HuagongsheHuagongshe Chemie-Druckbericht · Nur für Forschungszwecke
Hydrocodon
Hydrocodon · Dihydrocodeinone · Dico · 50-100g · Bekadid · Dicodid · Codinovo · Hydrocone
Identifikatoren & physikalische Daten
| CAS No. | 125-29-1 |
|---|---|
| Summenformel | C18H21NO3 |
| Durchschnittliche Molmasse | 299,4 g/mol |
| Monoisotopische Masse | 299,15214353 g/mol |
| SMILES | COc1ccc2c3c1O[C@H]1C(=O)CC[C@H]4[C@@H](C2)N(C)CC[C@]314 |
| InChIKey | LLPOLZWFYMWNKH-CMKMFDCUSA-N |
| PubChem CID | 5284569 |
| ChEMBL | CHEMBL1457 |
| ChEBI | CHEBI:5779 |
| EC No. | 204-733-9 |
| DTXSID | DTXSID8023131 |
| Lokaler Name | Hydrocodon |
Chemische & physikalische Eigenschaften
| XLogP | 2,2 |
|---|---|
| Polarare Oberfläche (TPSA) | 38,8 |
| H-Brücken-Donoren | 0 |
| H-Brücken-Akzeptoren | 4 |
| Frei drehbare Bindungen | 1 |
| Schwere Atome | 22 |
| Formalladung | 0 |
| Komplexität | 509 |
| Stoffklassen | Pharmaceutical |
| Arzneimittel | DEA NFLIS-Drug Category -> Narcotic AnalgesicsDEA Schedule II Controlled SubstancePharmaceuticals -> Synthetic Cannabinoids or Psychoactive CompoundsPharmaceuticals -> Listed in ZINC15 |
| LogP (Verteilungskoeffizient) | 1.2 |
| Color/Form | Prisms from alcohol |
| Löslichkeit | Soluble in acetone, ethyl acetate, chloroformSoluble in ethanol7.97e-01 g/LChloroform (Slightly), Ethyl Acetate (Slightly), Methanol (Slightly) |
| Flammpunkt | 9.7 °C (49.5 °F) - closed cup9℃ |
| Human Drugs | Breast FeedingLactationMilk, HumanAnalgesics, OpioidNarcoticsAntitussive AgentsFDA approved drugs -> Active ingredientPharmaceuticals |
| Endocrine Disruptors | Potential endocrine disrupting compound |
| Decomposition | When heated to decomposition it emits toxic fumes of /nitrogen oxide/. |
| Schmelzpunkt | 198 °CMP: 219-220 °C /Hydrocodone hydriodide/MP: 250-225 °C /Hydrocodone methiodide/194-197°C |
| Optical Rotation | Specific optical rotation = -203 deg at 25 °C/D ( c = 0.41 in CHCL3) |
| Physical Description | Solid |
| Siedepunkt | 440.69°C (rough estimate) |
| Dichte | 1.1613 (rough estimate) |
| Brechungsindex | 1.5500 (estimate) |
| Lagerbedingungen | Controlled Substance, -20°C Freezer |
| Aggregatzustand | Solid |
| pKa (Säurekonstante) | pKa 6.61(50% aq EtOH) (Uncertain) |
| Farbe | Prisms from EtOH |
| Hauptanwendungen | pharmaceutical |
| EPA chemische Informationen | Morphinan-6-one, 4,5-epoxy-3-methoxy-17-methyl-, (5.alpha.)- (125-29-1) |
Sicherheit & Vorschriften
| GHS-Einstufung | DangerH302 (97.7%): Harmful if swallowed [Warning Acute toxicity, oral]P233, P260, P261, P264, P270, P271, P272, P273, P280, P284, P301+P317, P302+P352, P304+P340, P321, P330, P333+P317, P342+P316, P362+P364, P391, P403, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 43 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.H225: Highly Flammable liquid and vapor [Danger Flammable liquids] |
|---|---|
| Regulatorische Informationen | DEA schedule II controlled substance |
| FDA-Anforderungen | Schedule II shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. Unless specifically excepted or unless listed in another schedule, any of the following substances whether produced directly or indirectly by extraction from substances of vegetable origin, or independently by means of chemical synthesis, or by a combination of extraction and chemical synthesis: (1) Opium and opiate, and any salt, compound, derivative, or preparation of opium or opiate excluding apomorphine, thebaine-derived butorphanol, dextrorphan, nalbuphine, nalmefene, naloxone, and naltrexone, and their respective salts, but including the following. Hydrocodone (DEA Code Number: 9193) is included on this list.The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including hydrocodone bitartrate approved on the basis of safety and effectiveness by FDA under sections 505 and 507 of the Federal Food, Drug, and Cosmetic Act. /Hydrocodone bitartrate/The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including hydrocodone polistirex approved on the basis of safety and effectiveness by FDA under sections 505 and 507 of the Federal Food, Drug, and Cosmetic Act. /Hydrocodone polistirex/ |
| Hazard Classes and Categories | Acute Tox. 4 (97.7%) |
| Hazardous Reactivities and Incompatibilities | Incompatible materials: Acids, Oxidizing agents, Alkali metals, Strong oxidizing agents, Strong acids, Acid chlorides, Acid anhydrides, Reducing agents, Strong reducing agents, Phosphorus halides |
