Tramadol vs. Codeine

  • Medical Editor: John P. Cunha, DO, FACOEP
    John P. Cunha, DO, FACOEP

    John P. Cunha, DO, FACOEP

    John P. Cunha, DO, is a U.S. board-certified Emergency Medicine Physician. Dr. Cunha's educational background includes a BS in Biology from Rutgers, the State University of New Jersey, and a DO from the Kansas City University of Medicine and Biosciences in Kansas City, MO. He completed residency training in Emergency Medicine at Newark Beth Israel Medical Center in Newark, New Jersey.

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Tramadol vs. codeine comparison

Tramadol (Ultram) and codeine are both opiates and narcotics prescribed for moderate pain. Codeine is also a cough suppressant. Codeine is derived from the poppy plant like other narcotics, including morphine, heroin, and opium. Tramadol, on the other hand, is synthetic, though it is similar to codeine.

Both these drugs are less potent that other opiates, which means their potential for addiction and withdrawal are lower. That doesn't mean they're safe, however. Both can be physically and psychologically habit-forming.

Side effects for both drugs - aside from potential addiction - may include dizziness, confusion, sedation, constipation and others.

Neither tramadol nor codeine should be taken with alcohol or other sedatives or tranquilizers because they may potentially magnify the effects. Particularly dangerous is the potential for respiratory depression, which can make you stop breathing if you take too much of either codeine or tramadol, or mix either of them with the wrong medication.

What are tramadol and codeine?

Tramadol and codeine are both opiates. Codeine is made from the poppy plant, just like morphine, heroin, and opium. Tramadol is chemically similar to codeine, but it's synthesized from precursor molecules in a lab. Many doctors like it because it has a lower potential for addiction than other opioids, though that doesn't mean it's non-addictive.

Opiates work because the central nervous system has three main opioid receptors in the nerve cells that, when coupled with natural opioids your body makes, govern pain sensation, reward, aspects of gastrointestinal function, aspects of respiratory function, and aspects of urogenital function. These receptors are named after Greek letters: Mu receptors, Delta receptors, and Kappa receptors. They sit on the membrane of nerve cells and activate when an opioid -- whether naturally occurring in the body or introduced in the form of a drug -- fits into the molecule like a key in a lock.

Opiate drugs mimic the natural opioids produced by the body. Their molecules fit into the same receptors and activate them. Codeine, tramadol, morphine, and all other poppy derivatives target and activate mostly the Mu receptors, meaning they are "Mu receptor agonists."

These receptors and the naturally occurring (endogenous) opioids they pair with are responsible for the body's own efforts to deaden pain. Because of this, flooding the Mu receptors with pharmaceutical opioids like codeine, tramadol, and others can increase the painkilling (analgesic) properties of that part of the central nervous system.

Unfortunately, because the endogenous opioid system also governs reward pathways, pharmaceutical opioids are highly addictive. Endorphins are the main endogenous opioids your nervous system secretes in response to sex, a delicious meal, and other forms of pleasure. Because opiate drugs activate the same Mu receptors endorphins do, euphoria and a profound sense of wellbeing are potential side effects of all the opiate drugs on the market. Patients can become addicted physically and mentally as both their bodies and minds begin to crave that state of bliss.

Tramadol and codeine are much less potent that other opiates like morphine, heroin, and its synthetic counterpart Fentanyl. Because of this, short-term use of tramadol and codeine for cough or moderate pain symptoms comes with a relatively low risk of addiction or withdrawal.

The endogenous opioid system, as mentioned before, helps govern the muscle reflex that expands and contracts your ribcage to breathe in and out in response to carbon dioxide levels in the blood. Because opiate drugs suppress this respiratory response, small doses of drugs like codeine and can help suppress coughing and reduce the pain of a sore throat in all sorts of diseases and conditions in which coughing and throat pain are symptoms. However, though researchers understand the cough reflex is associated with the endogenous opioid system, they haven't figured out the exact mechanism by which codeine suppresses coughs. They don't know why, for instance, it doesn't work for some chronic coughs.

