Risperidone and 9-hydroxyrisperidone concentrations are not dependent on age or creatinine clearance among elderly subjects

Risperidone is extensively metabolized to an active metabolite, 9-hydroxyrisperidone (9-OH), which is dependent on renal clearance. Risperidone and 9-OH clearances are reduced in the elderly when compared to young subjects. The objective of this study was to determine whether among elderly subjects, risperidone and 9-OH clearance would further decline with increasing age and decreasing creatinine clearance (CrCl). Twenty geriatric inpatients were evaluated in a naturalistic setting with regard to total daily risperidone dose and dosing interval. Creatinine clearance was determined using an 8-hour urine collection. Risperidone and 9-OH concentrations were determined by radioimmunoassay. Spearman's correlation coefficients were used to examine the impact of age and CrCl on concentrations of risperidone, 9-OH, their sum, and the quotient of 9-OH/risperidone. Mean age was 76.4 +/- 9 years (range 56-91). Mean CrCl was 55.4 +/- 32.8 mL/min/1.73 m2 (range 17-142 mL/min/1.73 m2). Mean risperidone daily dose was 1.3 +/- 0.7 mg. Steady-state risperidone and 9-OH concentrations were 4.1 +/- 5.3 ng/mL and 9.1 +/- 6.2 ng/mL, respectively. Mean 9-OH/risperidone was 6.2 +/- 6.1. Concentrations of risperidone, 9-OH, their sum, and 9-OH/risperidone were not significantly correlated with age or CrCl. These results were unchanged when concentrations were corrected for total daily risperidone dose. Among elderly subjects, risperidone and 9-OH clearance do not decline with increasing age or declining CrCl.     

Balloon dilation for achalasia of the cardia: experience in 76 patients

PURPOSE: To report our experience with balloon dilation for achalasia of the cardia. MATERIALS AND METHODS: Seventy-six patients (mean age, 51 years) underwent balloon dilation with radiologic guidance. A total of 110 procedures were performed from April 1994 to April 2000. Diagnosis of achalasia was established with clinical, radiologic, and manometric data. Dysphagia was a presenting symptom in most patients (90%), regurgitation was present in 39%, retrosternal pain in 22%, and weight loss in 12%. The dilations were performed in a progressive manner starting with a 15-mm-diameter balloon and progressing to 20-, 30-, and 40-mm balloons, as required. Follow-up data were collected retrospectively from patient notes and telephone interviews with the patients and/or their local doctors (mean follow-up, 26 months). RESULTS: There were no cases of esophageal perforation; 89% (98 of 110) of dilations were considered to be successful, with the patients having restoration of normal or near-normal swallowing (excellent or good initial responses). Fifty-two patients required a single dilation; 22 patients, between two and four dilations; and two patients, five dilations. CONCLUSION: Balloon dilation with fluoroscopic guidance is a safe and successful treatment for achalasia of the cardia.     

A Week and a Day

In an experiment conducted as part of Alcohol Alert Week, 30 employees of the New Zealand Department of Health were asked to abstain from alcohol for 8 days. Twelve abstained completely and two drank an only one occasion. Both abstainers and non-abstainers learned something about their own, and New Zealand, attitudes to alcohol during the course of the experiment.     

Comparative ultrasonographic study of the effect of pilocarpine 2% and Ocusert P 20 on the eye components

The ultrasonographic examination of pilocarpine 2%- and Ocusert P 20-treated eyes clearly demonstrated that the side effects, such as accommodative myopia and changes of the anterior chamber depth and of the lens thickness, were less pronounced in the Ocusert-treated group.     

Urethral hymenal fusion Experience with antibiotic withdrawal test

Repair of urethrohymenal fusion has been advocated as a method of controlling recurrent urinary tract infections. A means of selecting surgical candidates has been devised. Postcoital antibiotic therapy combined with vigorous vaginal and perineal hygiene is prescribed for a period of six weeks. The postcoital antibiotic therapy is then withdrawn. If the patient has recurrent symptoms after withdrawal of the antibiotic agent, she is considered to be a suitable candidate for surgical correction of the urethrohymenal fusion. There have been no surgical failures in a small series, as opposed to a 16.6 per cent failure before the test was devised.     

