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

It is well accepted that long-term administration of opioids results in a dose-related constipation. No data so far have demonstrated conclusively whether such constipation is also seen after intake of a controlled release formulation. It was therefore of interest to evaluate whether increasing doses of a controlled release formulation of dihydrocodeine (DHC, CAS 125-28-0) after oral administration also induces a dose-related increase in constipation. Additionally, it was of interest to study whether such a peripheral opioid-related side effect is also seen in another, central receptor-mediated effect, the constriction of the pupil, at clinically relevant doses. Twelve volunteers were given controlled release DHC (60 and 120 mg, respectively) or placebo orally within a randomized, double-blind cross-over study. In order to determine the degree of constipation, oro-cecal 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, peripherally and centrally mediated effects were compared to placebo. DHC at both dosages induced a significant (p < 0.01) prolongation of oro-cecal transit time when compared to placebo. However, prolongation of oro-cecal transit was not significantly longer when comparing the lower (60 mg) with the higher dose (120 mg). DHC also induced a significant (p < 0.005) depression of the pupillary light reflex from 53.9 mm (control) to 8.3 and 7.4 mm, respectively. Similar to intestinal transit, the pupillary light reflex was not significantly different among the two doses of DHC. Also, both dosages induced a similar amount of side effects. Tiredness and dry mouth were reported in 80% after both doses while vertigo was reported in 5% and 1% complained of headache. None of the volunteers reported nausea or emesis. It is concluded that opioid receptor sites, which are located in the plexus myentericus of the intestinal wall, are responsible for the delay in propulsion. Because of the controlled release of a fixed amount of DHC over time there is constant binding of the ligand followed by a constant conformational change of peripheral and central receptor sites. Thus constant release induces no dose-related increase in oro-cecal transit and inhibition of the pupillary light reflex.
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PMID:Dose-related effects of controlled release dihydrocodeine on oro-cecal transit and pupillary light reflex. A study in human volunteers. 1121 27

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