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PubMed2005

Comorbidity of epilepsy and headache in patients with Sturge-Weber syndrome.

Sturge-Weber syndrome is associated with leptomeningeal angioma, trigeminal port-wine stain, epilepsy, and glaucoma. Clinically, many patients with Sturge-Weber syndrome are observed to have both seizures and headaches, but this has never been described in the literature. A questionnaire was mailed to 190 patients with reported comorbid epilepsy and headache as identified by the Sturge-Weber Foundation. Sixty-eight surveys were returned anonymously; 55 reported both seizures and headaches. The median age at headache onset was 8 years, with a median of three headaches per month. Fifty-eight percent felt that headaches were an equal or greater problem. Ibuprofen and acetaminophen were the most frequently tried abortive medications; 22% had tried sumatriptan. Only 22% reported a neurologist suggesting the use of an anticonvulsant as a preventive agent. Subjects with a family history of headaches had an earlier age at headache onset (7.5 vs 11 years; P = .02), and those with a family history of seizures were more likely to report behavior problems (69% vs 33%; P = .02). Subjects reporting learning problems or hemiparesis had an earlier age at seizure onset. Migraine-like headaches can be as significant a problem as epilepsy for patients with Sturge-Weber syndrome. Despite this, triptans and prophylactic medications (including anticonvulsants) were used in less than half of the patients. Correlations of family history with both age at symptom onset and behavior problems suggest that genetic substrate could be one factor determining the variable neurologic manifestations seen in Sturge-Weber syndrome.

Age of Onset↗

PubMedDate not supplied

Pharmacologic management of postdural puncture headache.

OBJECTIVE: To discuss the pathogenesis, incidence, and clinical presentation of postdural puncture headaches (PDPHs) and to provide a comprehensive evaluation on the pharmacologic management of PDPH. DATA SOURCE: A MEDLINE search was used to identify pertinent literature published in English including review articles, case reports, letters, and abstracts. Information was also extracted from textbooks for background purposes. STUDY SELECTION: All clinical studies, case reports, abstracts, and letters were included because of the limited amount of literature available on the pharmacologic therapy for PDPH. Related research articles and review articles were also used to provide background information on PDPH. DATA EXTRACTION: Methodology and results from clinical trials and abstracts were described and evaluated. Case reports and letters were summarized and critically reviewed for the feasibility of the different treatment modalities. Information on the pathophysiology, incidence and severity, and clinical presentation of PDPH was extracted from related research articles, review articles, and textbooks. DATA SYNTHESIS: The epidural blood patch (EBP) is one of the most effective treatments for PDPH. Pharmacologic management of PDPH offers a less invasive treatment modality than the EBP. Numerous drug therapies have been presented in the literature, though few merit clinical application. Caffeine therapy, both oral and parenteral, is the most commonly used pharmacologic treatment modality. Theophylline and sumatriptan are potentially promising agents for the treatment of PDPH. Epidural administration of fluids and drugs is also effective in the treatment of PDPH. Epidural adrenocorticotropic hormone and epidural morphine also demonstrate some potential in the treatment of PDPH. Individual patient characteristics (i.e., HIV, sepsis) need to be considered when deciding on a treatment. More reports, especially clinical studies, are necessary before a definitive statement can be made regarding any one treatment. In the meantime, therapy will be guided by clinical judgement based on the literature reviewed in this article. CONCLUSIONS: Intravenous and oral caffeine are effective and noninvasive treatments for PDPH. Epidural NaCl 0.9% or dextran are alternatives when the EBP is unsuccessful or contraindicated. Several methods of pharmacologic management have been cited in the literature, but all require further evaluation.

Administration, Oral↗

PubMed2001

Acute treatments: some blind alleys.

