into the rectal canal suppository. It acts directly on the central nervous system (CNS) to induce analgesia and alter perception and emotional response to pain. Physical and psychological dependence and tolerance may develop with repeated administration. It can be taken for both acute pain and chronic pain and is frequently used for pain from myocardial infarction, kidney stones, and during labor. Its maximum effect is reached after about 20 minutes when administered intravenously and 60 minutes when administered by mouth, while the duration of its effect is 3–7 hours. Long-acting formulations of morphine are sold under the brand names MS Contin and Kadian, among others. Generic long-acting formulations are also available.

<span class="mw-page-title-main">Methadone</span> Opioid medication

Methadone, sold under the brand names Dolophine and Methadose among others, is a synthetic opioid used medically to treat chronic pain and opioid use disorder. Prescribed for daily use, the medicine relieves cravings and opioid withdrawal symptoms. Withdrawal management using methadone can be accomplished in less than a month, or it may be done gradually over a longer period of time, or simply maintained for the rest of the patient's life. While a single dose has a rapid effect, maximum effect can take up to five days of use. After long-term use, in people with normal liver function, effects last 8 to 36 hours. Methadone is usually taken by mouth and rarely by injection into a muscle or vein.

<span class="mw-page-title-main">Oxycodone</span> Opioid medication

Oxycodone, sold under the brand name Roxicodone and OxyContin among others, is a semi-synthetic opioid used medically for the treatment of moderate to severe pain. It is highly addictive and is a commonly abused drug. It is usually taken by mouth, and is available in immediate-release and controlled-release formulations. Onset of pain relief typically begins within fifteen minutes and lasts for up to six hours with the immediate-release formulation. In the United Kingdom, it is available by injection. Combination products are also available with paracetamol (acetaminophen), ibuprofen, naloxone, naltrexone, and aspirin.

<span class="mw-page-title-main">Narcotic</span> Chemical substance with psycho-active properties

The term narcotic originally referred medically to any psychoactive compound with numbing or paralyzing properties. In the United States, it has since become associated with opiates and opioids, commonly morphine and heroin, as well as derivatives of many of the compounds found within raw opium latex. The primary three are morphine, codeine, and thebaine.

<span class="mw-page-title-main">Tramadol</span> Opioid pain medication

Tramadol, sold under the brand name Ultram among others, is an opioid pain medication and a serotonin–norepinephrine reuptake inhibitor (SNRI) used to treat moderately severe pain. When taken by mouth in an immediate-release formulation, the onset of pain relief usually begins within an hour. It is also available by injection. It is available in combination with paracetamol (acetaminophen).

<span class="mw-page-title-main">Hydromorphone</span> Opioid medication used for pain relief

Hydromorphone, also known as dihydromorphinone, and sold under the brand name Dilaudid among others, is a morphinan opioid used to treat moderate to severe pain. Typically, long-term use is only recommended for pain due to cancer. It may be used by mouth or by injection into a vein, muscle, or under the skin. Effects generally begin within half an hour and last for up to five hours. A 2016 Cochrane review found little difference in benefit between hydromorphone and other opioids for cancer pain.

<span class="mw-page-title-main">Opioid</span> Psychoactive chemical

Opioids are a class of drugs that derive from, or mimic, natural substances found in the opium poppy plant. Opioids work on opioid receptors in the brain and other organs to produce a variety of morphine-like effects, including pain relief.

<span class="mw-page-title-main">Oxymorphone</span> Opioid analgesic drug

Oxymorphone is a highly potent opioid analgesic indicated for treatment of severe pain. Pain relief after injection begins after about 5–10 minutes, after oral administration it begins after about 30 minutes, and lasts about 3–4 hours for immediate-release tablets and 12 hours for extended-release tablets. The elimination half-life of oxymorphone is much faster intravenously, and as such, the drug is most commonly used orally. Like oxycodone, which metabolizes to oxymorphone, oxymorphone has a high potential to be abused.

<span class="mw-page-title-main">Dihydrocodeine</span> Opioid

Dihydrocodeine is a semi-synthetic opioid analgesic prescribed for pain or severe dyspnea, or as an antitussive, either alone or compounded with paracetamol (acetaminophen) or aspirin. It was developed in Germany in 1908 and first marketed in 1911.

<span class="mw-page-title-main">Dihydromorphine</span> Semi-synthetic opioid analgesic drug

Dihydromorphine is a semi-synthetic opioid structurally related to and derived from morphine. The 7,8-double bond in morphine is reduced to a single bond to get dihydromorphine. Dihydromorphine is a moderately strong analgesic and is used clinically in the treatment of pain and also is an active metabolite of the analgesic opioid drug dihydrocodeine. Dihydromorphine occurs in trace quantities in assays of opium on occasion, as does dihydrocodeine, dihydrothebaine, tetrahydrothebaine, etc. The process for manufacturing dihydromorphine from morphine for pharmaceutical use was developed in Germany in the late 19th century, with the synthesis being published in 1900 and the drug introduced clinically as Paramorfan shortly thereafter. A high-yield synthesis from tetrahydrothebaine was later developed.

