Comparative Analysis Between Tramadol and Ibuprofen

tramadol and ibuprofen

Both of these drugs Tramadol and ibuprofen were a giant leap in the advancement of medicine. They both work as pain relievers but have different potency levels, therefore, they are prescribed in different diseases. This will be a comparative analysis between Tramadol and Ibuprofen. Both belong to a different class of drugs. One being opioid and the other is an NSAID respectively. Following will be a step by step comparison of both drugs to establish which is ideal for a specific condition.

Mode of Action


Tramadol produces analgesic effects by a number of actions. It affects the noradrenergic system, the serotonin system, and the opioid receptor system. Some of the effects are listed below:

  • Tramadol has an agonist effect on the µ-opioid receptor. (MOR)
  • It is also a serotonin reuptake inhibitor (SRI) and norepinephrine reuptake inhibitor.
  • It also antagonizes serotonin 5HT-2C receptor.
  • Tramadol is also an M1 and M3 muscarinic acetylcholine receptor antagonist and an α-7 nicotinic acetylcholine receptor antagonist.

Lastly, all these effects cumulatively make tramadol an excellent analgesic for moderate and severe pain.


Ibuprofen is a non-steroidal anti-inflammatory drug. It primarily works by inhibiting the cyclooxygenase enzymes, 1 and 2. Therefore arachidonic acid is not converted in prostaglandin H2. Simultaneously causing the inhibition of the production of prostaglandin. It is the mediator of pain, swelling, and fever.


Tramadol with ibuprofen

Tramadol and ibuprofen are administered as a racemic mixture. Ibuprofen ‘s R-enantiomer undergoes extensive interconversion to the S-enantiomer in-vivo. Whereas tramadol positive enantiomer inhibits serotonin reuptake while the negative enantiomer inhibits noradrenaline reuptake, by binding to and blocking the transporter. Both of these enantiomers are the µ-opioid receptor agonists and its M1 metabolite.



Tramadol is an opioid derivative hence it can be addictive and is only given in serious conditions. It is prescribed for moderate to an extreme; both, acute and chronic pain. Tramadol produces an analgesic effect in an hour. It has about one-tenth potency of morphine. Though tramadol has evidence to be beneficial as the second choice of drug for the treatment of fibromyalgia. The active metabolite is desmethyl tramadol. Its metabolism depends on cytochrome P26 in the liver. So people with specific variants of it genetically might not have a better effect on them.


ibuprofen medication is used to treat fever. It is beneficial for mild to moderate pain including post-surgery pain relief. This drug is also favorable for menstrual pain, headache, dental pain or even kidney stone pain. Ibuprofen helps in inflammatory disorders like rheumatoid arthritis, osteoarthritis or pericarditis, etc.

Side Effects


Tramadol is an addictive drug with various side effects. They are usually physiological and in some cases can also be psychological. Some of them are listed below:

  • Indigestion
  • Dry Mouth
  • Vertigo
  • Vomit
  • Constipation

Tramadol also causes withdrawal syndrome after abrupt interruption after prolonged use. These are some of the psychiatric symptoms which include:

  • Numbness
  • Hallucination
  • Paranoia
  • Anxiety
  • Panic Attacks


Even though Ibuprofen is considered to be one of the safest OTC NSAIDs, it can cause harm. Prolong unsupervised use can an ample amount of side effects. These adverse effects include:

  • Indigestion
  • Constipation
  • Elevated Blood Flow
  • Rashes
  • Urinary Retention

Similar Side Effects

Despite having dissimilar potencies and indication, they still have some generalized yet similar side effects. These side effects include:

  • Nausea
  • Headache
  • Constipation
  • Abdominal Discomfort
  • Dizziness

Drug Interaction and Overdose

ibuprofen interactions

It’s also necessary to know that tramadol and ibuprofen can be used together. Ibuprofen is considered a weaker analgesic compared to tramadol. However, it can be used with tramadol to target the pain from a different angle.

Tramadol Interactions

Any drug which has a tendency to inhibit CYP2D6 may interact with tramadol. Tramadol can also interact with medications with a similar mechanism of action. It can interact with other serotonergic medications. These medications include cold and cough medications, SNRIs or serotonin inhibitors, etc. Tramadol can also act as an opioid agonist. Additionally increasing the risk of side effects of opioid analgesics if administered with them.


An overdose of tramadol can cause depression, addiction or even seizures. There have been reports of death regarding tramadol overdose. There were 253 deaths in the U.K in 2013.

Ibuprofen Interactions

Consuming alcohol with ibuprofen can profoundly elevate the chance of gastrointestinal blood loss. FDA officials claim that ibuprofen interacts with low dose aspirin. Hence it reduces the effectivity of aspirin. It’s best to take the respective medicine with a 30-minute interval. However, Ibuprofen is safe to administer with paracetamol in children.


Ibuprofen overdose is a common thing. This can be because of them being an OTC drug. Most symptoms include,

  • Dizziness
  • Nausea
  • Vomiting
  • Abdominal Pain
  • The High Blood Level of Potassium
  • Atrial Fibrillation
  • Bradycardia
  • Hepatic and Kidney Damage

In other severe cases, an ibuprofen overdose can lead to a state of comatose or even heart attack. Although it is vital to decontaminate the stomach in case of an ibuprofen overdose.

What’s New?

Tramadol was initially discovered in 1963 and was first brought in commercially in 1977. Meanwhile, Ibuprofen was discovered in 1961 and was available in the U.S.A by 1974. Ever since a lot of research has been in progress and some recent updates need to be brought in light.

Tramadol Is Associated With Elderly People Hip Fracture

According to a 2020 research, geriatric patients with pain medication, tramadol were more prone to getting pelvic cracking than other medications like codeine or commonly used NSAIDs.

Another study recently published in the “Journal of bones and mineral research” involved profound data involving 146,957 patients in the United Kingdom above the age of 50. The patients used tramadol during 2000 – 2017 for non-cancer related pain. They had no history of pelvic fractures or opioid use disorder. The same study was held out for codeine and naproxen with similar circumstances.

The primary outcome of the study was that the incidence of hip fractures over 1 year. The risk was higher for tramadol as compared to codeine and naproxen.

The numbers stated 517 cases of fracture in the tramadol cohort and 402 cases in the codeine cohort. Likewise, the risk was higher for tramadol as compared to naproxen.


There has been a recent study by a Canada based Aurin biotech research group under the supervision of Dr. Patrick McGeer. He is also the CEO of the same company suggests that a dose of ibuprofen daily can prevent the initiation of Alzheimer’s disease.

In 2016, Dr. McGeer and his team developed a saliva test which enabled them to diagnose Alzheimer’s before it’s symptoms appear. Furthermore, It also helps to find out whether the person will have Alzheimer’s in the future or not. The test is based on measuring the concentration of Alberta 42 secreted in saliva. In most people, the rate of Alberta 42 production is almost the same but if it is two or three times higher, those individuals will most probably suffer from Alzheimer’s.

This study suggests that if Alzheimer’s is predicted 10 years before the symptoms appear, There is a probability to treat it. Hence giving us a chance to start a precautionary step like administering ibuprofen. Unfortunately, most clinical trials have focused on patients after mild to moderate symptoms appear. Therefore if we try to treat it long before it develops, it can lead to a direction where a cure might be possible.

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