| Brandbekämpfungsverfahren | Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary. Use water spray to cool unopened containers.Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. |
| Lagerbedingungen | Store at 25 °C (77 °F)excursions permitted between 15-30 °C (59-86 °F). Dispense in tight, light-resistant container, as defined by the USP.Conditions for safe storage, including any incompatibilities: Keep container tightly closed in a dry and well-ventilated place. Containers which are opened must be carefully resealed and kept upright to prevent leakage. Recommended storage temperature -20 °CHydrocodone bitartrate is affected by light. Hydrocodone bitartrate preparations should be stored in tight, light-resistant containers at 15-30 °C. |
| Reinigungsverfahren | ACCIDENTAL RELEASE MEASURES. Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid breathing vapours, mist or gas. Ensure adequate ventilation. Remove all sources of ignition. Evacuate personnel to safe areas. Beware of vapours accumulating to form explosive concentrations. Vapours can accumulate in low areas.Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided.Methods and materials for containment and cleaning up: Contain spillage, and then collect with an electrically protected vacuum cleaner or by wet-brushing and place in container for disposal according to local regulations. |
| Entsorgungsverfahren | SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator. |
| Preventive Measures | Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.Appropriate engineering controls: Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling the product.Precautions for safe handlingAvoid contact with skin and eyes. Avoid inhalation of vapour or mist. Use explosion-proof equipment.Keep away from sources of ignition - No smoking.Take measures to prevent the build up of electrostatic charge. |
| Personal Protective Equipment (PPE) | Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face respirator with multipurpose combination (US) or type ABEK (EN 14387) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).Body Protection: Complete suit protecting against chemicals, Flame retardant antistatic protective clothing. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.Skin protection: Handle with gloves.Eye/face protection: Face shield and safety glasses Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU). |
| Körperbelastung | /FATAL/ There is limited data on postmortem oxycodone concentrations, consisting of three published reports with a total of 11 cases, many of which were polypharmacy cases. This report presents the results of a review of autopsy and coroner's reports from 10 counties for the years 2000 and 2001 to locate cases with oxycodone or hydrocodone exposure as a leading cause of death. Eighty-eight cases were located. Twenty-four deaths were attributed to oxycodone alone. Mean and median postmortem oxycodone blood concentrations were 1.23 mg/L and 0.43 mg/L, respectively. The range was 0.12 to 8.0 mg/L, with 13 cases (54%) < or = 0.5 mg/L. Seventeen deaths were attributed to hydrocodone alone. Mean and median postmortem hydrocodone blood concentrations were 0.53 mg/L and 0.40 mg/L, respectively. The range was 0.12 to 1.6 mg/L, with 11 cases (65%) < or = 0.5 mg/L. There were seven cases where the cause of death was attributed to the effects of a combination of hydrocodone and oxycodone. Mean oxycodone and hydrocodone blood concentrations were 0.34 mg/L and 0.14 mg/L, respectively. Forty cases involved polysubstance overdoses with significant involvement of other drugs and ethanol. Mean oxycodone and hydrocodone blood concentrations were 0.18 mg/L and 0.29 mg/L, respectively. The list of other substances involved was extensive but included ethanol, amitriptyline, methadone, codeine, propoxyphene, and acetaminophen. The findings of this study report oxycodone values associated with a fatality at blood concentrations lower than previously reported. This may represent enhanced information because of the larger sample group. Hydrocodone values associated with a fatality were similar to previously published values. |