The introduction of sumatriptan, a selective 5-HT(1B/1D) agonist, for the treatment of migraine sparked a new era of drug research in this field. Many novel targets have since been developed, and tested in the clinic. The promise of these approaches is to deliver an anti-migraine compound with the optimal efficacy and safety profile. In this chapter, blind alleys in anti-migraine development are discussed. The failing soldiers have included the NK-1 antagonists, some second-generation 5-HT(1B/1D) agonists, CP-122,288, 4991W93, the neurosteroid ganaxolone, selective 5-HT(1F) (LY334370) and 5-HT(1D) agonists (PNU-142,633), and the endothelin-1 antagonist bosentan. Some of these promising targets failed to demonstrate clinical efficacy, while others were stopped for preclinical toxicity.

Drug Evaluation, Preclinical↗

PubMed2001

Naratriptan.

Naratriptan is a selective 5-HT(1B/1D) receptor agonist, with a high affinity at the 5-HT(1B), 5-HT(1D) and 5-HT(1F) receptor subtypes. Naratriptan contracts a number of large isolated cerebral arteries from several species, and has little contractile effect on peripheral blood vessels. It has an inhibitory effect on the cranial neurogenic inflammation model. The clinically recommended dose is 2.5 mg. It was found significantly superior to placebo on headache relief and pain free at 2 and 4 hours, and in relieving nausea, photophobia and phonophobia. It also has a good within-patient consistency, and a low recurrence rate. The side-effect profile is that of the triptan class, wih an incidence no different from placebo at the 25 mg dose. The contraindications are similar to any triptan, including coronary disease. Naratriptan is unlikely to affect metabolism of other drugs. In comparison sumatriptan 100 mg, naratriptan 2.5 mg has a slower onset of action and a lower response rate at 4 h, but it has a lower recurrence rate, and is better tolerated.

Humans↗

PubMed2005

Usage of pain medications during stroke rehabilitation: the Post-Stroke Rehabilitation Outcomes Project (PSROP).

Pain remains one of the most common, yet most challenging, medical problems in health care today, and it is one of the most common complications that occurs after a stroke. Pain can affect the course of stroke rehabilitation adversely, and it occasionally may be a cause for transfer back to an acute care hospital. The Post-Stroke Rehabilitation Outcomes Project (PSROP) database was used to describe the incidence of pain by body location and trends in the use of different classifications of medications to treat pain. Of the 1,122 participants in the PSROP database, the most common locations of pain in stroke survivors were the head, leg, back, and shoulder. The most frequently prescribed classifications of pain medications were other analgesics (acetaminophen and tramadol), followed by narcotic analgesics, non-steroidal antiinflammatory drugs (NSAIDs), anticonvulsants, and tricyclic antidepressants. After acetaminophen, the most frequently prescribed medications in each classification, respectively, include hydrocodone APAP, cox-2 inhibitors, gabapentin, and amitriptyline. Other frequently prescribed pain medications included sumatriptan (migraine analgesic), cyclobenzaprine (muscle relaxant), and baclofen (antispasticity muscle relaxant). Medications should be chosen based upon the medical condition causing pain, the ability of the stroke survivor to comply with administration of the medication, and the cost of the medication. Appropriate and timely treatments of painful conditions result in maximum function and the ability to lead active lives and maintain an adequate quality of life.

Aged↗

PubMed1999

Naratriptan: an alternative for migraine.

