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Tramadol vs Hydrocodone

Last reviewed by Editorial Team on August 28th, 2018.

Is tramadol a controlled substance? What is Tramadol used for?

Tramadol is a Generic name for an opioid-narcotic painkiller drug that is used for the management of moderate to moderately severe acute or chronic pain.  This drug works by changing the way how brain responds to pain.

Tramadol is indicated for the treatment of postoperative, acute musculoskeletal, dental and cancer pain. Tramadol is often prescribed as an adjuvant to NSAID therapy for the management of osteoarthritis. It is also recommended for the treatment of chronic pain caused by condition called fibromyalgia.

A study from 2014 showed that administrating tramadol before surgery may be very helpful to ease condition called post-anesthesia shivering – a complication which usually develops in patients who are recovering from general anesthesia. Tramadol is available on the market in following dosage forms: tablet, extended release tablet, extended release capsule, suspension and disintegrating tablet.

Tramadol tablets are available in doses 50 mg and 100 mg and they are usually taken several times a day. Extended release tablets are available in doses of 100 mg, 150 mg, 200 mg, and 300 mg. Common Brand names for other medications on market containing tramadol are: Ultram, Ultram ER, ConZip, Ryzolt and Rybix ODT.

Ultracet is Brand name for a product that contains a combination of tramadol and acetaminophen.   FDA approved tramadol in 1995. Tramadol is originally manufactured by the drug company Janssen Pharmaceuticals under the brand name Ultram.

Is hydrocodone a narcotic? What is Hydrocodne used for?

Hydrocodone is a Generic name for an opioid drug which is synthesized from codeine. This drug is narcotic painkiller which is used orally for relieving moderate to severe pain, but it can be also used in liquid form as an antitussive agent for a relief of nonproductive cough, alone or together with expectorants or other cough suppressants.

This drug works by changing the pathway of how the brain and nervous system respond to pain. As an analgesic, hydrocodone is usually combined with acetaminophen, ibuprofen and aspirin for pain treatment. The analgesic action of hydrocodone begins in 20–30 minutes and effects last for about 4–8 hours. Hydrocodone is predominantly prescribed in the US.

According to the the International Narcotics Control Board, 99% of the worldwide hydrocodone supply in 2007 was consumed in the US. Other Brand names for products on the market containing hydrocodone as an active ingridient are: Hysingla ER, Norco, Zohydro ER, Vicodin and Robidone.

What is the difference between Tramadol and Hydrocodone in their mechanism of action?

Tramadol has two mechanisms of action. Tramadol binds to μ-opioid receptors causing inhibition of ascending pathways in the brain responsible for pain perception, but also tramadol can inhibit serotonin and norepinephrine reuptake. Tramadol may also lower seizure threshold because of its inhibitory effects on the serotonins 5-HT2C receptors.

This seizure threshold lowering may be also attributed with tramadol’s antagonism on GABA receptors in CNS when it is taken in higher doses. In addition, this drug’s active metabolite known as O-desmethyltramadol has a high affinity to the δ-opioid receptors in the brain, and by binding to these receptors it may provoke seizures in some individuals.

Hydrocodone acts as a weak agonist of mu, kappa, and delta opioid receptors in the CNS. Hydrocodone binds to opioid mu-type receptors coupled with G-protein receptors. It works as positive or negative modulator of synaptic transmission through G-proteins. Hydrocodone lowers levels of intracellular cAMP by inhibiting enzyme adenylate cyclase.

Furthermore, hydrocodone may inhibit transmission of neurotransmitters responsible for pain such as GABA, dopamine, substance P, acetylcholine, and noradrenaline. Hydrocodone can also inhibit hormone release including: vasopressin, insulin, glucagon and somatostatin.

When hydrocodone binds to kappa-receptor it closes N-type voltage calcium channels and by activating mu and delta receptors it opens calcium-dependent potassium channels. Final result is hyperpolarization of neural cell membrane and further reduces of neuronal excitability.

Differences and similarities between Tramadol and Hydrocodone

Tramadol and Hydrocodone are prescription drugs that are used to treat moderate to severe pain.  They belong to the same therapy class of drugs known as opioid analgesics or narcotics which work by changing how body feels and respond to pain.

