Tramadol

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DRUGS
Tramadol

Tramadol is a centrally acting analgesic with a unique, dual mechanism of action, within the central nervous system (CNS). It exerts agonistic properties at opiate receptors and interferes with neurotransmitter reuptake. Tramadol also binds weakly to µ-opiate receptors, blocking pain signal transmission to brain. Tramadol has been effective in controlling post-operative pain, but is not suitable as an adjunct to anesthesia because of low sedative properties. 

Introduction

Tramadol is a centrally acting analgesic with a unique, dual mechanism of action, within the central nervous system (CNS). It exerts agonistic properties at opiate receptors and interferes with neurotransmitter reuptake. Tramadol also binds weakly to µ-opiate receptors, blocking pain signal transmission to brain. Tramadol has been effective in controlling post-operative pain, but is not suitable as an adjunct to anesthesia because of low sedative properties.

Pharmacological Class: Opioid analgesic

Indications

  • Moderate to Severe Pain
  • Pain
  • Acute Musculosketetal Pain

Pharamcological Action

Tramadol is a centrally-acting opioid analgesic. Although its mode of action is not completely understood, from animal tests, at least two complementary mechanisms appear applicable: binding of parent and M1 metabolite to μ-opioid receptors and weak inhibition of reuptake of norepinephrine and serotonin. Opioid activity is due to both low affinity binding of the parent compound and higher affinity binding of the O-demethylated metabolite M1 to μ-opioid receptors. The relative contribution of both tramadol and M1 to human analgesia is dependent upon the plasma concentrations of each compound. Tramadol is known to inhibit reuptake of norepinephrine and serotonin in vitro, as some other opioid analgesics. These mechanisms may contribute independently to the overall analgesic profile of tramadol. 

Dosage

  • Adult dose: 50 to 100 mg orally every 4 to 6 hours as needed for pain
  • Pediatric dose: 1 to 2.5 mg/kg orally every 8 hours as needed for pain

Pharmacokinetics

Tramadol absorption is found to be 34% ±34. Volume of distribution is found to be 2.7 l/kg and plasma protein binding is 20%. Renal Excretion accounts for 30% (unchanged) 60% (as metabolite) and plasma half life is 6.3 hours.

Contraindications

  • Contraindicated in patients who are hypersensitive to opioids.
  • Contraindicated in situations where opioids are contraindicated including acute intoxication with any of the following: alcohol, hypnotics, centrally acting analgesics, opioids or psychotropic drugs. It may worsen CNS and respiratory depression in these patients.
  • Concomitant use of tramadol and MAO inhibitors (or within 14 days following discontinuation of such therapy) is contraindicated.

Drug Interactions

  • Concomitant administration of CYP2D6 and/or CYP3A4 inhibitors, such as quinidine, fluoxetine, paroxetine and amitriptyline (CYP2D6 inhibitors), and ketoconazole and erythromycin (CYP3A4 inhibitors), may reduce metabolic clearance of tramadol increasing the risk for serious adverse events including seizures and serotonin syndrome.
  • Patients taking carbamazepine may have a significantly reduced analgesic effect of tramadol hydrochloride.

Side effects

Common (affecting between 1 in10 to 1 in 100)

  • Abdominal problems (diarrhea, constipation, nausea, or stomach pain)
  • Depression
  • Skin problems (itchiness, rash, or sweating)
  • General aches and pains in the muscles and joints

Uncommon (affecting 1 in 100 to 1 in 1000)

  • Swollen joints
  • Weight changes
  • Severe headaches
  • Falling down
  • Confusion
  • Severe cough

Very rare (affecting less than 1 in 10,000)

  • Blisters under the skin
  • Blood in the urine
  • Chest pain
  • Convulsions
  • Seizures
  • Darker urine
  • Fainting
  • Numbness in the extremities
  • Yellowed eyes or skin

Precautions

  • In patients with pre-existing kidney disease, liver disease, seizure disorder, lungs disease, history of drug dependency or have any allergy.
  • During pregnancy or lactation
  • When taking medications such as tranquilizers, hypnotics or other opiate containing analgesics
  • In patients with acute abdominal conditions undergoing clinical assessment

Clinic Evidence

  • Tramadol is a centrally acting analgesic which is structurally related to codeine and morphine. It provides postoperative pain relief comparable to pethidine. The analgesic efficacy of tramadol can be improved by combination with a non-opioid analgesic. It is an effective and well tolerated agent to reduce pain resulting from trauma, renal or biliary colic and labour. It is also used for managing chronic pain of malignant or nonmalignant origin, particularly neuropathic pain. Tramadol produces less constipation and dependence than equianalgesic doses of strong opioids.
  • Tramadol efficacy for managing moderate to severe postoperative pain has been demonstrated in both inpatients and day surgery patients. Unlike other opioids, tramadol has no clinically relevant effects on respiratory or cardiovascular parameters. It may prove particularly useful in patients with poor cardiopulmonary function, including elderly, obese and smokers, in patients with impaired hepatic or renal function, and in patients in whom nonsteroidal anti-inflammatory drugs (NSAIDs) are not recommended or need to be used with caution. Parenteral or oral tramadol has proved to be an effective and well tolerated analgesic agent in the perioperative setting.
  • Tramadol is effective in different types of moderate-to-severe acute and chronic pain, including neuropathic pain, low back pain, osteoarthritis pain and breakthrough pain. It also causes fewer opioid-type adverse effects like, nausea, drowsiness, vomiting, dry mouth and constipation. Although trials in literature demonstrate immune-stimulating effects of tramadol, there are also trials suggesting immunosuppressive effects that are lesser than morphine. Owing to its pharmacological properties, tramadol is more appropriate than NSAIDs for patients suffering from gastrointestinal and renal problems. Besides its proven clinical efficacy, tramadol is a safe drug as respiratory depression, cardiovascular side effects, drug abuse and dependence are of minor clinical relevance, unlike some other opioids.

References

  • Grond S1, Sablotzki A. Clin Pharmacokinet. 2004;43(13):879-923.
  • Scott LJ1, Perry CM. Drugs. 2000 Jul; 60(1):139-76.
  • Keskinbora K1, Aydinli I. Agri. 2006 Jan; 18(1):5-19.
  • Drug Information System
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