Drug use
Tramadol hcl is a centrally acting non-narcotic analgesic that is indicated for the treatment of moderate or moderately severe pain. The analgesic effect of this medicine is thought to be produced by its action as an agonist at the mu opioid receptor and by inhibiting the reuptake of norepinephrine and serotonin in the CNS. It was originally marketed in 1977 in Germany and is now available in over 70 countries. Due to its mechanism of action, its place in therapy may be for patients who are more susceptible to adverse gastrointestinal effects. Although little evidence of abuse has been shown in foreign experience, tramadol should not be used in patients with a history of drug abuse or addiction to opioids.
Tramadol hcl adverse effects
The most common adverse effects reported with this medicine use in phase IV trials involved the central nervous system and the gastrointestinal tract. They included dizziness/vertigo (26%), headache (18%), somnolence (16%), central stimulation (7%), and euphoria. Gastrointestinal side effects that were reported included nausea (24%), constipation (24%), and vomiting (18%). (3,4) The frequency of adverse effects tended to increase with longer duration of use. Seizures are a very serious side effect that have been reported with the use of this drug.
The plasma half life of tramadol and its active metabolite are 6 and 7 hours respectively. Its steady state concentrations are achieved in two days based upon 4 times a day dosing. The volume of distribution is estimated to be between 2.5-3.4 L/kg and has plasma protein binding of 20%. Tramadol is extensively metabolized after oral administration with only 30% of the drug being excreted unchanged in the urine and 60% being excreted as metabolites. The only metabolite that is pharmacologically active is the M1 metabolite which is dependent on the cytochrome P450 CYP 2D6 isoenzyme. In patients with substantial hepatic impairment the half life of both the parent compound and active metabolite increases two to three times that of normal.
The incidence of seizures in the package insert is reported to be less than 1%. However, patients with conditions that predispose them to seizures, or who take medications that can lower the seizure threshold, or who exceed the recommended daily dose of tramadol hcl (400 mg/day ) may be at an increased risk for seizures. Therefore it should not be used concomitantly with MAO inhibitors, tricyclic antidepressant compounds, neuroleptics, or selective serotonin reuptake inhibitors. Quinidine, a selective inhibitor of CYP 2D6 isoenzyme, results in increased concentrations of tramadol and reduced concentrations of the M1 metabolite. Cimetidine, a known enzyme inhibitor does not significantly alter the metabolism of tramadol. The recommended daily dose may need to be doubled when individuals are taking the drug carbamazepine, an enzyme inducer, concomitantly with it.
Tramadol hcl toxicology
The expected symptoms of overdose are extensions of the pharmacologic effects and similar to other opioid agonists. The symptoms can include miosis, vomiting, coma, convulsions, and cardiovascular collapse. Two European case reports involving infants 5 weeks and 6 months old who mistakenly received 100 mg suppositories of tramadol were reported as having coma, miosis, respiratory depression, and convulsions in the 6 month old. Both infants were successfully treated with naloxone. The 6 month old required artificial ventilation, and IV diazepam along with the naloxone. In another case report, a 66 year old man received 679 mg of tramadol over 3.4 hours by infusion for surgical anesthesia. Six hours after the infusion the man presented with drowsiness, constricted pupils, and respiratory depression. The patient was intubated and respirations improved. There is one report of spontaneous respiratory depression following the administration of 75 mg of oral tramadol to an elderly patient with preexisting respiratory, cerebral, and coronary insufficiency.
In a prospective case series between 10/95 to 8/96 seven poison centers evaluated data on tramadol hcl overdoses alone. From 87 cases the most commonly reported side-effects were neurologic in nature. They included lethargy (30%), agitation (10%), dizziness (9%), seizures (8%), coma (5%), confusion (3%), respiratory depression, ataxia (2%), and diplopia (1%). The cardiovascular and gastrointestinal side-effects noted were tachycardia (13%), hypertension (5%), nausea (14%), and vomiting (6%).
