Codeine
*
Diarrhea*Mild to moderate
painCodeine is sometimes marketed in combination preparations with
paracetamol (
acetaminophen) as
co-codamol, with
aspirin co-codaprin or with
ibuprofen. These combinations provide greater pain relief than either agent used singly (q.v.
Drug Synergy).
In the
United States, codeine is regulated by the
Controlled Substances Act. It is a Schedule II controlled substance for pain-relief products containing codeine alone. In combination with aspirin or acetaminophen (
paracetamol) it is listed as Schedule III. Codeine is also available outside the United States as an
over-the-counter drug (Schedule V) in liquid cough-relief formulations. Internationally, codeine is a Schedule II drug under the
Single Convention on Narcotic Drugs.
In the
United Kingdom, codeine is regulated by the
Misuse of Drugs Act 1971; it is a
Class B Drug.
In
Australia,
New Zealand and
Canada, codeine is regulated, however it is available without prescription in combination preparations from licensed pharmacists in doses up to 15 mg/tablet (8 mg/tablet in Canada).
Codeine is considered a
prodrug, since it is metabolised
in vivo to the principal active analgesic agent
morphine. It is, however, less potent than morphine since only about 10% of the codeine is converted. It also has a correspondingly lower
dependence-liability than morphine.
Theoretically, a dose of approximately 200 mg (oral) of codeine must be administered to give equivalent analgesia to 30 mg (oral) of morphine (Rossi, 2004). It is not used, however, in single doses of greater than 60mg (and no more than 240 mg in 24 hours) since there is a
ceiling effect.
The conversion of codeine to morphine occurs in the liver and is catalysed by the
cytochrome P450 enzyme
CYP2D6. Approximately 6–10% of the Caucasian population have poorly functional CYP2D6 and codeine is virtually ineffective for analgesia in these patients (Rossi, 2004). Many of the adverse effects, however, are still experienced. Also, some medications are CYP2D6 inhibitors and reduce or even completely eliminate the efficacy of codeine. The most notorious of these are the
selective serotonin reuptake inhibitors, such as
fluoxetine (Prozac) and
citalopram (Celexa).
Codeine itself has weak affinity for the
μ-opioid receptor. Its principal analgesic actions are mediated by the affinity of morphine for the μ-opioid receptor, though other therapeutic and adverse effects are produced by activation of other opioid receptors.
Common adverse drug reactions (ADRs) associated with the use of codeine include: Itching, nausea, vomiting, drowsiness, dry mouth,
miosis,
orthostatic hypotension, urinary retention and constipation.
Tolerance to many of the effects of codeine develop with prolonged use, including therapeutic effects. The rate at which this occurs develops at different rates for different effects, with tolerance to the constipation-inducing effects developing particularly slowly for instance.
A potentially serious ADR, as with other opioids, is
respiratory depression. This depression is dose-related and is the mechanism for the potentially fatal consequences of overdose.
Codeine is often used as a
recreational drug. This may be due to its easy availability
over-the-counter or on
prescription in combination products (which, in the certain countries, are scheduled lower than codeine as a single-agent). People use it in order to obtain the
euphoric effects associated with use of opioids.
* In certain areas of the United States; more specifically Texas, codeine in syrup form is called
Lean. It is commonly mixed with alcohol, or a
blunt and smoked.
* When prepared with
promethazine, codeine is a Schedule V controlled substance in the United States. In a few states, such as New Jersey, you can get codeine with promethazine over-the-counter without a prescription if you tell the pharmacist your symptoms. The syrup, sometimes known as Phenergan With Codeine, contains 6.25mg of promethazine for every 10mg of codeine per teaspoonful.
* In some countries, cough syrups and tablets containing codeine are available without prescription; people will frequently purchase it from multiple pharmacies so as not to incur suspicions. It is reported that in
France, 95% of the consumption of
Néo-codion cough preparation, containing codeine, cannot be attributed to medical use, but is rather used as a substitute for
heroin. A heroin addict may use codeine to ward off the effects of a
withdrawal.
* In the
United Kingdom, people purchase tablets which combine codeine and
paracetamol (acetaminophen), and consume these at higher-than-recommended doses, without apparent concern of the hepatotoxicity associated with large doses of paracetamol. Some may try to
extract the codeine from the paracetamol through various methods, the most common and simplest being the
cold water extraction.
* In some areas of Canada and the Northern United States, a prescription combination of
acetaminophen and codeine, most commonly Tylenol-3, is often powdered and taken nasally.
* While the combination of codeine with
paracetamol, at higher-than-recommended doses, can possibly cause hepatotoxicity (
liver damage), combination with
ibuprofen can result in
kidney problems/failure and additional
stomach pain and
nausea and combination with
aspirin can lead to internal
hemorrhaging, particularly
gastrointestinal hemorrhage.
Certain codeine products are encountered on the illicit market, frequently in combination with
carisoprodol. Combinations of codeine and glutethimide (Doriden) used to be fairly commonplace, but are almost unheard of today, due to the withdrawal of glutethimide products from the marketplace in the US and almost all other countries. In South Asian countries it has become a multimillion dollar market in form of cough syrups which are easily available at chemist shops without any prescription.
*
Dihydrocodeine*
Morphine*
Opioid*
Psychoactive drug
