Tramadol Vs. Hydrocodone & Other Drug Comparison

Last Updated: April 30, 2024

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Hydrocodone medication is an opioid prescribed for severe discomfort. It is a depressant, which allows it to slow the central nervous system down. This way, it alleviates pain, and patients can find relief. However, some users might become addicted to the drug and use it for recreational purposes. Let’s compare popularly used opioids such as Codeine vs. Hydrocodone, and Tramadol vs. Hydrocodone, emphasizing respective potencies, side effects, and uses.

Tramadol vs. Hydrocodone

These drugs are both painkillers classified as opioids. They are used to relieve discomfort that cannot be controlled by weaker analgesics (painkillers). Other similarities they share include their mechanism of action. Both painkillers work by binding to a special type of receptor found in the CNS known as mu receptors, which changes the way your body perceives pain. Tramadol works majorly through its active metabolite desmetramadol, while the other works through its active metabolite hydromorphone.

Woman pouring pills put of the bottle.

When comparing Tramadol vs. Hydrocodone, there are other differences as well. Firstly, Tramadol is a less potent painkiller. Another difference between Tramadol vs. Hydrocodone is their effects on brain chemistry. Both painkillers affect pain receptors in the brain, but Tramadol also enables the chemical messengers serotonin and norepinephrine to remain available to the brain over a more extended period.

Hydrocodone vs. Tramadol also have different side effects, as Tramadol is more likely to cause a sore throat and flushing. On the contrary, Hydrocodone common side effects include respiratory depression and confusion. Tramadol has an onset of action typically between 30-60 minutes and a half-life of 5.1 hours. Hydrocodone starts working within 20-30 minutes and has an average half-life of 3.8 hours, but can range between 3.3-4.4 hours.

Both drugs come as oral tablets, oral capsules, oral extended-release capsules, and oral solutions. However, only Tramadol comes as an injectable.

Hydrocodone Comes In Common Combination Products With Other Drugs Such As:

  • Acetaminophen
  • Aspirin
  • Chlorpheniramine
  • Phenylephrine
  • Guaifenesin, etc.

Tramadol is usually combined with acetaminophen.

Codeine vs. Hydrocodone

Both of these drugs are painkillers, although the latter is more potent. Both painkillers work by binding to a special type of receptor found in the CNS known as mu-opioid receptors, which changes the way your body perceives pain. Hydrocodone has some activity but works majorly through its active metabolite hydromorphone. Codeine is a prodrug for its more active metabolite, morphine, and morphine-6-glucuronide.

Woman is about to take painkillers.

Codeine is commonly referred to as an opiate, which means it is a natural opioid. Both are prescribed to treat coughs, but when comparing Hydrocodone vs. Codeine cough syrup, Codeine cough syrup is considered quite mild and is even available OTC in some states, which isn’t true of any cough syrup containing the more potent drug. Codeine is also used in the management of diarrhea.

Codeine vs. Hydrocodone also have different side effects as Codeine is more likely to cause constipation and drowsiness, and the latter drug has some common side effects, which include respiratory depression and confusion. Codeine has an onset of action typically between 15-30 minutes and a half-life of approximately 3 hours.

Read more about Codeine side effects.

Both painkillers come as oral tablets, oral capsules, oral extended-release capsules as well as oral solutions.

Codeine is usually combined with aspirin, promethazine, chlorpheniramine, diphenhydramine, phenylephrine, guaifenesin, bromodiphenhydramine, and so on.

Hydromorphone vs. Hydrocodone

Both drugs are classified as opioids. They are used to relieve discomfort that is poorly controlled or unresponsive to weaker painkillers. Both drugs bind to a special type of receptor found in the CNS known as mu receptors, which changes the way your body perceives pain. When comparing the active metabolites of hydromorphone vs. Hydrocodone, the latter has some innate activity but works majorly through hydromorphone, its active metabolite.

Doctor pointing at tablets in the bottle.

When comparing the potency of hydromorphone vs. Hydrocodone, hydromorphone is the more potent of the two and is marketed as Dilaudid. It can help treat extremely severe pain caused by cancer, surgery, or broken bones. Both drugs should not be combined with alcohol, benzodiazepines, or any other CNS depressants due to the increased risk of respiratory depression, leading to a coma and even death.

Some Common Side Effects Of Both Drugs Include:

  • Nausea
  • Vomiting
  • Respiratory depression
  • Confusion

However, hydromorphone may also cause side effects, including sweating, flushing, itching, and dry mouth. Hydromorphone has an onset of action typically between 15-30 minutes and a half-life of 2.3 hours.

Both drugs come as oral tablets, oral capsules, and oral extended-release capsules. However, only hydromorphone comes also as an injectable.

Other Opioid Prescription Painkiller Alternatives

Over 200,000 Americans have died from overdoses related to prescription opioids since 1999 as they are very addictive. There are several alternative prescription painkillers that differ both in potency and side effects.

