Focus on headache as an adverse reaction to drugs

There are a large number of drugs inducing headache as an adverse reaction. Nevertheless, headaches as adverse reactions to drugs have received limited attention. Non-serious adverse reactions, such as headache, are not quantified and described as accurately as serious, life threatening ones. However, non-serious reactions can also be extremely troublesome, above all when they are chronic: they can affect patients' quality of life and contribute to non-compliance. It is absolutely possible that the number of patients with headache as an adverse reaction, which is going to increase, considering the growing use of medications. Physicians should, therefore, be aware of this issue. Indeed, it is difficult to attribute the diagnosis of adverse drug reaction to a condition, headache, which is also a very common symptom in general population

Riserva energetica funzionale della cellula epatica: studio dei meccanismi molecolari di epatotossicita in un modello di intossicazione acuta da etanolo nel ratto

Dottorato di ricerca in patologia sperimentale. 8. ciclo. Coordinatore L. Montanaro. Tutore U. MuscatelloConsiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7, Rome; Biblioteca Nazionale Centrale - P.za Cavalleggeri, 1, Florence / CNR - Consiglio Nazionale delle RichercheSIGLEITItal

Pharmacokinetics of indomethacin in chronic migraine patients after withdrawal from the overused combination of indomethacin, Prochlorperazine and caffeine

Indomethacin, in combination with prochlorperazine and caffeine (IPC), is often overused by migraine patients who develop medication-overuse headache. Indomethacin clearance is slower in chronic migraine patients overusing IPC combination than in migraine patients only occasionally taking it. The objective of this study was to verify if indomethacin reduced clearance reverted to normal values after withdrawal of the overused IPC combination. Therefore, we repeated the study of indomethacin pharmacokinetics in 9 female chronic migraine patients after 3 months from inpatient withdrawal treatment from IPC combination overuse. The IPC combination (indomethacin 50 mg, prochlorperazine 8 mg, caffeine 150 mg) habitually taken was administered by rectal route to each patient. Blood samples were drawn before dosing and at the following post-dose times: 0.5, 1, 2, 3, 4, and 6 h. Indomethacin concentrations were measured by HPLC method. We found that 4 of 9 patients (group A) who were still overusing the combination and suffering from daily headache had still high indomethacin concentrations after 6 hours, therefore showing a slow elimination of the drug. Instead, in the 5 patients (group B) who had discontinued overuse of IPC combination after withdrawal treatment, indomethacin concentrations after 6 hours were significantly lower than those measured before withdrawal (P < 0.05, Student’s t-test for paired data), and also than those observed in group A (P < 0.05, ANOVA and Newman-Keuls’test). Hence, by suspending IPC abuse indomethacin clearance reverts to normal values and this is associated with an improvement of migraine. Instead, the higher plasma levels of indomethacin in patients who continue IPC abuse do not solve migraine and might support medication-overuse headache

The link between pain patient and analgesic medication is greater in migraine than in rheumatic disease patients

Our aim was to measure and compare the link between pain patients and the different kinds of analgesic medications they use by the Leeds Dependence Questionnaire (LDQ). This is a self-completion 10-item instrument to measure the severity of dependence upon a variety of substances. LDQ was administered to 200 episodic migraine patients (EM group), 77 chronic migraine patients (CM group) overusing acute medications, and 114 patients suffering from rheumatic disease (RD group), consecutively attending the Headache Centre or the Rheumatology Clinic of the University Hospital of Modena in the course of the first semester of 2007. The link with analgesics was greater in migraine patients than in patients with rheumatic disease, since the LDQ total score was significantly higher in the EM (6.65 +/- 0.32, P < 0.005) and CM groups (9.61 +/- 0.59, P < 0.0001) than in the RD group (5.17 +/- 0.37) (Kruskal-Wallis and Mann-Whitney U-tests). Migraine patients were significantly more linked to triptans and to combined medications than to non-steroidal anti-inflammatory drugs. The strength of the link between migraine patients and the analgesic medications they take could represent a factor of vulnerability: overusing these medications could develop medication overuse headache

OPPIACEI: FARMACOCINETICA, DIPENDENZA, DETOSSIFICAZIONE, TRATTAMENTI AGONISTI ED ANTAGONISTI

Questo capitolo tratta la farmacodinamica, la farmacinetica, gli impieghi clinici e le procedure di utilizzo degli oppiacei nel trattamento delle dipendenze ed in particolare affronta: metadone, buprenorfina, LAAM (levo alfa acetilmetadolo) e le procedure di disintossicazione nei tossicodipendenti da oppiacei (con e senza farmaci sostitutivi) e il trattamento con antagonisti come il naltrexone

Are postnatal ampicillin levels actually related to the duration of intrapartum antibiotic prophylaxis prior to delivery? A pharmacokinetic study in 120 neonates

