Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vorozole is a triazole derivative which binds to the cytochrome P450 moiety of aromatase, thus causing reversible inhibition of the enzyme. Plasma estradiol levels are reduced by about 90% in postmenopausal women treated with vorozole. Phase II clinical studies found vorozole to be an effective agent for the treatment of postmenopausal women with advanced breast cancer, achieving objective responses in up to 35% of patients. In 2 large phase III studies, vorozole 2.5 mg/day demonstrated favourable clinical efficacy compared with aminoglutethimide and megestrol. Vorozole improved patients' quality of life to a greater extent than aminoglutethimide. Clinical trials to date indicate that the tolerability of vorozole is better than that of aminoglutethimide. Vorozole also appears to be at least as well tolerated as megestrol (although inappropriate bodyweight gain is more common in megestrol recipients). The most common adverse events with vorozole are hot flushes, and nausea, which are generally mild in severity.
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PMID:Vorozole. 930 82

Cholinesterase inhibitors are currently the most established treatment strategy in Alzheimer's disease. The treatment effect appears mainly to be symptomatic. Effects on progression of the disease following long term treatment, and possible neuroprotective effects, have been investigated. Delay until nursing home placement has been reported. Three cholinesterase inhibitors, tacrine, donepezil and rivastigmine, are in clinical use. Other cholinesterase inhibitors, such as galantamine (galanthamine), metrifonate, physostigmine, eptastigmine, are currently under clinical evaluation. So far the efficacy appears to be comparable between the various cholinesterase inhibitors; treatment for up to 6 months has produced an improvement in Alzheimer's Disease Assessment Scale -- Cognitive Subscale score (ADAS-cog) of between 1.8 and 4.9 in patients with Alzheimer's disease. Tacrine, donepezil, galantamine and physostigmine are reversible inhibitors of acetylcholinesterase and butyrylcholinesterase, while metrifonate is considered to be an irreversible inhibitor and rivastigmine a pseudoirreversible inhibitor. Tacrine and physostigmine have lower bioavailability, 17 to 37% and 3 to 8%, respectively, than the other cholinesterase inhibitors such as rivastigmine, galantamine and donepezil (40 to 100%). The elimination half-life is considerably longer for donepezil (70 to 80h) in comparison to most of the other cholinesterase inhibitors (0.3 to 12h). Donepezil is therefore administered once daily in comparison to rivastigmine which is administered twice daily and tacrine which is administered 4 times daily. Simultaneous food intake lowers the plasma concentration of tacrine and reduces the adverse effects of rivastigmine. Drugs like theophylline and cimetidine have been reported to change the pharmacokinetics of tacrine and donepezil. In contrast, concomitant medication with various drugs with rivastigmine does not seem to cause any drug interactions in patients with Alzheimer's disease. Tacrine, donepezil and galantamine are metabolised via the cytochrome P450 (CYP) liver enzymes. Active metabolites are known for tacrine and galantamine. Rivastigmine is not metabolised via CYP enzymes, but via esterases and is excreted in the urine. Tacrine is associated with hepatotoxicity while other cholinesterase inhibitors seem devoid this adverse effect. Increased liver enzyme values have been observed in 49% of patients with Alzheimer's disease treated with tacrine. Rechallenge with tacrine reduces the incidence of elevated liver enzyme levels. Peripheral cholinergic adverse effects are common for the cholinesterase inhibitors, with an incidence ranging between 7 to 30%. For some cholinesterase inhibitors, such as rivastigmine, the cholinergic adverse effects such as nausea, vomiting, dizziness, diarrhoea and abdominal pain can be reduced by slowing the rate of dose titration.
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PMID:Cholinesterase inhibitors in the treatment of Alzheimer's disease: a comparison of tolerability and pharmacology. 988 90

