Effects of barbiturates on human platelet aggregation differ depending on their chemical structures.

Sato M, Hirakata H, Ikeda M, Fukuda K.

Department of Anesthesia, Kyoto University Hospital, Sakyo-ku, Kyoto 606-8507, Japan.

The effects of barbiturates on human platelet function are not fully understood. Since we have already revealed the effects and mechanisms of thiopental, thiamylal, and pentobarbital in platelets, the present study attempted to elucidate (i) the effects of other barbiturates on human platelet aggregation, (ii) the underlying mechanisms, and (iii) the structure-function relationship of barbiturates in platelets. Barbiturates, including amobarbital, butalbital, secobarbital, barbital, phenobarbital, metharbital, and primidone, were examined. Human platelet aggregation induced by adenosine diphosphate (ADP), epinephrine, and (+)-9,11-epithia-11,12-methano-thromboxane A2 (STA2), a thromboxane A2 analog, was measured using an 8-channel light-transmission aggregometer. The cytosolic free calcium concentration ([Ca2+]i) was measured by fluorometer using fura-2 loaded platelets. Inositol 1,4,5-trisphosphate (IP3) formation induced by STA2 was determined by a commercially available IP3 assay kit. Amobarbital, butalbital, and secobarbital suppressed ADP-, epinephrine- and STA2-induced platelet aggregation and the STA2-induced [Ca2+]i increase, even when Ca2+ influx was blocked by Ni2+. However, they did not affect STA2-induced IP3 formation. Barbital, phenobarbital, metharbital, and primidone (up to 1 mM) had no effect on ADP- and epinephrine-induced platelet aggregation. Thus, we conclude that amobarbital, butalbital, and secobarbital inhibit platelet aggregation by suppressing [Ca2+]i increase without affecting IP3 formation. However, these antiaggregatory effects may not have clinical importance, since the barbiturate concentrations used were higher than clinically relevant ones. The other tested barbiturates had no effects on platelet aggregation. The data indicate that the effects of barbiturates on platelet aggregation differ depending on their chemical structures.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=&dopt=Abstract butalbital fioricet barbiturate




Oral phenobarbital loading: a safe and effective method of withdrawing patients with headache from butalbital compounds.

Loder E, Biondi D.

Headache and Pain Management Program, The Spaulding Rehabilitation Hospital, Boston, Mass 02114, USA.

BACKGROUND: The overuse of short-acting barbiturate medications for the acute treatment of headache is a common problem in the United States. Most experts agree that withdrawal from these medications is necessary for subsequent headache treatment to be successful, yet there are few published articles outlining effective methods of drug withdrawal. OBJECTIVE: To evaluate the safety and effectiveness of phenobarbital loading for withdrawal from overuse of short-acting barbiturate compounds in inpatients with headache. DESIGN AND METHODS: We performed a retrospective chart review of 18 consecutive patients in an inpatient pain rehabilitation program who were withdrawn from overuse of butalbital-combination medications using a phenobarbital-loading protocol. RESULTS: Eighteen patients with headache hospitalized in an inpatient pain unit for withdrawal from overuse of combination butalbital preparations underwent a phenobarbital-loading protocol. Short-acting barbiturate medications were discontinued, and patients received 120 mg of oral phenobarbital until their score on a predetermined scale reached target levels, and the drug was then discontinued. All patients were effectively treated with no serious adverse events. The median number of doses required varied significantly, and could not be predicted by the patient's prior intake. CONCLUSIONS: Management of butalbital withdrawal can be simplified by using a phenobarbital-loading protocol, taking advantage of the natural tapering afforded by the drug's long half-life. This method possesses most of the characteristics of an ideal drug withdrawal program for patients with headache who are overusing medications.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=&dopt=Abstract butalbital fioricet barbiturate




Simplified butalbital withdrawal protocol.

Mauskop A.

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Transformed migraine and medication overuse in a tertiary headache centre--clinical characteristics and treatment outcomes.

Bigal ME, Rapoport AM, Sheftell FD, Tepper SJ, Lipton RB.

Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, USA. mbigal aecom.yu.edu

Studies suggest that a substantial proportion of headache sufferers presenting to headache clinics may overuse acute medications. In some cases, overuse may be responsible for the development or maintenance of a chronic daily headache (CDH) syndrome. The objectives of this study are to evaluate patterns of analgesic overuse in patients consulting a headache centre and to compare the outcomes in a group of patients who discontinued medication overuse to those of a group who continued the overuse, in patients with similar age, sex and psychological profile. We reviewed charts of 456 patients with transformed migraine (TM) and acute medication overuse defined by one of the following criteria: 1. Simple analgesic use (>1000 mg ASA/acetaminophen) > 5 days/week; 2. Combination analgesics use (caffeine and/or butalbital) > 3 tablets a day for > 3 days a week; 3. Opiate use > 1 tablet a day for > 2 days a week; 4. Ergotamine tartrate use: 1 mg PO or 0.5 mg PR for > 2 days a week. For triptans, we empirically considered overuse > 1 tablet per day for > 5 days per week. Patients who were able to undergo detoxification and did not overuse medication (based on the above definition) after one year of follow-up were considered to have successful detoxification (Group 1). Patients who were not able to discontinue offending agents, or returned to a pattern of medication overuse within one year were considered to have unsuccessful detoxification (Group 2). We compared the following outcomes after one year of follow-up: Number of days with headache per month; Intensity of headache; Duration of headache; Headache score (frequency x intensity). The majority of patients overused more than one type of medication. Numbers of tablets taken ranged from 1 to 30 each day (mean of 5.2). Forty-eight (10.5%) subjects took >10 tablets per day. Considering patients seen in the last 5 years, we found the following overused substances: Butalbital containing combination products, 48%; Acetaminophen, 46.2%; Opioids, 33.3%; ASA, 32.0%; Ergotamine tartrate, 11.8%; Sumatriptan, 10.7%; Nonsteroidal anti-inflammatory medications other than ASA, 9.8%; Zolmitriptan, 4.6%; Rizatriptan, 1.9%; Naratriptan, 0.6%. Total of all triptans, 17.8%. Of 456 patients, 318 (69.7%) were successfully detoxified (Group 1), and 138 (30.3%) were not (Group 2). The comparison between groups 1 and 2 after one year of follow-up showed a decrease in the frequency of headache of 73.7% in group 1 and only 17.2% in group 2 (P < 0.0001). Similarly, the duration of head pain was reduced by 61.2% in group 1 and 14.8% in group 2 (P < 0.0001). The headache score after one year was 18.8 in group 1 and 54 in group 2 (P < 0.0001). A total of 225 (70.7%) successfully detoxified subjects in Group 1 returned to an episodic pattern of migraine, compared to 21 (15.3%) in Group 2 (P < 0.001). More rigorous prescribing guidelines for patients with frequent headaches are urgently needed. Successful detoxification is necessary to ensure improvement in the headache status when treating patients who overuse acute medications. Copyright Blackwell Publishing Ltd.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=&dopt=Abstract butalbital fioricet barbiturate




Migraine headache misconceptions: barriers to effective care.

Wenzel R, Dortch M, Cady R, Lofland JH, Diamond S.

Diamond Headache Clinic Inpatient Unit, Saint Joseph Hospital, Resurrection Health Care, Chicago, Illinois 60657, USA. rwenz hotmail.com

Migraine headaches affect 12% of the adult population in the United States and cause a significant economic loss due to decreased workplace productivity Although interactions between pharmacists and individuals with headache are common, few pharmacists receive adequate training regarding migraine therapy. We refute several misconceptions that hinder effective care, such as that migraine is a vascular disease, triptans cause rampant cardiacrelated morbidity and even mortality, a best oral triptan exists, sinus and tension headaches are prevalent, and migraine is a minor economic problem. Our pathophysiologic understanding demonstrates that migraine is a neurologic process of the trigeminovascular system, of which vascular effects are secondary. This process can result in a myriad of clinical signs and symptoms, often leading to a misdiagnosis of sinus or tension headache. The last decade's experience with triptans in more than half a billion people worldwide reveals a benign adverse-effect profile, particularly when taken early in an attack. Published reports and real-world experiences illustrate that these drugs do not merit fears of triptan-induced cardiac consequences in appropriately selected individuals. Society's productivity loss due to migraine is measured in billions of dollars. Restoring a patient's ability to function normally is now recognized as the primary treatment goal, not merely relieving pain. Thus, the overreliance on "pain killer" drugs such as butalbital-containing products and the continued underutilization of migraine-specific drugs need to be addressed. Opportunities exist for pharmacists and other health care providers to dispel continually propagated migraine misconceptions and familiarize themselves with advances in therapy. Such actions will benefit patients, the health care system, and society as a whole.

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