Because these drugs are narcotics, with a high potential for abuse, they are classified as Schedule II list of drugs. Both drugs may cause physical and mental dependency if they are abused and also severe withdrawal effects.  Symptoms of withdrawal may include: agitation, sweating, running nose, nausea, vomiting and diarrhea.

tramadol compared to hydrocodone

Chemically these drugs are different.  Tramadol contain methoxybenzene structure and belongs to the class of organic compounds known as anisoles. Hydrocodone belongs to the class of organic compounds known as morphinans.

These are polycyclic molecules with a four-ring skeleton that has three condensed six-member rings which forms a partially hydrogenated phenanthrene structure, one of which is aromatic while the two others are alicyclic.

Their mechanism of action has some differences. Both drugs relieve pain by binding to opioid receptors in the brain. Tramadol is weak agonist of opioid receptors while hydrocodone is moderate agonist.

Tramadol also works by inhibiting norepinephrine and serotonin reuptake, while hydrocodone does not have those actions. However, hydrocodone may inhibit transmission of neurotransmitters such as:  dopamine, GABA, substance P, acetylcholine, and norepinephrine.

Tramadol is primarily excreted in the urine with elimination half-life time of 6.3 hours. Hydrocodone is also primarily excreted in the urine and its half-life is in range between 1.25-3 hours, which means that hydrocodone stays in the body for a shorter period of time than tramadol.

Tramadol is almost completely and rapidly absorbed after oral administration. Absolute tramadol bioavailability is about 75% after oral administration of the dose of 100 mg. Maximum plasma levels of tramadol occurs after 2 and 3 hours of administration in healthy adults.

Hydrocodone is also well absorbed from gastrointestinal tract after oral use and its bioavailability is larger than 50 %. Both drugs bind to plasma proteins. Hydrocodone’s protein binding is in range between 20- 45% while tramadol’s is 20%.

Tramadol is metabolized in the liver. The primarily metabolic reactions for tramadol are N- and O- demethylation and glucuronidation or sulfation. One metabolite known as O- desmethyltramadol, or M1 is pharmacologically active in animal models. CYP3A4 and CYP2B6 have their actions in biotransformation of tramadol to N-desmethyl-tramadol.

CYP2D6 facilitates biotransformation of tramadol to active O-desmethyl-tramadol. Hydrocodone is metabolized in the liver but also in intestinal mucosa.  CYP2D6 facilitates biotransformation of hydrocodone to hydromorphone and CYP3A4 facilitates biotransformation of hydrocodone to norhydrocodone.

Both medicines are used with efficacy in therapy of moderate to severe acute or chronic pain caused by injury, osteoarthritis, dental, post-surgical pain, cancer and others. Studies have been showed that hydrocodone is potent as morphine; however some cases report even more potency than morphine. Tramadol’s potency is about one-tenth that of morphine.

According to one randomized, double-blind study which compared the efficacy of tramadol with a combination of hydrocodone + acetaminophen for relieving acute musculoskeletal pain, it has been showed that tramadol is not as effective an analgesic as combination of hydrocodone-acetaminophen.

In addition, it has been reported that side effects such as dizziness within seven days of use but also constipation, nausea, headache and somnolence may also cause problems in both short and long treatment. The decreased analgesic effect, relatively frequent side effects and increased cost make tramadol hydrochloride a less desirable choice in the treatment of minor to moderate acute musculoskeletal pain.

Tramadol may increase levels of serotonin in the body.  If it is overdosed or taken together with other drugs such as antidepressants – SSRI or MAO inhibitor it can lead to a potentially life-threatening condition known as serotonin syndrome. This syndrome causes muscle spasms and dangerous changes in heart rate, blood pressure, and body temperature.  If it is untreated, serotonin syndrome may cause death.

Compared to hydrocodone, tramadol may also cause seizures, which is generally not typical for opioid drugs. The incidence of seizure attack is higher in patients with a history of seizures and those who combine tramadol with antipsychotics, antidepressants, alcohol, or illicit drugs.  Tramadol abuse potential is significantly less than for hydrocodone.