| Treatment | Immediate treatment includes support of cardiorespiratory function and measures to reduce drug absorption. Vomiting should be induced mechanically, or with syrup of ipecac, if the patient is alert (adequate pharyngeal and laryngeal reflexes). Oral activated charcoal (1 g/kg) should follow gastric emptying. The first dose should be accompanied by an appropriate cathartic. If repeated doses are used, the cathartic might be included with alternate doses as required. Hypotension is usually hypovolemic and should respond to fluids. Vasopressors and other supportive measures should be employed as indicated. A cuffed endo-tracheal tube should be inserted before gastric lavage of the unconscious patient and, when necessary, to provide assisted respiration. Meticulous attention should be given to maintaining adequate pulmonary ventilation. In severe cases of intoxication, peritoneal dialysis, or preferably hemodialysis may be considered. Naloxone, a narcotic antagonist, can reverse respiratory depression and coma associated with opioid overdose. Naloxone hydrochloride 0.4 mg to 2 mg is given parenterally. Since the duration of action of hydrocodone may exceed that of the naloxone, the patient should be kept under continuous surveillance and repeated doses of the antagonist should be administered as needed to maintain adequate respiration. (L1712) |
| Wechselwirkungen | Hydrocodone may potentiate the effects of other opiate agonists, general anesthetics, tranquilizers, sedatives and hypnotics, tricyclic antidepressants, monoamine oxidase inhibitors, alcohol, and other CNS depressants.Concurrent use of anticholinergic agents with hydrocodone may produce paralytic ileus.Some tranquilizers, especially phenothiazines, may antagonize opiate agonist analgesia. /Opiate agonists/...Using the mouse radiant heat tail-flick nociception model, /investigators/ observed potent analgesia with hydrocodone. In contrast, ibuprofen as a single drug was inactive in this model of moderate to severe pain, perhaps reflecting its limited analgesic potential. Despite the inactivity of ibuprofen alone in this model, the inclusion of ibuprofen with hydrocodone markedly enhanced the analgesic response. Dose-response studies revealed a 50% effective dose for hydrocodone alone in mice of 11 mg/kg, SC. Inclusion of a fixed ibuprofen dose with the various hydrocodone doses shifted the 50% effective dose value almost seven-fold to the left to 1.6 mg/kg, SC, despite the lack of effect of ibuprofen alone in this model. Using a fixed hydrocodone:ibuprofen ratio (1:40) also revealed a marked four-fold shift to 2.6 mg/kg, SC. These findings suggest a synergistic interaction between ibuprofen and hydrocodone in a noninflammatory pain model. Opioids are frequently used in combination with nonsteroidal antiinflammatory drugs clinically. These studies demonstrate strong interactions between ibuprofen and hydrocodone, implying synergy between the two drugs, which may help explain their utility when given together.To describe the potential for interaction between opioids and serotonergic antidepressants leading to the development of serotonin syndrome (SS), mechanism of the interaction, and the spectrum of SS in elderly residents of a long-term care facility. Case series. Long-term care facility (LTCF) in California. Four elderly LTCF residents treated with serotonergic antidepressants including selective serotonin reuptake inhibitor (SSRI) or mirtazapine and opioids. Signs and symptoms suggestive of SS. /Investigators/ describe 4 cases of probable SS among elderly residents of a LTCF. The spectrum of serotonin toxicity ranged from visual hallucinations, muscle rigidity, myoclonus, or hypertension in patients taking an opiate with an SSRI to lethargy, hypotension, and hypoxia in a patient taking tramadol and mirtazapine. While many can benefit from coadministration of serotonergic antidepressants and opioids, it appears that some individuals are at increased risk for SS. Since SS is a clinical diagnosis, heightened clinician awareness of the possibility of SS among patients receiving SSRI or mirtazapine in combination with opioids may lead to earlier detection and avoidance of potentially lethal consequences. |
| Gesundheitliche Auswirkungen | Medical problems can include congested lungs, liver disease, tetanus, infection of the heart valves, skin abscesses, anemia and pneumonia. Death can occur from overdose. |
