Ultram - Tramal Description : Each Tramal Retard tablet also contains the following excipients: Microcrystalline cellulose, methylhydroxypropylcellulose, colloidal anhydrous silica, magnesium stearate, lactose, polyethylene glycol, propylene glycol, talc and titanium dioxide (E171). Tramadol HCl is (1RS; 2RS) 2-(dimethylaminomethyl)-1-(m-methoxyphenyl)-cyclohexanol hydrochloride. Molecular Formula: C16H25O2N?HCl. MW: 299.8.

Ultram - Tramal Actions : Pharmacology: Tramadol is a centrally acting opioid analgesic. It is a nonselective pure agonist at mc, ? and ? opioid receptors with a higher affinity for the mc receptor. Other mechanisms which contribute to its analgesic effect are inhibition of neuronal re-uptake of noradrenaline and enhancement of serotonin release. Tramadol has an antitussive effect. In contrast to morphine, analgesic doses of tramadol over a wide range have no respiratory depressant effect. Also, gastrointestinal motility is not affected. Effects on the cardiovascular system tend to be slight. The potency of tramadol is reported to be 1/10-1/6 that of morphine. The onset of the analgesic effect of tramadol HCl is rapid and the effect lasts for several hours. Tramadol HCl is a potent drug and should not be used for minor pain. It does not have an anti-inflammatory effect. Tramadol HCl has an analgesic effect in all the usual test models for centrally acting analgesics. On parenteral administration, the intensity of the effect is equivalent to that of other opioid analgesics, eg pentazocine and pethidine. On oral administration, tramadol HCl is practically as effective as on parenteral application. The onset of activity is rapid and the duration of the effect is similar to that of morphine. Tramadol HCl is a pure opiate agonist. The morphine antagonist, naloxone, neutralizes the analgesic effect of tramadol HCl. Pharmacokinetics: Tramal: After oral administration, about 90% of the active substance is absorbed. The absolute bioavailability of oral tramadol is about 68% and about 79% on rectal administration. Peak plasma concentrations are reached about 2 hrs after an oral dose. The high apparent total volume of distribution is proof of the tissue affinity of the active substance. Serum protein-binding is low (about 20%). The elimination half-life in the terminal phase is 6 hrs, with about 1/4-1/3 of the active substance appearing unchanged in the urine. One of the metabolites is pharmacologically active, but the concentration in the blood is lower than that of tramadol HCl itself. Excretion: Tramadol HCl and its metabolites are almost completely eliminated via the kidneys. Tramal Retard: More than 90% of Tramal Retard is absorbed after oral administration. The mean absolute bioavailability is approximately 70%, irrespective of the concomitant intake of food. The difference between absorbed and nonmetabolized available tramadol is probably due to the low first-pass effect. The first-pass effect after oral administration is a maximum of 30%. Tramadol has a high tissue affinity (V?,? = 203 ? 40 L). It has a plasma protein-binding of about 20%. After administration of Tramal Retard 100 mg, the peak plasma concentration Cmax = 141 ? 40 ng/mL is reached after 4.9 hrs. Tramadol passes the blood-brain and placental barriers. Very small amounts of the substance and its O-desmethyl derivative are found in the breast milk (0.1% and 0.02%, respectively of the applied dose). Elimination half-life t?,? is approximately 6 hrs, irrespective of the mode of administration. In patients >75 years, it may be prolonged by a factor or approximately 1.4. In humans, tramadol is mainly metabolized by means of N- and O-demethylation and conjugation of the O-demethylation products with glucuronic acid. Only O-desmethyltramadol is pharmacologically active. There are considerable interindividual quantitative differences between the other metabolites. So far, 11 metabolites have been found in the urine. Animal experiments have shown that O-desmethyltramadol is more potent than the parent substance by the factor 2-4. Its half-life t?,? (6 healthy volunteers) is 7.9 hrs (range 5.4-9.6 hrs) and is approximately that of tramadol. Tramadol and its metabolites are almost completely excreted via the kidneys. Cumulative urinary excretion is 90% of the total radioactivity of the administered dose. In cases of impaired hepatic and renal function, the half-life may be slightly prolonged. In patients with cirrhosis of the liver, elimination half-lives of 13.3 ? 4.9 hrs (tramadol) and 18.5 ? 9.4 hrs (O-desmethyltramadol), in an extreme case 22.3 and 96 hrs, respectively, have been determined. In patients with renal insufficiency (creatinine clearance <5 mL/min) the values were 11 ? 3.2 hrs and 16.9 ? 3 hrs, in an extreme case 19.5 and 43.2 hrs, respectively. Tramadol has a linear pharmacokinetic profile within the therapeutic dosage range. The relationship between serum concentrations and the analgesic effect is dose-dependent, but varies considerably in isolated cases. A serum concentration of 100-300 ng/mL is usually effective.