Opioid Analgesics Archive

Pain Management

An analgesic (colloquially known as a painkiller) is any member of the diverse group of drugs used to relieve pain Analgesic drugs act in various ways on the peripheral and central nervous systems; they include paracetamol (acetaminophen), the non-steroidal anti-inflammatory drugs (NSAIDs) such as the salicylates, narcotic drugs such as morphine, synthetic drugs with narcotic properties such as tramadol, and various others.

In choosing an analgesic, the severity of pain and response to other medication determines the choice of agent; the WHO “pain ladder”, originally developed in cancer-related pain, is widely applied to find suitable drugs in a stepwise manner. The choice of analgesia is also determined by the type of pain: for neuropathic pain, traditional analgesia is less effective, and there is often benefit from classes of drugs that are not normally considered analgesics, such as tricyclic antidepressants and anticonvulsants.

Pain management generally benefits from a multidisciplinary approach that includes pharmacologic measures (analgesics such as narcotics or NSAIDs and pain modifiers such as tricyclic antidepressants or anticonvulsants), non-pharmacologic measures (such as interventional procedures, physical therapy and physical exercise, application of ice and/or heat), and psychological measures (such as biofeedback and cognitive therapy).

Morphine, the archetypal opioid, and various other substances (e.g. codeine, oxycodone, hydrocodone, diamorphine, pethidine) all exert a similar influence on the cerebral opioid receptor system. Tramadol and buprenorphine are thought to be partial agonists of the opioid receptors. Dosing of all opioids may be limited by opioid toxicity (confusion, respiratory depression, myoclonic jerks and pinpoint pupils), but there is no dose ceiling in patients who tolerate this.

Opioids, while very effective analgesics, may have some unpleasant side-effects. Up to 1 in 3 patients starting morphine may experience nausea and vomiting (generally relieved by a short course of antiemetics). Pruritus (itching) may require switching to a different opioid. Constipation occurs in almost all patients on opioids, and laxatives (lactulose, macrogol-containing or co-danthramer) are typically co-prescribed.

When used appropriately, opioids and similar narcotic analgesics are otherwise safe and effective, however risks such as addiction and the body becoming used to the drug can occur. Due to the body getting used to the drug often the dose must be increased if it is for a chronic disease this is where the no ceiling limit of the drug comes into play. However what must be remembered is although there is no upper limit there is a still a toxic dose even if the body has become used to lower doses.

Ultram

Online Next Day Overnight Delivery of ultram Prescription Medication

You can now buy prescription Ultram online through a licensed US pharmacy located in your region using your credit card, including the one issued by your HSA. Ultram (Tramadol) is used to relieve moderate to moderately severe pain. It also may be used to treat pain caused by surgery and chronic conditions such as cancer or joint pain. This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.

Other items in this category include: Butalbital, Tramadol, Ultracet

Click any link below to complete the health questionnaire and order form or call one of our helpful customer service representatives at 1 (888) 738-3822.

Item Name Price Click to Buy

Ultram

Ultram 50mg 30 tablets $109.95 Click to Buy
Ultram 50mg 60 tablets $159.95 Click to Buy
Ultram 50mg 90 tablets $219.95 Click to Buy


Zen Pharmacy will process your Ultram order as soon as possible. In most cases, your prescription for Ultram will be processed within one business day and shipped via FedEx overnight delivery to you. Our network of physicians and pharmacists are based and licensed in the United States so you can be confident that you are receiving only US FDA approved medications in your order. Your prescription for Ultram will be handled with care and the utmost urgency. Please contact us at 1-888-738-3822 with any questions you may have regarding your order for Ultram.

ULTRAM DRUG INFO

IMPORTANT NOTE: The following information is intended to supplement, not substitute for, the expertise and judgment of your physician, pharmacist or other healthcare professional. It should not be construed to indicate that use of the drug is safe, appropriate, or effective for you. Consult your healthcare professional before using this drug.

TRAMADOL - ORAL (TRAH-muh-dall)

COMMON BRAND NAME(S): Ultram

USES: Tramadol is used for pain relief.

HOW TO USE: Take this medication by mouth as prescribed. It is usually taken every 4 to 6 hours as needed. Use this medication exactly as prescribed. Do not increase your dose, use it more frequently or use it for a longer period of time than prescribed because this drug can be habit-forming. Also, if used for an extended period of time, do not suddenly stop using this drug without your doctor's approval. When used for extended periods, this medication may not work as well and may require different dosing. Consult your doctor if the medication stops working well.

SIDE EFFECTS: This medication may cause dizziness, weakness, incoordination, nausea or vomiting, stomach upset, constipation, headache, drowsiness, anxiety, irritability, dry mouth, or increased sweating. If any of these effects persist or worsen, inform your doctor. Notify your doctor if you develop any of these serious effects while taking this medication: chest pain, rapid heart rate, skin rash or itching, mental confusion, disorientation, seizures, tingling of the hands or feet, trouble breathing. In the unlikely event you have an allergic reaction to this drug, seek immediate medical attention. Symptoms of an allergic reaction include: rash, itching, swelling, dizziness, breathing trouble. If you notice other effects not listed above, contact your doctor or pharmacist.

PRECAUTIONS: Tell your doctor your medical history, especially of: kidney disease, liver disease, seizure disorder, lung disease, history of drug or alcohol dependency, any allergies you may have. Limit alcohol as it may add to the dizziness or drowsiness effects caused by the medication. Because this drug may make you dizzy/drowsy, use caution performing tasks requiring alertness such as driving. This medication should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor. Tramadol is excreted into breast milk. Because the effects on a nursing infant are not known, consult your doctor before breast- feeding.

DRUG INTERACTIONS: Tell your doctor of all prescription and nonprescription medications you may use, especially of: carbamazepine, narcotic pain relievers (e.g., codeine), drugs used to aid sleep, antidepressants (e.g., SSRI-types such as fluoxetine or fluvoxamine), MAO inhibitors (e.g., furazolidone, linezolid, phenelzine, procarbazine, selegiline, tranylcypromine), psychiatric medicine (e.g., nefazodone), "triptan"-type drugs, anti-anxiety drugs (e.g., diazepam), sibutramine. Also, report use of certain antihistamines (e.g., diphenhydramine) which are also present in many cough-and-cold products. Do not start or stop any medicine without doctor or pharmacist approval.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. Symptoms of overdose may include cold and clammy skin, low body temperature, slowed breathing, slowed heartbeat, drowsiness, dizziness, lightheadedness, deep sleep, loss of consciousness, or seizures.

