Ilaria Tiraferri

Why pharmacokinetic differences among oral triptans have little clinical importance: a comment

Triptans, selective 5-HT1B/1D receptor agonists, are specific drugs for the acute treatment of migraine that have the same mechanism of action. Here, it is discussed why the differences among kinetic parameters of oral triptans have proved not to be very important in clinical practice. There are three main reasons: (1) the differences among the kinetic parameters of oral triptans are smaller than what appears from their average values; (2) there is a large inter-subject, gender-dependent, and intra-subject (outside/during the attack) variability of kinetic parameters related to the rate and extent of absorption, i.e., those which are considered as critical for the response; (3) no dose-concentration–response curves have been defined and it is, therefore, impossible both to compare the kinetics of triptans, and to verify the objective importance of kinetic differences; (4) the importance of kinetic differences is outweighed by non-kinetic factors of variability of response to triptans. If no oral formulations are found that can allow more predictable pharmacokinetics, the same problems will probably also arise with new classes of drugs for the acute treatment of migraine.

Impact of continuing or quitting smoking on episodic cluster headache: a pilot survey

BackgroundThe majority of patients suffering from cluster headache (CH) are smokers and it has been suggested that smoking may trigger the development of CH. The aim of this pilot survey was to describe: 1. the differences between current, former, and never smokers CH patients; 2. if smoking changed during an active cluster period; 3. if CH changed after quitting.MethodsAll outpatients with episodic CH according to the criteria of ICHD-II who were consecutively seen for the first time from October 2010 to April 2012 at a headache centre were interviewed by phone using a specifically prepared questionnaire. Statistical differences between continuous variables were analysed by the Student’s t- test or the one-way analysis of variance (ANOVA), followed by Newman-Keuls post-hoc testing. Comparisons between percentages were made using the Chi-square test or Fisher’s exact test. All data were expressed as the mean ± standard deviation (SD).ResultsAmong a total of 200 patients surveyed (172 males, 28 females; mean age ± SD: 48.41 ± 12 years) there were 60%, 21%, and 19% of current, former, and never smokers, respectively. Current smokers reported longer active periods (12.38 ± 10 weeks) and a higher maximum number of attacks per day (3.38 ± 1) compared to never smoker CH patients (5.68 ± 4 weeks, P <0.05 and 2.47 ± 1, P <0.05, respectively). During the active period most of the patients stated to decrease (45.7%) or not to change (45.7%) the number of cigarettes smoked. Among those who decreased smoking, most (83.8%) reported that they had less desire to smoke. After quitting, the majority of former smokers stated that their headache had not changed.ConclusionsPatients with episodic CH who are also smokers appear to have a more severe form of the disorder. However, it is unlikely that between CH and smoking there is a causal relationship, as CH patients rarely improve quitting smoking.

Clinical pharmacology of topiramate in migraine prevention.

Introduction: Migraine is a widespread disorder. Migraine patients experience worse health-related quality of life than the general population. The availability of effective and tolerable treatments for this disorder is an important medical need. This narrative review focuses on the clinical pharmacology of topiramate, an antiepileptic drug that was approved for the prophylaxis of migraine where it should act as a neuromodulator. Areas covered: A PubMed database search (from 2000 to 24 January 2011) and a review of the human studies published on topiramate and migraine was conducted. Expert opinion: Topiramate is an important option for the prophylaxis of migraine and is of proven efficacy and tolerability. It has also been studied in chronic migraine with encouraging results, even in patients with medication overuse. However, in migraine prevention its efficacy is comparable to the other first-line drugs and there are no published trials with a superiority design which can establish topiramates role in the available therapeutic armamentarium.

O015. Evaluation of the genetic polymorphism of the α3 (CHRNA3) and α5 (CHRNA5) nicotinic receptor subunits, in patients with cluster headache

About 80% of patients with cluster headache (CH) have a history of cigarette smoking[1]; a common genetic basis between CH and smoking has been suggested by the identification of a gene cluster on chromosome 15q25, encoding for neuronal acetylcholine receptor subunits α3, α5 and β4 (CHRNA5-CHRNA3-CHRNB4). Receptors containing the α5 subunit contribute to nicotine withdrawal symptoms and anxiety modulation[2, 3].

Hair analysis to monitor abuse of analgesic combinations containing butalbital and propyphenazone.

Butalbital, a barbiturate, is present in analgesic combinations used by headache sufferers. Overuse/abuse of these combinations may cause dependence, chronic migraine, and medication-overuse headache (MOH). MOH is difficult to manage: it improves interrupting analgesic overuse, but requires monitoring, because relapses are frequent. A gas chromatography-mass spectrometry (GC-MS) method for hair analysis has been developed and validated to document abuse of an analgesic combination containing butalbital and propyphenazone by a patient with MOH. For over ten years the patient managed her headache using eight suppositories/day of an analgesic combination containing butalbital 150mg, caffeine 75mg, and propyphenazone 375mg per suppository. An outpatient detoxification treatment was carried out. After three weeks, the patient reduced the consumption to one suppository/day. At the first control visit, after three months from the beginning of detoxification, the patient increased the use of the combination to four suppositories/day and at the second control visit, after seven months from the beginning of detoxification, she was back to eight suppositories/day. At the two control visits, a hair sample was taken for determination of butalbital and propyphenazone. Moreover blood and urine samples for determination of butalbital were drawn at the beginning of detoxification treatment and at the two control visits. With the segmental analysis of two hair samples the medication history of ten months could be estimated. In the first hair sample, collected at the first control visit, in the distal segment, butalbital and propyphenazone concentrations were, respectively, 17.5ng/mg and 56.0ng/mg, confirming the prolonged abuse; in the proximal segment, concurrently with the detoxification treatment, butalbital and propyphenazone concentrations had reduced respectively to 5.45ng/mg and 11.1ng/mg. The second hair sample, collected at the second control visit, proved the fair course of the detoxification treatment in the distal segment and signalled relapse in the abuse of the analgesic combination in the proximal segment. In the clinical context, hair analysis can be advantageously used to monitor the abuse of analgesic combinations with butalbital, common among headache patients. The validation data showed that GC-MS method developed for determination of butalbital and propyphenazone was rapid, highly sensitive, specific and selective.

Can cigarette smoking worsen the clinical course of cluster headache

Up to 90% of cluster headache (CH) patients have a prolonged history of cigarette smoking prior to the headache onset. It has been suggested a genetic link between CH and nicotine addiction and, also, that toxic agents found in cigarette smoke have a direct effect on the hypothalamus, a pivotal area for the pathogenesis of CH. [1-3]