Tramadol Vs Hydrocodone side effects

Constipation (24-46%)Constipation (8-11%)
Nausea (24-40%)Nausea (7-10%)
Dizziness (10-33%)Vomiting (3-5%)
Vertigo (26-33%)Somnolence (1-5%)
Headache (18-32%)UTI (1-5%)
Somnolence (7-25%)Headache (4%)
Vomiting (9-17%)Fatigue (1-4%)
Agitation (7-14%)Back pain (1-4%)
Anxiety (7-14%)Dry mouth (3%)
Emotional lability (7-14%)Pruritus (3%)
Euphoria (7-14%)Tremor (3%)
Hallucinations (7-14%) Dizziness (2-3%)
Nervousness (7-14%)Peripheral edema (1-3%)
Spasticity (7-14%)URI infection (1-3%)
Dyspepsia (5-13%)Muscle spasms (1-3%)
Asthenia (6-12%)
Pruritus (8-11%)
Diarrhea (5-10%)
Dry mouth (5-10%)
Sweating (6-9%)
Hypertonia (1-5%)
Malaise (1-5%)
Menopausal symptoms (1-5%)
Rash (1-5%)
Urinary frequency (1-5%)
Urinary retention (1-5%)
Vasodilation (1-5%)
Visual disturbance (1-5%)

Which one is expensive, Tramadol or Hydrocodone?

According to drugs.com:

·         The cost for Tramadol 50 mg tablet is around $8 for a supply of 6 tablets

·         The cost for Zohydro (hydrocodone) 10 mg capsule is around $225 for a supply of 30 capsules

·         The cost for Zohydro (hydrocodone) 10 mg capsule is around $225 for a supply of 30 capsules

·         The cost for Zohydro (hydrocodone) 15 mg capsule is around $240 for a supply of 30 capsules

·         The cost for Zohydro (hydrocodone) 20 mg capsule is around $245 for a supply of 30 capsules

·         The cost for Zohydro (hydrocodone) 30 mg capsule is around $255 for a supply of 30 capsules

·         The cost for Zohydro (hydrocodone) 40 mg capsule is around $260 for a supply of 30 capsules

·         The cost for Zohydro (hydrocodone) 50 mg capsule is around $272 for a supply of 30 capsules

Prices depend on the pharmacy you visit. Prices are for cash paying customers only and are not valid with insurance plans.

Warnings and precautions during Tramadol and Hydrocodone use

  • Patient who have severe breathing problems or asthma, stomach or intestines blockage, or patients who have recently use sedatives, tranquilizers, or narcotic medications should not use tramadol and hydrocodone.
  • In some patients who are on tramadol therapy, seizures may occur. Patients who have epilepsy or other seizure disorder, or a history of head injury, some metabolic disorder or history of alcohol or drug abuse should talk with their doctors about seizure risk before taking tramadol. They should also tell their doctor if they are using certain drugs to treat migraine headaches, muscle spasms, mental illness, depression, nausea and vomiting. These drugs can increase the risk of seizures if they are used together with tramadol at the same time.
  • Tramadol and Hydrocodone will more likely provoke breathing problems in older patients (+65) with severely illness, who are malnourished, or if they have other risk factors.
  • Tramadol and Hydrocodone should never be shared with another person, especially with someone who has a history of drug abuse or addiction.
  • Pregnant patients should never use Tramadol or Hydrocodone; because their babies could gain drug dependency after birth, increasing the risk of life-threatening withdrawal symptoms. Those babies may need medical treatment for several weeks. Patients should tell doctor if they are pregnant or plan to become pregnant.
  • Tramadol can be excreted into breast milk and harm a nursing baby. Patients should not breast-feed after administration of this medicine.
  • Hydrocodone should not be used together with Monoamine oxidase (MAO) inhibitor drugs such as: isocarboxazid, linezolid, selegiline, phenelzine, tranylcypromine, and rasagiline, and also with selective serotonin reuptake inhibitors (SSRIs) such as: fluoxetine, duloxetine, paroxetine because dangerous drug interaction could occur.
  • Taking hydrocodone or tramadol with other drugs that make you sleepy, drowsy or slow your breathing can cause dangerous or life-threatening side effects. Always ask your doctor before taking hydrocodone or tramadol with a sleeping pill, other pain medicine,  muscle relaxer or medicine for anxiety, depression, or seizures.
  • These drugs should not be taken with alcohol.  Side effects from their combination may include: slowed respiration, severe nausea, respiratory failure, vomiting, chest pain (heart is not getting enough oxygen), heart attacks, liver failure, dizziness, euphoria, slurred speech, loss of consciousness and “blackouts” and death.

What happens if I mix Hydrocodone with Tramadol?

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