To assess ampicillin levels according to the duration of intrapartum antibiotic prophylaxis (IAP).Objective To assess ampicillin levels according to the duration of intrapartum antibiotic prophylaxis (IAP). Design Prospective cohort single-centre study. Setting Tertiary care centre (Modena, Italy). Patients 120 neonatesâ¥35 weeks' gestation exposed to IAP. Interventions Neonates were divided into four groups, according to the duration of IAP prior to delivery: group 1 (n=30; &lt;1 hour), group 2 (n=30; â¥1 and &lt;2 hours), group 3 (n=30; â¥2 and &lt;4 hours) and group 4 (n=30; â¥2 doses, â¥4 hours). Main outcome measures Blood samples were collected at delivery (from the umbilical cord) and at age 4 hours (from a peripheral vessel). Results Median duration of IAP was 121 min (range 7-2045 min). Median ampicillin levels in umbilical cord blood were 10.4 μg/mL (IQR 6.4-14.9) and in peripheral blood were 4.7 μg/mL (IQR 2.8-6.4μg/mL). Umbilical cord blood levels reached a peak approximately 30 min after IAP and then declined significantly (p&lt;0.001). Peripheral blood levels did not differ among study groups. Neonates exposed to a full loading dose (n=115) had peripheral blood levels 2.5-70 times higher than the minimal inhibitory concentration for group B streptococcus. There was no relationship between neonatal ampicillin concentrations and the duration of IAP prior to delivery (β=â '0.0003, 95% CI â '0.02 to 0.001, p=0.680). Conclusions Ampicillin levels reach a peak in the umbilical cord blood within 30 min of intrapartum administration. After a full loading dose, bactericidal levels persist for at least 4 hours after birth and seem independent of the duration of IAP prior to delivery

Switching from HPLC/UV to MEIA for whole blood sirolimus quantitation: Comparison of methods

Sirolimus is a immunosuppressive agent for renal transplant recipients. Monitoring of whole blood sirolimus concentration is necessary in order to improve clinical outcomes. An increasing number of clinical laboratories (4-14% during 2005) are using microparticle enzyme immunoassay (MEIA) for sirolimus quantitation but previous reports indicated a high variability, with a mean difference of 17% for MEIA method vs. high-performance liquid chromatography/ultraviolet (HPLC/UV). This study was aimed at comparing the reliability of MEIA with the HPLC/UV method. Blood samples from transplant patients were processed using both HPLC/UV and MEIA assays. Comparison and Bland-Altman plots, as well as regression analysis and paired t-test were used to compare results of the assays. Concentrations were stratified into three groups and used to investigate whether any observed difference between methods could be influenced by sirolimus concentration. Regression analysis yielded a coefficient of correlation R of 0.9756, the line of best fit being y = 0.9832x + 0.1976. The statistical analysis showed no difference between the two sets of experimental data. The average percentage difference between the two methods was found to be -0.2 +/- 19.2%. On the basis of our present results, the tested MEIA assay is able to quantify sirolimus concentration with a clinically acceptable imprecision, similar to that of HPLC/UV method

Effect of overuse of the antimigraine combination of indomethacin, prochlorperazine and caffeine (IPC) on the disposition of its components in chronic headache patients

Background: The combination of indomethacin, prochlorperazine and caffeine (IPC) is one of the most utilized formulations for the treatment of migraine attacks in Italy. Several patients suffering from chronic headache overuse this symptomatic medication in the attempt to control their headache. Objective: To verify whether overuse of IPC combination by chronic headache patients is associated with modified disposition of its components. Methods: We studied indomethacin, prochlorperazine, and caffeine disposition in 34 female subjects suffering from primary headaches, subdivided into four groups: eight migraine patients occasionally using IPC combination suppositories-group 1; nine patients with chronic headache and probable medication-overuse headache, daily taking one or more suppositories of the IPC combination-group 2; 11 migraine patients occasionally using mild suppositories of the IPC combination-group 3; six migraine patients occasionally taking tablets of the IPC combination-group 4. The IPC combination habitually used was administered to each patient. Blood samples were taken at baseline and at fixed intervals up to 6 h after administration. Plasma levels of indomethacin and prochlorperazine were assayed by high-pressure liquid chromatographic (HPLC) method; caffeine levels were assayed by enzyme multiplied immunoassay test (EMIT). Pharmacokinetic parameters were calculated by means of a computer software (P K Solutions 2.0. Summit Research Services, Montrose, CO, USA). Results: Half-life of indomethacin was longer, and clearance lower, in group 2 than in the other groups; AUC of indomethacin in group 2 was twice that in group 1 (P infinity) of caffeine were significantly higher in group 2 than in the other groups (P < 0.05, Newman-Keuls´ test). We could not define prochlorperazine disposition because it was not detectable in the majority of blood samples. Conclusion: Overuse of IPC combination in chronic headache patients is associated with increased plasma levels of indomethacin and caffeine, and with delayed elimination of indomethacin; the high and sustained concentrations of these drugs may cause rebound headache, organ damages, and perpetuate medication-overuse headache