NOTES: Do not share this medication with others.

MISSED DOSE: If you miss a dose, take it as soon as remembered; do not take it if it is near the time for the next dose, instead, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store this medication at room temperature between 59 and 86 degrees F (15 to 30 degrees C) away from heat and light. Do not store in the bathroom. Keep this and all medications out of the reach of children.

Tramadol

From Wikipedia, the free encyclopedia

Chemical structure of Tramadol
Tramadol
Systematic (IUPAC) name
rac-(1R,2R)-2-(dimethylaminomethyl)-1-
(3-methoxyphenyl)-cyclohexanol
Identifiers
CAS number 27203-92-5
ATC code N02AX02
PubChem 33741
DrugBank APRD00028
Chemical data
Formula C16H25NO2 
Mol. mass 263.4 g/mol
SMILES search in eMolecules, PubChem
Pharmacokinetic data
Bioavailability 68–72% Increases with repeated dosing.
Protein binding 20%
Metabolism Hepatic demethylation and glucuronidation
Half life 5–7 hours
Excretion Renal
Therapeutic considerations
Pregnancy cat.

C(AU) C(US)
Legal status

Prescription Only (S4)(AU) POM(UK)
Routes oral, IV, IM

Tramadol (INN) (IPA: [ˈtræməˌdɒl]) is an atypical opioid which is a centrally acting analgesic, used for treating moderate to severe pain. It is a synthetic agent, as a 4-phenyl-piperidine analogue of codeine,[1][2] and appears to have actions on the GABAergic, noradrenergic and serotonergic systems. Tramadol was developed by the German pharmaceutical company Grünenthal GmbH and marketed under the trade name Tramal. Grünenthal has also cross licensed the drug to many other pharmaceutical companies that market it under various names, some of which are listed below.

Tramadol is usually marketed as the hydrochloride salt (tramadol hydrochloride) and is available in both injectable (intravenous and/or intramuscular) and oral preparations (e.g. Zydol in UK and Australia, Ultram in U.S., Zytrim in Spain and Canada, and Calmador in Argentina). It is also available in conjunction with paracetamol (acetaminophen) as Ultracet or Tramacet.

Dosages vary depending on the degree of pain experienced by the patient. Tramadol is approximately 10% as potent as morphine, when given by the IV/IM route. Oral doses range from 50–400 mg daily, with up to 600 mg daily when given IV/IM. The 'combination' pills each contain 37.5 mg of tramadol and 325 mg of paracetamol, with the recommended dose being one or two pills every four to six hours.

Unlike most other opioids, Tramadol is not considered a controlled substance in many countries (U.S. and Canada, among others), and is available with a normal prescription. Tramadol is available over-the-counter without prescription in a few countries.[3]

Contents

Uses

Tramadol is often used to treat moderate and severe pain and most types of neuralgia, including trigeminal neuralgia.[citation needed]

It is suggested that tramadol could be effective for alleviating symptoms of depression and anxiety because of its action on GABAergic, noradrenergic and specifically serotonergic systems. However, health professionals have not yet endorsed its use on a large scale for disorders such as this.

Off-label and investigational uses

Veterinary

Tramadol is used to treat post-operative and/or chronic (e.g. cancer-related) pain in dogs.

Mechanism of action

The mode of action of tramadol has yet to be fully understood, but it is believed to work through modulation of the GABAergic, noradrenergic and serotonergic systems. The contribution of non-opioid activity is demonstrated by the analgesic effects of tramadol not being fully antagonised by the μ-opioid receptor antagonist naloxone.

Tramadol is marketed as a racemic mixture with a weak affinity for the μ-opioid receptor (approximately 1/6th that of morphine). The (+)-enantiomer is approximately four times more potent than the (-)-enantiomer in terms of μ-opioid receptor affinity and 5-HT reuptake, whereas the (-)-enantiomer is responsible for noradrenaline reuptake effects (Shipton, 2000). These actions appear to produce a synergistic analgesic effect, with (+)-tramadol exhibiting 10-fold higher analgesic activity than (-)-tramadol (Goeringer et al., 1997).

The serotonergic modulating properties of tramadol mean that it has the potential to interact with other serotonergic agents. There is an increased risk of serotonin syndrome when tramadol is taken in combination with serotonin reuptake inhibitors (e.g. SSRIs), since these agents not only potentiate the effect of 5-HT but also inhibit tramadol metabolism.

Tramadol is also thought to have some NMDA-type antagonist effects which has given it a potential application in neuropathic pain states.

Metabolism

Tramadol undergoes hepatic metabolism via the cytochrome P450 isozyme CYP2D6, being O- and N-demethylated to 5 different metabolites. Of these, M1 is the most significant since it has 200 times the μ-affinity of (+)-tramadol, and furthermore has an elimination half-life of 9 hours compared to 6 hours for tramadol itself. In the 6% of the population who have slow CYP2D6 activity, there is therefore a slightly reduced analgesic effect. Phase II hepatic metabolism renders the metabolites water-soluble and they are excreted by the kidneys. Thus reduced doses may be used in renal and hepatic impairment.

Adverse effects

The most commonly reported adverse drug reactions are nausea, vomiting and sweating. Drowsiness is reported, although it is less of an issue compared to other opioids. Respiratory depression, a common side effect of most opioids, is not clinically significant in normal doses. By itself, it can decrease the seizure threshold. When combined with SSRIs, tricyclic antidepressants, or in patients with epilepsy, the seizure threshold is further decreased. Seizures have been reported in humans receiving excessive single oral doses (700 mg) or large intravenous doses (300 mg). An Australian study finds that of 97 confirmed new-onset seizures, 8 were associated with Tramadol, and that in the authors' First Seizure Clinic, "Tramadol is the most frequently suspected cause of provoked seizures" (Labate 2005). Dosages of coumadin/warfarin may need to be reduced for anticoagulated patients to avoid bleeding complications.