The macrolides are a well established group of antibacterials frequently used in general practice. The most frequently used macrolides in paediatric patients are erythromycin, a naturally occurring compound, and clarithromycin and azithromycin, recently developed macrolides. Overall adverse effect rates of 7 to 26% for erythromycin, 14 to 26% for clarithromycin, and 6 to 27% for azithromycin have been described in children. Adverse gastrointestinal effects, including nausea, vomiting, diarrhoea and abdominal cramps, are the most common problems in children. Allergic reactions, hepatotoxicity, ototoxicity and adverse effects involving the central and peripheral nervous systems have also been observed in children. Stevens-Johnson, Schonlein-Henoch and Churg-Strauss syndromes have been rarely described in children. Treatment-related laboratory abnormalities have been recorded in 2 to 4% of erythromycin- and in 0 to 1% of both clarithromycin- and azithromycin-treated children. Elevation in liver function tests was the most common abnormality cited. Increased macrolide use in children in recent years has resulted in a growing potential for drug interactions between them and other pharmacologically active agents via the inhibition of cytochrome P450 (CYP) microsomal enzymes. Drug interactions with theophylline, cyclosporin, carbamazepine, terfenadine and warfarin limit erythromycin use. Clarithromycin is a weak inducer of CYP and exhibits fewer drug-drug interactions than erythromycin. However, its use with theophylline, carbamazepine and terfenadine is contraindicated. In contrast, no significant interactions have been reported with azithromycin to date. Macrolides have been proven to be well tolerated in the treatment of upper and lower respiratory tract infections, skin and soft tissue infections, and also in less frequent infections occurring in paediatric patients. In addition, clarithromycin and azithromycin have shown good tolerability profiles in immunocompromised paediatric patients. In conclusion, macrolides antibacterials have proven to be well tolerated in paediatric patients. Although the incidence of adverse effects is similar with the use of erythromycin and the newer macrolides, drug interactions occur significantly less when clarithromycin or azithromycin are administered.
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PMID:Comparative tolerability of erythromycin and newer macrolide antibacterials in paediatric patients. 993 75

A 33-year-old man was admitted 8 hours after voluntary ingestion of 1875 mg of chlorophacinone (C'Operat 750 mL). The examination revealed excitation and nausea, with a normal prothrombin index (PI). Comprehensive testing for abused and therapeutic drugs in blood confirmed chlorophacinone (maximum plasma level: 27.6 mg/L), an antivitamin K (AVK) rodenticide. In a search for easy toxicological management of chlorophacinone poisoning treated by phytomenadione and a cytochrome P450 inducer (phenobarbital), PI and chlorophacinone plasma levels were monitored concomitantly during 17 days. A simple HPLC procedure for the determination of chlorophacinone in human plasma is reported for that purpose. Under phenobarbital 200 mg/day, chlorophacinone exhibited an apparent elimination half-life (3.27 days) shorter than in previously reported cases. If PI is useful for planning phytomenadione treatment and used for therapeutic monitoring of AVK, the chlorophacinone concentrations follow-up may provide a better estimation of the duration of hospitalisation. Chlorophacinone accumulation in target cells or existence of an unidentified metabolite may explain persistence of the hypocoagulability syndrome at low plasmatic concentrations of chlorophacinone. This case illustrates how toxicological management may facilitate toxicokinetics and therapeutic data acquisition.
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PMID:Toxicological management of chlorophacinone poisoning. 1021 74

A meta-analysis of 20 short term comparative studies of 5 selective serotonin reuptake inhibitors (SSRIs; citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline) has shown no difference in efficacy between individual compounds but a slower onset of action of fluoxetine. There were suggestions that fluoxetine caused more agitation, weight loss and dermatological reactions than the other SSRIs. More patients discontinued fluvoxamine and fewer patients stopped sertraline because of adverse effects than their comparator SSRIs. The most common adverse reactions to the SSRIs were gastrointestinal (especially nausea) and neuropsychiatric (particularly headache and tremor). Data from the Committee on Safety of Medicines showed more reports of suspected reactions (including discontinuation reactions) to paroxetine, and of gastrointestinal reactions to fluvoxamine and paroxetine, than the other SSRIs during their first 2 years of marketing. Prescription-event monitoring revealed a higher incidence of adverse events related to fluvoxamine than its comparators. There were higher incidences of gastrointestinal symptoms, malaise, sedation and tremor during treatment with fluvoxamine and of sedation, tremor, sweating, sexual dysfunction and discontinuation reactions with paroxetine. Fluoxetine was not associated with a higher incidence of suicidal, aggressive and related events than the other SSRIs. Patients have survived large overdoses of each of the compounds, but concern has been expressed over 6 fatalities following overdoses of citalopram. Drug interactions mediated by cytochrome P450 enzymes are theoretically less likely to occur during treatment with citalopram and sertraline, but there is a sparsity of clinical data to support this. Methodological difficulties and price changes do not allow choice for recommendations on the choice of SSRI based on pharmacoeconomic data. Taking into account the strengths and weaknesses of the methods used to compare drugs, guidelines to the selection of individual SSRIs in clinical practice are proposed. Citalopram should be avoided in patients likely to take overdoses. Fluoxetine may not be the drug of first choice for patients in whom a rapid antidepressant effect is important or for those who are agitated, but it may have advantages over other SSRIs in patients who are poorly compliant with treatment and those who have previously had troublesome discontinuation symptoms. Fluvoxamine, and possibly paroxetine, should not be used as first choice in patients especially prone to SSRI-related adverse reactions, while paroxetine should be avoided if previous discontinuation of treatment was troublesome. When in doubt about the risks of drug interactions, citalopram or sertraline should be considered given the lower theoretical risk of interactions.
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PMID:Systematic review and guide to selection of selective serotonin reuptake inhibitors. 1065 95

