Butalbital APAP Information Digest

Butalbital/APAP/Caffeine is a barbiturate sedative mixed with a non-aspirin pain medication (acetaminophen) and caffeine. This non-narcotic pain medication and relaxant is often prescribed for tension headaches caused by contractions of the muscles in the neck and shoulder area, and migraine.

Efficacy and safety of sumatriptan 50 mg in patients not responding to standard care, in the treatment of mild to moderate migraine. The Sumatriptan 50 mg Italian Study Group.

The tolerability and efficacy of oral sumatriptan 50 mg for the treatment of mild to moderate migraine attacks were assessed in a double-blind, multicenter placebo-controlled study on a group of patients who had not responded sufficiently to analgesic preparations. Three-hundred-and-twenty-eight migraine sufferers treated a first migraine attack with a nontriptan standard care medication: a mixture containing phenazone, butalbital and caffeine (optalidon) or indomethacin plus prochlorperazine plus caffeine (difmetre) or paracetamol 100 mg (tachipirine), depending on their habits. Of these patients, 32.6% reported headache relief with this treatment and were not included in phase II of the study. The 219 patients not reporting relief during the first phase of the study entered the second phase and were randomized to sumatriptan 50 mg or to placebo; 167 of these patients treated a second attack according to the protocol and were evaluated for efficacy. Of the patients with migraine taking sumatriptan, 58% reported headache relief compared with 35% of placebo-treated patients (p = 0.008). The reduction of nausea and vomiting was significantly better in the sumatriptan group. No differences were detected for the recurrence rate, while rescue medication was used more by the placebo group. The safety profile of sumatriptan 50 mg was confirmed. This study demonstrates the usefulness of this dose of oral sumatriptan against the pain and the accompanying symptoms of mild and moderate migraine.

Comparison of the serum barbiturate fluorescence polarization immunoassay by the COBAS INTEGRA to a GC/MS method.

The authors evaluated a new Cassette Serum Barbiturates fluorescence polarization immunoassay (FPIA) on the COBAS INTEGRA. The assay was calibrated with secobarbital standards at 0, 0.5, and 4.0 microg/mL. The assay range was 0.030 to 80 microg/mL using an automatic 1/20 postdilution feature. Precision was established for two COBAS INTEGRA instruments for ten days by assaying secobarbital target concentrations ranging from 0.125 to 2.2 microg/mL. The coefficients of variation (CV) for the above target concentrations for the first instrument ranged from 2.7% to 8.3%, and for a second instrument, 3.8 to 8.3%. Seven clinically elevated bilirubin samples were spiked with 0.46 and 1.77 microg/mL secobarbital. Bilirubin interference was less than 10.9 and less than 7.9%, respectively. The average recovery ranged from 85% to 94%. The mean difference in recovery in serum versus plasma was < or = 3%. Fifty-two clinical samples were analyzed for butalbital, pentobarbital, secobarbital, and phenobarbital by GC/MS, and the results were compared to the new Cassette Serum Barbiturates FPIA. The diagnostic sensitivity and specificity were 95% and 100%, respectively. Both FPIA and GC/MS assays are clinically efficacious for monitoring serum barbiturates.

Intractable vomiting, convulsions and megaloblastic anemia: anamnesis, key to diagnosis

In July 1996 a 43-year-old illiterate Hispanic woman presented with uncontrollable vomiting, palpitations and confusion. In 1994, despite several hospitalisations in other medical centres where a cerebral CT-scan, oesogastroduodenoscopy, colonoscopy and abdominal ultrasound were performed, no satisfactory diagnosis could be found. A psychiatric origin was finally considered. On admission, the laboratory findings showed severe metabolic alkalosis with associated hypokalaemia, confirmatory evidence of vomiting. The ECG showed tremendous P waves (5 mV) in the standard derivations, which can be explained by the hypokalaemia, with multiple supraventricular extrasystoles. Echocardiography and pulmonary scintigraphy ruled out pulmonary hypertension and a pulmonary embolus. After additional discussion with her daughter we discovered that the patient had been treating chronic headaches for years with 4-5 Cafergot-PB suppositories per day. This drug contains 2 mg ergotamine tartrate, 100 mg butalbital, 100 mg caffeine and 0.25 mg belladona alkaloids. As is known, vomiting is a classical symptom of ergotamine intoxication. After rehydration we discovered a megaloblastic anaemia with a folate deficiency compatible with chronic barbiturate intoxication. Folate and iron supplementation allowed a rapid normalisation of the haemoglobin values. Five months after having stopped the Cafergot-PB, the patient was well and did not vomit anymore. The headaches were treated with chlorpromazine with a good result. Despite sophisticated technical means, the diagnosis could only be established after a thorough history taking. This message should be heard in times when high tech medicine tends to obscure the place of a good history taking!

