Is this reaction caused by this drug?

The case report on cotrimoxazole-induced pancreatitis by Versleijen et al. deals with the assessment of the probability that cotrimoxazole induced the acute pancreatitis: a causality assessment. In this editorial, we comment on this assessment from a clinical, pharmacological and epidemiological perspective. Moreover, the consequences of the results of the assessment are discussed.

[Urinary retention in 2 children after the use of antiemetic agents during acute gastroenteritis]. / Urineretentie bij 2 kinderen na gebruik van anti-emetica tijdens een acute gastro-enteritis.

Two girls, aged 2 and 4 years, with acute gastroenteritis and vomiting, received domperidone and metoclopramide, respectively. Urinary retention developed, but after catheterisation of the bladder was performed once and the medication was withdrawn, both children recovered without further sequelae. Anti-dopaminergic antiemetic agents should be prescribed with caution, especially in young children.

Is decreased libido associated with the use of HMG-CoA-reductase inhibitors?

AIMS AND METHODS: To describe patients with decreased libido during use of a HMG-CoA-reductase-inhibitor, and to discuss causality and pharmacological hypotheses for this association by analysis of the adverse drug reactions (ADR) database of the Netherlands Pharmacovigilance Centre Lareb. RESULTS: Eight patients were identified as having decreased libido during use of statins. In two of these cases testosterone levels were determined and appeared to be decreased. CONCLUSION: Decreased libido is a probable adverse drug reaction of HMG-CoA-reductase-inhibitors and is reversible. The ADR may be caused by low serum testosterone levels, mainly due to intracellular cholesterol depletion.

Chest pain during use of bupropion as an aid in smoking cessation.

AIMS: To investigate the cause of chest pain during the use of bupropion as an aid to stop smoking. METHODS: The Netherlands Pharmacovigilance Centre received 22 reports of chest pain, associated with the use of bupropion as an aid to smoking cessation. Additional information about long-term follow up was collected to analyze whether these complaints herald manifest cardiac disease. RESULTS: All but one patient recovered after withdrawal of bupropion. Seven patients were additionally investigated and in six of them, a cardiac cause could be excluded. During long-term follow-up, no coronary heart diseases were diagnosed. CONCLUSIONS: These reports indicate that chest pain seems to be associated with the use of bupropion, but its origin remains unclear.

Prognostic factors for the vascular components of erectile dysfunction in patients on renal replacement therapy.

A total of 76 male patients on renal replacement therapy (RRT) were investigated. Erectile dysfunction (ED) was defined as insufficient erection during visual erotic stimulation (VES) or during sleep as measured with Rigiscan and Erectiometer. Data on medical history, physical examination, and laboratory variables were collected. Furthermore, penile pharmacological duplex ultrasonography (PPDU) was performed. Univariate and multivariate logistic regressions were used to determine prognostic values and to develop prognostic models. Independent prognostic factors for ED were the number of cardiovascular events, waist-hip ratio, body mass index, and acceleration time (AT) as measured with PPDU. Independent prognostic factors for an abnormal AT (>100 ms) were number of cardiovascular events, age category, and the presence of carotid bruits. Independent prognostic factors for insufficient veno-occlusion during PPDU were number of cardiovascular events and supine diastolic blood pressure. The vascular contribution to ED in patients on RRT is substantial. Data from medical history, limited physical examination, and PPDU contribute to the prediction of the vascular contribution to ED.

[Deterioration of schizoaffective disorder due to an interaction between haloperidol and carbamazepine]. / Verergering van schizoaffectieve stoornis door interactie tussen haloperidol en carbamazepine.

A 40-year-old woman with a schizoaffective disorder was initially treated with lithium carbonate and haloperidol decanoate, but after three years the lithium was replaced with carbamazepine. Following this, her performance deteriorated over several years despite increasing dosages of haloperidol. After withdrawal of the carbamazepine a remarkable recovery occurred. A pharmacokinetic interaction between haloperidol and carbamazepine, which results in decreased haloperidol blood levels, provides a good explanation of this clinical picture. This clinically relevant interaction should be incorporated into pharmacovigilance systems.

Determinants of signal selection in a spontaneous reporting system for adverse drug reactions.

