Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042571 (vertigo)
 7,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As has been demonstrated in binding studies the two opioids tilidine (CAS 27107-79-7)/naloxone (CAS 357-08-4) and tramadol (CAS 36282-47-0) differ in regard to their affinities to the opioid receptor site. Therefore it is of interest to evaluate whether such a difference in opioid affinity is also seen in the pharmacological effects of clinically relevant doses in man. Following institutional approval by the local ethical committee and informed consent, 12 volunteers received oral doses of tramadol (100 mg), tilidine/naloxone (100 mg) and placebo, respectively, in a randomized, double-blind cross-over design. In order to determine the degree of constipation, oral-caecal transit time was measured using the H2-exhalation test. Additionally, in order to evaluate a centrally mediated effect, the response of the pupil to light was quantified using the pupillary light reflex technique. Both, peripheral and central mediated effects were compared to placebo. Tramadol as well as tilidine/naloxone induced a significant (p < 0.05) prolongation of oral-caecal transit when compared to placebo. However, prolongation of oral-caecal transit was significantly longer in the tilidine/naloxone (p < 0.05) than in the tramadol group. Compared to tramadol, the pronounced constipating effect of tilidine/naloxone is likely to be due to the 10 fold higher affinity of that drug to the peripheral opioid receptor sites in the intestinal tract, which are responsible for normal propulsion. Such difference in binding is underlined by a central effect, the pupillary light reflex response. The amount of constriction of the iris to light was reduced after both opioids. Again, tilidine/naloxone significantly reduced (p < 0.001) the pupillary light reflex when compared to tramadol. Other side effects such as tiredness, nausea, emesis and dry mouth were more often reported after tilidine/naloxone than after tramadol (40% versus 15%; p < 0.05). Vertigo and perspiration were more often reported after tramadol than after after tilidine/naloxone (58% and 78% versus 8%; p < 0.01). All these data support the findings that while tramadol is considered an opioid, it does not mediate its main clinical relevant properties via binding at the opioid receptor. More likely, due to its monoaminergic reuptake mechanism, to a lesser extent opioid-like effects are induced.
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PMID:Effects of tramadol and tilidine/naloxone on oral-caecal transit and pupillary light reflex. 1068 12

Tramadol, a mixed mu-opioid agonist and a monoamine-reuptake blocking analgesic, has been supposed to have little effect on propulsive gastrointestinal motility. However, this has not been specifically studied in man. Following institutional approval, 18 human volunteers were given 50 mg of tramadol, tilidine/naloxone, and codeine, respectively, in a double-blind randomised cross-over design. Additionally, 12 further volunteers were given 100 mg of each opioid in a double-blind, randomised fashion, followed by measurement of gastrocoecal transit time. Gastrointestinal transit time was measured using the lactulose H(2)-breath test. A threefold increase in end-expiratory hydrogen when compared to the control value was considered the end point of gastrocoecal transit. At the low dose (50 mg) the three opioids did not differ significantly with regard to their effect on gastrointestinal motility. Gastrocoecal transit time was 90.8 (+/- 10.1 SEM) min for tramadol, 100.6 (+/- 9.8 SEM) min for tilidine/naloxone, and 104.2 (+/- 8.7 SEM) min for codeine. Doubling the dose of each opioid resulted in an increase in mean gastrocoecal transit, namely 97.8 (+/- 11.2 SEM) min for tramadol, 129.2 (+/- 12.2 SEM) min for tilidine/naloxone and 135.9 (+/- 9.2 SEM) min for codeine. The increase in gastrocoecal transit time was significant (P < 0.01) for high doses of tilidine/naloxone and codeine in contrast to the effect of the low doses. This lesser constipation effect may be due to the reduced affinity of tramadol to the mu-opioid receptor. Sedation was significantly higher for codeine after 50 mg (P < 0.05) and 100 mg (P < 0.005) than for tilidine/naloxone and tramadol. Vertigo was significantly higher after 50 mg (P < 0.05) and 100 mg (P < 0.005) of tilidine/naloxone and codeine than after tramadol. Perspiration was significantly higher after tramadol 100 mg (P < 0.005) than after tilidine/naloxone and codeine. Sedation is considered a typical symptom of analgesics interacting with centrally located opioid receptor sites. The higher incidence of perspiration after tramadol suggests that monominergic pathways may be involved in thermoregulation. In conclusion, the opioids tilidine/naloxone and codeine at the doses used significantly prolong gastrointestinal transit time in the high-dose range. Since tramadol does not induce a dose-related increase in gastrocoecal transit time, it may be a useful analgesic in patients who are prone to developing constipation during high-dose opioid therapy.
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PMID:[Constipation after tilidine/naloxone and tramadol in comparison to codeine. A dose response study in human volunteers]. 1503 43

