What Are the Symptoms of Codeine Addiction?

Codeine, severe dry cough and irritating cough caused by various reasons, especially for severe dry cough with chest pain. As this product can inhibit the secretion of respiratory glands and ciliary movement, it should be used in combination with expectorants for severe cough with a small amount of sputum. can be used for analgesia of moderate pain. Adjuvant drugs for local or general anesthesia, have sedative effect.

On September 4, 2018, in order to further protect the safety of drug use by the public, the State Food and Drug Administration decided to amend the "taboo" and "children's medicine" items of codeine-containing cold medicines. Among them, the relevant content in "Contraindications" was revised to "Disabled for young children under 18 years of age", and the relevant content in "Children's medication" was revised to "Disabled for young children under 18 years of age". ^[1]

Chinese name: Codeine
English name: Morphinan-6-ol; Codeine ^[2]
nickname: 17-methyl-3-methoxy-4,5-epoxy-7,8-didehydromorphinan-6-ol

Chemical formula: C18H21NO3 ^[2]
Molecular weight: 299
Melting point: 157.5 ^[3]
Boiling point: 250 ^[2]

Physical and chemical properties of codeine

Phosphate is usually a fine white needle-like crystalline powder. Odorless, weathering, acidic reaction in aqueous solution. Soluble in water, slightly soluble in ethanol, very slightly soluble in chloroform or ether.

Codeine pharmacology

It can directly inhibit the coughing center of Yannao, and its cough suppressing effect is rapid and powerful. Its strength is about 1/4 of morphine. It also has analgesic effect, about 1/12 to 1/7 of morphine, but stronger than general antipyretic analgesics. Its analgesic, respiratory depression, constipation, tolerance and addiction are weaker than morphine. Oral absorption is fast and complete, and its bioavailability is 40% to 70%. After one oral administration, the plasma concentration reached a peak in about 1 hour, and t1 / 2 was about 3 to 4 hours. It easily penetrates the blood-brain barrier and placenta, and is mainly combined with glucuronic acid in the liver, and about 15% is transformed into morphine through demethylation. Its metabolites are excreted mainly through the urine.

Codeine indications

Various dry cough and irritating cough caused by various reasons, especially suitable for severe dry cough with chest pain. As this product can inhibit the secretion of respiratory glands and ciliary movement, it should be used in combination with expectorants for severe cough with a small amount of sputum. can be used for analgesia of moderate pain. Adjuvant drugs for local or general anesthesia, have sedative effect.

Codeine usage and dosage

Due to different dosage forms and specifications, please read the drug instructions carefully or follow the doctor's advice.

Codeine adverse reactions

When an oral dose exceeds 60 mg, some patients may experience excitement, irritability, diminished pupils, respiratory depression, hypotension, and slow heart rate. Overdose in children can cause convulsions, which can be countered by naloxone. Nausea, vomiting, constipation and dizziness are also seen.

Codeine contraindications

Disabled for children under 18 years of age. ^[1]

Codeine considerations

Long-term application can also produce tolerance and addiction. The application of this product during pregnancy can make the fetus addicted through the placenta and cause withdrawal symptoms in newborns, such as diarrhea, vomiting, yawning, excessive crying and so on. Application during childbirth can cause respiratory depression in newborns. Sustained-release tablets must be swallowed whole, do not chew or break apart.

Codeine drug interactions

(1) When combined with anticholinergic drugs, this product can aggravate the adverse reactions of constipation or urinary retention. (2) When combined with methadone or other morphine central inhibitors, it can aggravate central respiratory depression. (3) When combined with muscle relaxants, respiratory depression is more significant. (4) This product inhibits zidovudine metabolism and avoids the combination of both. (5) Combined with methaqualone, it can enhance the antitussive and analgesic effects of this product. (6) This product can enhance the analgesic effect of antipyretic analgesics. (7) Combination with barbiturates can aggravate central inhibitory effects. (8) Combined with cimetidine, it can induce confusion, disorientation and shortness of breath.