Ibutilide--recent molecular insights and accumulating evidence for use in atrial flutter and fibrillation

Ibutilide is a 'pure' class III antiarrhythmic drug, used intravenously against atrial flutter and fibrillation. At a cellular level it exerts two main actions: induction of a persistent Na+ current sensitive to dihydropyridine Ca2+ channel blockers and potent inhibition of the cardiac rapid delayed rectifier K+ current, by binding within the channel pore cavity upon channel gating. Ibutilide has been shown to terminate atrial flutter and fibrillation in animal studies, with some risk of ventricular pro-arrhythmia. Experimental models of hypertrophy/heart failure show altered sensitivity to ibutilide, with increased dispersion of repolarisation and incidence of pro-arrhythmia. Patient trials show that ibutilide is effective at terminating atrial arrhythmias when given alone, and that it can increase effectiveness and reduce energy requirements of electrical cardioversion. The risk to patients of polymorphic ventricular tachycardia necessitates careful patient selection and monitoring during and after treatment. An ibutilide analogue, trecetilide, requires further investigation but may offer a less readily metabolised and pro-arrhythmic alternative to ibutilide.     

Anti-CD2 monoclonal antibody and tacrolimus in adult liver transplantation

BACKGROUND: Blockade of costimulation and adhesion signaling is an attractive approach to interfere with graft rejection METHODS: Between January 1997 and May 1999, forty adults having benign liver diseases were included in a prospective, randomized study comparing tacrolimus plus low-dose short-term steroids without (n=20, TAC group) or with a 10-day course of antihuman CD2 monoclonal antibody (n=20, BTI group). RESULTS: At day 7, histological rejection expressed by mean Banff scores (2.3+/-1.6 vs. 5.4+/-1.6 in the TAC group; P<0.0001) and incidence of moderate to severe rejection (score>or=6) (0 vs. 10 [50%] in the TAC group; P<0.001) were significantly lower in the BTI group. Rejection was treated in 10% (two patients) of BTI patients during the first 3 months and in 15% during the whole follow-up and in 25% (five patients) of TAC patients (P=NS). None of the BTI-patients presented with an adverse event. Three-month, 1-year, and 5-year actual patient survival rates were 100%, 95%, and 95% in the BTI group and 100%, 100%, and 85% in the TAC group. Graft survival rates were 100%, 90%, and 90% in the BTI group and 95%, 95%, and 80% in the TAC group (P=NS). The mAb had no negative impact on infectious or tumor events. CONCLUSIONS: Antihuman CD2 monoclonal antibody is a safe immunosuppressive drug which has a favorable impact on early immunological follow-up of liver transplanted patients. The antibody had no impact on late patient and graft survival.     

Polymorphisme génétique et interactions médicamenteuses : leur importance dans le traitement de la douleur

OBJECTIVES: To evaluate the impact of certain genetic polymorphisms on variable responses to analgesics SOURCES: Systematic review, by means of a structured computerized search in the Medline database (1966-2004). KEY WORDS: pharmacogenetics, polymorphism, cytochrome P450 (CYP), glycoprotein P (P-gp), pain, antalgics, opiates, morphine, codeine, tramadol, non-steroidal anti-inflammatory drugs (NSAID). Articles in English and French were selected. References in relevant articles were also retrieved. MAIN FINDINGS: Most analgesics are metabolized by CYP isoenzymes subject to genetic polymorphism. NSAIDs are metabolized by CYP2C9; opioids described as "weak" (codeine, tramadol), anti-depressants and dextromethorphan are metabolized by CYP2D6 and some "potent" opioids (buprenorphine, methadone or fentanyl) by CYP3A4/5. After the usual doses have been administered, drug toxicity or, on the contrary, therapeutic ineffectiveness may occur, depending on polymorphism and the substance. Drug interactions mimicking genetic defects because of the existence of CYP inhibitors and inducers, also contribute to the variable response to analgesics.Some opioids are substrates of P-gp, a transmembrane transporter also subject to genetic polymorphism. However, P-gp could only play a minor modulating role in man on the central effects of morphine, methadone and fentanyl. CONCLUSION: In the near future, pharmacogenetics should enable us to optimize therapeutics by individualizing our approach to analgesic drugs and making numerous analgesics safer and more effective. The clinical usefulness of these individualized approaches will have to be demonstrated by appropriate pharmacoeconomic studies and analyses.