OBJECTIVE: To critically evaluate the literature regarding naratriptan's clinical pharmacology, efficacy, safety, and indications. DATA SOURCE: A MEDLINE search was conducted for the period from January 1990 to June 1998. Key words used included naratriptan, triptan, serotonin agonists, migraine, and migraine therapy. In addition, pertinent references cited in articles obtained from MEDLINE and product information for triptans were reviewed. STUDY SELECTION AND DATA EXTRACTION: All original and review articles and abstracts pertaining to naratriptan were reviewed, as were product information extracts. Clinical trials of naratriptan were critically reviewed and compared with pertinent clinical trials of other oral triptans. DATA SYNTHESIS: The treatment of migraine has been dramatically improved with the use of sumatriptan, other triptans, and serotonin-receptor subtype 1B and 1D agonists. Drawbacks to these medications, however, have included poorly tolerated adverse effects and the recurrence of the migraine. Naratriptan has been recently approved for acute oral migraine therapy. In two Phase III trials of naratriptan compared with placebo, relief at four hours was obtained in 60% and 68% of patients using the 2.5-mg dose, with recurrence of headache in 24 hours in 27% and 28% of patients. The data on migraine recurrence were similar to those of other oral triptans; the efficacy of naratriptan at two hours was not specifically analyzed. Adverse effects of naratriptan were similar to placebo, and its tolerability seemed superior compared with studies of other oral triptans. CONCLUSIONS: Naratriptan is a promising new oral therapy for acute migraine; it may successfully treat patients who poorly tolerate other triptan therapies or have longer duration migraine headaches.

Animals↗

PubMedDate not supplied

Cerebral circulatory changes during migraine headache with aura.

Many authors report alterations of cephalic (both intracranial and extracranial) blood flow and vascular responsiveness in patients with migraine. In the majority of reports, rCBF has been decreased during the prodromal phase and increased during and immediately after the headache phase of migraine attacks. Abnormal vascular responsiveness has been demonstrated, not only during each attack, but also between attacks. Pharmacological and therapeutic evidence that many vasoactive agents induce, prevent or abolish attacks of migraine headache are consonant with the close relationships that exist between vascular abnormalities and the pathogenesis of migraine with aura. This is particularly true of the marked therapeutic effectiveness of calcium entry blockers, which are effective in the prophylaxis of migraine, and sumatriptan, which has direct vasoconstrictive effects, with relief of the headache, which lends strong support to a vascular hypothesis.

Brain↗

PubMed2001

Advances in pharmacological treatment of migraine.

Migraine is a paroxysmal disorder with attacks of headache, nausea, vomiting, photo- and phonophobia and malaise. This review summarises new treatment options both for the therapy of the acute attack as well as for migraine prophylaxis. Analgesics like aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) are effective in treating migraine attacks. Few controlled trials were performed for the use of ergotamine or dihydroergotamine. These trials indicate inferior efficacy compared with serotonin (5-HT(1B/D)) agonists (triptans). The triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan and zolmitriptan), are highly effective. They improve headache as well as nausea, photo- and phonophobia. The different triptans show only minor differences in efficacy, headache recurrence and adverse effects. The knowledge of their different pharmacological profile allows a more specific treatment of the individual migraine characteristics. Migraine prophylaxis is recommended, when more than three attacks occur per month, if attacks do not respond to acute treatment or if side effects of acute treatment are severe. Substances with proven efficacy include the beta-blockers metoprolol and propranolol, the calcium channel blocker flunarizine, several 5-HT antagonists and amitriptyline. Recently anti-epileptic drugs (valproic acid, gabapentin, topiramate) were evaluated for the prophylaxis of migraine. The use of botulinum toxin is under investigation.

Adult↗

PubMed1998

Zolmitriptan: a new acute treatment for migraine.

Zolmitriptan is a new oral acute treatment for migraine. It is a selective and potent agonist at the serotonin (5-HT)(1B/1D) receptor and was developed to improve on the oral bioavailability, tissue selectivity and CNS penetration of earlier compounds. Animal studies confirmed that these objectives had been attained. In man, zolmitriptan is rapidly absorbed after oral administration, with at least 75% of the eventual C(max) reached within 1 h. Oral bioavailability is approximately 40%. The elimination half-life of zolmitriptan is approximately 2.5 h and the primary route of elimination is metabolism, with one of the metabolites being pharmacologically active. A consistent 2-h headache response rate of 60-70% was observed at doses of 2.5 mg and above. Long-term treatment response is high (> 80%) and consistent. In addition, there is evidence from electrophysiology in migraineurs that zolmitriptan has a central action not shared by sumatriptan. Zolmitriptan is well-tolerated. The nature and incidence of the most frequently reported adverse events are similar to those of other 5-HT(1B/1D) agonists. Long-term zolmitriptan usage was associated with an improvement in quality of life. Zolmitriptan is a suitable first-line drug for acute treatment for migraine.