Dependence

Some controversy exists regarding the dependence liability of tramadol. Grünenthal has promoted it as an opioid with a low risk of opioid dependence compared to traditional opioids, claiming little evidence of such dependence in clinical trials. They offer the theory that since the M1 metabolite is the principal agonist at μ-opioid receptors, the delayed agonist activity reduces dependence liability. The noradrenaline reuptake effects may also play a role in reducing dependence.

Despite these claims it is apparent, in community practice, that dependence to this agent does occur. This would be expected since analgesic and dependence effects are mediated by the same μ-opioid receptor. However, this dependence liability is considered relatively low by health authorities, such that tramadol is classified as a Schedule 4 Prescription Only Medicine in Australia, rather than as a Schedule 8 Controlled Drug like other opioids (Rossi, 2004). Similarly, tramadol is not currently scheduled by the U.S. DEA, unlike other opioid analgesics. Nevertheless, the Prescribing Information for Ultram warns that tramadol "may induce psychological and physical dependence of the morphine-type." In addition, there are widespread reports by consumers of extremely difficult withdrawal experiences. [citation needed]

A controlled study that compared different medications found "the percent of subjects who scored positive for abuse at least once during the 12-month follow-up were 2.5% for NSAIDs, 2.7% for tramadol, and 4.9% for hydrocodone. When more than one hit on the [dependency] algorithm was used as a measure of persistence, abuse rates were 0.5% for NSAIDs, 0.7% for tramadol, and 1.2% for hydrocodone. Thus, the results of this study suggest that the prevalence of abuse/dependence over a 12-month period in a CNP population that was primarily female was equivalent for tramadol and NSAIDs, with both significantly less than the rate for hydrocodone."

Proprietary preparations

Grünenthal, which still owns the patent to tramadol, has cross-licensed the agent to various pharmaceutical companies internationally. Thus tramadol is marketed under many trade names including: Adolan, Adolonta, Anadol, Calmador, Contramal, Crispin, Lumidol, Mandolgine, Mosepan, Nobligan, Poltram, Sintradon, Siverol, Tiparol, Toplagic, Tradol, Tradolan, Tralgit, Tramacet, Tramacip, Tramadin, Tramal, Tramahexal, Tramazac, Trama-Klosidol, Tramedo, Trodon, Ultracet, Ultram, Zaldiar, Zamadol, Zydol and Zytram.

Trivia

Footnotes

  1. ^ Dayer P, Desmeules J, Collart L (1997). "[Pharmacology of tramadol]". Drugs 53 Suppl 2: 18–24. PMID 9190321. 
  2. ^ Opioids.com
  3. ^ Erowid
  4. ^ Harati Y, Gooch C, Swenson M, et al (1998). "Double-blind randomized trial of tramadol for the treatment of the pain of diabetic neuropathy". Neurology 50 (6): 1842-6. PMID 9633738. 
  5. ^ Harati Y, Gooch C, Swenson M, et al (2000). "Maintenance of the long-term effectiveness of tramadol in treatment of the pain of diabetic neuropathy". J. Diabetes Complicat. 14 (2): 65-70. PMID 10959067. 
  6. ^ Göbel H, Stadler T (1997). "[Treatment of post-herpes zoster pain with tramadol. Results of an open pilot study versus clomipramine with or without levomepromazine]" (in French). Drugs 53 Suppl 2: 34-9. PMID 9190323. 
  7. ^ Boureau F, Legallicier P, Kabir-Ahmadi M (2003). "Tramadol in post-herpetic neuralgia: a randomized, double-blind, placebo-controlled trial". Pain 104 (1-2): 323-31. PMID 12855342. 
  8. ^ Bennett RM, Kamin M, Karim R, Rosenthal N (2003). "Tramadol and acetaminophen combination tablets in the treatment of fibromyalgia pain: a double-blind, randomized, placebo-controlled study". Am. J. Med. 114 (7): 537-45. PMID 12753877. 
  9. ^ Lauerma H, Markkula J (1999). "Treatment of restless legs syndrome with tramadol: an open study". The Journal of clinical psychiatry 60 (4): 241-4. PMID 10221285. 
  10. ^ Sobey PW, Parran TV, Grey SF, Adelman CL, Yu J (2003). "The use of tramadol for acute heroin withdrawal: a comparison to clonidine". J Addict Dis 22 (4): 13-25. PMID 14723475. 
  11. ^ Threlkeld M, Parran TV, Adelman CA, Grey SF, Yu J (2006). "Tramadol versus buprenorphine for the management of acute heroin withdrawal: a retrospective matched cohort controlled study". Am J Addict 15 (2): 186-91. DOI:10.1080/10550490500528712. PMID 16595358. 
  12. ^ Engindeniz Z, Demircan C, Karli N, et al (Jun 2005). "Intramuscular tramadol vs. diclofenac sodium for the treatment of acute migraine attacks in emergency department: a prospective, randomised, double-blind study". J Headache Pain 6 (3): 143-8. DOI:10.1007/s10194-005-0169-y. PMID 16355295. 
  13. ^ Goldsmith TB, Shapira NA, Keck PE (1999). "Rapid remission of OCD with tramadol hydrochloride". The American journal of psychiatry 156 (4): 660-1. PMID 10200754. 
  14. ^ Salem EA, Wilson SK, Bissada NK, Delk JR, Hellstrom WJ, Cleves MA (2007). "Tramadol HCL has Promise in On-Demand Use to Treat Premature Ejaculation". The Journal of Sexual Medicine (OnlineEarly Articles). PMID 17362279. 
  15. ^ King, Steven A. (2007-06-01). "NSAIDs and Cardiovascular Disease". Psychiatric Times 24 (7). Retrieved on 2007-08-01. 
  16. ^ Adams, Edgar; Breiner, Scott; Cicero, Theodore; Geller, Anne; Inciardi, James; Schnoll, Sidney; Senay, Edward; Woody, George (May 2006). "A Comparison of the Abuse Liability of Tramadol, NSAIDs, and Hydrocodone in Patients with Chronic Pain". Journal of Pain and Symptom Management 31 (5): 465-476. Retrieved on 2007-01-13. 
  17. ^ Zahlaway, Jon. "Autopsy shows ODB died of accidental drug overdose", LiveDaily, December 15, 2004. Retrieved on 2007-01-13. 