The safety and tolerability of quinupristin/dalfopristin were assessed in both comparative and non-comparative trials (2298 quinupristin/dalfopristin-treated patients). In comparative clinical trials, the most frequent systemic adverse events related to quinupristin/dalfopristin were nausea (4.6%), diarrhoea (2.7%), vomiting (2.7%) and skin rash (2.5%). The comparator group showed similar rates, except that nausea was significantly more common (7.2%; P = 0.01). In non-comparative trials, arthralgia and myalgia were reported most frequently but were reversible upon treatment discontinuation. The renal, inner ear, cardiovascular and central nervous systems were not implicated as significant target organs for toxicity. The most frequent local adverse events related to infusion of quinupristin/dalfopristin were inflammation, pain, oedema, infusion site reaction and thrombophlebitis. Results of laboratory tests while on therapy were comparable for quinupristin/dalfopristin and comparator groups, except that increases in conjugated bilirubin of >5 x the upper limit of normal were reported in 5.5% of quinupristin/dalfopristin recipients; increases in total bilirubin of >5 x the upper limit of normal occurred in 1.5%. Comparator recipients more frequently had increases in alanine aminotransferase and alkaline phosphatase. Quinupristin/dalfopristin inhibits the cytochrome P450 3A4-mediated metabolism of drugs including midazolam, nifedipine, terfenadine and cyclosporin. Therefore, plasma drug monitoring and/or dosage reduction of these agents is prudent. Concomitant administration of drugs that can prolong the electrocardiographic QTc interval should be avoided. Quinupristin/dalfopristin is visually and chemically compatible with commonly used drugs of various classes, but it is not compatible with sodium chloride solution and certain other drugs, including some antimicrobials. Therefore, when prescribing quinupristin/dalfopristin, clinicians should be aware of the potential for peripheral venous intolerance, arthralgias and myalgias, increases in conjugated bilirubin, interactions with drugs metabolized by the cytochrome P450 3A4 isoenzyme and certain physico-chemical incompatibilities. However, multiple studies have shown that the safety and tolerability of quinupristin/dalfopristin are generally favourable, and that it provides clear benefits to ill patients with severe gram-positive infections.
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PMID:Safety and tolerability of quinupristin/dalfopristin: administration guidelines. 1051 96

Geriatric patients with major depression present clinical challenges not encountered in younger individuals, including a greater incidence of medical comorbidity, higher rates of multiple medication use, changes in drug metabolism due to age or physical illness, and increased sensitivity to antidepressant side effects. Nevertheless, successful treatment of depressive disorders in the elderly improves mental and physical functioning, decreases morbidity and perhaps mortality, and enhances quality of life. Recent research indicates that newer antidepressants are effective for late life depression and safer for older individuals. Among newer antidepressants, venlafaxine has a pharmacological profile that makes it an attractive choice for geriatric patients. It has limited potential to interact with other medications because it only weakly inhibits the cytochrome P450 system and binds to plasma proteins at a low level. Dosing may have to be adjusted for patients with renal failure, but typically not for those with liver disease or other medical conditions. Data from three double-blind and four open clinical trials support the safety and efficacy of venlafaxine for geriatric depression. Patients may experience transient, generally tolerable side effects such as insomnia, nausea, agitation, or dry mouth early in treatment, but more serious problems such as falls or cardiac rhythm disturbances seem to be rare. Treatment emergent hypertension occurs in a small percentage of older patients, generally at doses above 150 mg/day. Finally, emerging data suggest that venlafaxine may be effective for conditions such as stroke, anxiety, and neuropathic pain that frequently accompany depressive disorders in the elderly.
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PMID:Efficacy of venlafaxine in geriatric depression. 1109 16

