Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alcohol withdrawal syndrome (AWS) may result in nausea, vomiting, diarrhea, weakness, sweating, tremors, tachycardia, hypertension, agitation, delirium, hallucinations, seizures, and death beginning 6 hours after alcohol cessation in alcoholics. Benzodiazepines are cross-tolerant with ethanol and are considered first-line therapy for treating AWS. Chlordiazepoxide and diazepam are first metabolized by hepatic oxidation, then glucuronidation. Lorazepam and oxazepam undergo only hepatic glucuronidation. Benzodiazepine oxidation is decreased in persons with liver disease and the elderly. Accumulation with resultant excessive sedation and respiratory depression may be significant when administering chlordiazepoxide or diazepam to patients with impaired oxidative metabolism. Lorazepam and oxazepam metabolism is minimally affected by age and liver disease. Chlordiazepoxide and diazepam are erratically absorbed by the intramuscular route. Lorazepam is predictably absorbed by the intramuscular route. Oxazepam is not available in parenteral form. Lorazepam appears to be the safest empiric choice among the various benzodiazepines for treating AWS in the elderly and in patients with liver disease, or those who require therapy by the intramuscular route.
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PMID:Benzodiazepines for alcohol withdrawal in the elderly and in patients with liver disease. 870 Jul 92

cAMP-specific phosphodiesterase inhibitors display a range of activities in vitro and in vivo which suggest they may be useful in the treatment of inflammatory diseases. However, these compounds elicit a number of side-effects which may limit their therapeutic potential. Certain side-effects of PDE4 inhibitors such as emesis and gastric acid secretion are associated with their actions at a high affinity rolipram binding site (HARBS). In contrast, a number of anti-inflammatory actions of PDE4 inhibitors are better correlated with inhibition of PDE4 catalytic activity than with displacement of [3H] rolipram from HARBS. This suggests that native PDE4s in different cell-types can be discriminated pharmacologically. Although known to be associated with PDE4, the nature of HARBS is uncertain. The majority of evidence suggests it represents particular conformational states of PDE subtypes with which rolipram interacts with high potency (KD approximately 2 nM) (High-affinity PDE4, HPDE4). Rolipram is generally moderately or weakly active (IC50-200 nM-2000 nM) in inhibiting catalytic activity of the majority of crude, partially-purified or recombinant PDE4-preparations (Low-affinity PDE4, LPDE4). Solubilization or V/GSH treatment of particulate eosinophil PDE4, cAMP-dependent kinase activation of RNPDE4D3 and membrane association of HSPDE4A4 increase the potencies of some (e.g., rolipram) but not other (e.g., trequinsin) inhibitors. In eosinophils, the changes in enzyme properties brought about by solubilization result in a close correlation between the potency order of compounds in inhibiting cAMP hydrolysis and displacing [3H] rolipram from HARBS. The identification of distinct pharmacological PDE4 forms may have therapeutic consequences since it may be possible to synthesize potent inhibitors of LPDE4 with low affinity for HARBS which should, theoretically, be less emetic. Most inhibitors synthesized to date (rolipram, denbufylline nitraquazone, etc.) display high-affinity for HARBS but are much weaker in inhibiting cAMP hydrolysis. Other compounds (RP 73401, trequinsin, CDP 840) display slightly higher potency against LPDE4 or do not discriminate between the two putative PDE4 forms. Recently, inhibitors have been synthesized which are considerably more active against LPDE4 than HPDE4. Such compounds with appropriate pharmacokinetic properties may retain anti-inflammatory activity but have a reduced capacity to cause nausea and emesis and, consequently, have a wider therapeutic window than compounds currently undergoing clincial evaluation.
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PMID:Proposal for pharmacologically distinct conformers of PDE4 cyclic AMP phosphodiesterases. 921 22

The synthesis and biological activity of a novel series of 2, 2-disubstituted indan-1,3-dione-based PDE4 inhibitors are described. This structurally unique class of PDE4 inhibitors is markedly different from the known PDE4 inhibitors such as RP 73401 (2) and CDP 840 (3). Structure-activity relationship (SAR) studies led to the identification of inhibitors with nanomolar potency and oral activity in a murine endotoxemia model for TNF-alpha inhibition. Unlike other classical PDE4 inhibitors, several analogues were found to be nonemetic in a canine emesis model at intravenous doses of up to 3 mg/kg.
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PMID:Novel cyclic compounds as potent phosphodiesterase 4 inhibitors. 978 96

The antiemetic efficacy of granisetron, ondansetron and tropisetron was evaluated in patients treated with cisplatin-Adriamycin (CDP/ADM) and ifosfamide (IFO) by continuous infusion (CI). In all, 90 patients with osteosarcoma were randomly assigned to receive granisetron (2 mg/m2), or ondansetron (5.3 mg/m2), or tropisetron (3.3 mg/m2) plus dexamethasone 8 mg/m2. Chemotherapy consisted of CDP (120 mg/m2, 48-h CI) followed by ADM (75 mg/m2, 24-h CI) and then, in the second cycle, delivered 3 weeks later, IFO 15 g/m2 (120-h CI). Complete protection (CP) from emesis was obtained on 59% of the 717 days of treatment, without significant differences among the three study drugs. A significantly higher rate of CP was obtained during chemotherapy with IFO than with CDP/ ADM (69% vs 44%; P<0.0001). The rate of CP declined from the first to the last day of treatment for both CDP/ADM (61% to 27%, P<0.0001) and IFO (95% to 43%) cycles (P<0.0001). When CDP/ ADM and IFO are delivered on multiple days by CI, granisetron, ondansetron and tropisetron have the same antiemetic efficacy, which declines from the first day onward through successive days.
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PMID:Granisetron, tropisetron, and ondansetron in the prevention of acute emesis induced by a combination of cisplatin-Adriamycin and by high-dose ifosfamide delivered in multiple-day continuous infusions. 1073 60

Patient (ASA PS I-III, mean age 68 +/- 14 yr) who had undergone lower extremity surgery under spinal anesthesia were studied to determine the effect of intrathecal administration of morphine 0.1 mg on intra- and postoperative pain relief and its side effects. They were randomly divided into control (C) and intrathecal morphine (M) groups (n = 25, respectively) and received 10 mg tetracaine in 4 ml of a quarter saline with 7.5 micrograms epinephrine. Incidence of intraoperative tourniquet pain was significantly lower in M group (36.8%) than in C group (64.3%). Postoperative pain was examined in terms of the duration until the first supplemental analgesic within 24 hr. The mean duration was 7.0 +/- 4.3 hr in the control group, but 11 patients in the M group needed it within 24 hr (18.1 +/- 6.8 hr, excluding 6 patients who did not receive analgesic). Although incidences of postoperative nausea, vomiting, and itching were higher in M group than in C group, none required antiemetic or naloxone. Both groups showed no difference in postoperative respiratory depression measured by apnea monitor (Eden Trace II, Mallinkrodt Japan, Tokyo). The results suggest that a low dose of intrathecal morphine is effective on postoperative 24 hr pain relief in elderly patients and that its side effects are negligible.
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PMID:[Low dose intrathecal morphine and postoperative pain relief in elderly patients]. 1171 41