Ondansetron Morphine

Lidocaine Morphine Ondansetron Pravastatin Procainamide Ranitidine Sumatriptan Vigabatrin ... 

Fig. 20.11. Substrate quality obtained by comparing basolateral-to-apical with apical-to-basolateral transport of substrates in polarized cell monolayers of MDR1-transfected cell lines [86] plotted versus (A) the log of the air/water partition coefficient, or (B) H-bond energy (arbitrary units, EUh cf. text). Units of the air/ water partition coefficient were [M ]. Compound (concentrations in Ref. [86] in brackets) were clozapine (50 nM) (1) cyclosporin A (2 tM) (2) daunorubicin (3) dexamethasone (2 tM) (4) digoxin (2 pM) (5) domperidone (2 pM) (6) etoposide (7) flunitrazepam (500 nM) (8) haloperidol (50 nM) (9) ivermectin (50 nM) (10) loperamide (2 pM) (11) morphine (2 pM) (12) ondansetron...

Fig. 4.3 CSF concentration/free (unbound) plasma concentration ratios for neutral and basic drugs 1, ritropirronium 2, atenolol 3, sulpiride 4, morphine 5, cimetidine 6, meto-prolol 7, atropine 8, tacrine 9, digoxin 10, propranolol 11, carbamazepine 12, ondansetron 13, diazepam 14, imipramine 15, digitonin 16, chlorpromazine and acidic drugs, a, salicylic acid b, ketoprofen c, oxyphenbutazone and d, indomethacin compared to log D.

Rifampin is known to induce the hepatic microsomal enzymes that metabolize various drugs such as acetaminophen, oral anticoagulants, barbiturates, benzodiazepines, beta blockers, chloramphenicol, clofibrate, oral contraceptives, corticosteroids, cyclosporine, disopyramide, estrogens, hydantoins, mexiletine, quinidine, sulfones, sulfonylureas, theophyllines, tocainide, verapamil, digoxin, enalapril, morphine, nifedipine, ondansetron, progestins, protease inhibitors, buspirone, delavirdine, doxycycline, fluoroquinolones, losartan, macrolides, sulfonylureas, tacrolimus, thyroid hormones, TCAs, zolpidem, zidovudine, and ketoconazole. The therapeutic effects of these drugs may be decreased. 

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. 

Antiemetics that act on the vomiting centre have antimuscarinic (their principal mode) and anti-histaminic action (hyoscine, promethazine) they alleviate vomiting from any cause. In contrast, drugs that act on the CTZ (haloperidol, ondansetron) are effective only for vomiting mediated by stimulation of the chemoreceptors (by morphine, digoxin, cytotoxics, uraemia). The most efficacious drugs act at more than one site (Table 31.1). 

Intravenous ondansetron (4 mg at induction of anesthesia and 0.13 mg with each 1 mg bolus of morphine) has been compared with intravenous droperidol (0.5 mg at induction and 0.05 mg with each bolus of morphine) in a double-blind trial in 142 patients (22). The two regimens had similar efficacy in the prevention of postoperative nausea and vomiting. The most important adverse effect was sedation significantly more patients given droperidol (15%) had excessive sedation than patients given ondansetron (5%). 

Yeh HM, Chen LK, Lin CJ, Chan WH, Chen YP, Lin CS, Sun WZ, Wang MJ, Tsai SK. Prophylactic intravenous ondansetron reduces the incidence of intrathecal morphine-induced pruritus in patients undergoing cesarean delivery. Anesth Analg 2000 91(l) 172-5. 

In a prospective randomized, double-blind, placebo-controlled study in 100 patients scheduled for elective orthopedic surgery and presenting with pruritus induced by epidural or intrathecal morphine, intravenous ondansetron 8 mg was effective in 70% of cases and placebo in 30% (23). Ondansetron was well tolerated, did not change the degree of analgesia, and was not associated with adverse effects usually associated with ondansetron, such as headache, abdominal pain, and cardiac dysrhythmias. 

Borgeat A, Stirnemann HR. Ondansetron is effective to treat spinal or epidural morphine-induced pruritus. Anesthesiology 1999 90(2) 432-6. 

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. 

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. 

Ondansetron reduces the analgesic efficacy of tramadoi and at ieast double the dose was required in one ciinicai study. This resuited in more vomiting despite the ondansetron. In contrast, in studies in healthy subjects, ondansetron had no effect on the analgesic effects of morphine and alfentanil. 

A double-blind, placebo-controlled study in 12 healthy subjects found that a single 16-mg intravenous dose of ondansetron given 30 minutes after a single 10-mg intravenous dose of morphine did not alter the pharmacokinetics of morphine or its metabolites, morphine-3- and morphine-6-glu-curonides. The analgesic eifect of morphine (as measured by a contact thermode system) was also unaffected by ondansetron. ... 

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. 

The interaction between ondansetron and tramadol appears to be established and of clinical importance. Ondansetron may double the dose requirement of tramadol, and so result in increased emetic effects, consequently ondansetron does not appear to be the best antiemetic to use with tramadol. Although not tested, other 5-HT3-receptor antagonists would be expected to interact similarly. Ondansetron appears to have no effect on alfentanil or morphine. 

Crews KR, Murthy BP, Hussey EK, Passannante AN, Palmer JL, Maixner W, Brouwer KLR Lack of effect of ondansetron on the pharmacokinetics and analgesic effects of morphine and metabolites after single-dose morphine administration in healthy volunteers. BrJClin Phar-macol (2001)51, 309-16. 

Quinidine sulfate 600 mg, given one hour before intravenous morphine sulfate 150 mierograms/kg, did not alter morphine-induced miosis in healthy subjects. However, the same dose of quinidine given before oral morphine sulfate 30 mg (with ondansetron as an antiemetic) increased morphine-induced miosis by 56%. This increase was considered proportionate to the increase in morphine AUC (60%) and maximum level (88%). There was no change in the elimination half-life of morphine. Similarly, in another study in healthy subjects, quinidine 800 mg, given one hour before intravenous morphine 7.5 mg did not alter the respiratory depressant nor mitotic effects of morphine, and there was no change in plasma morphine or morphine glucuronide levels. ... 

Morphine-induced pruritus responded to both intravenous pentazocine 15 mg ( =104) and intravenous ondansetron 4 mg ( =104) [148. However, the recurrence rate of pruritus within 4 hours was only 12% with pentazocine compared with 32% with ondansetron. 

Common adverse events sedation, respiratory depression, pruritus, nausea/vomiting, constipation, and urinary retention, which are treated with a naloxone 40-80 pg IV bolus followed by an infusion of 50-100 pg/h. However, these adverse events are relatively less commonly observed with epidural hydromorphone than with neuraxial morphine regimens. Pruritus is treated with a naloxone infusion of 50-100 pg/h, diphenhydramine 12.5-50 mg or propofol infusion of 10 mg/h. Nausea and vomiting is best treated with either ondansetron (4-8 mg IV), low-dose droperidol (0.625-1.25 mg IV), metoclopramide (10 mg IV every 4-6 h), or transdermal scopolamine patch during the first 10 hours following administration. 

Ondansetron In a randomized, double-blind study in 150 patients undergoing abdominal surgery with patient-controlled analgesia using morphine 1.5 mg, the combination of ondansetron 30 mg and prochlorperazine 20 mg reduced postoperative nausea and vomiting in the first 24 hours after surgery but not during the next 24 hours [130 J. 

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