Codeine preparation

Tablet: 15mg, 30mg

Codeine Pharmacopeia Introduction

[Identification] (1) Take about 0.2g of this product, add 4ml of water to dissolve, and add 20% sodium hydroxide solution dropwise under continuous stirring until white precipitate appears, rub the wall with a glass rod to complete the precipitation, and filter; Wash, dry at 105 ° C for 1 hour, and measure according to law (Appendix VI C). Melting point is 154 ~ 158 ° C. (2) Take about 0.1g of this product, add 5ml of water to dissolve it, and add ammonia test solution dropwise to make it alkaline. No precipitate should be formed. (3) Take about 1mg of this product, put it on a white porcelain plate, add 0.5ml of sulfuric acid containing 2.5mg of selenite, immediately green, and blue. (4) The infrared absorption spectrum of this product should be consistent with the control spectrum (spectrum set 92). (5) Identification of phosphates in aqueous solution (Appendix III). [Check] Take 0.4g of this product for acidity, dissolve it by adding 10ml of water, and measure it according to law (Appendix VI H). The pH should be 4.0 5.0. Clarity and color of the solution should be 0.4g of this product. After adding 10ml of freshly boiled cold water to dissolve, the solution should be clear and colorless; if it is turbid, compare with No. 1 turbidity standard solution (Appendix B), it should not be more concentrated; If the color is developed, it must not be deeper than the standard yellow colorimetric solution No. 2 (Appendix A, first method). Take 0.10g of this product as a gaseous substance and check it according to law (Appendix A). Compared with the control solution made of 5.0ml of standard sodium chloride solution, it must not be more concentrated (0.05%). Take 0.20g of this product and check it according to law (Appendix B). If turbidity occurs, it must not be more concentrated (0.1%) than the control solution made from 2.0ml of standard potassium sulfate solution. Relevant substances are taken from this product, accurately weighed, dissolved in mobile phase and diluted to make a solution containing 10mg per lml as the test solution; another morphine reference substance is weighed precisely, dissolved in mobile phase and diluted to make each The solution containing lmg in lml was used as the reference solution; 0.2ml of the test solution and 1ml of the reference solution were precisely measured, placed in the same 100ml measuring bottle, diluted to the mark with mobile phase, and shaken as the control solution. According to the effective liquid chromatography (Appendix VD) test, octadecylsilane bonded silica gel was used as the filler; 0.03mol / L sodium acetate solution (pH adjusted to 3.5 with glacial acetic acid)-methanol (60:10 ) Is the mobile phase; the detection wavelength is 230nm; the theoretical number of plates based on the codeine phosphate peak is not less than 2000, and the resolution of the morphine peak and the codeine phosphate peak should meet the requirements. Take 10 l of the control solution and inject it into the liquid chromatograph, and adjust the detection sensitivity so that the peak height of the main component chromatographic peak is about 20% of the full scale. Then accurately measure 10 l each of the test solution and the control solution, and inject them into the liquid chromatograph respectively. Record the chromatogram to 3 times the peak retention time of the main component. If the chromatogram of the test solution is consistent with the morphine peak retention time, The peak area of the chromatographic peak should not be larger than the morphine peak area (0.1%) in the control solution; the peak area of other single impurities should not be larger than 2.5 times (0.5%) the codeine phosphate peak area in the control solution; The sum should not be greater than 5 times (1.0%) the codeine phosphate peak area in the control solution. Loss on drying: Take this product and dry it to constant weight at 105 . The weight loss should be 5.0% ~ 7.5% (Appendix L). [Content determination] Take about 0.25g of this product, accurately weigh, add 10ml of glacial acetic acid to dissolve, add 1 drop of crystal violet indicator solution, titrate with chlorochloric acid titration solution (0.1mol / L) until the solution becomes green, and The results of the titration were corrected with a blank test. Each 1ml of perchloric acid titration solution (0.1mol / L) is equivalent to 39.74mg of C18H21N03 · H3PO4 [category] analgesics, antitussives. [Storage] shading and sealed.

^[4] ^[5] ^[6] ^[7]

Codeine amendments

The full text is as follows

In order to further protect the safety of medication for the public, the State Drug Administration has decided to revise the [taboo] and [children's medication] instructions for codeine-containing cold medicines. The related matters are announced as follows:

I. All drug manufacturers of codeine-containing cold medicines shall submit supplementary applications for amendments to the specifications in accordance with the Regulations for the Administration of Drug Registration and other relevant regulations, in accordance with the amendments to the specifications of codeine-containing cold medicines (see annex). Reported to the provincial drug regulatory department for record before November 5, 2014.
Where the amendments involve drug labels, they shall be revised together; other contents of the instructions and labels shall be consistent with the original approval. Within 6 months after the filing of the supplementary application, the manufacturer's instructions and labels must be replaced.
Each drug manufacturer of codeine-containing cold medicines should conduct in-depth research on the mechanism of new adverse reactions, take effective measures to do good publicity and training on use and safety issues, and guide physicians in rational drug use.

2. Clinicians should carefully read the revised contents of the drug specifications for codeine-containing cold medicines. When selecting medications, they should perform a full benefit / risk analysis based on the new revised specifications.

3. Patients should strictly follow the doctor's orders to take the medicine, and should read the instructions carefully before taking the medicine.

4. Provincial drug regulatory authorities are required to urge the enterprises to do a good job of modifying product specifications and replacing label instructions in daily supervision.

Special announcement.

Attachment: Revision requirements for drug specifications for codeine cold medicines

State Drug Administration September 4, 2018 ^[1]