References

  • Goeringer K, Logan B, Christian G. "Identification of tramadol and its metabolites in blood from drug-related deaths and drug-impaired drivers.". J Anal Toxicol 21 (7): 529-37. PMID 9399121. 
  • Labate A, Newton M, Vernon G, Berkovic S (2005). "Tramadol and new-onset seizures.". emja: The Medical Journal of Australia 182 (1): 42-43. 
  • (2004) in Ed. Rossi S: Australian Medicines Handbook. Adelaide: Australian Medicines Handbook. ISBN 0-9578521-4-2. 
  • Shipton E (2000). "Tramadol--present and future.". Anaesth Intensive Care 28 (4): 363-74. PMID 10969362. 
  • Ultram (PDF). Ortho-McNeil. – U.S. Prescribing Information
  • McDiarmid T, Mackler L, Schneider D (January 2005). "Clinical inquiries. What is the addiction risk associated with tramadol?". J Fam Pract 54 (1): 72-3. PMID 15623411. 

External links

v • d • e
Analgesics (N02A, N02B)
Opioids Buprenorphine, Butorphanol, Codeine, Dextropropoxyphene, Diamorphine, Dihydrocodeine, Fentanyl, Hydrocodone, Hydromorphone, Ketobemidone, Levorphanol, Methadone, Morphine, Nicomorphine, Opium, Oxycodone, Oxymorphone, Pethidine (see also longer list)
Salicylic acid and derivatives Aspirin (Acetylsalicylic Acid), Diflunisal, Ethenzamide, Salicin, Salicylamide -- See also: NSAIDs
Pyrazolones Aminophenazone, Metamizole, Phenazone
Cannabinoids Cannabis, Tetrahydrocannabinol, AM404
Anilides Paracetamol (acetaminophen), Phenacetin
Others Ziconotide, Ibuprofen, Ketoprofen, Mefenamic Acid, Naproxen, Diclofenac, Flurbiprofen, Diflunisal, Indomethacin, Ketorolac, Meloxicam, Piroxicam

Ultracet

Online Next Day Overnight Delivery of ultracet Prescription Medication

You can now buy prescription Ultracet online through a licensed US pharmacy located in your region using your credit card, including the one issued by your HSA. Ultracet is a combination medicine containing tramadol and acetaminophen used to relieve pain. An opioid analgesic and acetaminophen used together may provide better pain relief than either medicine used alone. In some cases, you may get relief with lower doses of each medicine.

Other items in this category include: Butalbital, Tramadol, Ultram

Click any link below to complete the health questionnaire and order form or call one of our helpful customer service representatives at 1 (888) 738-3822.

Item Name Price Click to Buy

Generic Ultracet

Generic Ultracet 37.5/325mg 30 tablets $109.95 Click to Buy
Generic Ultracet 37.5/325mg 60 tablets $119.95 Click to Buy
Generic Ultracet 37.5/325mg 90 tablets $139.95 Click to Buy

Ultracet

Ultracet 37.5/325mg 30 tablets $109.95 Click to Buy
Ultracet 37.5/325mg 60 tablets $139.95 Click to Buy
Ultracet 37.5/325mg 90 tablets $199.95 Click to Buy


Zen Pharmacy will process your Ultracet order as soon as possible. In most cases, your prescription for Ultracet will be processed within one business day and shipped via FedEx overnight delivery to you. Our network of physicians and pharmacists are based and licensed in the United States so you can be confident that you are receiving only US FDA approved medications in your order. Your prescription for Ultracet will be handled with care and the utmost urgency. Please contact us at 1-888-738-3822 with any questions you may have regarding your order for Ultracet.

ULTRACET DRUG INFO

Description

Combination medicines containing opioid analgesics (nar-KOT-ik an-al-JEE-zicks ) such as tramadol (TRA-ma-dole) and acetaminophen (a-seat-a-MIN-oh-fen ) are used to relieve pain. An opioid analgesic and acetaminophen used together may provide better pain relief than either medicine used alone. In some cases, you may get relief with lower doses of each medicine.

Opioid analgesics act in the central nervous system (CNS) to relieve pain. Many of their side effects are also caused by actions in the CNS. When opioids are used for a long time, your body may get used to them so that larger amounts are needed to relieve pain. This is called tolerance to the medicine. Also, when opioids are used for a long time or in large doses, they may become habit-forming (causing mental or physical dependence). Physical dependence may lead to withdrawal symptoms when you stop taking the medicine.

Acetaminophen does not become habit-forming when taken for a long time but it may cause other unwanted effects, when taken in large doses including liver damage, if too much is taken.

This medicine is available only with your doctor's prescription, in the following dosage form:

    Oral
  • Tablets (U.S.)


Before Using This Medicine

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For tramadol and acetaminophen, the following should be considered:

Allergies—Tell your doctor if you have ever had any unusual or allergic reaction to tramadol, other opioid analgesics or acetaminophen. Also tell your health care professional if you are allergic to any other substances, such as foods, preservatives, or dyes.

Pregnancy—Tramadol and acetaminophen has not been studied in pregnant women. However, studies in animals have shown that tramadol and acetaminophen causes birth defects and other problems. Before taking this medicine, make sure your doctor knows if you are pregnant or if you may become pregnant.

Too much use of an opioid during pregnancy may cause the fetus to become dependent on the medicine. This may lead to withdrawal side effects in the newborn baby. Newborn seizures, symptoms of withdrawal from opioids, death of the fetus and still birth have been reported.

Breast-feeding—Tramadol and acetaminophen pass into breast milk and may cause unwanted side effects in nursing babies. It may be necessary for you to take another medicine or to stop breast-feeding during treatment. Be sure you have discussed the risks and benefits of the medicine with your doctor.