Alzheimer's disease is, in part, characterised by the loss of neurones in the basal forebrain cholinergic cells that project to the cerebral cortex and hippocampus. These impairments have correlated with the memory loss noted in dementia of the Alzheimer's type. This 'cholinergic hypothesis' has led to the rational design of drugs to enhance or stimulate acetylcholine-mediated neurotransmission. Early acetylcholinesterase inhibitors, such as tacrine and physostigmine, are poorly tolerated and have a short duration of action. Rivastigmine is a centrally-selective acetylcholinesterase inhibitor with a relatively long duration of action and is a 'pseudo-irreversible' cholinesterase inhibitor due to slow dissociation of a carbamoyl derivative from the esteratic site of acetylcholinesterase. Preclinical studies confirmed the central selectivity of the drug and its distribution into the cerebrospinal fluid (CSF). Early studies demonstrated that rivastigmine improved cognition and was relatively well-tolerated at moderate doses. Clinical investigations of rivastigmine administered at doses of 6 - 12 mg/day significantly improved cognition, as measured by the ADAS-Cog score, and activities of daily living, as measured by the Progressive Deterioration Scale. Significant global improvements were also noted as measured by the Clinician's Interview Based Impression of Change that required the use of caregiver information. The most frequent adverse effects noted in clinical trials were consistent with peripheral cholinergic stimulation and included nausea, vomiting, abdominal pain, dizziness and diarrhoea. These effects were dose-related and minimised by slow dose-escalation upon initiation of therapy. Rivastigmine undergoes minimal metabolism by the cytochrome P450 system. As a result, it has few drug interactions. The drug is currently marketed widely in over 60 countries worldwide. In the United States, the drug received 'approvable' status subsequent to the NDA filing, and should be available later this year.
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PMID:Rivastigmine, a brain-region selective acetylcholinesterase inhibitor for treating Alzheimer's disease: review and current status. 1113 19

The HIV-1 protease inhibitor (PI) saquinavir is available as a soft gelatin capsule (SGC) formulation. At the recommended dosage of saquinavir SGC (1200mg 3 times daily), this formulation provides around 8-fold greater exposure than the established hard gelatin capsule (HGC) formulation at the recommended dosage of 600mg 3 times daily. As with the HGC formulation, the most common adverse events seen with saquinavir SGC are gastrointestinal symptoms (e.g. diarrhoea, abdominal discomfort and nausea). Some of these may occur with a slightly higher frequency with the SGC than with the HGC formulation. Saquinavir SGC has only a minimal effect on nonfasting serum lipid and cholesterol levels. Like other PIs, saquinavir is metabolised by the cytochrome P450 (CYP) 3A4 isoenzyme and is susceptible to interactions with inducers (e.g. rifabutin and rifampicin) and inhibitors (e.g. clarithromycin and ketoconazole) of this enzyme. Ritonavir, nelfinavir, indinavir and delavirdine, all CYP3A4 inhibitors, greatly increase saquinavir plasma concentrations and the therapeutic implications of these interactions continue to be evaluated. While saquinavir is the least potent CYP 3A inhibitor among the PIs, several drugs (notably terfenadine, astemizole and cisapride) should not be given in combination with saquinavir. Therefore, although the SGC formulation enhances saquinavir exposure, it has a similar safety profile to the HGC formulation.
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PMID:Saquinavir soft gelatin capsule: a comparative safety review. 1134 24

Significant safety issues that have arisen with fluoroquinolones include phototoxicity, cardiotoxicity, tendinitis, CNS effects and drug interactions. Ciprofloxacin is well tolerated; the incidence of adverse events is low and serious adverse events are rare. Levofloxacin has a reduced CNS adverse event rate compared with ofloxacin. Sparfloxacin has significant phototoxicity and potential cardiac toxicity. Grepafloxacin has significantly increased adverse event rates, particularly gastrointestinal intolerance. Taste perversion and nausea are common. Trovafloxacin has an increased potential for CNS adverse reactions, notably dizziness. Post-marketing surveillance data indicate the possibility of serious hepatic reactions and pancreatitis. Interactions between fluoroquinolones and drugs metabolised by the hepatic cytochrome P450 system affect the clearance of theophylline and caffeine. Quinolone absorption is significantly reduced by co-administration of antacids. Hospitalised patients are likely to be receiving multiple-drug therapy, but drug interactions are avoidable. The interactions of specific fluoroquinolones should be checked prior to prescription.
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PMID:Safety of the new fluoroquinolones compared with ciprofloxacin. 1141 83


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