AIMS: Detection of new adverse drug reactions (ADR) after marketing is often based on a manual review of reports sent to a Spontaneous Reporting System (SRS). Among the many potential signals that are identified, only a limited number are important enough to require further attention. The goal of this study is to gain insight into factors contributing to the selection and dissemination of possible signals originating from the SRS maintained by the Netherlands Pharmacovigilance Foundation. METHODS: In a case control design, all signals (n = 42) disseminated to the Medicines Evaluation Board from the second quarter of 1997 until the third quarter of 2000, which could be expressed as a combination of a single ATC code and a single WHO preferred term, were included. For each case, four controls were matched in time. Logistic regression analysis was used to investigate the influence of various factors, such as the fact whether the ADR or drug is new, the strength of the association, the seriousness of the reaction and the documentation of the reports. RESULTS: Multivariate analysis showed that the presence of a 'serious report' (Odds Ratio 3.8, 95% CI 1.3, 11.0), a WHO 'critical term' (OR 4.7, 95% CI 1.8, 13), the ADR being unlabelled (OR 6.1, 95% CI 2.3, 16) and the presence of a disproportionate association (OR 3.5, 95% CI 1.4, 8) were all independently associated with signal selection. The number of reports and the time after marketing of the drug had no influence. CONCLUSIONS: This study showed that selection of signals is based on both qualitative and quantitative aspects. Knowledge of these factors may improve the efficiency of the underlying signal selection process.

The value of sildenafil as mode of stimulation in pharmaco-penile duplex ultrasonography.

The purpose of this work was to assess whether a single intracavernous injection (ICI) of a low dose of the combination of papaverine-phentolamine is replaceable by a high dose of the oral erectogenic agent sildenafil as mode of stimulation during pharmaco-penile duplex ultrasonography (PPDU). Eleven patients with complaints of erectile dysfunction were included in a crossover study. With an interval of two weeks the patients were exposed to ICI with papaverine/phentolamine (3.75 mg/0.125 mg) and oral administration with sildenafil (100 mg) preceding PPDU. Five patients started with ICI. Six patients started with sildenafil. In the sildenafil stimulation mode, visual erotic stimulation (VES) was used to initiate erection. VES was applied by personal LCD monitor. Cut-off values to define sufficient arterial response were: peak flow velocity (PSV) >25 cm/s and acceleration time (AT) <72 ms. Cut-off value to define sufficient veno-occlusion was a resistance index > or =1.00. Statistical analysis of PPDU parameters shows no significant difference between the two modes of stimulation for arterial response (PSV, AT), whereas the resistance index, as a parameter of veno-occlusive response was significantly higher in the sildenafil mode. This finding is confirmed in the clinical translation of the results: two patients with an insufficient arterial response to ICI had a sufficient arterial response to sildenafil and only one patient showed an insufficient arterial response following sildenafil, whereas the response following ICI was sufficient. Analysis of veno-occlusive responses shows remarkable differences between both modes of stimulation. Whereas following the administration of sildenafil all veno-occlusive responses were classified as sufficient, seven patients showed an insufficient veno-occlusive response following ICI. As mode of stimulation in PPDU, high dose sildenafil yields significantly less false positive diagnoses of 'veno-occlusive dysfunction' than intracavernous injection of the combination papaverine/phentolamine. No difference was found in the quality of the arterial response. Based on this study we conclude that sildenafil may replace ICI as mode of stimulation during PPDU.

Sexual dysfunction after renal replacement therapy.

The existence of a sexual problem as the subjective evaluation of sexual function was assessed with a simple questionnaire. Those questioned were patients undergoing dialysis treatment (n = 400) or with a functioning renal transplant (RTx; n = 300) and both men and women in the general Dutch population (n = 591). In the Dutch control population, 8.7% of the men and 14.9% of the women reported a sexual problem, showing a significant gender difference but unrelated to age. In patients, the prevalence of a sexual problem was significantly greater (hemodialysis, men, 62.9%; women, 75.0%; peritoneal dialysis, men, 69.8%; women, 66.7%; renal transplantation, men, 48.3%; women, 44.4%). In RTx recipients, sexual problems were significantly less prevalent than in patients undergoing dialysis (P < 0.001). Only in male patients was an association between prevalence of a sexual problem and age found. The results of the simple questionnaire were sufficiently validated when 102 of 104 patients confirmed their responses in a subsequent structured interview. This study shows that the prevalence of sexual problems in patients undergoing renal replacement therapy is high and clinically relevant.

Nefazodone-induced clitoral priapism.