<span class="mw-page-title-main">Thebacon</span> Opioid medication

Thebacon, or dihydrocodeinone enol acetate, is a semisynthetic opioid that is similar to hydrocodone and is most commonly synthesised from thebaine. Thebacon was invented in Germany in 1924, four years after the first synthesis of hydrocodone. Thebacon is a derivative of acetyldihydrocodeine, where only the 6–7 double bond is saturated. Thebacon is marketed as its hydrochloride salt under the trade name Acedicon, and as its bitartrate under Diacodin and other trade names. The hydrochloride salt has a free base conversion ratio of 0.846. Other salts used in research and other settings include thebacon's phosphate, hydrobromide, citrate, hydroiodide, and sulfate.

<span class="mw-page-title-main">Hydrocodone/paracetamol</span> Combination pain relief drug

Hydrocodone/paracetamol is the combination of the pain medications hydrocodone and paracetamol (acetaminophen). It is used to treat moderate to severe pain. It is taken by mouth. Recreational use is common in the United States.

<span class="mw-page-title-main">Codeine</span> Opiate and prodrug of morphine used to treat pain

Codeine is an opiate and prodrug of morphine mainly used to treat pain, coughing, and diarrhea. It is also commonly used as a recreational drug. It is found naturally in the sap of the opium poppy, Papaver somniferum. It is typically used to treat mild to moderate degrees of pain. Greater benefit may occur when combined with paracetamol (acetaminophen) or a nonsteroidal anti-inflammatory drug (NSAID) such as aspirin or ibuprofen. Evidence does not support its use for acute cough suppression in children. In Europe, it is not recommended as a cough medicine for those under 12 years of age. It is generally taken by mouth. It typically starts working after half an hour, with maximum effect at two hours. Its effects last for about four to six hours. Codeine exhibits abuse potential similar to other opioid medications, including a risk of addiction and overdose.

<span class="mw-page-title-main">Tapentadol</span> Opioid analgesic of benzenoid class

Tapentadol, sold under the brand names Nucynta and Palexia among others, is a synthetic opioid analgesic of the benzenoid class with a dual mode of action as a highly selective full agonist of the μ-opioid receptor and as a norepinephrine reuptake inhibitor (NRI). Tapentadol is used medically for the treatment of moderate to severe pain. It is addictive, a commonly abused drug, and poses a high risk of physical and/or mental dependence.

An equianalgesic chart is a conversion chart that lists equivalent doses of analgesics. Equianalgesic charts are used for calculation of an equivalent dose between different analgesics. Tables of this general type are also available for NSAIDs, benzodiazepines, depressants, stimulants, anticholinergics and others.

<span class="mw-page-title-main">Opiate</span> Substance derived from opium

An opiate is an alkaloid substance derived from opium. It differs from the similar term opioid in that the latter is used to designate all substances, both natural and synthetic, that bind to opioid receptors in the brain. Opiates are alkaloid compounds naturally found in the opium poppy plant Papaver somniferum. The psychoactive compounds found in the opium plant include morphine, codeine, and thebaine. Opiates have long been used for a variety of medical conditions, with evidence of opiate trade and use for pain relief as early as the eighth century AD. Most opiates are considered drugs with moderate to high abuse potential and are listed on various "Substance-Control Schedules" under the Uniform Controlled Substances Act of the United States of America.

<span class="mw-page-title-main">Hydrocodone/ibuprofen</span> Combination drug

Hydrocodone/ibuprofen (INNs), sold under the brand name Vicoprofen, is a fixed-dose combination analgesic medication used in short-term therapy to relieve severe pain. Vicoprofen combines the analgesic and antitussive properties of hydrocodone with the analgesic, anti-inflammatory, and antipyretic properties of ibuprofen. In contrast to hydrocodone/acetaminophen combination analgesics such as Vicodin, this hydrocodone/ibuprofen avoids some of the liver toxicity which may occur from acetaminophen, but still presents significant dangers in hydrocodone overdose, namely respiratory depression. Vicoprofen is supplied in a fixed dose combination tablet which contains hydrocodone bitartrate, USP 7.5 mg with ibuprofen, USP 200 mg. Additional strengths of generic Vicoprofen are now available, in combinations of 5 mg/200 mg and 10 mg/200 mg respectively.

<span class="mw-page-title-main">Benzhydrocodone</span> Chemical compound

Benzhydrocodone (INN) is an opioid prodrug of the morphinan class. Its chemical structure consists of hydrocodone coupled with benzoic acid. Benzhydrocodone itself is inactive and acts as a prodrug to hydrocodone upon cleavage of the benzoate portion of the molecule.

<span class="mw-page-title-main">Mitragynine</span> Opioid analgesic compound

Mitragynine is an indole-based alkaloid and is one of the main psychoactive constituents in the Southeast Asian plant Mitragyna speciosa, commonly known as kratom. It is an opioid that is typically consumed as a part of kratom for its pain-relieving and euphoric effects. It has also been researched for its use to potentially manage symptoms of opioid withdrawal.

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