Caffeine appears in breastmilk rapidly after maternal ingestion. Insufficient high-quality data are available to make good evidence-based recommendations on safe maternal caffeine consumption.[1] Fussiness, jitteriness and poor sleep patterns have been reported in the infants of mothers with very high caffeine intakes equivalent to about 10 or more cups of coffee daily. Studies in mothers taking 5 cups of coffee daily found no stimulation in breastfed infants 3 weeks of age and older. A maternal intake limit of 300 to 500 mg daily might be a safe level of intake for most mothers, although European authorities set a likely safe level at 200 mg.[2-4] Maternal doses of caffeine greater than 130 mg daily may decrease weight gain in their exclusively breastfed infants, but this needs further confirmation.[5] However, preterm and younger newborn infants metabolize caffeine very slowly and may have serum levels of caffeine and other active caffeine metabolites similar to their mothers' levels, so a lower intake level preferable in the mothers of these infants.[2,6,7] Coffee is thought to decrease milk supply in some cultures, but there is no scientific information on coffee and milk supply.[8] Other sources of caffeine, such as cola and energy drinks, yerba mate or guarana, will have similar dose-related effects on the breastfed infant. Coffee intake of more than 450 mL daily may decrease breastmilk iron concentrations and result in mild iron deficiency anemia in some breastfed infants.[9]

After aspirin ingestion, salicylic acid is excreted into breastmilk, with higher doses resulting in disproportionately higher milk levels. Long-term, high-dose maternal aspirin ingestion probably caused metabolic acidosis in one breastfed infant. Reye's syndrome is associated with aspirin administration to infants with viral infections, but the risk of Reye's syndrome from salicylate in breastmilk is unknown. An alternate drug is preferred over continuous high-dose, aspirin therapy. After daily low-dose aspiring (75 to 325 mg daily), no aspirin is excreted into breastmilk and salicylate levels are low. Daily low-dose aspirin therapy may be considered as an antiplatelet drug for use in breastfeeding women.[1-3] If it is used by a nursing mother, monitor the infant for bruising and bleeding.

Butalbital in breastmilk has caused poor feeding and vomiting in one infant. Other agents are preferred, especially while nursing a newborn or preterm infant.

Butalbital (Fiorinal(®)), used in the treatment of migraines and muscle pain, is the most commonly encountered barbiturate in impaired driving cases. It has central nervous system (CNS) depressant properties, including sedation, drowsiness, and feelings of intoxication, which can contribute to driving impairment. Twenty-six driving under the influence cases are reviewed including results from field sobriety tests and toxicology testing. Blood samples were screened using enzyme multiplied immunoassay technique immunoassay, and the presence of butalbital was confirmed and quantified using gas chromatography/mass spectrometry, gas chromatography with flame ionization detection, or gas chromatography nitrogen/phosphorus detection. Butalbital concentrations ranged from 1.0 to 30.2 mg/L, with a mean and median of 16.0 mg/L. General impairment indicators in these cases included horizontal and vertical nystagmus, lack of convergence, poor motor coordination, and balance and speech problems, which are common to CNS depressant intoxication, similar to that associated with alcohol. These findings indicate the importance of toxicological testing for butalbital in cases where CNS depressants are indicated.

The aim of this study was to examine efficacy and tolerability of eletriptan in patients switched from barbiturate-containing combinations (Fiorinal), Fioricet. Migraineurs (n = 160) meeting IHS criteria, with unsatisfactory response in the past year to butalbital-containing combinations, treated up to 16 attacks over 3 months with eletriptan 40 mg. Assessments included headache response and pain-free rates and functional impairment at baseline and 2 h postdose, and global ratings of treatment satisfaction at 24 h. At 2 h postdose, average headache response and pain-free rates were 71% (95% CI, 69-74%) and 37% (95% CI, 35-40%), respectively; 68.5% of patients (95% CI, 65-72%) reported functional response. Within-patient analysis found no efficacy diminution over time (no tolerance). Average headache recurrence rate was 20% (95% CI, 18-23%). Eletriptan was well-tolerated; 6 (3.7%) patients discontinued due to adverse events. There were no serious treatment-related adverse events. We conclude that in poor responders to butalbital-caffeine combinations, switching to eletriptan 40 mg was well-tolerated and efficacious.

Butorphanol tartrate is a synthetic mixed agonist-antagonist opioid analgesic. Its transnasal dosage form, which may be self-administered when the use of an opioid analgesic is appropriate, was previously shown to provide rapid relief of migraine pain. In this double-blind, parallel-group, outpatient study, we compared butorphanol nasal spray 1 mg followed in 1 hour by an optional second 1-mg dose with the orally administered analgesic, Fiorinal with Codeine (one capsule containing butalbital 50 mg, caffeine 40 mg, aspirin 325 mg, and codeine phosphate 30 mg). Patients (N=321) were assigned by randomization to one of two treatment groups (butorphanol or Fiorinal with Codeine) and instructed to self-administer medication when migraine pain reached an intensity of moderate or severe and to record study-related events in a diary for 24 hours posttreatment. Efficacy analyses were performed on data from 275 patients who took study medication and returned a patient diary; 136 in the butorphanol group and 139 in the Fiorinal with Codeine group. During the first 2 hours after treatment, butorphanol was more effective than Fiorinal with Codeine in treating migraine pain as measured by pain intensity difference scores, percentage of responders (pain decreased to mild or none), percentage of pain-free patients, and degree of pain relief, with a more rapid time to onset of 15 minutes. A similar percentage of patients in the two groups used rescue medication during the first 4 hours, after which more butorphanol-treated than Fiorinal with Codeine-treated patients used rescue medication. Butorphanol patients had more side effects, less improvement in digestive symptoms, and less improvement in functional ability than Fiorinal with Codeine patients.

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.

Although the diamond anvil cell (DAC) has been used in many forensic science laboratories for the analysis of trace evidence, few applications of this technique for the analysis of controlled substances have been reported. This may be due to both an unfamiliarity on the part of forensic drug chemists with this accessory and the nature and quality of spectra that result from use of a DAC on a dispersive instrument. Along with low energy throughput, which results in relatively high noise levels, strong broad diamond absorptions occur. With the use of a Fourier transform infrared instrument, these do not present a problem and nanogram quantities of materials can be analyzed when the DAC is used with an infrared microscope. Since single crystals can be sampled with the DAC, simple physical separations (involving particle-picking) can be used in certain cases to isolate drugs from particulate mixtures for infrared analysis. This method is especially useful for some "difficult" mixtures and residues, and several examples of such analyses involving samples of forensic science interest are presented.

This report describes an acute organic brain syndrome with a fugue-like state in association with antimigraine pharmacotherapy. The differential diagnosis of: 1. possible psychotoxic effects of the combination of propranolol, imipramine, and butalbital; 2. confusional migraine with amnesia; and 3. psychogenic dissociation is considered. Although organically induced dissociative states are of clinical, neuropsychological and medico-legal significance, the DSM-III and DSM-III-R have specific categories only for dissociative conditions that are strictly psychogenic in origin.