Children—Studies on this medicine have been done only in adult patients, and there is no specific information comparing use of tramadol and acetaminophen in children up to 16 years of age with use in other age groups.

Older adults—This medicine has been tested and has not been shown to cause different side effects or problems in older people than it does in younger adults.

Other medicines—Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking tramadol and acetaminophen, it is especially important that your health care professional know if you are taking any of the following:

    Tramadol and acetaminophen
  • Anticoagulants (e.g., Coumadin [blood thinners])—Tramadol and acetaminophen may increase the amount of blood thinners in your blood, which can cause problems with bleeding.
  • Alcohol and products with alcohol in them—Taking these medicines with tramadol and acetaminophen may cause problems with your liver.
    For acetaminophen:
  • Acetaminophen-containing products (e.g., Tylenol, Nyquil, Chlor-Trimeton Sinus)—Taking additional acetaminophen may increase the risk of liver problems.
    For tramadol:
  • Analgesics, opioid (e.g., codeine, morphine) or
  • Antidepressants such as tricyclic antidepressants (e.g., amitriptyline [Elavil], doxepin [Sinequan]), and selective serotonin reuptake inhibitors (e.g., citalopram [Celexa], fluvoxamine [Luvox], sertraline [Zoloft]), and medicines with Monoamine oxidase (MAO) inhibitor activity (isocarboxazid [e.g., Marplan], phenelzine [e.g., Nardil], procarbazine [e.g., Matulane], selegiline [e.g., Eldepryl], tranylcypromine [e.g., Parnate]) or
  • Neuroleptics (e.g., Thorazine, Prolixin)—Taking these medicines with tramadol may increase the possibility of seizures or convulsions.
  • Alcohol and products with alcohol in them or
  • Anesthetic medicines or
  • Central nervous system (CNS) depressants such as , narcotic pain relievers (e.g., Codeine, Darvon), phenothiazines (e.g., Thorazine, Prolixin), sedative hypnotics (e.g., Valium, Xanax), tranquilizers (e.g., Ativan, Haldol—Taking these medicines with tramadol may increase the chance of serious side effects.
  • Carbamazepine (e.g., Tegretol)— May decrease the blood levels of Tramadol, which increases the chance of serious side effects
  • Monoamine oxidase (MAO) inhibitor activity (isocarboxazid [e.g., Marplan], phenelzine [e.g., Nardil], procarbazine [e.g., Matulane], selegiline [e.g., Eldepryl], tranylcypromine [e.g., Parnate]) (taken currently or within the past 2 weeks)—Taking tramadol with these medicines may cause more of a chance for seizures. It may also cause high blood pressure, unusual heartbeats, or headache
  • Selective serotonin reuptake inhibitors (SSRI) (citalopram [e.g., Celexa], fluvoxamine [e.g., Luvox], and sertraline [e.g., Zoloft] —Taking these medicines with tramadol and acetaminophen may increase the possibility of seizures or convulsions

Other medical problems—The presence of other medical problems may affect the use of tramadol and acetaminophen. Make sure you tell your doctor if you have any other medical problems, especially:
  • Alcohol and/or other drug abuse, or history of, or
  • Convulsions (seizures), history of, or
  • Head injury, or
  • Hormonal problems or
  • Infections of the central nervous system or
  • Kidney disease or
  • Liver disease, or
  • Respiratory difficulty or troubled breathing, or
  • Severe abdominal problems—The chance of serious side effects may be increased


Proper Use of This Medicine

Take this medicine only as directed by your medical doctor or dentist. Do not take more of it, do not take it more often, and do not take it for a longer time than your medical doctor or dentist ordered. This is especially important for young children and elderly patients, who may be more sensitive than other people to the effects of analgesics. If too much of a analgesic is taken, it may become habit-forming (causing mental or physical dependence) or lead to medical problems because of an overdose. Taking too much acetaminophen may cause liver damage.

Dosing—

The dose of tramadol and acetaminophen will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of tramadol and acetaminophen. If your dose is different, do not change it unless your doctor tells you to do so.

The number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are taking tramadol and acetaminophen

  • For oral dosage form (tablets):
    • For pain:
      • Adults and adolescents 16 years and older—Take 2 tablets every 4–6 hours as needed for up to 5 days.
      • Children under 16 years of age–use and dose must be determined by your doctor.

Storage—

To store this medicine:

  • Keep out of the reach of children. Overdose of tramadol and acetaminophen is very dangerous in young children.
  • Do not store in the bathroom, near the kitchen sink, or in other damp places. heat or moisture may cause the medicine to break down.
  • Do not keep outdated medicine or medicine no longer needed. Ask your health care professional how you should dispose of any medicine you do not use. Be sure that any discarded medicine is out of the reach of children.

Precautions While Using This Medicine

The analgesic in this medicine will add to the effects of alcohol and other CNS depressants (medicines that slow down the nervous system, possibly causing drowsiness). Some examples of CNS depressants are antihistamines or medicine for hay fever, other allergies, or colds; sedatives, tranquilizers, or sleeping medicine; other prescription pain medicine or narcotics; opioids; barbiturates; medicine for seizures; muscle relaxants; or anesthetics, including some dental anesthetics. Also, there may be a greater risk of liver damage if you drink three or more alcoholic beverages while you are taking acetaminophen. Do not drink alcoholic beverages, and check with your medical doctor or dentist before taking any of the medicines listed above, while you are using this medicine.

This medicine may cause some people to become drowsy, dizzy, or less alert than they are normally. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are dizzy or are not alert.

Dizziness, lightheadedness, or fainting may occur, especially when you get up suddenly from a lying or sitting position. Getting up slowly may help lessen this problem.

Nausea or vomiting may occur, especially after the first couple of doses. This effect may go away if you lie down for a while. However, if nausea or vomiting continues, check with your medical doctor or dentist. Lying down for a while may also help relieve some other side effects, such as dizziness or lightheadedness, that may occur.

Before having any kind of surgery (including dental surgery) or emergency treatment, tell the medical doctor or dentist in charge that you are taking this medicine.

