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Difference Between Codeine and Hydrocodone

Codeine vs. Hydrocodone

Pain is highly subjective and a very individual experience. However, humans have developed several drugs to manipulate the body’s ability to control pain. Codeine and hydrocodone are some of these drugs in which they both belong to opioid agonist group. These drugs stimulate the activity of opioid receptors sites in the central nervous system altering its perception and emotional response to an ache. Hence, they relieve moderate to moderately severe pain. Aside from them being narcotics, these two drugs can also be classified as antitussive to treat coughs. Antitussives suppress the cough reflex by direct action on the cough center in the medulla. Suppression is typically unnecessary and may be harmful unless damage is being done to tissue during excessive coughing spasms.

On the other note, codeine and hydrocodone are technically two different drugs. However, they have numerous similarities and are sometimes confused as being the same. One of the notable differences between these drugs is their chemical structures. Codeine is a 3-methylmorphine while the chemical structure of hydrocodone is quite similar to codeine’s but not the same. It is a combination of different compounds. Hydrocodone was originally synthesized from codeine and thebaine and is known to be “semi-synthetic.” They also differ in terms of their action in the body. Codeine, with its nearly inactive form, must be converted into morphine through the enzyme CYP2D6 found in the liver to cause opioid effects, and hence it’s considered a prodrug of morphine. People having a lack of this certain liver enzyme won’t feel any therapeutic effects of codeine since it will not be converted to morphine inside the body. Hydrocodone must undergo complex hepatic metabolism through O-demethylation, N-demethylation, and also with 6-keto reduction to the corresponding 6-alpha- and 6-beta-hydroxy active metabolites. A portion of hydrocodone is converted to hydromorphone by cytochrome P450-2D6 (CYP2D6). Hydromorphone seem to have no major role in the effects profile of hydrocone. Additionally, hydrocone is not considered a prodrug.

Hydrocodone is a lot like codeine except that codeine is naturally derived from opium plants while hydrocodone is synthetically made and has an extra added hydrogen molecule. Hydrocodone has more sedating effects than codeine. Hydrocodone is much stronger than codeine and proven to be more effective in reducing severe pain. This is the reason why codeine is usually used to treat mild to moderate pain while hydrocodone is prescribed to treat moderate to severe pain. The effects of hydrocodone are about six times much stronger than those of codeine, but the general effects of hydrocodone are nearly similar to that of codeine. Hydrocodone also has less side effects to include: itchiness, nausea, drowsiness, constipation, urinary retention, dry mouth, skin rash, depression, blurred or double vision, nausea, vomiting, delirium, and impaired breathing as compared to codeine although they may be present but to a lesser degree. Effects and duration of these drugs may be the same but their peak hours vary greatly. One to 2 hours for codeine while 30 to 60 minutes for hydrocodone. Codeine cannot be safely administered intravenously as it may result in pulmonary edema, swelling of the face, a dangerous release of histamines, and numerous cardiovascular effects. Hydrocodone is safer to administer orally, intramuscularly, subcutaneously, rectally, intranasally (or sniffing), and intravenously but typically is not.

Since hydrocodone is not a prodrug, it has no ceiling dosage above which the effects will not escalate. In simple words, the hydrocodone’s dosage can be increased indefinitely to achieve greater effects unlike codeine. All of these reasons make hydrocodone a preferred drug over codeine.

Here are additional and more specific differences between these two drugs:

1. Hydrocodone is man-made while codeine occurs in nature.

2. Hydrocodone is a very effective cough suppressant compared to codeine and a more potent painkiller.

3. Hydrocodone has a more sedating effect than codeine.

4. Effects and duration of these drugs may be the same, but their peak hours vary greatly. One to 2 hours for codeine while 30 to 60 minutes for hydrocodone.

5. They differ in the way the molecules are bonded in the formula.

6. Codeine is not usually given intravenously as it can cause pulmonary edema and may result in death. Hydrocodone may be administered by IV but typically is not.

7. Hydrocodone has less side effects than codeine.

8. Hydrocodone has no ceiling effect unlike codeine.


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