Ondansetron Opioids

B. Two medicines, ipecac and apomorphine, induce vomiting. Metoclopramide is a prokinetic with antiemetic properties and therefore would have the opposite of the desired effect. Morphine is an opioid with analgesic and sedating properties. Promethazine and ondansetron are also antiemetics, not emetics. 

The 5-HT3 receptor is the only monoamine neurotransmitter receptor that functions as a lig-and-gated ion channel, controlling the flux of Na-i- and K+ ions. 5-HT3 receptors are located on parasympathetic nerve terminals in the gastrointestinal tract, and high densities are found in areas of the brain associated with the emetic response, such as the area postrema. The antiemetic effects of 5-HT3 antagonists, such as ondansetron, result from actions at these sites. 5-HT3 receptors in the dorsal horn of the spinal cord have been implicated in nociception and development of new 5-HT3 receptor-related compounds may have potential as non-opioid, non-addictive analgesics. 

Ondansetron is well tolerated by patients but may be less effective if vomiting is established or if the emesis is due to opioid analgesia. A number of comparative studies with other antiemetics have appeared in the literature and ondansetron appears to be more effective than some of these drugs. However differences in efficacy from some older drugs are not always large, and advantage may lie more in a lesser side-effect profile of 5-HT3 antagonists. 

Like other opioids, fentanyl can cause pruritus. Prophylactic intravenous ondansetron 8 mg with hyperbaric bupivacaine 7-10 mg and fentanyl 25 pg significantly reduced the incidence of intrathecal fentanyl-induced pruritus in 125 patients undergoing knee arthroscopy or urological surgery in a randomized, double-blind, placebo-controlled trial (17). The incidence of pruritus was 39% with ondansetron and 68% with placebo. 

Dimitriou V, Voyagis GS, Kyriakides K. Opioid-induced pruritus repeated vs single dose ondansetron administration in preventing pruritus after intrathecal morphine. Br J Anaesth 1999 83(5) 822-3. 

Ondansetron Alcohol Ondansetron is a serotonin 5-HT3 receptor antagonist, with low affinity for al-adrenergic, 5-HTiB, 5-HTiC, and J-opioid receptors [251]. It is used primarily to treat nausea and vomiting (antiemetic) following chemotherapy. 

Morphine appears to antagonise the effects of metoclopramide on gastric emptying. As a reduction in gastric motility occurs with all opioids they would all be expected to interact with metoclopramide, and other motility stimulants such as domperidone. However, these drugs are commonly used together and the clinical significance of such effects is not clear. Consider also Opioids + Antiemetics Ondansetron , below. 

On theoretical grounds ondansetron (a S-HTj-receptor antagonist) might be expected to decrease the effects of drugs that reduce pain transmission because serotonin (5-HT) is thought to affect pain responses via presynap-tic 5-HTj receptors in the spinal dorsal horn. This has been demonstrated for tramadol, ch is not a pure opioid and also acts by enhancing the effects of serotonin and noradrenaline (norepinephrine). However, ondansetron had no effect on alfentanil or morphine analgesia in healthy subjects. 

A placebo-controlled, crossover study in 26 healthy subjects found that both intravenous granisetron 3 mg and tropisetron 5 mg blocked the analgesic effect of a single 1 oral dose of paracetamol given 90 minutes later. The pharmacokinetics of paracetamol were unaffected by the two drugs. The interaction was thought to involve the serotonergic system, see Mechanism, in Opioids + Antiemetics Ondansetron , p.l61. 

For the treatment of nausea and vomiting ondansetron or metoclopramide is often useful. For management of constipation one should consider that tolerance does not usually develop for the constipating effects of opioids. Laxatives and/or stool softeners should be used prophylactically from the beginning of opioid therapy. Agents that increase gastrointestinal propulsion should not be used as it may increase the risk of bowel perforation, if the patient has ileus and impacted stool. 

Rung G Claybon L, Hord A, et aL The intravenous ondansetron for postsurgical opioid-induced nausea and vomiting. Anesth Analg 1997 84 832-838. 

In a prospective, randomized, doubleblind comparison of ramosetron or ondansetron in the management of opioid-induced postoperative nausea and vomiting, 94 patients received fentanyl 25 micrograms/kg in a total volume of 100 ml at a rate of 2 ml/hour and 0.5 ml per demand with a 15-minute lockout period [77 ]. Ramosetron was superior to ondansetron in preventing vomiting and reducing the severity of nausea. 

Ondansetron versus ramosetron In a double-blind, randomized study of intravenous ramosetron 0.3 mg and ondansetron 4 mg followed by 12 mg in preventing nausea and vomiting related to opioid-based patient-controUed analgesia in 94 women... 

---