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What are the uses for tramadol and codeine?

Tramadol is used in the management of moderate to moderately severe pain. Extended release tablets are used for moderate to moderately severe chronic pain in adults who require continuous treatment for an extended period.

Codeine is used for the relief of mild to moderately severe pain and for suppressing cough.

What are the side effects of tramadol and codeine?

SIDE EFFECTS: The most frequent side effects of codeine and tramadol include:

Some patients who received tramadol have reported seizures. It may cause serotonin syndrome when combined with other drugs that also increase serotonin (see drug interactions section).

This is not a full list of side effects for either tramadol or codeine. Make sure you ask your doctor about the potential side effects of these drugs if you are prescribed them.

For more information, please visit the MedicineNet drug monographs for these medications:

Can I get addicted to tramadol and codeine?

Codeine and tramadol are habit forming. Mental and physical dependence can occur but are unlikely when used for short-term pain relief. If tramadol or codeine is suddenly withdrawn after prolonged use, symptoms of withdrawal may develop.

The psychological or physical dependence tramadol and codeine can cause is similar to other narcotics. Tramadol is a schedule IV medication on the federal list of controlled substances as outlined by the U.S. Controlled Substance Act. Codeine has a more serious Schedule II classification because of its higher potential for abuse.

What are the withdrawal symptoms of tramadol and codeine?

Abrupt withdrawal from tramadol and codeine may result in

Withdrawal symptoms are similar to other opiates. Prescribing doctors should gradually reduce doses of codeine and tramadol in order to avoid these symptoms.

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How should tramadol and codeine be taken (dosage)?

Tramadol

  • The recommended dose of tramadol is 50-100 mg (immediate release tablets) every 4-6 hours as needed for pain.
  • The maximum dose is 400 mg/day.
  • To improve tolerance patients should be started at 25 mg/day, and doses may be increased by 25-50 mg every 3 days to reach 50-100 mg/day every 4 to 6 hours.
  • Tramadol may be taken with or without food.
  • The recommended dose for extended release tablets is 100 mg daily which may be increased by 100 mg every 5 days but not to exceed 300 mg /day. To convert from immediate release to extended release, the total daily dose should be rounded down to the nearest 100 mg. Extended release tablets should be swallowed whole and not crushed or chewed.

Codeine

  • The usual adult dose of codeine for pain is 15-60 mg every 4-6 hours as needed.
  • The dose for cough is 10 to 20 mg every 4-6 hours as needed.
  • The maximum dose for treating cough is 120 mg every 24 hours.

Which drugs interact with tramadol and codeine?

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Which drugs interact with tramadol and codeine?

Both tramadol and codeine may increase central nervous system and respiratory depression when combined with alcohol. Alcohol and anesthetics, narcotics, tranquilizers (like alprazolam [Xanax]), or sedative hypnotics can produce further brain impairment and even confusion when combined with tramadol or codeine. Therefore, alcohol and other sedatives should not be used when taking tramadol or codeine.

 Carbamazepine (Tegretol, Tegretol XR , Equetro, Carbatrol) reduces the effect of tramadol by increasing its inactivation in the body.

Quinidine (Quinaglute, Quinidex) reduces the inactivation of tramadol, thereby increasing the concentration of tramadol by 50% to 60%.

Combining tramadol with monoamine oxidase inhibitors or MAOIs (for example, tranylcypromine [Parnate]) or selective serotonin inhibitors (SSRIs), for example, fluoxetine (Prozac), may result in severe side effects such as seizures or a condition called serotonin syndrome.

Drugs that stimulate and also block opioid receptors (for example, pentazocine) reduce the effect of codeine. Such drugs should not be combined with codeine.

Drugs that block the action of acetylcholine (anticholinergic drugs) increase the occurrence of urinary retention and constipation when combined with codeine.

Monoamine oxidase inhibitors (MAOIs) class of antidepressants (for example, isocarboxazid [Marplan], phenelzine [Nardil], tranylcypromine [Parnate], selegiline [Eldepryl], and procarbazine [Matulane]) significantly increase the action of codeine. Codeine should not be used in patients taking MAOIs or within 14 days of stopping MAOIs.