Analgesics may cause dryness of the mouth. For temporary relief, use sugarless candy or gum, melt bits of ice in your mouth, or use a saliva substitute. However, if dry mouth continues for more than 2 weeks, check with your dentist. Continuing dryness of the mouth may increase the chance of dental disease, including tooth decay, gum disease, and fungus infections.

If you have been taking this medicine regularly , do not suddenly stop taking it without first checking with your doctor. Your doctor may want you to reduce gradually the amount you are taking before stopping completely, to lessen the chance of withdrawal side effects. This will depend on which of these medicines you have been taking, and the amount you have been taking every day.


Side Effects of This Medicine
Side Effects of This Medicine

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

  • Rare
    • Burning, itching, and redness of skin; vomiting ;  chest pain;  cough; difficulty swallowing; dizziness; fast heartbeat; hives; itching; puffiness or swelling of the eyelids or around the eyes, face, lips or tongue; shortness of breath; skin rash; tightness in chest; unusual tiredness or weakness; wheezing;  seizures 

  • Symptoms of Overdose

    If you think you, or someone else may have taken an overdose, get emergency help at once. Get emergency help immediately if any of the following symptoms of overdose occur

    • Chest pain or discomfort;  convulsions ;  difficulty breathing 

Other side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. However, check with your doctor if any of the following side effects continue or are bothersome.

  • Less common
    • Abdominal pain;  aches, pains or weakness of muscles; numbness or tingling of hands, legs, and feet;  acid or sour stomach; belching; heartburn; indigestion; stomach discomfort ;  anxiety;  bloated full feeling; excess air or gas in stomach or intestines;  confusion;  constipation;  dizziness;  dry mouth;  false or unusual sense of well-being;  feeling of warmth; redness of the face, neck, arms, and occasionally the upper chest;  headache;  increased sweating;  increase in bowel movements; loose stools; soft stools;  itching skin;  loss of appetite; weight loss;  loss of strength or energy; muscle pain or weakness;  mood or mental changes;  nausea;  nervousness;  painful or difficult urination;  rash;  sleepiness or unusual drowsiness;  sleeplessness; trouble sleeping; unable to sleep;  unusual tiredness or weakness;  vomiting 

  • Rare
    • Abnormal thinking;  bloody or black, tarry stools; vomiting of blood or material that looks like coffee grounds; sever stomach pain; constipation;  blurred vision; dizziness; severe or continuing, dull headache; pounding in the ears; slow or fast heartbeat;  change in vision;  chills; cold sweats; confusion; dizziness; faintness, or light-headedness when getting up from lying or sitting position;  continuing ringing or buzzing or other unexplained noise in ears;  crying; depersonalization; dysphoria; euphoria; mental depression; paranoia; quick to react or overreact emotionally; rapidly changing moods ;  decreased awareness or responsiveness;  decrease in amount of urine;  decrease in urine volume; decrease in frequency of urination; difficulty in passing urine [dribbling]; painful urination;  depression ;  difficulty swallowing;  dizziness or lightheadedness; feeling of constant movement of self or surroundings; sensation of spinning;  drug abuse and dependence ;  fainting; fast, pounding, or irregular heartbeat or pulse; palpitations;  feeling unusually cold; shivering ;  high or low blood pressure; dizziness; lightheadedness ;  increased muscle tone;  involuntary muscle contractions;  loss in sexual ability, desire, drive, or performance; decreased interest in sexual intercourse; inability to have or keep an erection;  loss of memory; problems with memory;  loss of sense of reality;  morbid dreaming;  migraine headache;  seeing, hearing, or feeling things that are not there;  shakiness and unsteady walk; clumsiness, unsteadiness, trembling, or other problems with muscle control or coordination;  shortness of breath; difficult or labored breathing; tightness in chest; wheezing ;  swelling of tongue;  trouble in holding or releasing urine; painful urination;  unusual tiredness or weakness;  weight loss;  yellow eyes or skin 

    After you stop using this medicine, your body may need time to adjust. The length of time this takes depends on which of these medicines you were taking, the amount of medicine you were using, and how long you used it. During this time check with your doctor if you notice any of the following side effects:

  • Anxiety;  diarrhea;  fever, runny nose, or sneezing ;  gooseflesh;  increased sweating;  nausea or vomiting;  nervousness, restlessness, or irritability;  pain ;  seeing, hearing, or feeling things that are not there;  shivering or trembling;  trouble in sleeping 

Other side effects not listed above may also occur in some patients. If you notice any other effects, check with your doctor.

Tramadol

From Wikipedia, the free encyclopedia

Chemical structure of Tramadol
Tramadol
Systematic (IUPAC) name
rac-(1R,2R)-2-(dimethylaminomethyl)-1-
(3-methoxyphenyl)-cyclohexanol
Identifiers
CAS number 27203-92-5
ATC code N02AX02
PubChem 33741
DrugBank APRD00028
Chemical data
Formula C16H25NO2 
Mol. mass 263.4 g/mol
SMILES search in eMolecules, PubChem
Pharmacokinetic data
Bioavailability 68–72% Increases with repeated dosing.
Protein binding 20%
Metabolism Hepatic demethylation and glucuronidation
Half life 5–7 hours
Excretion Renal
Therapeutic considerations
Pregnancy cat.

C(AU) C(US)
Legal status

Prescription Only (S4)(AU) POM(UK)
Routes oral, IV, IM

Tramadol (INN) (IPA: [ˈtræməˌdɒl]) is an atypical opioid which is a centrally acting analgesic, used for treating moderate to severe pain. It is a synthetic agent, as a 4-phenyl-piperidine analogue of codeine,[1][2] and appears to have actions on the GABAergic, noradrenergic and serotonergic systems. Tramadol was developed by the German pharmaceutical company Grünenthal GmbH and marketed under the trade name Tramal. Grünenthal has also cross licensed the drug to many other pharmaceutical companies that market it under various names, some of which are listed below.

Tramadol is usually marketed as the hydrochloride salt (tramadol hydrochloride) and is available in both injectable (intravenous and/or intramuscular) and oral preparations (e.g. Zydol in UK and Australia, Ultram in U.S., Zytrim in Spain and Canada, and Calmador in Argentina). It is also available in conjunction with paracetamol (acetaminophen) as Ultracet or Tramacet.