Journal Article↗

PubMed2002

Treatment of paediatric headache.

Headaches are very common during childhood and become increasingly frequent during adolescence. The diagnosis of primary headache disorders (e.g., migraine and tension-type headache) rests principally on clinical criteria as set forth by the International Headache Society. Treatment options include acute or episodic measures, prophylactic agents and non-pharmacological or behavioural interventions. From review of available evidence, the most efficacious acute treatments of paediatric migraine include the non-steroidal anti-inflammatory agent ibuprofen at 7.5 - 10 mg/kg/dose or nasal sumatriptan at doses of 5 or 20 mg. For those patients with headaches that occur with sufficient frequency and severity to warrant daily prophylaxis, controlled data are limited. Agents which are likely to be beneficial include amitriptyline, flunarizine (not available in the US) and cyproheptadine. Clinical experience with the anti-epileptic agents topiramate and valproate suggests an expanding role for the prevention of paediatric migraine in the future.

Adolescent↗

PubMed2003

Emerging drugs in migraine treatment.

Ergot alkaloids have been the mainstay of acute migraine therapy for most of the 20th century. They have been supplanted by sumatriptan-like drugs ('triptans'), which, while keeping some of the ergotś mechanisms of action, show improved safety profiles due to their increased receptor selectivity. However, triptans are still far from being perfect drugs: they can constrict human coronary arteries at therapeutic doses and, therefore, are contra-indicated in the presence of cardiovascular disease. Another problem with these agents is recurrence of moderate-to-severe pain within 24 h of initial headache relief. While mechanism-driven drug design has led to the development of various novel, albeit still imperfect, acute antimigraine medications, only a few new prophylactic agents have been made available to migraine clinicians. The efficacy of most, if not all of them has been discovered serendipitously. This is probably due to the fact that, while the pathophysiology of a migraine attack is now reasonably understood, the mechanisms leading to an attack are still mostly unknown. This update analyses the profile of some antimigraine drugs in clinical trials, their mode of action and their potential advantages or drawbacks over already available agents.

Adrenergic beta-Antagonists↗

PubMed2006

Pharmacokinetics and interactions of headache medications, part I: introduction, pharmacokinetics, metabolism and acute treatments.

Recent progress in the treatment of primary headaches has made available specific, effective and safe medications for these disorders, which are widely spread among the general population. One of the negative consequences of this undoubtedly positive progress is the risk of drug-drug interactions. This review is the first in a two-part series on pharmacokinetic drug-drug interactions of headache medications. Part I addresses acute treatments. Part II focuses on prophylactic treatments. The overall aim of this series is to increase the awareness of physicians, either primary care providers or specialists, regarding this topic. Pharmacokinetic drug-drug interactions of major severity involving acute medications are a minority among those reported in literature. The main drug combinations to avoid are: i) NSAIDs plus drugs with a narrow therapeutic range (i.e., digoxin, methotrexate, etc.); ii) sumatriptan, rizatriptan or zolmitriptan plus monoamine oxidase inhibitors; iii) substrates and inhibitors of CYP2D6 (i.e., chlorpromazine, metoclopramide, etc.) and -3A4 (i.e., ergot derivatives, eletriptan, etc.), as well as other substrates or inhibitors of the same CYP isoenzymes. The risk of having clinically significant pharmacokinetic drug-drug interactions seems to be limited in patients with low frequency headaches, but could be higher in chronic headache sufferers with medication overuse.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2004

Oral almotriptan: practical uses in the acute treatment of migraine.