| Hepatotoxicity | Despite wide scale use for many decades, hydrocodone by itself has not been convincingly linked to instances of clinically apparent acute liver injury. However, when combined with acetaminophen, hydrocodone combinations have become a common cause of acetaminophen acute liver injury. The typical history is of a patient who began taking more than the prescribed number of pills over several days, attempting to achieve more of an opiate effect and leading secondarily and unintentionally to an overdose of acetaminophen. Because of their potential for hepatotoxicity, opioid combinations in which the dose of acetaminophen is greater than 325 mg per tablet or capsule were discontinued. |
| Umweltverhalten | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1,100(SRC), determined from a structure estimation method(2), indicates that hydrocodone is expected to have low mobility in soil(SRC). The pKa of hydrocodone is 8.23(3), indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of the neutral species of hydrocodone from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 6.4X10-12 atm-cu m/mole(SRC), using a fragment constant estimation method(5). Hydrocodone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.2X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Hydrocodone is not biodegraded in wastewater treatment plants(6), suggesting that biodegradation is not an important environmental fate process in soil(SRC).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1,100(SRC), determined from a structure estimation method(2), indicates that hydrocodone is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces of the neutral species is not expected(3) based upon an estimated Henry's Law constant of 6.8X10-12 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). A pKa of 8.23(5) indicates hydrocodone will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process(SRC). According to a classification scheme(6), an estimated BCF of 12(SRC), from an estimated log Kow of 2.16(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Hydrocodone is not biodegraded in wastewater treatment plants(7), suggesting that biodegradation is not an important environmental fate process in water(SRC).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), hydrocodone, which has an estimated vapor pressure of 1.2X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase hydrocodone is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC)the half-life for this reaction in air is estimated to be 1 hr(SRC), calculated from its rate constant of 1.8X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase hydrocodone may be removed from the air by wet and dry deposition(SRC). Hydrocodone absorbs UV light at wavelengths 280 nm(4) and, therefore, is not expected to be susceptible to direct photolysis by sunlight since sunlight consists of wavelengths above 290 nm(SRC). |
| Unerwünschte Wirkungen | The most common adverse effects of hydrocodone include frequent constipation and nausea. Additional adverse effects of hydrocodone include the following: |
| Expositionspfade | Oral. Well absorbed from the gastrointestinal tract. |
| Milk Concentrations | EXPERIMENTAL: Two mothers who were taking an acetaminophen and hydrocodone combination product donated pumped milk for analysis of hydrocodone. Their infants received an estimated 3.1% and 3.7% of the maternal weight-adjusted dosage, but the absolute hydrocodone dosages were 8.58 ug/kg per day and 3.07 ug/kg per day because of the differences in the dosages ingested by their mothers. Moderate dosages of hydrocodone appear acceptable during breastfeeding, but more data are needed to determine the maximum safe dosage for nursing mothers. Neonates and preterm infants may be more susceptible than older infants to adverse effects of hydrocodone and its metabolites in breast milk. |