Dosages vary depending on the degree of pain experienced by the patient. Tramadol is approximately 10% as potent as morphine, when given by the IV/IM route. Oral doses range from 50–400 mg daily, with up to 600 mg daily when given IV/IM. The 'combination' pills each contain 37.5 mg of tramadol and 325 mg of paracetamol, with the recommended dose being one or two pills every four to six hours.

Unlike most other opioids, Tramadol is not considered a controlled substance in many countries (U.S. and Canada, among others), and is available with a normal prescription. Tramadol is available over-the-counter without prescription in a few countries.[3]

Contents

Uses

Tramadol is often used to treat moderate and severe pain and most types of neuralgia, including trigeminal neuralgia.[citation needed]

It is suggested that tramadol could be effective for alleviating symptoms of depression and anxiety because of its action on GABAergic, noradrenergic and specifically serotonergic systems. However, health professionals have not yet endorsed its use on a large scale for disorders such as this.

Off-label and investigational uses

Veterinary

Tramadol is used to treat post-operative and/or chronic (e.g. cancer-related) pain in dogs.

Mechanism of action

The mode of action of tramadol has yet to be fully understood, but it is believed to work through modulation of the GABAergic, noradrenergic and serotonergic systems. The contribution of non-opioid activity is demonstrated by the analgesic effects of tramadol not being fully antagonised by the μ-opioid receptor antagonist naloxone.

Tramadol is marketed as a racemic mixture with a weak affinity for the μ-opioid receptor (approximately 1/6th that of morphine). The (+)-enantiomer is approximately four times more potent than the (-)-enantiomer in terms of μ-opioid receptor affinity and 5-HT reuptake, whereas the (-)-enantiomer is responsible for noradrenaline reuptake effects (Shipton, 2000). These actions appear to produce a synergistic analgesic effect, with (+)-tramadol exhibiting 10-fold higher analgesic activity than (-)-tramadol (Goeringer et al., 1997).

The serotonergic modulating properties of tramadol mean that it has the potential to interact with other serotonergic agents. There is an increased risk of serotonin syndrome when tramadol is taken in combination with serotonin reuptake inhibitors (e.g. SSRIs), since these agents not only potentiate the effect of 5-HT but also inhibit tramadol metabolism.

Tramadol is also thought to have some NMDA-type antagonist effects which has given it a potential application in neuropathic pain states.

Metabolism

Tramadol undergoes hepatic metabolism via the cytochrome P450 isozyme CYP2D6, being O- and N-demethylated to 5 different metabolites. Of these, M1 is the most significant since it has 200 times the μ-affinity of (+)-tramadol, and furthermore has an elimination half-life of 9 hours compared to 6 hours for tramadol itself. In the 6% of the population who have slow CYP2D6 activity, there is therefore a slightly reduced analgesic effect. Phase II hepatic metabolism renders the metabolites water-soluble and they are excreted by the kidneys. Thus reduced doses may be used in renal and hepatic impairment.

Adverse effects

The most commonly reported adverse drug reactions are nausea, vomiting and sweating. Drowsiness is reported, although it is less of an issue compared to other opioids. Respiratory depression, a common side effect of most opioids, is not clinically significant in normal doses. By itself, it can decrease the seizure threshold. When combined with SSRIs, tricyclic antidepressants, or in patients with epilepsy, the seizure threshold is further decreased. Seizures have been reported in humans receiving excessive single oral doses (700 mg) or large intravenous doses (300 mg). An Australian study finds that of 97 confirmed new-onset seizures, 8 were associated with Tramadol, and that in the authors' First Seizure Clinic, "Tramadol is the most frequently suspected cause of provoked seizures" (Labate 2005). Dosages of coumadin/warfarin may need to be reduced for anticoagulated patients to avoid bleeding complications.

Dependence

Some controversy exists regarding the dependence liability of tramadol. Grünenthal has promoted it as an opioid with a low risk of opioid dependence compared to traditional opioids, claiming little evidence of such dependence in clinical trials. They offer the theory that since the M1 metabolite is the principal agonist at μ-opioid receptors, the delayed agonist activity reduces dependence liability. The noradrenaline reuptake effects may also play a role in reducing dependence.

Despite these claims it is apparent, in community practice, that dependence to this agent does occur. This would be expected since analgesic and dependence effects are mediated by the same μ-opioid receptor. However, this dependence liability is considered relatively low by health authorities, such that tramadol is classified as a Schedule 4 Prescription Only Medicine in Australia, rather than as a Schedule 8 Controlled Drug like other opioids (Rossi, 2004). Similarly, tramadol is not currently scheduled by the U.S. DEA, unlike other opioid analgesics. Nevertheless, the Prescribing Information for Ultram warns that tramadol "may induce psychological and physical dependence of the morphine-type." In addition, there are widespread reports by consumers of extremely difficult withdrawal experiences. [citation needed]

A controlled study that compared different medications found "the percent of subjects who scored positive for abuse at least once during the 12-month follow-up were 2.5% for NSAIDs, 2.7% for tramadol, and 4.9% for hydrocodone. When more than one hit on the [dependency] algorithm was used as a measure of persistence, abuse rates were 0.5% for NSAIDs, 0.7% for tramadol, and 1.2% for hydrocodone. Thus, the results of this study suggest that the prevalence of abuse/dependence over a 12-month period in a CNP population that was primarily female was equivalent for tramadol and NSAIDs, with both significantly less than the rate for hydrocodone."

Proprietary preparations

Grünenthal, which still owns the patent to tramadol, has cross-licensed the agent to various pharmaceutical companies internationally. Thus tramadol is marketed under many trade names including: Adolan, Adolonta, Anadol, Calmador, Contramal, Crispin, Lumidol, Mandolgine, Mosepan, Nobligan, Poltram, Sintradon, Siverol, Tiparol, Toplagic, Tradol, Tradolan, Tralgit, Tramacet, Tramacip, Tramadin, Tramal, Tramahexal, Tramazac, Trama-Klosidol, Tramedo, Trodon, Ultracet, Ultram, Zaldiar, Zamadol, Zydol and Zytram.