A case is presented of painful priapism of the clitoris lasting 3 days, with a strong temporal association with the administration of nefazodone hydrochloride. Priapism has been described as a rare side-effect of drugs with high alpha1-adrenergic blocking potential. However, the alpha1-adrenergic blocking potential of nefazodone is moderate. Drug-induced clitoral priapism has been described for citalopram, bromocriptine, fluoxetine and trazodone combined with fluoxetine. To our knowledge, this is the first report in the literature about priapism of the clitoris associated with nefazodone.

Bladder dysfunction during the use of tramadol.

The Netherlands Pharmacovigilance Foundation LAREB received five case reports concerning transient impairment of micturition or urinary retention, suspected to be induced by tramadol. In all patients--three women and two men--the symptoms occurred in temporal association with the use of tramadol and promptly recovered after stopping of the drug. Tramadol was taken orally in doses within the recommended therapeutic range (150 mg or less daily). Disturbance of micturition is not mentioned as a side-effect in the summary of product characteristics of Tramal 50 and 100. Tramadol is an opioid agonist, however, and morphine is known to increase the tonus of the bladder sphincter and to cause urinary retention.

The post-investigation questionnaire (PIO-R): a practical instrument to assess erectile response after intracavernous injection.

Erectile response to intracavernous pharmacological stimulation is highly susceptible to stress and anxiety provoked by the test-situation. To reduce false-positive diagnosis of veno-occlusive dysfunction and to limit the need for high-dosage pharmacotesting, we developed the Post-Investigation Questionnaire (PIQ-R), a self-report instrument to assess erectile response to pharmacological stimulation after the patient has left the office. In this study veno-occlusive sufficiency was not demonstrated in 80 of 105 patients with erectile dysfunction at the time of pharmaco-penile duplex ultrasonography. PIQ-R detected sufficient erectile response in 40 of these patients, thus reducing false-positive diagnosis of veno-occlusive dysfunction by 50%. We also found that reports of sexual activity after investigation increased interest in auto-injection therapy. PIQ-R is a practical self-report measure to assess erectile response after clinical pharmacotesting, and to more carefully select patients for auto-injection therapy.

Investigation of erectile dysfunction. Diagnostic testing for vascular factors in erectile dysfunction.

To date, several accurate tests for diagnosing vascular ED may be chosen. It is necessary to be well aware of the purpose of testing: global assessment of erectile capacity in preparation for auto-injection therapy, or detailed assessment of arterial and erectile response in preparation for surgical treatment. Pharmacotesting may be sufficient for the majority of patients. Other, more invasive tests are reserved for preparing surgical treatment or scientific studies.

Enhanced pharmacological testing in patients with erectile dysfunction.

This study was designed to evaluate the practical use of the combination of a low-dose intracavernous injection test (ICI) and visual erotic stimulation (VES) in the assessment of patients with erectile dysfunction. Additionally, a postinvestigation questionnaire (PIQ) was used to rate the erection following the investigation when the patient had left the office. It was hypothesized that the combination (ICIVES) and the PIQ would yield a higher erectile response rate than ICI or VES alone and would minimize the occurrence of prolonged erection. Of the 90 patients studied, 17 (19%) showed adequate erections to VES, 10 (11%) to ICI, and 60 (67%) to ICIVES. Of the 30 non-responders, 7 (23%) reported adequate erections on the PIQ. Overall, in 75% of the patients adequate erections were achieved. No prolonged erections were encountered. It is concluded that the combination of a low-dose ICI and VES, and the application of a postinvestigation questionnaire, is a powerful and safe test to select patients for autoinjection therapy.

Low-dose isradipine once daily effectively controls 24-h blood pressure in essential hypertension.

In one study of 10 patients with mild-to-moderate hypertension, equivalent total daily doses (13 +/- 2 mg) of isradipine given twice daily and a modified-release formulation of isradipine (isradipine MR) given once daily were found to control adequately 24 h ambulatory blood pressure compared with placebo (P less than .001 for each v placebo). In another study of 22 patients with essential hypertension, 5 and 10 mg isradipine MR once daily has been shown to reduce the average 24 h blood pressure by 11 +/- 1/6 +/- 1 mm Hg (P less than .001) and 13 +/- 2/9 +/- 1 mm Hg (P less than .001), respectively, compared with placebo. There was no loss of efficacy with isradipine MR during the 24 h observation period with either dose. In conclusion, low-dose isradipine MR once daily is an effective first-line treatment in essential hypertension.