Codeine

Chemical Name: (5alpha,6alpha)-7,8-Didehydro-4,5-epoxy-3-methoxy-17-methylmorphinan-6-ol

Classification: Opiate

Primary Uses: Anagesia, cough suppression, diarrhea, irritable bowel syndrome (IBS)

Brand Names: Tylenol #3, Codate, Codephos

Pharmacology & Pharmacokinetics

Codeine exerts its effects on the central nervous system and the bowel.  Codeine itself only weakly binds to mu-opiod receptors, and correspondingly, a higher dose of codeine must be taken for an equivalent dose of morphine (200mg codeine is approximately equal to 30 mg of morphine in analgesia).  While codeine itself has a weak binding affinity, 5 – 10% of codeine is converted to morphine, and other active compounds (codeine-6-glucuronide (~70%), norcodeine (~10%), and hydromorphone (~1%)).

Conversion of codeine to morphine occurs in the liver via cytochrome P450 enzyme CYP2D6. A point to keep in mind is that approximately 6-10% of the Caucasian population, 2% of Asians, and 1% of Arabic have poorly functional CYP2D6 and codeine is much less effective for these people, although it is speculated that codeine-6-glucuronide is responsible for a large percentage of the analgesia of codeine and thus these patients should experience some analgesia.

Some drugs may interfere with the effectiveness of codeine. Certain selective serotonin reuptake inhibitors (anti-depressants) are CYP2D6 inhibitors, which consequently reduces the efficacy of codeine. Combining codeine with gluthethimide, a sleeping agent, is said to act as an enzyme-inducer, allowing the body to convert up to 10% of codeine into morphine. Other drugs may reduce or raise the effectiveness of codeine, and care should be taken when mixing medications.

Legal Status

Under United States law, codeine can appear as both a Schedule II or Schedule III substance depending on the formulation. Here are the differences between the two:

• Schedule II — Includes codeine products containing more than 90 mg per dosage unit. Written prescription required for refills.
• Schedule III — Includes codeine products containing less than 90 mg per dosage unit. May be refilled using phoned prescription.

Schedule II substances meet the following criteria according to the Controlled Substances Act:

1. The drug or other substance has a high potential for abuse.
2. The drug or other substance has a currently accepted medical use in treatment in the United States (or) a currently accepted medical use with severe restrictions.
3. Abuse of the drug may lead to severe psychological or physical dependence.

Schedule III substances meet the following criteria according to the Controlled Substances Act:

1. The drug or other substance has a potential for abuse less than the drugs or other substances in Schedules I and II.
2. The drug or other substance has a currently accepted medical use in treatment in the United States of America.
3. Abuse of the drug or other substance may lead to moderate or low physical dependence or high psychological dependence.

Side Effects

• Pain relief
• Dizziness
• Nausea and/or vomiting
• Constipation
• Headache
• Sweating
• Nervousness and anxiety
• Euphoria or dysphoria
• Urinary retention
• Insomnia
• Dry mouth

Withdrawal

Codeine withdrawal typically starts within 12-24 hours after the last dose. The time it takes for codeine withdrawal to begin varies due to factors such as frequency of use, dosage, and body chemistry. Acute withdrawal symptoms peak between 48 and 72 hours and are generally gone within a week; however, post-acute withdrawal syndrome (PAWS) can affect a person for weeks or months after the initial withdrawal phase.

• Cravings
• Muscle and bone pain
• Restlessness
• Goose bumps
• Involuntary leg and arm movements
• Profuse sweating
• Insomnia
• Nausea and vomiting
• Depression

Sources