Trivia

Footnotes

  1. ^ Dayer P, Desmeules J, Collart L (1997). "[Pharmacology of tramadol]". Drugs 53 Suppl 2: 18–24. PMID 9190321. 
  2. ^ Opioids.com
  3. ^ Erowid
  4. ^ Harati Y, Gooch C, Swenson M, et al (1998). "Double-blind randomized trial of tramadol for the treatment of the pain of diabetic neuropathy". Neurology 50 (6): 1842-6. PMID 9633738. 
  5. ^ Harati Y, Gooch C, Swenson M, et al (2000). "Maintenance of the long-term effectiveness of tramadol in treatment of the pain of diabetic neuropathy". J. Diabetes Complicat. 14 (2): 65-70. PMID 10959067. 
  6. ^ Göbel H, Stadler T (1997). "[Treatment of post-herpes zoster pain with tramadol. Results of an open pilot study versus clomipramine with or without levomepromazine]" (in French). Drugs 53 Suppl 2: 34-9. PMID 9190323. 
  7. ^ Boureau F, Legallicier P, Kabir-Ahmadi M (2003). "Tramadol in post-herpetic neuralgia: a randomized, double-blind, placebo-controlled trial". Pain 104 (1-2): 323-31. PMID 12855342. 
  8. ^ Bennett RM, Kamin M, Karim R, Rosenthal N (2003). "Tramadol and acetaminophen combination tablets in the treatment of fibromyalgia pain: a double-blind, randomized, placebo-controlled study". Am. J. Med. 114 (7): 537-45. PMID 12753877. 
  9. ^ Lauerma H, Markkula J (1999). "Treatment of restless legs syndrome with tramadol: an open study". The Journal of clinical psychiatry 60 (4): 241-4. PMID 10221285. 
  10. ^ Sobey PW, Parran TV, Grey SF, Adelman CL, Yu J (2003). "The use of tramadol for acute heroin withdrawal: a comparison to clonidine". J Addict Dis 22 (4): 13-25. PMID 14723475. 
  11. ^ Threlkeld M, Parran TV, Adelman CA, Grey SF, Yu J (2006). "Tramadol versus buprenorphine for the management of acute heroin withdrawal: a retrospective matched cohort controlled study". Am J Addict 15 (2): 186-91. DOI:10.1080/10550490500528712. PMID 16595358. 
  12. ^ Engindeniz Z, Demircan C, Karli N, et al (Jun 2005). "Intramuscular tramadol vs. diclofenac sodium for the treatment of acute migraine attacks in emergency department: a prospective, randomised, double-blind study". J Headache Pain 6 (3): 143-8. DOI:10.1007/s10194-005-0169-y. PMID 16355295. 
  13. ^ Goldsmith TB, Shapira NA, Keck PE (1999). "Rapid remission of OCD with tramadol hydrochloride". The American journal of psychiatry 156 (4): 660-1. PMID 10200754. 
  14. ^ Salem EA, Wilson SK, Bissada NK, Delk JR, Hellstrom WJ, Cleves MA (2007). "Tramadol HCL has Promise in On-Demand Use to Treat Premature Ejaculation". The Journal of Sexual Medicine (OnlineEarly Articles). PMID 17362279. 
  15. ^ King, Steven A. (2007-06-01). "NSAIDs and Cardiovascular Disease". Psychiatric Times 24 (7). Retrieved on 2007-08-01. 
  16. ^ Adams, Edgar; Breiner, Scott; Cicero, Theodore; Geller, Anne; Inciardi, James; Schnoll, Sidney; Senay, Edward; Woody, George (May 2006). "A Comparison of the Abuse Liability of Tramadol, NSAIDs, and Hydrocodone in Patients with Chronic Pain". Journal of Pain and Symptom Management 31 (5): 465-476. Retrieved on 2007-01-13. 
  17. ^ Zahlaway, Jon. "Autopsy shows ODB died of accidental drug overdose", LiveDaily, December 15, 2004. Retrieved on 2007-01-13. 

References

  • Goeringer K, Logan B, Christian G. "Identification of tramadol and its metabolites in blood from drug-related deaths and drug-impaired drivers.". J Anal Toxicol 21 (7): 529-37. PMID 9399121. 
  • Labate A, Newton M, Vernon G, Berkovic S (2005). "Tramadol and new-onset seizures.". emja: The Medical Journal of Australia 182 (1): 42-43. 
  • (2004) in Ed. Rossi S: Australian Medicines Handbook. Adelaide: Australian Medicines Handbook. ISBN 0-9578521-4-2. 
  • Shipton E (2000). "Tramadol--present and future.". Anaesth Intensive Care 28 (4): 363-74. PMID 10969362. 
  • Ultram (PDF). Ortho-McNeil. – U.S. Prescribing Information
  • McDiarmid T, Mackler L, Schneider D (January 2005). "Clinical inquiries. What is the addiction risk associated with tramadol?". J Fam Pract 54 (1): 72-3. PMID 15623411. 

External links

v • d • e
Analgesics (N02A, N02B)
Opioids Buprenorphine, Butorphanol, Codeine, Dextropropoxyphene, Diamorphine, Dihydrocodeine, Fentanyl, Hydrocodone, Hydromorphone, Ketobemidone, Levorphanol, Methadone, Morphine, Nicomorphine, Opium, Oxycodone, Oxymorphone, Pethidine (see also longer list)
Salicylic acid and derivatives Aspirin (Acetylsalicylic Acid), Diflunisal, Ethenzamide, Salicin, Salicylamide -- See also: NSAIDs
Pyrazolones Aminophenazone, Metamizole, Phenazone
Cannabinoids Cannabis, Tetrahydrocannabinol, AM404
Anilides Paracetamol (acetaminophen), Phenacetin
Others Ziconotide, Ibuprofen, Ketoprofen, Mefenamic Acid, Naproxen, Diclofenac, Flurbiprofen, Diflunisal, Indomethacin, Ketorolac, Meloxicam, Piroxicam