Oxycodone (Oxycontin)

Both these drugs are semi-synthetic opioids, with OxyContin being the extended-release form of Oxycodone. Both treat discomfort to an equal extent, taking effect within half an hour on average. Oxycodone is associated with constipation more frequently.


Percocet is a combination of Oxycodone and acetaminophen. It is also an opioid narcotic pain reliever, but the addition of acetaminophen improves pain relief. Percocet comes with specific side effects, including shock, paralytic ileus, and severe skin reactions.


These two drugs have comparable rewarding properties in the conditioned place preference paradigm (CPP) in rats. They both exert their effects through signal transduction pathways known to be involved in reinforcement and reward.

These findings indicate that these drugs can produce rewarding and euphoric effects to an equal extent. This would imply that they would be equally effective in managing discomfort and equally addictive.

Hydrocodone VS Non-Opioid Over-the-Counter Painkillers

Pain management involves a stepwise guide known as the WHO analgesic ladder. The first analgesics which should be used in the treatment of most types of pain are ideally over-the-counter (OTC) non-opioid analgesics such as acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) such as diclofenac.

Pharmacist giving pills to a patient.

These are safer alternatives to opioids due to their safer side effect profile and lack of addictive potential. Opioids are only introduced in situations when OTC non-opioid analgesics cannot control the discomfort.

Hydrocodone vs. Tylenol

When a person is suffering from pain, the WHO recommends starting with an OTC painkiller such as Tylenol or Advil and proceeding to stronger options only if this has proved ineffective. Tylenol is the brand name of acetaminophen (or paracetamol) and also functions as an antipyretic. It is a weaker analgesic. The exact mechanism of acetaminophen action is not well understood, but it is suspected that it inhibits prostaglandin production.

Naproxen vs. Hydrocodone

Naproxen is a nonsteroidal anti-inflammatory drug (NSAID) used in the treatment of mild to moderate pain, fever, and inflammatory conditions. Comparing the analgesic potency of Naproxen vs. Hydrocodone shows that Naproxen is a weaker analgesic than the latter but has no risk of potential physical addiction or respiratory depression. It works by blocking the body’s ability to produce pain modulators known as prostaglandins by blocking a key enzyme in their production known as cyclooxygenase (or COX).

Other Cough Suppressants

Cough syrup containing this painkiller is frequently used in patients with severe pain and cough, like those with a cough from lung cancer.

Alternatives to it include guaifenesin, an expectorant that helps loosen congestion in the throat and chest, alleviating symptoms, and pseudoephedrine, a decongestant that constricts blood vessels in nasal pathways. A stuffy nose can be caused by dilated blood vessels. A combination of all three works best.

Young woman suffering from cough.

Another option is dextromethorphan (DM), a cough suppressant often sold in combination with antihistamines, expectorates, or decongestants.

Getting Help With Opioid Addiction

As mentioned, Hydrocodone is a very addictive drug. If one feels that they have been abusing it for too long and become dependent, perhaps the time for Hydrocodone addiction treatment has come. It is not advised to quit the drug cold-turkey, because Hydrocodone withdrawal can be extremely severe and requires medical assistance.

Treatment for patients with symptoms of opioid addiction can be administered through inpatient or outpatient programs. These programs are available at Methadone clinics across the country. A qualified addiction expert will show how to stop the drug use and find a suitable, less dangerous pain management alternative.

Page Sources

  1. Center for Disease Control and Prevention. Opioid Overdose.
  2. Hydrocodone and Morphine Possess Similar Rewarding Effects and Reduce ERK and CREB Phosphorylation in the Nucleus Accumbens. John M. Tenayuca and Arbi Nazarian. July 2012.
  3. Comparative efficacy of 4 oral analgesics for the initial management of acute musculoskeletal extremity pain. Andrew Chang, M.D; David Esses, M.D; E. John Gallagher, M.D. May 2015.
  4. Hydrocodone versus Codeine in acute musculoskeletal pain. M.A Turturro, P.M Paris, D.M Yealy, J.J Menegazzi. Ann Emerg Med. October 1991.
  5. Pharmacology of Tramadol. P. Dayer, J. Desmeules, L. Collart. 1997.
  6. WHO Analgesic Ladder. Anekar AA, Cascella M. May 2020.
  7. Naproxen. Brutzkus JC, Shahrokhi M, Varacallo M. May 2020.
  8. Metabolism of Tramadol in Postoperative Surgical Patients (METRAS). Josip Juraj Strossmayer University of Osijek. March 2020.
  9. Tramadol Pill Alone May Cause Serotonin Syndrome. Hamed Aminiahidashti, Sajjad Shafiee, Seyed Jaber Mousavi, and Gholamhossein Hajiaghae. April 2016.
  10. Opioid Metabolism. Howard S. Smith, MD. July 2009.
  11. Fioricet with Codeine C-III (Butalbital, Acetaminophen, Caffeine, and Codeine Phosphate) Capsules Rx only. October 2013.
  12. Hydromorphone. Abi-Aad KR, Derian A. July 2020.

Published on: September 21st, 2018

Updated on: April 30th, 2024

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