Tramadol is a synthetic, centrally acting opioid analgesic. An extended-release tablet formulation of tramadol (tramadol ER) allows gradual release of the active drug, permitting once-daily administration. Tramadol ER administered once daily is equivalent in bioavailability to immediate-release tramadol administered four times daily, with prolonged absorption and lower peak plasma concentrations. Tramadol ER was significantly more effective than placebo in the treatment of moderate to moderately severe chronic pain in patients with osteoarthritis of the knee and/or hip in randomised, double-blind, placebo-controlled trials. In a flexible-dose trial in patients with osteoarthritis of the knee, the mean reduction from baseline in pain intensity scores over 12 weeks was significantly greater in recipients of tramadol ER than in placebo recipients. In a fixed-dose trial in patients with osteoarthritis of the knee and/or hip, the mean improvements from baseline in the pain and physical function subscale scores of the Western Ontario and McMaster Universities Osteoarthritis Index over 12 weeks were significantly greater in tramadol ER than placebo recipients. Common adverse events reported in patients with moderate to moderately severe chronic pain treated with tramadol ER 100-300 mg once daily were dizziness (excluding vertigo), nausea, constipation, somnolence and flushing.
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PMID:Tramadol extended-release tablets. 1710 Apr 15

This placebo-controlled study examined the analgesic efficacy, safety, and clinical benefit of Tramadol Contramid OAD, a once-daily formulation with both immediate- and extended-release components. Five hundred and fifty-two patients with moderate to severe pain due to osteoarthritis (OA) of the knee were randomized into this multicenter, double-blind, parallel arm study. After randomization to Tramadol Contramid OAD 100, 200, or 300 mg, or to placebo, patients' dose was titrated to the fixed randomized dose and maintained for 12 weeks. Efficacy was evaluated with the Patients' Global Rating of Pain Relief (median ratings at maintenance visits), and the Western Ontario and McMaster University (WOMAC) Pain and Physical Function subscales (percent difference, baseline to end of study) as coprimary endpoints. A responder analysis was conducted (percentage of patients who achieved a 30 percent improvement on their baseline WOMAC pain score). The difference from placebo on the median Patient Global Rating of Pain Relief at the four maintenance visits was statistically significant (200 and 300 mg: p < or = 0.001). Treatment was rated effective or very effective by 75 percent and 80 percent of patients randomized to Tramadol Contramid OAD 200 mg and 300 mg, respectively. There was a 46 percent (300-mg dose; p = 0.016) and 43 percent (200-mg dose; p = 0.05) improvement on the WOMAC pain score (baseline to the end of the study) with Tramadol Contramid OAD compared with 32percent for placebo. The responder analysis demonstrated a statistically significant difference in the percentage of patients who achieved a 30 percent improvement in their baseline WOMAC pain score for both Tramadol Contramid OAD 200 mg (65 percent; p = 0.0095) and 300 mg (65 percent; p = 0.0104) compared with placebo (50 percent). The type and incidence of adverse events were typical of tramadol (nausea, dizziness/vertigo, vomiting, somnolence, and constipation) and the intensity was mild to moderate in 87percent of patients who experienced them regardless of dose. This study shows the efficacy and safety of Tramadol Contramid OAD 200 mg and 300 mg in patients with moderate or severe pain of the knee due to OA.
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PMID:Efficacy and safety of 12 weeks of osteoarthritic pain therapy with once-daily tramadol (Tramadol Contramid OAD). 1818 82