Barbiturate withdrawal syndrome: a case associated with the abuse of a headache medication

Barbiturates can produce psychological and physical dependence and produce a withdrawal syndrome on the second to fourth day after the drug is suspended. Symptoms include anxiety, restlessness, insomnia, rhythmic intention tremor, dizziness, seizures, and psychosis. If the syndrome is not recognized and correctly treated, hyperthermia, circulatory failure, and death may ensue. Although barbiturates are less frequently used nowadays, they are employed in combination with other drugs in many medications used for the treatment of headache. We report the case of a 54-year-old woman who developed a barbiturate abstinence syndrome when she suspended self-administration of a drug containing butalbital. The patient had been using barbiturates, 900 mg/die, for 2+ years for persistent headache. She was admitted to the hospital because of seizures, hallucinations and delirium not controlled by benzodiazepine and phenothiazine administration. Her symptoms resolved after parenteral phenobarbital administration.

Vitamin B2 interference with TDx drugs-of-abuse assays.

Migraine is a headache condition found in significant frequency in the general population. One recent study has shown that riboflavin, Vitamin B2, is an effective prophylactic treatment for this headache condition. One subject in a recent study conducted by the Division of Forensic Toxicology, Armed Forces Institute of Pathology (AFIP) was taking 200 mg of riboflavin twice daily for the prevention of migraine headaches. When that subjects urine was tested using Abbott TDx drugs-of-abuse assays a number of tests resulted in a MX BKG error and all samples had BLK I values greater than those observed with normal urine specimens. The MX BKG error occurs when the BLK I value is greater than the upper limit determined by the manufacturer for a particular assay. High BLK I values may result if the specimen being analyzed contains a fluorophore that will compete with the fluorescein-labeled antibody used in the assay. This error serves as a notification that an interfering substance may be present and the assay is not performing according to manufacturer-specifications. Upon termination of riboflavin therapy the subjects BLK I values began to decrease within 60 h of the last 200 mg dose. A second subject began chronic riboflavin use to confirm this interferent effect. Elevated BLK I values resulted within 3 h of a single 200 mg dose and MX BKG errors occurred 1 h after a second 400 mg dose. No false negative results were noted with either subject (both subjects used butalbital and the first subject also used hydrocodone and diazepam during the study), suggesting that riboflavin is not an adulterant. Riboflavin use, however, does interfere with the TDx DAU assays and may result in quantitative values being determined which are of questionable validity in the face of an elevated BLK I value or may result in only an MX BKG error and no quantitative value reported. It is unclear if the interfering fluorophore is simply riboflavin itself or a combination of riboflavin and its metabolic products. Results obtained on urine samples collected from individuals using prophylactic riboflavin for migraine prevention and analyzed by TDx may be of questionable validity. Such samples may require analysis utilizing another immunoassay technique that does not employ a fluorescein-labeled antibody.

Supercritical fluid extraction and negative ion electrospray liquid chromatography tandem mass spectrometry analysis of phenobarbital, butalbital, pentobarbital and thiopental in human serum.

Four commonly used barbiturates (phenobarbital, butalbital, pentobarbital and thiopental) were analyzed in human serum using supercritical fluid extraction (SFE) and negative ionization LC/ESI-MS/MS. Barbital was used as the internal standard. Carbon dioxide SFE was performed at 40 degrees C and 500 atm, with a total extraction time of 35 min. The analytes were collected off-line in a liquid trap containing absolute methanol. Samples were then concentrated by vacuum centrifugation. The high performance liquid chromatography separation utilized gradient elution with a total analysis time of 21 min. The precursor and major product ions for the four barbiturates were monitored on a triple quadrupole mass spectrometer with negative ion electrospray ionization (ESI) in the multiple reaction monitoring mode as follows: (1) thiopental (m/z 241.20-->58.00), (2) phenobarbital (m/z 231.10-->188.0), (3) pentobarbital (m/z 225.10-->181.90) and (4) butalbital (m/z 222.80-->179.90). In the case of phenobarbital, pentobarbital and butalbital, the most abundant product ion arises from the loss of 43 u (HCNO loss). However, in the case of thiopental, the most abundant product ion was observed at m/z 58.0 (the [M-183]-ion, or NCS-). Mechanisms for the formation of the collision induced dissociation reaction products of these barbiturates are proposed.

GC/MS confirmation of barbiturates in blood and urine.

A gas chromatography-mass spectrometric method is described for the quantitative measurement of 6 commonly used barbiturates in blood and urine specimens. The targeted barbiturates are butalbital, amobarbital, pentobarbital, secobarbital, mephobarbital and phenobarbital. They are recovered along with the internal standard, tolybarb, from blood and urine using liquid extraction then alkalated to form the N-ethyl derivatives. The ethylated barbiturates have symmetrical peaks which are well separated from each other on a non-polar methylsilicone capillary column. The derivatives on a non-polar methylsilicone capillary column. The derivatives facilitate quantitations between 50 and 10,000 ng/mL. The day-to-day CVs for all 6 barbiturates were between 4 and 9% at 200 and 5000 ng/mL. The method has been extended for identifying other acidic drugs and drug metabolites. They are mainly non-steroidal anti-inflammatory drugs, diuretics, and anticonvulsants. An additional 83 compounds can be qualitatively identified.

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