ABSTRACT
We assessed several classes of serotonergic drugs in order to evaluate whether they constitute a risk factor for hospitalization for bleeding (gastrointestinal, intracranial, or in the female genital tract). A case-control study was conducted using data from the PHARMO record linkage system (RLS). The study population comprised 28,289 cases and 50,786 matched controls. Current use of antidepressant drugs was associated with all three types of bleeding, whereas antipsychotic drugs were associated with an increased risk of gastrointestinal and intracranial bleeding. Current use of ergoline derivatives increased the risk of female genital tract bleeding. The risks of gastrointestinal and intracranial bleeding were higher in new users of antidepressant and antipsychotic drugs as compared with those who were already receiving these drugs. No clear association was found between the degree of affinity for the serotonin (5-HT) transporter or the 5-HT(2A) receptor and the risk of any of the three types of bleeding. The association between antipsychotic drugs and gastrointestinal bleeding may warrant further research, in view of the fact that this association was rather unexpected.
Subject(s)
Hemorrhage/chemically induced , Hemorrhage/epidemiology , Serotonin Agents/adverse effects , Adolescent , Adult , Aged , Aged, 80 and over , Antidepressive Agents/adverse effects , Antidepressive Agents/metabolism , Antipsychotic Agents/adverse effects , Antipsychotic Agents/metabolism , Case-Control Studies , Ergolines/adverse effects , Ergolines/metabolism , Female , Gastrointestinal Hemorrhage/chemically induced , Gastrointestinal Hemorrhage/epidemiology , Genital Diseases, Female , Hospitalization/statistics & numerical data , Humans , Intracranial Hemorrhages/chemically induced , Intracranial Hemorrhages/epidemiology , Male , Medical Record Linkage , Middle Aged , Receptor, Serotonin, 5-HT2A/metabolism , Risk Factors , Serotonin 5-HT2 Receptor Agonists/adverse effects , Serotonin 5-HT2 Receptor Agonists/metabolism , Serotonin Agents/metabolism , Serotonin Plasma Membrane Transport Proteins/metabolism , Young AdultABSTRACT
BACKGROUND: Drug-induced photosensitivity is difficult to predict and remains a challenge for both the dermatological clinical practice and pharmacovigilance. PURPOSE: To assess the association between spectroscopic and molecular characteristics and the occurrence of photosensitivity reactions. METHODS: For 143 well-known photosensitisers (e.g. tetracyclines, diuretics), we retrieved information on spectroscopic and molecular parameters, including: absorption maximum lambda(max), molar absorption coefficient epsilon, area under the absorption curve (AUC), molecular weight and configuration, hetero and aromatic halogen atoms, lipophilicity (log P) and acid/base status (pKa). In the WHO-ADR database, all reports with suspected adverse drug reactions of the study drugs were selected. We identified all reports on photosensitivity reactions and defined them as cases. All other reports were selected as non-cases. A case-non-case approach was performed to assess the spectroscopic and molecular exposure variables as a factor for photosensitivity reactions. Logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI). RESULTS: A lambda(max) between 290 and 320 nm (OR 3.74, 95% CI 3.45-4.06), and an epsilon > 20,000 M(-1) cm(-1) (OR 5.49, 95% CI 5.10-5.92) were highly associated with the reporting of photosensitivity reactions. Risk of the photosensitivity reactions was significantly increased among intermediate or high AUCs compared to low AUC. Low molecular weight and aromatic halogen atoms were associated with photosensitivity reactions (OR 2.37, 95% CI 2.07-2.71 resp. OR 3.37, 95% CI 3.15-3.61) as were log p < 1 and pKa < 7. CONCLUSION: The reporting of photosensitivity reactions to established phototoxic drug classes is strongly influenced by spectroscopic and physicochemical characteristics of individual drugs.