This is not a complete list of drug interactions for tramadol and codeine. If a doctor prescribes you either of these narcotics, make sure you provide a full list of other medications you're taking to avoid dangerous interactions.

Are tramadol and codeine safe to take during pregnancy or while breastfeeding?

No one has systematically studied the safety of tramadol or codeine during pregnancy, but pregnant mothers should avoid using any opiate because of the risk of dependence in the developing fetus. Small amounts of both tramadol and codeine are secreted in breast milk, but the dose is typically too tiny to cause problems with the baby. Still, if you are prescribed either of these medications while breastfeeding, you and your doctor should carefully evaluate the risks before you make a decision on whether to take it.

REFERENCES:

FDA Prescribing information

Tramadol Compound Summary
PubChem

Codeine Compound Summary
PubChem

"Tramadol: Seizures, Serotonin Syndrome, and Coadministered Antidepressants"
Randy A. Sansone, MD and Lori A. Sansone, MD
Psychiatry (Edgemont)
April, 2009

"How Does The Opioid System Control Pain, Reward And Addictive Behavior?"
European College of Neuropsychopharmacology
ScienceDaily
Oct., 2007

"Molecular Mechanisms of Opioid Receptor-Dependent Signaling and Behavior"
Ream Al-Hasani, Ph.D and Michael R. Bruchas, Ph.D
Anesthesiology
Dec. 2011

"Opioid Receptors: A video on Mu, Delta, Kappa and ORL1 receptors"
Flavio Guzman, MD
PsychopharmacologyInstitute.com

"Reward Processing by the Opioid System in the Brain"
Julie Le Merrer, Jérome A. J. Becker, Katia Befort, and Brigitte L. Kieffer
Physiological Reviews
Oct. 2009

Incidence, Reversal, and Prevention of Opioid-induced Respiratory Depression
Albert Dahan, M.D., Ph.D.; Leon Aarts, M.D., Ph.D.; Terry W. Smith, Ph.D.
Anesthesiology
Jan. 2010

"Central and peripheral mechanisms of narcotic antitussives: codeine-sensitive and -resistant coughs"
Kazuo Takahama and Tetsuya Shirasaki
Cough
July, 2007

"Drug Scheduling"
U.S. Drug Enforcement Agency
DEA.gov

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Reviewed on 5/3/2017
References
REFERENCES:

FDA Prescribing information

Tramadol Compound Summary
PubChem

Codeine Compound Summary
PubChem

"Tramadol: Seizures, Serotonin Syndrome, and Coadministered Antidepressants"
Randy A. Sansone, MD and Lori A. Sansone, MD
Psychiatry (Edgemont)
April, 2009

"How Does The Opioid System Control Pain, Reward And Addictive Behavior?"
European College of Neuropsychopharmacology
ScienceDaily
Oct., 2007

"Molecular Mechanisms of Opioid Receptor-Dependent Signaling and Behavior"
Ream Al-Hasani, Ph.D and Michael R. Bruchas, Ph.D
Anesthesiology
Dec. 2011

"Opioid Receptors: A video on Mu, Delta, Kappa and ORL1 receptors"
Flavio Guzman, MD
PsychopharmacologyInstitute.com

"Reward Processing by the Opioid System in the Brain"
Julie Le Merrer, Jérome A. J. Becker, Katia Befort, and Brigitte L. Kieffer
Physiological Reviews
Oct. 2009

Incidence, Reversal, and Prevention of Opioid-induced Respiratory Depression
Albert Dahan, M.D., Ph.D.; Leon Aarts, M.D., Ph.D.; Terry W. Smith, Ph.D.
Anesthesiology
Jan. 2010

"Central and peripheral mechanisms of narcotic antitussives: codeine-sensitive and -resistant coughs"
Kazuo Takahama and Tetsuya Shirasaki
Cough
July, 2007

"Drug Scheduling"
U.S. Drug Enforcement Agency
DEA.gov

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