Almotriptan (Almogran, Lundbeck; Almirall Prodesfarma; Axert, Ortho-McNeil) is a novel 5-HT(1B/1D) receptor agonist (triptan) that is widely available on prescription for the acute treatment of migraine. Almotriptan has pharmacodynamic and pharmacokinetic profiles that make it suitable for use in this indication. It is a potent agonist at 5-HT(1B), (1D) and (1F) receptors, while having a low affinity for other 5-HT receptors. It is also a potent inhibitor of neurogenic inflammation. Almotriptan has a high oral bioavailability, is absorbed rapidly, has a relatively short plasma half-life and its route of elimination presents few potential problems. Placebo-controlled dose-finding studies have demonstrated that almotriptan tablets are effective and well-tolerated in the acute treatment of migraine, with a 12.5 mg dose providing the best balance between efficacy and tolerability. Large placebo-controlled studies show that the efficacy of oral almotriptan is comparable with that of the other oral triptans. In direct comparator-controlled studies, almotriptan was as effective as sumatriptan 50 and 100 mg but had a superior tolerability profile. Furthermore, the efficacy and tolerability of almotriptan is sustained in the long term following open-label administration. Meta-analyses and post hoc analyses of clinical data confirm these findings. In conclusion, almotriptan 12.5 mg is a good therapeutic choice for the symptomatic treatment of acute migraine attacks.

Acute Disease↗

PubMed2003

[New drugs for the treatment of functional dyspepsia].

BACKGROUND: Functional dyspepsia is defined by upper gastrointestinal symptoms without any evidence of structural abnormalities or organic disease. Current pharmacological treatment of functional dyspepsia is largely empirical and involves anti-secretory or prokinetic drugs. AIMS: To review recent advances in the understanding of the mechanisms involved in symptom production in functional dyspepsia, as well as the development of new drugs that may interfere with these mechanisms, which may lead to more rational and effective treatment of this clinical condition. METHOD: Systematic review of papers published in English for the last 10 years. RESULTS: New drugs that increase propulsive gastroduodenal motor activity include new benzamides similar to cisapride, CCK-A blockers, agonists of opiate receptors and motilin agonists similar to erythromycin. A number of agents, including sumatriptan and buspirone, stimulates serotonin receptors in the myoenteric plexuses and have been shown to increase gastric accommodation to a meal. Finally, a number of new drugs that either increase thresholds for visceral perception or modify sensations is currently under investigation. This includes agents of several groups, such as octreotide, loxiglumide, ondansetron and other serotonin blockers, fedotozine and tricyclic antidepressant at low doses. CONCLUSIONS: Although these new drugs may improve the pharmacological approach to the treatment of functional dyspepsia, there is a need for randomized, controlled trials to assess their efficacy. Moreover, difficulties related to the identification of the mechanisms underlying symptoms may limit the utilization of these new drugs.

Dyspepsia↗

PubMed2003

The triptan formulations: a critical evaluation.

The migraine-specific triptans have revolutionized the treatment of migraine and are usually the drugs of choice to treat a migraine attack in progress. Different triptans are available in different strengths and formulations including oral tablets, orally disintegrating tablets, nasal sprays and subcutaneous injections. In Europe, sumatriptan is also available as a suppository. Specific differences among the triptans exist as evidenced by different pharmacological profiles including T1/2, Tmax, Cmax, AUC, metabolism, drug-drug interaction profiles, amongst other parameters. How or whether these differences translate to clinical efficacy and tolerability differences is not well differentiated. Clinical distinctions among these agents are subtle and proper choice of triptan requires attention to the specific characteristics of each individual patient, knowledge of patient preference, accurate history of the efficacy of previous acute care medications as well as individual features of the drug being considered. Delivery systems may play an important role in the onset of action of triptans. The selection of an acute antimigraine drug for a patient depends upon the stratification of the patient's migraine attack by peak intensity, time to peak intensity, level of associated symptoms such as nausea and vomiting, time to associated symptoms, comorbid diseases, and concomitant treatments that might cause drug-drug interactions. The clinician has in his armamentarium an ever-expanding variety of medications, available in multiple formulations and dosages, with good safety and tolerability profiles. Continued clinical use will yield familiarity with the various triptans, and it should become possible for the interested physician to match individual patient needs with the specific characteristics of a triptan to optimize therapeutic benefit.