| Toxizitätsübersicht | IDENTIFICATION AND USE: Hydrocodone bitartrate (HD) is a phenanthrene-derivative opiate agonist antitussive and analgesic agent. HUMAN EXPOSURE AND TOXICITY: Serious overdose with hydrocodone is characterized by respiratory depression (a decrease in respiratory rate and/or tidal volume, Cheyne-Stokes respiration, cyanosis), extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, and sometimes bradycardia and hypotension. In severe overdosage, apnea, circulatory collapse, cardiac arrest and death may occur. A 3-year-old child died of the combined effects of a bacterial superinfection and a relative overdose of hydrocodone prescribed for a cough due to a presumed viral respiratory tract infection. Poison center rates of abuse and misuse were highest for hydrocodone at 3.75 per 100,000 population, followed by oxycodone at 1.81 per 100,000 population. DAWN emergency department (ED) data illustrate a similar pattern of abuse with most mentions involving hydrocodone and oxycodone. Poison center data indicate that people aged 18 to 25 had the highest rates of abuse. DAWN reported the majority of ED mentions among 35 to 44-year-olds. ANIMAL STUDIES: LD50 in rats was 150 mg/kg for sc administration and 375 mg/kg when given orally. HB was evaluated in rats (25/sex/group) and in rabbits (20 females/group) given daily po doses of 0 (Vehicle), 10, 33 and 100 mg/kg and 0 (Vehicle), 5.3, 16 and 48 mg/kg, respectively. Female rats were dosed gestation days (DGs) 7-17 and Cesarean-sectioned (CS) on DG 21 and female rabbits were dosed DGs 6-18 and CS on DG 29. Toxicokinetics was evaluated in the range-finding studies for both species at 0.5. 1, 2, 4, 6, 16 and 24 hr postdosage on the first and last days of dose administration. Survival was not affected in either species. Exaggerated pharmacological effects of HB and reduced body weight gain and absolute and relative feed consumption values were observed at all dosage levels in both studies. Rodent fetal body weights were reduced and a reduction in the number of ossifications sites for the caudal vertebrae, hindlimb phalanges and metatarsals occurred in the 100 mg/kg group. The number of late resorptions was increased in the 48 mg/kg groupno other CS parameters were affected and no gross, visceral or skeletal malformations attributed to HB. The maternal NOAELs were less than 10 mg/kg and 5.3 mg/kg for the rat and rabbit studies, respectively. The developmental NOAELs were 16 and 33 mg/kg for the rat and rabbit studies, respectively.Signs and Symptoms of OverdoseHydrocodone acts as a weak agonist at OP1, OP2, and OP3 opiate receptors within the central nervous system (CNS). Hydrocodone primarily affects OP3 receptors, which are coupled with G-protein receptors and function as modulators, both positive and negative, of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine, and noradrenaline is inhibited. Opioids such as hydrocodone also inhibit the release of vasopressin, somatostatin, insulin, and glucagon. Opioids close N-type voltage-operated calcium channels (OP2-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (OP3 and OP1 receptor agonist). This results in hyperpolarization and reduced neuronal excitability. |
| Signs and Symptoms | Symptoms of overdose include respiratory depression (a decrease in respiratory rate and/or tidal volume, Cheyne-Stokes respiration, cyanosis), extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, dizziness, ringing in the ears, confusion, blurred vision, eye problems, cold and clammy skin, and sometimes bradycardia and hypotension. In severe overdose, apnea, circulatory collapse, cardiac arrest and death may occur. |
| Effluent Concentrations | Hydrocodone was detected, not quantified in secondary effluent samples from nine municipal sewage plants in the region of Stuttgart, Germany(1). The compound was detected at 1.47 ug/L in effluent from a sewage treatment plant in Stuttgart, Germany(2). Hydrocodone influent and effluent concentrations were 70 and 8.6 ng/L, respectively, at the 26th Ward wastewater treatment plant, Jamaica Bay, NY, an 88% removal efficiency(3). |
| Wassergefährdungsklasse (WGK) | 1 |
| UN-Transportnummer | 1544 |
| Zollcode | 2939110000 |
| R-Sätze (R) | 11-23/24/25-39/23/24/25 |
| Toxizität | LD50 s.c. in mice: 85.7 mg/kg (Eddy, Reid) |
| Gefahrensymbole | F,T |
| Sicherheitshinweise (S) | 16-36/37-45 |
| Gefahrenklasse | 6.1(b)Acute Tox. 4 OralSTOT SE 3 |
| Verpackungsgruppe | III |
| Lagerklasse | 11 - Combustible Solids |
| Gefahrstoffdaten | 125-29-1(Hazardous Substances Data) |
Anwendungen & Verwendung
Verwenden
Hydrocodone is a powerful anticough drug that is widely used for suppressing the cough reflex. It is widely used in effective commercial anticough drugs in combination with guaiphenesin (entuss), with homatropine (hycodan), with phenylpropanolamine (hycomine), phenyltoloxamine (tussionex), and pseudoephedrine and guaiphenesin (tussened).