Analgesics↗

PubMed1999

Migraine: a comprehensive review of new treatment options.

Headaches are among the most common complaints reported to health care professionals and are classified by the International Headache Society as migraine, tension-type, or cluster, with additional subtypes. Classification and etiology of headache should be determined after thorough review of the patient's history. Once diagnosed, migraine can be treated by preventive or abortive measures. Recent developments add new options, including availability of drugs for intranasal administration (sumatriptan, dihydroergotamine) and 5-HT1B/1D agonists (rizatriptan, zolmitriptan, naratriptan, eletriptan). Although placebo-controlled trials are available, few comparative clinical trials of these agents have been conducted; however, important pharmacologic, pharmacokinetic, and clinical differences exist among the drugs.

Analgesics, Opioid↗

PubMed1990

Safety by design.

Safety by design for any kind of drug requires it to act selectively on the cells which mediate the desired effect, and affect other cellular functions as little as possible. To illustrate this, the treatment of bronchial asthma was much improved during the past 20 years by the development of inhalation treatment based on drugs such as salbutamol (albuterol), a selective beta 2-adrenoceptor stimulant, and beclomethasone dipropionate, a topical anti-inflammatory steroid, from their parent physiological mediators epinephrine (adrenaline) and hydrocortisone (cortisol). Their development and that of H1- and H2-antagonists from histamine are described. From these and other sources the general conditions for safe, selective drug action and the range of drug effects that may be attained by modifying physiological mediators are deduced. This involves the identification and definition of type 1 and type 2 agonism. This analysis led to the discovery of salmaterol (salmeterol), a new uniquely long acting beta 2-adrenergic bronchodilator, by modification of salbutamol. The development, by modification of serotonin (5-hydroxytryptamine), of ondansetron, a new antiemetic for use in cancer chemotherapy, and sumatriptan, a new type of drug for treating migraine, are also described. All these new drugs are more efficacious and safer than their predecessors.

Animals↗

PubMed1998

Migraine in pregnancy: what are the safest treatment options?

The occurrence of migraine in women is influenced by hormonal changes throughout the lifecycle. A beneficial effect of pregnancy on migraine, mainly during the last 2 trimesters, has been observed in 55 to 90% of women who are pregnant, irrespective of the type of migraine. A higher percentage of women with menstrual migraine find that their condition improves when they are pregnant. However, in rare cases migraine may appear for the first time during pregnancy. The positive effects of pregnancy on migraine and the possible worsening post partum are probably related to the uniformly high and stable estrogen levels during pregnancy and the rapid fall-off thereafter. Nondrug therapies (relaxation, sleep, massage, ice packs, biofeedback) should be tried first to treat migraine in women who are pregnant. For treatment of acute migraine attacks 1000 mg of paracetamol (acetaminophen) preferably as a suppository is considered the first choice drug treatment. The risks associated with use of aspirin (acetylsalicylic acid) and ibuprofen are considered to be small when the agents are taken episodically and if they are avoided during the last trimester of pregnancy. The 'triptans' (sumatriptan, zolmitriptan, naratriptan), dihydroergotamine and ergotamine tartrate are contraindicated in women who are pregnant. Prochlorperazine for treatment of nausea is unlikely to be harmful during pregnancy. Metoclopramide is probably acceptable to use during the second and third trimester. Prophylactic treatment is rarely indicated and the only agents that can be given during pregnancy are the beta-blockers metoprolol and propranolol.

Acetaminophen↗